The umbilical cord in Cantrell: Pentalogy or Hexalogy?

Objective: Pentalogy of Cantrell (PC) is a rare congenital defect associated with five midline anomalies. The type of cardiac malformation and the size of the abdominal wall defect is often responsible for the high mortality. Of interest, the embryonic period in which PC develops is similar to that of the umbilical cord’s (UC) formation. The aim of the following study was to investigate the relationship between UC anomalies and PC. Methods: Charts of four cases with PC from 2002–08 were retrospectively reviewed for associated UC anomalies. UC anomalies were defined as single umbilical artery (SUA), short cord (during 1st trimester less than CRL or less than 30cm at term) or atypical UC coiling pattern. Results: We identified four cases: 3 singletons and one monochorionic diamniotic twin pregnancy with TRAP sequence. All cases showed a normal karyotype. All but one demonstrated the classical pulsatile omphalocele with ectopia cordis and all others anomalies of PC. One case was characterized by a major cranial omphalocele without ectopia cordis and no UC anomaly. This fetus was delivered by Cesarean at term and successfully operated on d1. In all other cases the parents requested ToP. Among the three cases with ectopia cordis, two had a short UC with SUA and one a short three-vessel cord; all these three UC were markedly uncoiled. Conclusions: Our data suggest a strong association between Cantrell and the development of the UC, in particular in cases with ectopia cordis. One might speculate that hemodynamic alterations of the feto-placental blood flow because of the cardiac malformation or structural changes at the umbilical ring (omphalocele) influence the development of the UC. More observations are needed to decide if Cantrell is a ‘‘hexalogy’’ instead of pentalogy.

BAYESIAN PHASE I DOSE FINDING IN CANCER TRIALS

This dissertation explores phase I dose-finding designs in cancer trials from three perspectives: the alternative Bayesian dose-escalation rules, a design based on a time-to-dose-limiting toxicity (DLT) model, and a design based on a discrete-time multi-state (DTMS) model. We list alternative Bayesian dose-escalation rules and perform a simulation study for the intra-rule and inter-rule comparisons based on two statistical models to identify the most appropriate rule under certain scenarios. We provide evidence that all the Bayesian rules outperform the traditional ``3+3'' design in the allocation of patients and selection of the maximum tolerated dose. The design based on a time-to-DLT model uses patients' DLT information over multiple treatment cycles in estimating the probability of DLT at the end of treatment cycle 1. Dose-escalation decisions are made whenever a cycle-1 DLT occurs, or two months after the previous check point. Compared to the design based on a logistic regression model, the new design shows more safety benefits for trials in which more late-onset toxicities are expected. As a trade-off, the new design requires more patients on average. The design based on a discrete-time multi-state (DTMS) model has three important attributes: (1) Toxicities are categorized over a distribution of severity levels, (2) Early toxicity may inform dose escalation, and (3) No suspension is required between accrual cohorts. The proposed model accounts for the difference in the importance of the toxicity severity levels and for transitions between toxicity levels. We compare the operating characteristics of the proposed design with those from a similar design based on a fully-evaluated model that directly models the maximum observed toxicity level within the patients' entire assessment window. We describe settings in which, under comparable power, the proposed design shortens the trial. The proposed design offers more benefit compared to the alternative design as patient accrual becomes slower.

Is a black eye a useful sign of facial fractures in patients with minor head injuries? A retrospective analysis in a level I trauma centre over 10 years

Orbital blunt trauma is common, and the diagnosis of a fracture should be made by computed tomographic (CT) scan. However, this will expose patients to ionising radiation. Our objective was to identify clinical predictors of orbital fracture, in particular the presence of a black eye, to minimise unnecessary exposure to radiation. A 10-year retrospective study was made of the medical records of all patients with minor head trauma who presented with one or two black eyes to our emergency department between May 2000 and April 2010. Each of the patients had a CT scan, was over 16 years old, and had a Glasgow Coma Score (GCS) of 13-15. The primary outcome was whether the black eye was a valuable predictor of a fracture. Accompanying clinical signs were considered as a secondary outcome. A total of 1676 patients (mean (SD) age 51 (22) years) and minor head trauma with either one or two black eyes were included. In 1144 the CT scan showed a fracture of the maxillofacial skeleton, which gave an incidence of 68.3% in whom a black eye was the obvious symptom. Specificity for facial fractures was particularly high for other clinical signs, such as diminished skin sensation (specificity 96.4%), diplopia or occulomotility disorders (89.3%), fracture steps (99.8%), epistaxis (95.5%), subconjunctival haemorrhage (90.4%), and emphysema (99.6%). Sensitivity for the same signs ranged from 10.8% to 22.2%. The most striking fact was that 68.3% of all patients with a black eye had an underlying fracture. We therefore conclude that a CT scan should be recommended for every patient with minor head injury who presents with a black eye.

STUDIES ON THE CLASS I GLYCOPROTEINS OF THE MURINE MAJOR HISTOCOMPATIBILITY COMPLEX (TRANSPLANTATION ANTIGEN, LYMPHOCYTE, CELL SURFACE MOLECULE)

A series of studies were undertaken to analyze and compare various aspects of murine class I glycoproteins. An initial area of investigation characterized the Qa-1 alloantigens using two-dimensional gel electrophoresis. Analysis of the products of the Qa-1('b), Qa-1('c) and Qa-1('d) alleles indicated that these were distinct molecules as determined by their lack of comigration upon comparative two-dimensional gel analysis. The importance of asparagine-linked glycosylation in the cell surface expression of class I molecules was also examined. These studies employed tunicamycin, an inhibitor of N-linked glycosylation. Tunicamycin treatment of activated T lymphocytes diminished the surface expression of Qa-1 to undetectable levels; the levels of other class I molecules exhibited little or no decrease. These results indicated that N-linked glycosylation has a differential importance in the cell surface expression of various class I molecules. The molecular weight diversity of class I molecules was also investigated. Molecular weight determination of both the fully glycosylated and unglycosylated forms of H-2 and Qa/Tla region encoded molecules established that there is a significant variation in the sizes of these forms of various class I molecules. The most significant difference ((TURN)9,000 daltons) exists between the unglycosylated forms of H-2K('b) and Qa-2, suggesting that the structural organization of these two molecules may be very different. A comparative two-dimensional gel analysis of various class I glycoproteins isolated from resting and activated T and B lymphocytes indicated that class I molecules expressed on activated T cells exhibited an isoelectrophoretic pattern that was distinct from the isoelectrophoretic pattern of class I molecules expessed on the other cell populations. This difference was attributed to a lower sialic acid content of the molecules expressed on activated T cells. Analysis of cell homogenates determined that activated T cells contained a higher level of endogenous neuraminidase activity than was detected in the other populations, suggesting that this may be the basis of the lower sialic acid content. The relationship of the Qa-4 and Qa-2 alloantigens was also examined. It was established that upon mitogen activation, the expression of Qa-4 was greatly decreased, whereas Qa-2 expression was not decreased. However, an anti-Qa-2 monoclonal antibody blocked the binding of an anti-Qa-4 monoclonal antibody to resting cells. These studies established that Qa-4 is a determinant restricted to resting cells, which is closely associated on the surface with the Qa-2 molecule. ^

Molecular interactions and signal transfer between sensory rhodopsin-I and its cognate transducer

SRI is unique among known photoreceptors in that it produces opposite signals depending on the color of light stimuli. Absorption of orange light (587 nm) triggers an attractant response by the cell, whereas absorption of orange light followed by near-UV light (373 run) triggers a repellent response. Using behavioral mutants that exhibit aberrant color-sensing ability, we tested a two-conformation equilibrium model, using FRET and EPR spectroscopy. The essence of the model applied to SRI-HtrI is that the complex exists in a metastable two-conformer equilibrium which is shifted in one direction by orange light absorption (producing an attractant signal) and in the opposite direction by a second UV-violet photon (producing a repellent signal). First, by FRET we found that the E-F cytoplasmic loop of SRI moves toward the RAMP domain of the HtrI transducer during the formation of the orange-light activated signaling state of the complex. This is the first localization of a change in the physical relationship between the receptor and transducer subunits of the complex and provides a structural property of the two proposed conformers that we can monitor. Second, EPR spectra of a spin label probe at this cytoplasmic position showed shifts in the dark in the mutants toward shorter or longer EF loop-RAMP distances, explaining their behavior in terms of their mutations causing pre-stimulus shifts into one or the other conformer. ^ Next, we applied a novel electrophysiological method for monitoring the directionality of proton movement during photoactivation of SRI, to investigate the process of proton transfer in the photoactive site from the chromophore to proton acceptors on both the wildtype and aberrant color-response mutants. We observed an unexpected and critical difference in the two signaling conformations of the SRI-HtrI complex. The finding is that the vectoriality (i.e. movement away or toward the cytoplasm) of the light-induced proton transfer from the chromophore to the protein is opposite in formation of the two conformations. Retinylidene proton transfer is a common critical process in rhodopsins and these results are the first to show differences in vectoriality in a rhodopsin receptor, and to demonstrate functional importance of the direction of proton transfer. ^

UNDERSTANDING INTERRUPTIONS IN HEALTHCARE: DEVELOPING A MODEL

Developing a Model Interruption is a known human factor that contributes to errors and catastrophic events in healthcare as well as other high-risk industries. The landmark Institute of Medicine (IOM) report, To Err is Human, brought attention to the significance of preventable errors in medicine and suggested that interruptions could be a contributing factor. Previous studies of interruptions in healthcare did not offer a conceptual model by which to study interruptions. As a result of the serious consequences of interruptions investigated in other high-risk industries, there is a need to develop a model to describe, understand, explain, and predict interruptions and their consequences in healthcare. Therefore, the purpose of this study was to develop a model grounded in the literature and to use the model to describe and explain interruptions in healthcare. Specifically, this model would be used to describe and explain interruptions occurring in a Level One Trauma Center. A trauma center was chosen because this environment is characterized as intense, unpredictable, and interrupt-driven. The first step in developing the model began with a review of the literature which revealed that the concept interruption did not have a consistent definition in either the healthcare or non-healthcare literature. Walker and Avant’s method of concept analysis was used to clarify and define the concept. The analysis led to the identification of five defining attributes which include (1) a human experience, (2) an intrusion of a secondary, unplanned, and unexpected task, (3) discontinuity, (4) externally or internally initiated, and (5) situated within a context. However, before an interruption could commence, five conditions known as antecedents must occur. For an interruption to take place (1) an intent to interrupt is formed by the initiator, (2) a physical signal must pass a threshold test of detection by the recipient, (3) the sensory system of the recipient is stimulated to respond to the initiator, (4) an interruption task is presented to recipient, and (5) the interruption task is either accepted or rejected by v the recipient. An interruption was determined to be quantifiable by (1) the frequency of occurrence of an interruption, (2) the number of times the primary task has been suspended to perform an interrupting task, (3) the length of time the primary task has been suspended, and (4) the frequency of returning to the primary task or not returning to the primary task. As a result of the concept analysis, a definition of an interruption was derived from the literature. An interruption is defined as a break in the performance of a human activity initiated internal or external to the recipient and occurring within the context of a setting or location. This break results in the suspension of the initial task by initiating the performance of an unplanned task with the assumption that the initial task will be resumed. The definition is inclusive of all the defining attributes of an interruption. This is a standard definition that can be used by the healthcare industry. From the definition, a visual model of an interruption was developed. The model was used to describe and explain the interruptions recorded for an instrumental case study of physicians and registered nurses (RNs) working in a Level One Trauma Center. Five physicians were observed for a total of 29 hours, 31 minutes. Eight registered nurses were observed for a total of 40 hours 9 minutes. Observations were made on either the 0700–1500 or the 1500-2300 shift using the shadowing technique. Observations were recorded in the field note format. The field notes were analyzed by a hybrid method of categorizing activities and interruptions. The method was developed by using both a deductive a priori classification framework and by the inductive process utilizing line-byline coding and constant comparison as stated in Grounded Theory. The following categories were identified as relative to this study: Intended Recipient - the person to be interrupted Unintended Recipient - not the intended recipient of an interruption; i.e., receiving a phone call that was incorrectly dialed Indirect Recipient – the incidental recipient of an interruption; i.e., talking with another, thereby suspending the original activity Recipient Blocked – the intended recipient does not accept the interruption Recipient Delayed – the intended recipient postpones an interruption Self-interruption – a person, independent of another person, suspends one activity to perform another; i.e., while walking, stops abruptly and talks to another person Distraction – briefly disengaging from a task Organizational Design – the physical layout of the workspace that causes a disruption in workflow Artifacts Not Available – supplies and equipment that are not available in the workspace causing a disruption in workflow Initiator – a person who initiates an interruption Interruption by Organizational Design and Artifacts Not Available were identified as two new categories of interruption. These categories had not previously been cited in the literature. Analysis of the observations indicated that physicians were found to perform slightly fewer activities per hour when compared to RNs. This variance may be attributed to differing roles and responsibilities. Physicians were found to have more activities interrupted when compared to RNs. However, RNs experienced more interruptions per hour. Other people were determined to be the most commonly used medium through which to deliver an interruption. Additional mediums used to deliver an interruption vii included the telephone, pager, and one’s self. Both physicians and RNs were observed to resume an original interrupted activity more often than not. In most interruptions, both physicians and RNs performed only one or two interrupting activities before returning to the original interrupted activity. In conclusion the model was found to explain all interruptions observed during the study. However, the model will require an even more comprehensive study in order to establish its predictive value.

Proyecto de Investigación. Aproximaciones teóricas. Identidades en juego: prácticas lúdicas en jóvenes mapuches

El siguiente artículo tiene dos lecturas: una primera parte en la que expongo de manera sucinta, algunas razones por las cuales considero necesario llevar a cabo éste proyecto de investigación, lo que podría ser leído, como el área de interés. En segundo término, me sumerjo en cuestiones más complejas, concretamente, desde que perspectivas es posible enmarcar conceptualmente, algunas de las categorías que sustenten teóricamente el "proyecto" de investigación. Muchos conceptos provienen de diferentes autores, por lo que éste eclecticismo, intentará ser compensado con precisiones teóricas mas ajustadas en una fase posterior, el marco teórico de la tesis. En ésta propuesta, la cuestión central, es comprender de qué manera, los jóvenes de ascendencia mapuche, logran a través de diferentes prácticas lúdicas significar diferentes procesos de identificaciones culturales. Por tal motivo, algunas referencias, a los conceptos de: Alteridad-otredad, Identidad Cultural, Prácticas, Representaciones, Juego, aparecen como categorías necesarias a ser explicitadas en el marco del trabajo. Aquí, por cuestiones de espacio haré un desarrollo dispar, priorizando algunas sobre otras. La investigación se vinculará, a la vertiente cualitativa-etnográfica, pues, éste parece ser el camino mas adecuado para captar la comprensión de un fenómeno social, desde la perspectiva de los "actores" ("agentes" o "sujetos sociales)" (Guber, R. 2001:20).

Proyecto de Investigación. Aproximaciones teóricas. Identidades en juego: prácticas lúdicas en jóvenes mapuches

El siguiente artículo tiene dos lecturas: una primera parte en la que expongo de manera sucinta, algunas razones por las cuales considero necesario llevar a cabo éste proyecto de investigación, lo que podría ser leído, como el área de interés. En segundo término, me sumerjo en cuestiones más complejas, concretamente, desde que perspectivas es posible enmarcar conceptualmente, algunas de las categorías que sustenten teóricamente el "proyecto" de investigación. Muchos conceptos provienen de diferentes autores, por lo que éste eclecticismo, intentará ser compensado con precisiones teóricas mas ajustadas en una fase posterior, el marco teórico de la tesis. En ésta propuesta, la cuestión central, es comprender de qué manera, los jóvenes de ascendencia mapuche, logran a través de diferentes prácticas lúdicas significar diferentes procesos de identificaciones culturales. Por tal motivo, algunas referencias, a los conceptos de: Alteridad-otredad, Identidad Cultural, Prácticas, Representaciones, Juego, aparecen como categorías necesarias a ser explicitadas en el marco del trabajo. Aquí, por cuestiones de espacio haré un desarrollo dispar, priorizando algunas sobre otras. La investigación se vinculará, a la vertiente cualitativa-etnográfica, pues, éste parece ser el camino mas adecuado para captar la comprensión de un fenómeno social, desde la perspectiva de los "actores" ("agentes" o "sujetos sociales)" (Guber, R. 2001:20).

Proyecto de Investigación. Aproximaciones teóricas. Identidades en juego: prácticas lúdicas en jóvenes mapuches

El siguiente artículo tiene dos lecturas: una primera parte en la que expongo de manera sucinta, algunas razones por las cuales considero necesario llevar a cabo éste proyecto de investigación, lo que podría ser leído, como el área de interés. En segundo término, me sumerjo en cuestiones más complejas, concretamente, desde que perspectivas es posible enmarcar conceptualmente, algunas de las categorías que sustenten teóricamente el "proyecto" de investigación. Muchos conceptos provienen de diferentes autores, por lo que éste eclecticismo, intentará ser compensado con precisiones teóricas mas ajustadas en una fase posterior, el marco teórico de la tesis. En ésta propuesta, la cuestión central, es comprender de qué manera, los jóvenes de ascendencia mapuche, logran a través de diferentes prácticas lúdicas significar diferentes procesos de identificaciones culturales. Por tal motivo, algunas referencias, a los conceptos de: Alteridad-otredad, Identidad Cultural, Prácticas, Representaciones, Juego, aparecen como categorías necesarias a ser explicitadas en el marco del trabajo. Aquí, por cuestiones de espacio haré un desarrollo dispar, priorizando algunas sobre otras. La investigación se vinculará, a la vertiente cualitativa-etnográfica, pues, éste parece ser el camino mas adecuado para captar la comprensión de un fenómeno social, desde la perspectiva de los "actores" ("agentes" o "sujetos sociales)" (Guber, R. 2001:20).

Chapter 8 Location Choice of Japanese Multinationals: Country Characteristics or Region Characteristics?

In the present global era in which firms choose the location of their plants beyond national borders, location characteristics are important for attracting multinational enterprises (MNEs). The better access to countries with large market is clearly attractive for MNEs. For example, special treatments on tariffs such as the Generalized System of Preferences (GSP) are beneficial for MNEs whose home country does not have such treatments. Not only such country characteristics but also region characteristics (i.e. province-level or city-level ones) matter, particularly in the case that location characteristics differ widely between a nation's regions. The existence of industrial concentration, that is, agglomeration, is a typical regional characteristic. It is with consideration of these country-level and region-level characteristics that MNEs decide their location abroad. A large number of academic studies have investigated in what kinds of countries MNEs locate, i.e. location choice analysis. Employing the usual new economic geography model (i.e. constant elasticity of substitution (CES) utility function, Dixit-Stiglitz monopolistic competition, and ice-berg trade costs), the literature derives the profit function, of which coefficients are estimated using maximum likelihood procedures. Recent studies are as follows: Head, Rise, and Swenson (1999) for Japanese MNEs in the US; Belderbos and Carree (2002) for Japanese MNEs in China; Head and Mayer (2004) for Japanese MNEs in Europe; Disdier and Mayer (2004) for French MNEs in Europe; Castellani and Zanfei (2004) for large MNEs worldwide; Mayer, Mejean, and Nefussi (2007) for French MNEs worldwide; Crozet, Mayer, and Mucchielli (2004) for MNEs in France; and Basile, Castellani, and Zanfei (2008) for MNEs in Europe. At the present time, three main topics can be found in this literature. The first introduces various location elements as independent variables. The above-mentioned new economic geography model usually yields the profit function, which is a function of market size, productive factor prices, price of intermediate goods, and trade costs. As a proxy for the price of intermediate goods, the measure of agglomeration is often used, particularly the number of manufacturing firms. Some studies employ more disaggregated numbers of manufacturing firms, such as the number of manufacturing firms with the same nationality as the firms choosing the location (e.g., Head et al., 1999; Crozet et al., 2004) or the number of firms belonging to the same firm group (e.g., Belderbos and Carree, 2002). As part of trade costs, some investment climate measures have been examined: free trade zones in the US (Head et al., 1999), special economic zones and opening coastal cities in China (Belderbos and Carree, 2002), and Objective 1 structural funds and cohesion funds in Europe (Basile et al., 2008). Second, the validity of proxy variables for location elements is further examined. Head and Mayer (2004) examine the validity of market potential on location choice. They propose the use of two measures: the Harris market potential index (Harris, 1954) and the Krugman-type index used in Redding and Venables (2004). The Harris-type index is simply the sum of distance-weighted real GDP. They employ the Krugman-type market potential index, which is directly derived from the new economic geography model, as it takes into account the extent of competition (i.e. price index) and is constructed using estimators of importing country dummy variables in the well-known gravity equation, as in Redding and Venables (2004). They find that "theory does not pay", in the sense that the Harris market potential outperforms Krugman's market potential in both the magnitude of its coefficient and the fit of the model to be estimated. The third topic explores the substitution of location by examining inclusive values in the nested-logit model. For example, using firm-level data on French investments both in France and abroad over the 1992-2002 period, Mayer et al. (2007) investigate the determinants of location choice and assess empirically whether the domestic economy has been losing attractiveness over the recent period or not. The estimated coefficient for inclusive value is strongly significant and near unity, indicating that the national economy is not different from the rest of the world in terms of substitution patterns. Similarly, Disdier and Mayer (2004) investigate whether French MNEs consider Western and Eastern Europe as two distinct groups of potential host countries by examining the coefficient for the inclusive value in nested-logit estimation. They confirm the relevance of an East-West structure in the country location decision and furthermore show that this relevance decreases over time. The purpose of this paper is to investigate the location choice of Japanese MNEs in Thailand, Cambodia, Laos, Myanmar, and Vietnam, and is closely related to the third topic mentioned above. By examining region-level location choice with the nested-logit model, I investigate the relative importance of not only country characteristics but also region characteristics. Such investigation is invaluable particularly in the case of location choice in those five countries: industrialization remains immature in those countries which have not yet succeeded in attracting enough MNEs, and as a result, it is expected that there are not yet crucial regional variations for MNEs within such a nation, meaning the country characteristics are still relatively important to attract MNEs. To illustrate, in the case of Cambodia and Laos, one of the crucial elements for Japanese MNEs would be that LDC preferential tariff schemes are available for exports from Cambodia and Laos. On the other hand, in the case of Thailand and Vietnam, which have accepted a relatively large number of MNEs and thus raised the extent of regional inequality, regional characteristics such as the existence of agglomeration would become important elements in location choice. Our sample countries seem, therefore, to offer rich variations for analyzing the relative importance between country characteristics and region characteristics. Our empirical strategy has a further advantage. As in the third topic in the location choice literature, the use of the nested-logit model enables us to examine substitution patterns between country-based and region-based location decisions by MNEs in the concerned countries. For example, it is possible to investigate empirically whether Japanese multinational firms consider Thailand/Vietnam and the other three countries as two distinct groups of potential host countries, by examining the inclusive value parameters in nested-logit estimation. In particular, our sample countries all experienced dramatic changes in, for example, economic growth or trade costs reduction during the sample period. Thus, we will find the dramatic dynamics of such substitution patterns. Our rigorous analysis of the relative importance between country characteristics and region characteristics is invaluable from the viewpoint of policy implications. First, while the former characteristics should be improved mainly by central government in each country, there is sometimes room for the improvement of the latter characteristics by even local governments or smaller institutions such as private agencies. Consequently, it becomes important for these smaller institutions to know just how crucial the improvement of region characteristics is for attracting foreign companies. Second, as economies grow, country characteristics become similar among countries. For example, the LCD preferential tariff schemes are available only when a country is less developed. Therefore, it is important particularly for the least developed countries to know what kinds of regional characteristics become important following economic growth; in other words, after their country characteristics become similar to those of the more developed countries. I also incorporate one important characteristic of MNEs, namely, productivity. The well-known Helpman-Melitz-Yeaple model indicates that only firms with higher productivity can afford overseas entry (Helpman et al., 2004). Beyond this argument, there may be some differences in MNEs' productivity among our sample countries and regions. Such differences are important from the viewpoint of "spillover effects" from MNEs, which are one of the most important results for host countries in accepting their entry. The spillover effects are that the presence of inward foreign direct investment (FDI) aises domestic firms' productivity through various channels such as imitation. Such positive effects might be larger in areas with more productive MNEs. Therefore, it becomes important for host countries to know how much productive firms are likely to invest in them. The rest of this paper is organized as follows. Section 2 takes a brief look at the worldwide distribution of Japanese overseas affiliates. Section 3 provides an empirical model to examine their location choice, and lastly, we discuss future works to estimate our model.

Semi-supervised subspace clustering and applications to neuroscience

Machine learning techniques are used for extracting valuable knowledge from data. Nowa¬days, these techniques are becoming even more important due to the evolution in data ac¬quisition and storage, which is leading to data with different characteristics that must be exploited. Therefore, advances in data collection must be accompanied with advances in machine learning techniques to solve new challenges that might arise, on both academic and real applications. There are several machine learning techniques depending on both data characteristics and purpose. Unsupervised classification or clustering is one of the most known techniques when data lack of supervision (unlabeled data) and the aim is to discover data groups (clusters) according to their similarity. On the other hand, supervised classification needs data with supervision (labeled data) and its aim is to make predictions about labels of new data. The presence of data labels is a very important characteristic that guides not only the learning task but also other related tasks such as validation. When only some of the available data are labeled whereas the others remain unlabeled (partially labeled data), neither clustering nor supervised classification can be used. This scenario, which is becoming common nowadays because of labeling process ignorance or cost, is tackled with semi-supervised learning techniques. This thesis focuses on the branch of semi-supervised learning closest to clustering, i.e., to discover clusters using available labels as support to guide and improve the clustering process. Another important data characteristic, different from the presence of data labels, is the relevance or not of data features. Data are characterized by features, but it is possible that not all of them are relevant, or equally relevant, for the learning process. A recent clustering tendency, related to data relevance and called subspace clustering, claims that different clusters might be described by different feature subsets. This differs from traditional solutions to data relevance problem, where a single feature subset (usually the complete set of original features) is found and used to perform the clustering process. The proximity of this work to clustering leads to the first goal of this thesis. As commented above, clustering validation is a difficult task due to the absence of data labels. Although there are many indices that can be used to assess the quality of clustering solutions, these validations depend on clustering algorithms and data characteristics. Hence, in the first goal three known clustering algorithms are used to cluster data with outliers and noise, to critically study how some of the most known validation indices behave. The main goal of this work is however to combine semi-supervised clustering with subspace clustering to obtain clustering solutions that can be correctly validated by using either known indices or expert opinions. Two different algorithms are proposed from different points of view to discover clusters characterized by different subspaces. For the first algorithm, available data labels are used for searching for subspaces firstly, before searching for clusters. This algorithm assigns each instance to only one cluster (hard clustering) and is based on mapping known labels to subspaces using supervised classification techniques. Subspaces are then used to find clusters using traditional clustering techniques. The second algorithm uses available data labels to search for subspaces and clusters at the same time in an iterative process. This algorithm assigns each instance to each cluster based on a membership probability (soft clustering) and is based on integrating known labels and the search for subspaces into a model-based clustering approach. The different proposals are tested using different real and synthetic databases, and comparisons to other methods are also included when appropriate. Finally, as an example of real and current application, different machine learning tech¬niques, including one of the proposals of this work (the most sophisticated one) are applied to a task of one of the most challenging biological problems nowadays, the human brain model¬ing. Specifically, expert neuroscientists do not agree with a neuron classification for the brain cortex, which makes impossible not only any modeling attempt but also the day-to-day work without a common way to name neurons. Therefore, machine learning techniques may help to get an accepted solution to this problem, which can be an important milestone for future research in neuroscience. Resumen Las técnicas de aprendizaje automático se usan para extraer información valiosa de datos. Hoy en día, la importancia de estas técnicas está siendo incluso mayor, debido a que la evolución en la adquisición y almacenamiento de datos está llevando a datos con diferentes características que deben ser explotadas. Por lo tanto, los avances en la recolección de datos deben ir ligados a avances en las técnicas de aprendizaje automático para resolver nuevos retos que pueden aparecer, tanto en aplicaciones académicas como reales. Existen varias técnicas de aprendizaje automático dependiendo de las características de los datos y del propósito. La clasificación no supervisada o clustering es una de las técnicas más conocidas cuando los datos carecen de supervisión (datos sin etiqueta), siendo el objetivo descubrir nuevos grupos (agrupaciones) dependiendo de la similitud de los datos. Por otra parte, la clasificación supervisada necesita datos con supervisión (datos etiquetados) y su objetivo es realizar predicciones sobre las etiquetas de nuevos datos. La presencia de las etiquetas es una característica muy importante que guía no solo el aprendizaje sino también otras tareas relacionadas como la validación. Cuando solo algunos de los datos disponibles están etiquetados, mientras que el resto permanece sin etiqueta (datos parcialmente etiquetados), ni el clustering ni la clasificación supervisada se pueden utilizar. Este escenario, que está llegando a ser común hoy en día debido a la ignorancia o el coste del proceso de etiquetado, es abordado utilizando técnicas de aprendizaje semi-supervisadas. Esta tesis trata la rama del aprendizaje semi-supervisado más cercana al clustering, es decir, descubrir agrupaciones utilizando las etiquetas disponibles como apoyo para guiar y mejorar el proceso de clustering. Otra característica importante de los datos, distinta de la presencia de etiquetas, es la relevancia o no de los atributos de los datos. Los datos se caracterizan por atributos, pero es posible que no todos ellos sean relevantes, o igualmente relevantes, para el proceso de aprendizaje. Una tendencia reciente en clustering, relacionada con la relevancia de los datos y llamada clustering en subespacios, afirma que agrupaciones diferentes pueden estar descritas por subconjuntos de atributos diferentes. Esto difiere de las soluciones tradicionales para el problema de la relevancia de los datos, en las que se busca un único subconjunto de atributos (normalmente el conjunto original de atributos) y se utiliza para realizar el proceso de clustering. La cercanía de este trabajo con el clustering lleva al primer objetivo de la tesis. Como se ha comentado previamente, la validación en clustering es una tarea difícil debido a la ausencia de etiquetas. Aunque existen muchos índices que pueden usarse para evaluar la calidad de las soluciones de clustering, estas validaciones dependen de los algoritmos de clustering utilizados y de las características de los datos. Por lo tanto, en el primer objetivo tres conocidos algoritmos se usan para agrupar datos con valores atípicos y ruido para estudiar de forma crítica cómo se comportan algunos de los índices de validación más conocidos. El objetivo principal de este trabajo sin embargo es combinar clustering semi-supervisado con clustering en subespacios para obtener soluciones de clustering que puedan ser validadas de forma correcta utilizando índices conocidos u opiniones expertas. Se proponen dos algoritmos desde dos puntos de vista diferentes para descubrir agrupaciones caracterizadas por diferentes subespacios. Para el primer algoritmo, las etiquetas disponibles se usan para bus¬car en primer lugar los subespacios antes de buscar las agrupaciones. Este algoritmo asigna cada instancia a un único cluster (hard clustering) y se basa en mapear las etiquetas cono-cidas a subespacios utilizando técnicas de clasificación supervisada. El segundo algoritmo utiliza las etiquetas disponibles para buscar de forma simultánea los subespacios y las agru¬paciones en un proceso iterativo. Este algoritmo asigna cada instancia a cada cluster con una probabilidad de pertenencia (soft clustering) y se basa en integrar las etiquetas conocidas y la búsqueda en subespacios dentro de clustering basado en modelos. Las propuestas son probadas utilizando diferentes bases de datos reales y sintéticas, incluyendo comparaciones con otros métodos cuando resulten apropiadas. Finalmente, a modo de ejemplo de una aplicación real y actual, se aplican diferentes técnicas de aprendizaje automático, incluyendo una de las propuestas de este trabajo (la más sofisticada) a una tarea de uno de los problemas biológicos más desafiantes hoy en día, el modelado del cerebro humano. Específicamente, expertos neurocientíficos no se ponen de acuerdo en una clasificación de neuronas para la corteza cerebral, lo que imposibilita no sólo cualquier intento de modelado sino también el trabajo del día a día al no tener una forma estándar de llamar a las neuronas. Por lo tanto, las técnicas de aprendizaje automático pueden ayudar a conseguir una solución aceptada para este problema, lo cual puede ser un importante hito para investigaciones futuras en neurociencia.

Identificación de áreas prioritarias para la conservación de razas de maíz en la sierra de Ecuador

En Ecuador el maíz es el cultivo más importante en superficie y es base de la alimentación para la población rural que vive en los Andes. A diferencia de lo que sucede en la Costa, en la región Sierra todavía se cultivan numerosas variedades tradicionales que se agrupan en veinticuatro razas. Mantener esta diversidad es, pues, de gran importancia no solo para la seguridad alimentaria, sino también como fuente de genes para tolerancia a factores abióticos que podrían ser incorporados a las variedades modernas. Si bien parte de esta diversidad fue recolectada a mediados del siglo pasado y está siendo conservada en distintos bancos de germoplasma, es deseable que su conservación in situ también esté asegurada, entre otras razones, porque de esta manera el cultivo puede seguir evolucionando. Para poder implementar un plan de conservación en finca que contribuya a preservar este patrimonio, resulta imprescindible identificar áreas idóneas donde concentrar los recursos y conocer las características y tipologías de los agricultores que manejan la diversidad actual. Generar esta información es el objetivo principal de esta investigación y para lograrlo se han llevado a cabo cuatro estudios: (1) Análisis de la diversidad a nivel de razas e identificación de áreas de alta riqueza de razas, alta diversidad morfológica y/o alta diversidad ecogeográfica en la Sierra de Ecuador, (2) Identificación del perfil y las características de los agricultores que conservan y manejan las variedades tradicionales de maíz en la Sierra de Ecuador, (3) Análisis del conocimiento local, manejo y usos de variedades tradicionales de maíz en la Sierra de Ecuador, y (4) Identificación de áreas de alta diversidad y bajo riesgo de pérdida para la conservación en finca de maíz en la Sierra de Ecuador. Para el primer estudio se visitaron 303 fincas distribuidas a lo largo de la Sierra y se recolectaron 636 muestras que fueron caracterizadas morfológicamente mediante 14 variables: 8 relacionadas con la mazorca (forma, longitud y diámetro de la mazorca, color y diámetro de olote y número y disposición de hileras) y 7 referidas el grano (número total de granos, color, forma, longitud, anchura y grosor de grano y tipo de endospermo). Adicionalmente, las fincas donde se tomaron las muestras fueron caracterizadas ecogeográficamente mediante 5 variables climáticas (temperatura media estacional, rango de temperatura media anual, temperatura mínima de diciembre, precipitación estacional y precipitación de octubre), 2 geofísicas (altitud y pendiente) y 5 edáficas (textura principal del suelo, profundidad a roca, pH, contenido en materia orgánica y fertilidad). A partir de esta información y mediante técnicas de sistemas de información geográfica (SIG), se generaron mapas de distribución por raza en formato vectorial y un mapa de riqueza de razas, un mapa de diversidad morfológica y un mapa de diversidad ecogeográfica en formato ráster con celdas de 10 km x 10 km. Los resultados permitieron constatar que, en los últimos 60 años, no se ha perdido ninguna raza. Sin embargo, Canguil, Chaucho y Clavito han dejado de cultivarse en algunas provincias con la consiguiente erosión genética del cultivo. La caracterización morfológica detectó diferencias en el grado de variabilidad intra-raza, siendo Patillo Ecuatoriano, Racimo de Uva y Uchima las razas más heterogéneas tanto para los caracteres cualitativos como cuantitativos. A nivel climático y geofísico, también se detectaron diferencias en el grado de variación intra-raza; Cuzco Ecuatoriano, Kcello Ecuatoriano y Montaña Ecuatoriana fueron las razas que en promedio presentaron mayores rangos y coeficientes de variación para estas variables ecogeográficas. En cuanto a las condiciones edáficas todas las razas, excepto Cónico Dentado, presentaron una gran heterogeneidad, pudiendo crecer tanto en suelos ricos como pobres, con valores de pH entre ácido y moderadamente alcalino. La comparación entre razas reveló diferencias significativas en los rangos ambientales de algunas razas como Cónico Dentado, que tiende a cultivarse a menor altitud y, por tanto, en ambientes menos fríos y de mayor precipitación que Blanco Blandito, Patillo Ecuatoriano, Sabanero Ecuatoriano, Uchima y Zhima. Para la mayoría de las razas se encontraron materiales potencialmente adaptados a condiciones de estrés (precipitación estacional inferior a 500 mm y suelos con pH entre 4.5 y 5.5). Finalmente, los mapas de riqueza, de diversidad morfológica y de diversidad ecogeográfica mostraron 36 celdas de alta diversidad repartidas en las 10 provincias de la Sierra: 11 celdas en las provincias del norte, 11 en las provincias del centro y 14 en las provincias del sur. Para la caracterización e identificación de las tipologías de los agricultores que cultivan maíz en la Sierra de Ecuador y el análisis de los posibles factores de riesgo de pérdida de diversidad, se realizaron entrevistas individuales y semiestructuradas a los agricultores dueños de las fincas donde se recolectaron las muestras para el estudio de diversidad (254 en total). Las preguntas que se formularon (11 abiertas y 5 cerradas) estuvieron organizadas en seis bloques: datos del agricultor, características de la finca, diversidad y conocimiento del cultivo, manejo del cultivo, usos y flujo de semillas. Los resultados indicaron que la diversidad de maíz que hay en la Sierra de Ecuador es manejada mayoritariamente por agricultores mestizos, de entre 30 y 55 años, que cultivan una o dos variedades tradicionales para autoconsumo, en parcelas de menos de 0.5 ha y en asocio con fréjol. El análisis de segmentación mediante el algoritmo Chi-square automatic interaction detection (CHAID) permitió identificar un pequeño grupo de agricultores indígenas con parcelas medianas (entre 0.5 ha y 1.5 ha) que conservan un mayor número de variedades tradicionales por finca que el agricultor promedio. Los análisis estadísticos no detectaron diferencias significativas entre etnias (mestizo vs. indígena), géneros (hombre vs. mujer) y grupos de edad (jóvenes menores de 30 años, adultos entre 30 y 55 años y adultos mayores de 55 años) en lo que respecta al conocimiento del cultivo (criterios de reconocimiento y razones de preferencia) y manejo (tipo de cultivo), pero sí detectaron diferencias entre regiones, principalmente en el modo de cultivar el maíz; mientras que en el norte y sur tienden a sembrarlo en asocio y con un mayor número de especies, en el centro acostumbran a cultivarlo preferentemente solo. En cuanto a los usos, se recopilaron hasta 39 modos diferentes de consumir maíz, siendo Kcello Ecuatoriano y Zhima las razas para las que se registró un mayor número de usos. La comparación del número medio de usos por variedad entre etnias evidenció que los agricultores mestizos utilizan sus variedades tradicionales de forma más variada que los indígenas. Entre los factores de riesgo que se analizaron, el bajo porcentaje de jóvenes agricultores que se ocupan de las fincas podría suponer una amenaza a medio plazo por falta de relevo generacional. Adicionalmente, las numerosas sinonimias y homonimias que se detectaron y el bajo intercambio de semillas también podrían ser causa de pérdida de diversidad, bien por reemplazo o por envejecimiento de la semilla. Finalmente, se concluyó que las razas Chaucho, Complejo Chillo-Huandango, Complejo Mishca-Huandango, Cónico Dentado, Montaña Ecuatoriana y Sabanero Ecuatoriano son particularmente vulnerables, no solo por su baja presencia, sino también por el color de grano que tienen (los mismos que la mayoría de las razas más comunes) y carecer de nombres y usos específicos. Finalmente, para la priorización de áreas de conservación en finca para maíz en la Sierra de Ecuador, se utilizaron 13 criterios de diferente naturaleza: 2 ecogeográficos (precipitación, diversidad ecogeográfica), 6 biológicos (grado de presencia del cultivo, riqueza de razas, diversidad morfológica, presencia de mezclas, presencia de razas locales y riesgo de erosión genética), 3 culturales (abundancia de variedades por finca, diversidad de usos y frecuencia de intercambio) y 2 demográficos (tamaño de la población y distancia a núcleos urbanos). Mediante técnicas SIG y de evaluación multicriterio, los valores originales de las capas-criterio fueron transformados a una escala de 0 a 100. Posteriormente, las capas-criterio normalizadas fueron sumadas utilizando tres métodos de ponderación: (1) mismo peso, (2) diferente peso según la puntuación otorgada por 72 expertos, y (3) diferente peso según el método de comparación entre pares de criterios. Los resultados permitieron identificar ocho celdas de 10 km x 10 km con alta puntuación (> 65): tres celdas en el norte (una en cada una de las provincias), una celda en el centro (en la provincia de Cotopaxi), y cuatro celdas en la región sur (dos en Azuay y otras dos en Loja). ABSTRACT In Ecuador, the maize is the most important cultivation in surface and it is a base of the feeding for the rural population who lives in the Andes. In contrast to what it happens on the Coast, in the Sierra region still there are cultivated numerous traditional varieties that are grouped into twenty-four races. Maintaining this diversity is, therefore, of great importance not only for food security, but also as a source of genes for tolerance to abiotic factors could be incorporated into modern varieties. Although part of this diversity was collected in the middle of the last century and is still preserved in various germplasm banks, it is desirable for the in situ conservation also is assured, among other reasons, because in this way the crop can continue to evolve. To be able to implement a conservation plan on farm that contribute to preserving this heritage, it is essential to identify suitable areas where to concentrate resources and know the characteristics and typology of farmer who managed the current diversity. To generate this information is the main target of this investigation and to achieve this, four studies have been carried out: (1) Analysis of the diversity at races and identification of areas of high richness of races, high morphological diversity and / or ecogeographical high diversity in the Sierra of Ecuador, (2) Identification of the profile and characteristics of farmers who conserve and manage traditional varieties of maize in the Sierra of Ecuador, (3) Analysis of local knowledge, management and use of traditional varieties of maize in the Sierra of Ecuador, and (4) Identification of areas of high diversity and low risk of loss for the conservation of maize in the Sierra of Ecuador. For the first study were visited 303 farms distributed along the Sierra and collected 636 samples that were characterized morphologically by 14 variables: 8 related to the ear (shape, length and diameter of the cob, colour, and diameter of cob and number and arrangement of rows) and 7 referred to the grain (total number of grain, colour, shape, length, width, and thickness and type of grain endosperm). In addition, the farms where the samples were taken were characterized ecogeographically through 5 climatic variables (seasonal average temperature, range of average annual temperature, minimum temperature for December, seasonal precipitation and precipitation of October), 2 geophysical (altitude and slope) and edaphic 5 (main texture of the soil, deep rock, pH, content of organic matter and fertility). From this information and techniques of geographic information systems (GIS), maps were generated for distribution by race in vector format and a map of richness of races, a map of morphological diversity and a map of ecogeographical diversity in raster format with cells of 10 km x 10 km. The results allowed observing that, over the past 60 years, it has not lost any race. Nevertheless, Canguil, Chaucho and Clavito have stopped being cultivated in some provinces with the consequent genetic erosion of the cultivation. The morphological characterization detected differences in the degree of variability intra-race, being Patillo Ecuatoriano, Racimo de Uva and Uchima races more heterogeneous both for the qualitative and quantitative characters. At climate and geophysical level, also detected differences in the degree of variation intra-race; Cuzco Ecuatoriano, Kcello Ecuatoriano and Montaña Ecuatoriana were races that, on average, showed higher ranges and coefficients of variation for these geographical characters. In terms of the edaphic conditions, all races, except Cónico Dentado, showed a great heterogeneity, and can grow both in rich and poor soils, with pH values between acid and moderately alkaline. The comparison between races revealed significant differences in the environmental ranges in some races as Cónico Dentado, which tends to be grown at lower elevations and, therefore, in environments less cold and greater precipitation than Blanco Blandito, Patillo Ecuatoriano, Sabanero Ecuatoriano, Uchima and Zhima. For most of the races were found materials potentially adapted to stress conditions (seasonal precipitation less than 500 mm and soil with a pH between 4.5 and 5.5). Finally, the maps of richness, morphologic diversity and ecogeographical diversity showed 36 cells high diversity distributed in 10 provinces of the Sierra: 11 cells in the northern provinces, 11 in the central provinces and 14 in the southern provinces. For the characterization and identification of the typology of the farmers who cultivate corn in the Sierra of Ecuador and the analysis of the possible factors of risk of loss of diversity, there were realized interviews individual and semistructured to the farmers’ owners of the farms where the samples were gathered for the study of diversity (254 in whole). The questions that were formulated (11 opened ones and 5 closed ones) were organized in six blocks: data of the farmer, characteristics of the farm, diversity and knowledge of the crop, crop management, uses and seed flow. The results indicated that the maize diversity that exist in the Sierra of Ecuador is managed mainly by mestizo farmers, aged between 30 and 55, who cultivate one or two traditional varieties for self-consumption, on plots of less than 0.5 has and in associated with beans. The segmentation analysis algorithm using the Chi-square automatic interaction detection (CHAID technique), allowed to identify a small group of indigenous farmers with medium-sized plots (between 0.5 there is and 1.5 it is) that a major number of traditional varieties preserves for farm that the average farmer. The statistical analysis did not detect significant differences between ethnic groups (mestizos vs. indigenous), genres (man vs. women) and age groups (young people under 30 years of age, adults between 30 and 55 years and adults over 55 years old) in regards to the knowledge of the cultivation (recognition criteria and reasons of preference) and management (type of crop), but if detected differences between regions, mainly on the mode of cultivating the maize; while in the north and south they tend to sow in associate and with a greater number of species, in the center accustomed to cultivate it preferably only. In regards to the uses, they were compiled up to 39 different ways of consuming maize, being Kcello Ecuatoriano and Zhima the races for which a major number of uses registered. The comparison of the average number of uses per variety between ethnic groups showed that the mestizo farmers used their traditional varieties of form more varied than the indigenous people. Between the factors of risk that were analyzed, the low percentage of young farmers who deal with the farms might suppose a medium-term threat for lack of generational relief. In addition, the numerous synonyms and homonyms that were detected and the low seed exchange could also be a cause of loss of diversity, either by replacement or by aging of the seed. Finally, it was concluded that the races Chaucho, Complex Chillo-Huandango, Complex Mishca-Huandango, Cónico Dentado, Montaña Ecuatoriana and Sabanero Ecuatoriano are particularly vulnerable, not only because of their low presence, but also by the grain color they have (the same as the majority of races more common) and lack of names and specific uses. Finally, for the prioritization of maize conservation areas on farm in the Sierra of Ecuador, used 13 criteria of different nature: 2 ecogeographic (precipitation, diversity ecogeographical), 6 biological (degree of presence of the crop, races richness, morphological diversity, the presence of mixtures, presence of local races and risk of genetic erosion), 3 cultural (abundance of varieties per farm, diversity of uses and frequency of exchange) and 2 demographic (population size and distance to urban centers). Using GIS techniques and multicriteria evaluation, the original values of the layers-criterion were transformed to a scale of 0 to 100. Later, the normalized layers - criteria were added using three weighting methods: (1) the same weight, (2) different weight according to the score given by 72 experts, and (3) different weight according to the method of comparison between pairs of criteria. The results allowed to identify eight 10 km cells x 10 km with high punctuation (> 65): three cells in the north (one in each of the provinces), a cell in the center (in the Cotopaxi province), and four cells in the south region (two in Azuay and other two in Loja).

Prototipos experimentales modernos: la colonia de Schorlemerallee y las villas Am Rupenhorn de los Luckhardt y Anker. Berlín 1924-1930

La colonia experimental de Schorlemerallee y las villas Am Rupenhorn son dos proyectos concluidos en 1930 por los hermanos Wassili y Hans Luckhardt con Alfons Anker en Berlín. Ambos proyectos forman parte del mismo proceso, que comienza en la Colonia -una exploración sobre el lenguaje moderno en una serie de fases sucesivas- y culmina con las Villas. Éstas últimas, realizadas inmediatamente después de la Colonia, son la síntesis de esa experiencia, aunque finalmente acabaron trascendiéndola, ya que se convirtieron en un modelo sobre la casa en la naturaleza, sobre la idea de la villa clásica y sobre los nuevos modos de habitar, alcanzando con el tiempo la condición de canon moderno. A pesar de ello, no es esta condición lo más importante. Lo singular en este caso, es el propio proceso de proyecto –Colonia versus Villas- un verdadero experimento en su concepción, método y resultados, a través del cual sus autores investigan nuevas tecnologías aplicadas a nuevas formas de habitar y desarrollan un nuevo lenguaje, cuyo resultado son unos prototipos tecnológicos, con los que pretenden, como diría Mies van der Rohe: “Me he esforzado por construir una arquitectura para una sociedad tecnológica. He intentado que todo resultara razonable y claro.....para que cualquiera pueda hacer arquitectura.” El momento y lugar no pueden ser más propicios: Berlín entre 1924 y 1930, en el mismo origen del Movimiento Moderno. El experimento se plantea con auténtico rigor científico. Los arquitectos diseñan, construyen y financian su proyecto, controlando todas sus variables. Especialmente, por lo insólito, es el control de la variable económica. Porque este factor, la economía, es para ellos una clave fundamental del proceso. Se trataba de demostrar que la Nueva Arquitectura (o Neues Bauen, como les gustaba denominarla) era capaz de construir mejor y más rápido la vivienda para una nueva sociedad. La revolución y la vanguardia van de la mano: son el Zeitgeist o espíritu de la época, un contexto que es parte sustancial del proceso, y como lo calificarían los Smithson, un contexto heroico. El concepto se centra en la tríada Bauhaus: diseño + tecnología x economía. En cuanto al método, se fijan una serie de parámetros –las variables del experimento- que se agrupan en tres categorías distintas: topología, tipología y tecnología. La combinación de las variables de cada categoría dará lugar a un sistema con unas características determinadas: una definición del espacio, una forma, un lenguaje y una tecnología, características que permiten establecer las reglas para su desarrollo. Los sistemas resultantes son tres, denominados según su doble condición tipológica/ tecnológica: 1. Sistema de muro de carga: Viviendas adosadas en zig-zag o Mauerwerksbauten. 2. Sistema de esqueleto de acero: Viviendas aisladas o Stahlskelettbauten 3. Sistema de hormigón armado: Viviendas en hilera recta o Betonbauten Las villas Am Rupenhorn se plantean a continuación como verificación de este proceso: la síntesis de las categorías desarrolladas en la Colonia. Pero llegan en un momento de gracia, justo cuando los Luckhardt y Anker se encuentran profundamente implicados en el proceso de desarrollo de un nuevo lenguaje y con la reciente experiencia de la Colonia, que ha sido un éxito en casi todos los aspectos posibles. “En 1930, están en la cumbre”, como diría su mejor crítico y antiguo colaborador: Achim Wendschuh. En las Villas, los arquitectos integran su lenguaje, ya plenamente moderno, con sus experiencias previas: las que los relacionan con su reciente expresionismo (que se podría calificar como Kunstwollen) y con la tradición clásica de la cultura arquitectónica alemana: el sentido del material que deben a Semper y la sensibilidad hacia el paisaje, que toman de Schinkel. El extraordinario interés de las Villas se debe a factores como el tratamiento de la relación dual, poco habitual en la arquitectura moderna, la síntesis de lenguajes y las circunstancias de su momento histórico, factores que las han convertido en una propuesta única e irrepetible de una de las vías experimentales más interesantes y desconocidas de la Modernidad. ABSTRACT The experimental Housing Estate of Schorlemerallee and the Am Rupenhorn Villas are two projects completed by the brothers Wassili and Hans Luckhardt with Alfons Anker in Berlin in 1930. Both projects are part of the same process, starting with the Housing Estate --an exploration of the modern language in a series of phases- which culminates with the Villas project. The Villas Am Ruperhorn, designed immediately after the Housing development, are the synthesis and crowning point of this experience, even finally over passing it, since they have become a model of the house in nature, related with both the ideal of the classical villa and the new ways of life, reaching the condition of a modern canon. However, this is not its most important issue. The most remarkable condition is the project process itself -Housing versus Villas- a true experiment in concept, method and results, in which the authors research new technologies for new ways of living, developing an innovative language, with results in new prototypes, in the way Mies van der Rohe was looking for: “I have tried to make an architecture for a technological society. I have wanted to keep everything reasonable and clear… to have an architecture that anybody can do." The time and place could not be more favourable: Berlin from 1924 to 1930, in the very origin of Modern Movement. The experiment takes place with genuine scientific accuracy. Architects design, build and finance their own project, controlling all variables. Especially, and quite unusual, the control of the economic variable. Precisely the economic factor is for them a fundamental key to the process. It was shown to prove that the new architecture (or Neues Bauen, as they liked to call it) was able to build not only faster, better and more efficient dwellings for a new society, but also at lower cost. Revolution and Avant-garde use to move forward together, because they share the Zeitgeist --or time's spirit--, a context which is a substantial part of the process, and as the Alison & Peter Smithsons would describe, an heroic context. The concept focuses on the Bauhaus triad: Design + Technology x Economy. For the method, a number of variables are fixed --the experimental parameters-- that are later grouped into three distinct categories: Topology, Typology and Technology. The combination of these variables within each category gives way to several systems, with specific characteristics: a definition of space, a form, a language and a technology, thus allowing to establish the rules for its development: The resulting systems are three, called by double typological / technological issue: 1. Terraced Housing in zig-zag or Mauerwerksbauten (bearing wall system) 2. Detached Housing or Stahlskelettbauten (steel skeleton system) 3. Terraced Housing in one row or Betonbauten (reinforced concrete system) The Am Rupenhorn Villas are planned as the check of this process: the synthesis of the categories developed all through the Housing Estate research. The Am Ruperhorn project is developed in a crucial moment, just as the Luckhardts and Anker are deeply involved in the definition process of a new language after the recent experience of Schorlemerallee, which has been a success in almost all possible aspects. "In 1930, they are on the top” has said his best critic and long-time collaborator, Achim Wendschuh. In the Villas, the authors make up their fully modern language with their own background, related with their recent Expressionist trend (Kunstwollen) and with the classical tradition of the German architectural culture: the notion of material related with Semper and the sensible approach to the landscape, linked with Schinkel. Its extraordinary interest lay on diverse factors, such as dual relationships, unusual in modern architecture, synthesis of languages and circumstances of their historical moment, all factors that have become a unique and unrepeatable proposal in one of the most extraordinary experimental ways of Modernity.

Interaction of the Hsp70 molecular chaperone, DnaK, with its cochaperone DnaJ

Chaperones of the Hsp70 family bind to unfolded or partially folded polypeptides to facilitate many cellular processes. ATP hydrolysis and substrate binding, the two key molecular activities of this chaperone, are modulated by the cochaperone DnaJ. By using both genetic and biochemical approaches, we provide evidence that DnaJ binds to at least two sites on the Escherichia coli Hsp70 family member DnaK: under the ATPase domain in a cleft between its two subdomains and at or near the pocket of substrate binding. The lower cleft of the ATPase domain is defined as a binding pocket for the J-domain because (i) a DnaK mutation located in this cleft (R167H) is an allele-specific suppressor of the binding defect of the DnaJ mutation, D35N and (ii) alanine substitution of two residues close to R167 in the crystal structure, N170A and T173A, significantly decrease DnaJ binding. A second binding determinant is likely to be in the substrate-binding domain because some DnaK mutations in the vicinity of the substrate-binding pocket are defective in either the affinity (G400D, G539D) or rate (D526N) of both peptide and DnaJ binding to DnaK. Binding of DnaJ may propagate conformational changes to the nearby ATPase catalytic center and substrate-binding sites as well as facilitate communication between these two domains to alter the molecular properties of Hsp70.

Two functionally dependent acetylcholine subunits are encoded in a single Caenorhabditis elegans operon

The deg-3 gene from the nematode Caenorhabditis elegans encodes an α subunit of a nicotinic acetylcholine receptor that was first identified by a dominant allele, u662, which produced neuronal degeneration. Because deg-3 cDNAs contain the SL2 trans-spliced leader, we suggested that deg-3 was transcribed as part of a C. elegans operon. Here we show that des-2, a gene in which mutations suppress deg-3(u662), is the upstream gene in that operon. The des-2 gene also encodes an α subunit of a nicotinic acetylcholine receptor. As expected for genes whose mRNAs are formed from a single transcript, both genes have similar expression patterns. This coexpression is functionally important because (i) des-2 is needed for the deg-3(u662) degenerations in vivo; (ii) an acetylcholine-gated channel is formed in Xenopus oocytes when both subunits are expressed but not when either is expressed alone; and (iii) channel activity, albeit apparently altered from that of the wild-type channel, results from the expression of a u662-type mutant subunit but, again, only when the wild-type DES-2 subunit is present. Thus, the operon structure appears to regulate the coordinate expression of two channel subunits.