Numerical analysis of the relation between interactions and structure in a molecular fluid

Coarse graining is a popular technique used in physics to speed up the computer simulation of molecular fluids. An essential part of this technique is a method that solves the inverse problem of determining the interaction potential or its parameters from the given structural data. Due to discrepancies between model and reality, the potential is not unique, such that stability of such method and its convergence to a meaningful solution are issues.rnrnIn this work, we investigate empirically whether coarse graining can be improved by applying the theory of inverse problems from applied mathematics. In particular, we use the singular value analysis to reveal the weak interaction parameters, that have a negligible influence on the structure of the fluid and which cause non-uniqueness of the solution. Further, we apply a regularizing Levenberg-Marquardt method, which is stable against the mentioned discrepancies. Then, we compare it to the existing physical methods - the Iterative Boltzmann Inversion and the Inverse Monte Carlo method, which are fast and well adapted to the problem, but sometimes have convergence problems.rnrnFrom analysis of the Iterative Boltzmann Inversion, we elaborate a meaningful approximation of the structure and use it to derive a modification of the Levenberg-Marquardt method. We engage the latter for reconstruction of the interaction parameters from experimental data for liquid argon and nitrogen. We show that the modified method is stable, convergent and fast. Further, the singular value analysis of the structure and its approximation allows to determine the crucial interaction parameters, that is, to simplify the modeling of interactions. Therefore, our results build a rigorous bridge between the inverse problem from physics and the powerful solution tools from mathematics. rn

Comprehensive analysis of CpG island methylator phenotype (CIMP)-high, -low, and -negative colorectal cancers based on protein marker expression and molecular features

CpG island methylator phenotype (CIMP) is being investigated for its role in the molecular and prognostic classification of colorectal cancer patients but is also emerging as a factor with the potential to influence clinical decision-making. We report a comprehensive analysis of clinico-pathological and molecular features (KRAS, BRAF and microsatellite instability, MSI) as well as of selected tumour- and host-related protein markers characterizing CIMP-high (CIMP-H), -low, and -negative colorectal cancers. Immunohistochemical analysis for 48 protein markers and molecular analysis of CIMP (CIMP-H: ? 4/5 methylated genes), MSI (MSI-H: ? 2 instable genes), KRAS, and BRAF were performed on 337 colorectal cancers. Simple and multiple regression analysis and receiver operating characteristic (ROC) curve analysis were performed. CIMP-H was found in 24 cases (7.1%) and linked (p < 0.0001) to more proximal tumour location, BRAF mutation, MSI-H, MGMT methylation (p = 0.022), advanced pT classification (p = 0.03), mucinous histology (p = 0.069), and less frequent KRAS mutation (p = 0.067) compared to CIMP-low or -negative cases. Of the 48 protein markers, decreased levels of RKIP (p = 0.0056), EphB2 (p = 0.0045), CK20 (p = 0.002), and Cdx2 (p < 0.0001) and increased numbers of CD8+ intra-epithelial lymphocytes (p < 0.0001) were related to CIMP-H, independently of MSI status. In addition to the expected clinico-pathological and molecular associations, CIMP-H colorectal cancers are characterized by a loss of protein markers associated with differentiation, and metastasis suppression, and have increased CD8+ T-lymphocytes regardless of MSI status. In particular, Cdx2 loss seems to strongly predict CIMP-H in both microsatellite-stable (MSS) and MSI-H colorectal cancers. Cdx2 is proposed as a surrogate marker for CIMP-H.

TUNING, AVO, AND FLAT-SPOT EFFECTS IN A SEISMIC ANALYSIS OF NORTH SEA BLOCK F3

Reflection seismic data from the F3 block in the Dutch North Sea exhibits many large-amplitude reflections at shallow horizons, typically categorized as “brightspots ” (Schroot and Schuttenhelm, 2003), mainly because of their bright appearance. In most cases, these bright reflections show a significant “flatness” contrasting with local structural trends. While flatspots are often easily identified in thick reservoirs, we have often occasionally observed apparent flatspot tuning effects at fluid contacts near reservoir edges and in thin reservoir beds, while only poorly understanding them. We conclude that many of the shallow large-amplitude reflections in block F3 are dominated by flatspots, and we investigate the thin-bed tuning effects that such flatspots cause as they interact with the reflection from the reservoir’s upper boundary. There are two possible effects to be considered: (1) the “wedge-model” tuning effects of the flatspot and overlying brightspots, dimspots, or polarity-reversals; and (2) the stacking effects that result from possible inclusion of post-critical flatspot reflections in these shallow sands. We modeled the effects of these two phenomena for the particular stratigraphic sequence in block F3. Our results suggest that stacking of post-critical flatspot reflections can cause similar large-amplitude but flat reflections, in some cases even causing an interface expected to produce a ‘dimspot’ to appear as a ‘brightspot’. Analysis of NMO stretch and muting shows the likely exclusion of critical offset data in stacked output. If post-critical reflections are included in stacking, unusual results will be observed. In the North Sea case, we conclude the tuning effect was the primary reason causing for the brightness and flatness of these reflections. However, it is still important to note that care should be taken while applying muting on reflections with wide range of incidence angles and the inclusion of critical offset data may cause some spurious features in the stacked section.

Phenotypic and genotypic analysis of mouse hepatitis virus (JHM) complementation group A temperature-sensitive mutants

Temperature sensitive (ts) mutant viruses have helped elucidate replication processes in many viral systems. Several panels of replication-defective ts mutants in which viral RNA synthesis is abolished at the nonpermissive temperature (RNA$\sp{-})$ have been isolated for Mouse Hepatitis Virus, MHV (Robb et al., 1979; Koolen et al., 1983; Martin et al., 1988; Schaad et al., 1990). However, no one had investigated genetic or phenotypic relationships between these different mutant panels. In order to determine how the panel of MHV-JHM RNA$\sp{-}$ ts mutants (Robb et al., 1979) were genetically related to other described MHV RNA$\sp{-}$ ts mutants, the MHV-JHM mutants were tested for complementation with representatives from two different sets of MHV-A59 ts mutants (Koolen et al., 1983; Schaad et al., 1990). The three ts mutant panels together were found to comprise eight genetically distinct complementation groups. Of these eight complementation groups, three complementation classes are unique to their particular mutant panel; genetically equivalent mutants were not observed within the other two mutant panels. Two complementation groups were common to all three mutant panels. The three remaining complementation groups overlapped two of the three mutant sets. Mutants MHV-JHM tsA204 and MHV-A59 ts261 were shown to be within one of these overlapping complementation groups. The phenotype of the MHV-JHM mutants within this complementation class has been previously characterized (Leibowitz et al., 1982; Leibowitz et al, 1990). When these mutants were grown at the permissive temperature, then shifted up to the nonpermissive temperature at the start of RNA synthesis, genome-length RNA and leader RNA fragments accumulated, but no subgenomic mRNA was synthesized. MHV-A59 ts261 produced leader RNA fragments identical to those observed with MHV-JHM tsA204. Thus, these two MHV RNA$\sp{-}$ ts mutants that were genetically equivalent by complementation testing were phenotypically similar as well. Recombination frequencies obtained from crosses of MHV-A59 ts261 with several of the gene 1 MHV-A59 mutants indicated that the causal mutation(s) of MHV-A59 ts261 was located near the overlapping junction of ORF1a and ORF1b, in the 3$\sp\prime$ end of ORF1a, or the 5$\sp\prime$ end of ORF1b. Sequence analysis of this junction and 1400 nucleotides into the 5$\sp\prime$ end of ORF1b of MHV-A59 ts261 revealed one nucleotide change from the wildtype MHV-A59. This substitution at nucleotide 13,598 (A to G) was a silent mutation in the ORF1a reading frame, but resulted in an amino acid change in ORF1b gene product (I to V). This amino acid change would be expressed only in the readthrough translation product produced upon successful ribosome frameshifting. A revertant of MHV-A59 ts261 (R2) also retained this guanidine residue, but had a second substitution at nucleotide 14,475 in ORF1b. This mutation results in the substitution of valine for an isoleucine.^ The data presented here suggest that the mutation in MHV-A59 ts261 (nucleotide 13,598) would be responsible for the MHV-JHM complementation group A phenotype. A second-site reversion at nucleotide 14,475 may correct this defect in the revertant. Sequencing of gene 1 immediately upstream of nucleotide 13,296 and downstream of nucleotide 15,010 must be conducted to test this hypothesis. ^

Systematic Review and Cumulative Analysis of Oncologic and Functional Outcomes After Robot-assisted Radical Cystectomy

CONTEXT Although open radical cystectomy (ORC) is still the standard approach, laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy (RARC) are increasingly performed. OBJECTIVE To report on a systematic literature review and cumulative analysis of pathologic, oncologic, and functional outcomes of RARC in comparison with ORC and LRC. EVIDENCE ACQUISITION Medline, Scopus, and Web of Science databases were searched using a free-text protocol including the terms robot-assisted radical cystectomy or da Vinci radical cystectomy or robot* radical cystectomy. RARC case series and studies comparing RARC with either ORC or LRC were collected. A cumulative analysis was conducted. EVIDENCE SYNTHESIS The searches retrieved 105 papers, 87 of which reported on pathologic, oncologic, or functional outcomes. Most series were retrospective and had small case numbers, short follow-up, and potential patient selection bias. The lymph node yield during lymph node dissection was 19 (range: 3-55), with half of the series following an extended template (yield range: 11-55). The lymph node-positive rate was 22%. The performance of lymphadenectomy was correlated with surgeon and institutional volume. Cumulative analyses showed no significant difference in lymph node yield between RARC and ORC. Positive surgical margin (PSM) rates were 5.6% (1-1.5% in pT2 disease and 0-25% in pT3 and higher disease). PSM rates did not appear to decrease with sequential case numbers. Cumulative analyses showed no significant difference in rates of surgical margins between RARC and ORC or RARC and LRC. Neoadjuvant chemotherapy use ranged from 0% to 31%, with adjuvant chemotherapy used in 4-29% of patients. Only six series reported a mean follow-up of >36 mo. Three-year disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) rates were 67-76%, 68-83%, and 61-80%, respectively. The 5-yr DFS, CSS, and OS rates were 53-74%, 66-80%, and 39-66%, respectively. Similar to ORC, disease of higher pathologic stage or evidence of lymph node involvement was associated with worse survival. Very limited data were available with respect to functional outcomes. The 12-mo continence rates with continent diversion were 83-100% in men for daytime continence and 66-76% for nighttime continence. In one series, potency was recovered in 63% of patients who were evaluable at 12 mo. CONCLUSIONS Oncologic and functional data from RARC remain immature, and longer-term prospective studies are needed. Cumulative analyses demonstrated that lymph node yields and PSM rates were similar between RARC and ORC. Conclusive long-term survival outcomes for RARC were limited, although oncologic outcomes up to 5 yr were similar to those reported for ORC. PATIENT SUMMARY Although open radical cystectomy (RC) is still regarded as the standard treatment for muscle-invasive bladder cancer, laparoscopic and robot-assisted RCs are becoming more popular. Templates of lymph node dissection, lymph node yields, and positive surgical margin rates are acceptable with robot-assisted RC. Although definitive comparisons with open RC with respect to oncologic or functional outcomes are lacking, early results appear comparable.

Finite element analysis in asymptomatic, symptomatic, and ruptured abdominal aortic aneurysms: in search of new rupture risk predictors.

OBJECTIVES To compare biomechanical rupture risk parameters of asymptomatic, symptomatic and ruptured abdominal aortic aneurysms (AAA) using finite element analysis (FEA). STUDY DESIGN Retrospective biomechanical single center analysis of asymptomatic, symptomatic, and ruptured AAAs. Comparison of biomechanical parameters from FEA. MATERIALS AND METHODS From 2011 to 2013 computed tomography angiography (CTA) data from 30 asymptomatic, 15 symptomatic, and 15 ruptured AAAs were collected consecutively. FEA was performed according to the successive steps of AAA vessel reconstruction, segmentation and finite element computation. Biomechanical parameters Peak Wall Rupture Risk Index (PWRI), Peak Wall Stress (PWS), and Rupture Risk Equivalent Diameter (RRED) were compared among the three subgroups. RESULTS PWRI differentiated between asymptomatic and symptomatic AAAs (p < .0004) better than PWS (p < .1453). PWRI-dependent RRED was higher in the symptomatic subgroup compared with the asymptomatic subgroup (p < .0004). Maximum AAA external diameters were comparable between the two groups (p < .1355). Ruptured AAAs showed the highest values for external diameter, total intraluminal thrombus volume, PWS, RRED, and PWRI compared with asymptomatic and symptomatic AAAs. In contrast with symptomatic and ruptured AAAs, none of the asymptomatic patients had a PWRI value >1.0. This threshold value might identify patients at imminent risk of rupture. CONCLUSIONS From different FEA derived parameters, PWRI distinguishes most precisely between asymptomatic and symptomatic AAAs. If elevated, this value may represent a negative prognostic factor for asymptomatic AAAs.

Health care policy analysis of Medicaid's early and periodic screening, diagnosis, and treatment (EPSDT) benefit in Colorado

The purpose of this thesis is to identify "best practice" recommendations for successful implementation of the EPSDT outreach program at Memorial Health System's Hospital for Children in Colorado Springs through a policy analysis of Medicaid EPSDT services in Colorado. A successful program at Memorial will increase education and awareness of EPSDT services, enrollment, and access to and utilization of health care services for eligible children. Methodology utilized in this study included questionnaires designed for the EPSDT contract administrator and outreach coordinators/workers; analysis of current federal and state policies; and studies conducted at the federal and state level, and by various advocacy groups. The need for this analysis of EPSDT came about in part through an awareness of increasingly high numbers of children in poverty and who are uninsured. Though the percentage of children living in poverty in Colorado is slightly below the national average (see Table 2), according to data analyzed by The Annie E. Casey Foundation, the percentage of children (0-18) living in poverty in Colorado increased from 10% in 2000 to 16% in 2006, a dramatic increase of 60% surpassed by only one other state in the nation (The Annie E. Casey Foundation, 2008). By comparison, the U.S. percentage of children in poverty during the same time frame rose from 17% to 18% (The Annie E. Casey Foundation, 2008). What kind of health care services are available to this vulnerable and growing group of Coloradans, and what are the barriers that affect their enrollment in, access to and utilization of these health care services? Barriers identified included difficulty with the application process; system and process issues; a lack of providers; and a lack of awareness and knowledge of EPSDT. Fiscal restraints and legislation at the federal and state level are also barriers to increasing enrollment and access to services. Outreach services are a critical component of providing EPSDT services, and there were several recommendations regarding outreach and case management that will benefit the program in the future. Through this analysis and identification of a broad range of barriers, a clearer picture emerged of current challenges within the EPSDT program as well as a broad range of strategies and recommendations to address these challenges. Through increased education and advocacy for EPSDT and the services it encompasses; stronger collaboration and cooperation between all groups involved, including providing a Medical Home for all eligible children; and new legislation putting more money and focus on comprehensive health care for low-income uninsured children; enrollment, access to and utilization of developmentally appropriate and quality health care services can be achieved. ^

Policy analysis of Texas Senate Bill 532 and the regulation of nurse practitioners in the convenience care model

Background. Retail clinics, also called convenience care clinics, have become a rapidly growing trend since their initial development in 2000. These clinics are coupled within a larger retail operation and are generally located in "big-box" discount stores such as Wal-mart or Target, grocery stores such as Publix or H-E-B, or in retail pharmacies such as CVS or Walgreen's (Deloitte Center for Health Solutions, 2008). Care is typically provided by nurse practitioners. Research indicates that this new health care delivery system reduces cost, raises quality, and provides a means of access to the uninsured population (e.g., Deloitte Center for Health Solutions, 2008; Convenient Care Association, 2008a, 2008b, 2008c; Hansen-Turton, Miller, Nash, Ryan, Counts, 2007; Salinsky, 2009; Scott, 2006; Ahmed & Fincham, 2010). Some healthcare analysts even suggest that retail clinics offer a feasible solution to the shortage of primary care physicians facing the nation (AHRQ Health Care Innovations Exchange, 2010). ^ The development and performance of retail clinics is heavily dependent upon individual state policies regulating NPs. Texas currently has one of the most highly regulated practice environments for NPs (Stout & Elton, 2007; Hammonds, 2008). In September 2009, Texas passed Senate Bill 532 addressing the scope of practice of nurse practitioners in the convenience care model. In comparison to other states, this law still heavily regulates nurse practitioners. However, little research has been conducted to evaluate the impact of state laws regulating nurse practitioners on the development and performance of retail clinics. ^ Objectives. (1). To describe the potential impact that SB 532 has on retail clinic performance. (2). To discuss the effectiveness, efficiency, and equity of the convenience care model. (3). To describe possible alternatives to Texas' nurse practitioner scope of practice guidelines as delineated in Texas Senate Bill 532. (4). To describe the type of nurse practitioner state regulation (i.e. independent, light, moderate, or heavy) that best promotes the convenience care model. ^ Methods. State regulations governing nurse practitioners can be characterized as independent, light, moderate, and heavy. Four state NP regulatory types and retail clinic performance were compared and contrasted to that of Texas regulations using Dunn and Aday's theoretical models for conducting policy analysis and evaluating healthcare systems. Criteria for measurement included effectiveness, efficiency, and equity. Comparison states were Arizona (Independent), Minnesota (Light), Massachusetts (Moderate), and Florida (Heavy). ^ Results. A comparative states analysis of Texas SB 532 and alternative NP scope of practice guidelines among the four states: Arizona, Florida, Massachusetts, and Minnesota, indicated that SB 532 has minimal potential to affect the shortage of primary care providers in the state. Although SB 532 may increase the number of NPs a physician may supervise, NPs are still heavily restricted in their scope of practice and limited in their ability to act as primary care providers. Arizona's example of independent NP practice provided the best alternative to affect the shortage of PCPs in Texas as evidenced by a lower uninsured rate and less ED visits per 1,000 population. A survey of comparison states suggests that retail clinics thrive in states that more heavily restrict NP scope of practice as opposed to those that are more permissive, with the exception of Arizona. An analysis of effectiveness, efficiency, and equity of the convenience care model indicates that retail clinics perform well in the areas of effectiveness and efficiency; but, fall short in the area of equity. ^ Conclusion. Texas Senate 532 represents an incremental step towards addressing the problem of a shortage of PCPs in the state. A comparative policy analysis of the other four states with varying degrees of NP scope of practice indicate that a more aggressive policy allowing for independent NP practice will be needed to achieve positive changes in health outcomes. Retail clinics pose a temporary solution to the shortage of PCPs and will need to expand their locations to poorer regions and incorporate some chronic care to obtain measurable health outcomes. ^

IDENTIFICATION AND ANALYSIS OF A NOVEL ROLE FOR THE TOUSLED-LIKE KINASE IN REGULATING MITOTIC SPINDLE DYNAMICS

Deregulation of kinase activity is one example of how cells become cancerous by evading evolutionary constraints. The Tousled kinase (Tsl) was initially identified in Arabidopsis thaliana as a developmentally important kinase. There are two mammalian orthologues of Tsl and one orthologue in C. elegans, TLK-1, which is essential for embryonic viability and germ cell development. Depletion of TLK-1 leads to embryonic arrest large, distended nuclei, and ultimately embryonic lethality. Prior to terminal arrest, TLK-1-depleted embryos undergo aberrant mitoses characterized by poor metaphase chromosome alignment, delayed mitotic progression, lagging chromosomes, and supernumerary centrosomes. I discovered an unanticipated requirement for TLK-1 in mitotic spindle assembly and positioning. Normally, in the newly-fertilized zygote (P0) the maternal pronucleus migrates toward the paternal pronucleus at the posterior end of the embryo. After pronuclear meeting, the pronuclear-centrosome complex rotates 90° during centration to align on the anteroposterior axis followed by nuclear envelope breakdown (NEBD). However, in TLK-1-depleted P0 embryos, the centrosome-pronuclear complex rotation is significantly delayed with respect to NEBD and chromosome congression, Additionally, centrosome positions over time in tlk-1(RNAi) early embryos revealed a defect in posterior centrosome positioning during spindle-pronuclear centration, and 4D analysis of centrosome positions and movement in newly fertilized embryos showed aberrant centrosome dynamics in TLK-1-depleted embryos. Several mechanisms contribute to spindle rotation, one of which is the anchoring of astral microtubules to the cell cortex. Attachment of these microtubules to the cortices is thought to confer the necessary stability and forces in order to rotate the centrosome-pronuclear complex in a timely fashion. Analysis of a microtubule end-binding protein revealed that TLK-1-depleted embryos exhibit a more stochastic distribution of microtubule growth toward the cell cortices, and the types of microtubule attachments appear to differ from wild-type embryos. Additionally, fewer astral microtubules are in the vicinity of the cell cortex, thus suggesting that the delayed spindle rotation could be in part due to a lack of appropriate microtubule attachments to the cell cortex. Together with recently published biochemical data revealing the Tousled-like kinases associate with components of the dynein microtubule motor complex in humans, these data suggest that Tousled-like kinases play an important role in mitotic spindle assembly and positioning.

Compilation of sedimentation rates and smear slide analysis of DSDP sites

A history of Mesozoie and Cenozoic palaeoenvironments of the North Atlantie Oeean has been developed based on a detailed analysis of the temporal and spatial distribution of major pelagie sediment facies, of hiatuses. of bulk sediment accumulation rates, and of concentrations and fluxes of the main deep-sea sediment components. The depositional history of the North Atlantic can be subdivided into three major phase: (a) Late Jurassie and Early Cretaceous phase: clastic terrigenous and biogenic pelagic sediment components accumulated rapidly under highly productive surface water masses over the entire occan basin; (b) Late Cretaceous to Early Miocene phase: relatively little terrigenous and pelagic biogenic sediment reached the North Atlantic Ocean floor, intensive hiatus formation occurred at variable rates, and wide stretches of the deep-ocean floor were covered by slowly accumulating terrigenous muds: (c) Middle Miocene to Recent phase: accumulation rates of biogenic and terrigenous deep-sea sediment components increased dramatically up to Quaternary times, rates of hiatus formation and the intensity of deep-water circulation inferred from them seem to have decreased. However, accumulation rate patterns of calcareous pelagic sediment components suggest that large scale reworking and di splacement of deep-sea sediments occurred at a variable rate over wide areas of the North Atlantic during this period.

First steps in the discovery of patterns in the academic results of telecommunication engineering students in the subjects Analysis of Circuits and Mathematics

In this paper, the results of six years of research in engineering education, in the application of the European Higher Education Area (EHEA) to improve the performance of the students in the subject Analysis of Circuits of Telecommunication Engineering, are analysed taking into consideration the fact that there would be hidden variables that both separate students into subgroups and show the connection among several basic subjects such as Analysis of Circuits (AC) and Mathematics (Math). The discovery of these variables would help us to explain the characteristics of the students through the teaching and learning methodology, and would show that there are some characteristics that instructors do not take into account but that are of paramount importance

A multi-scale analysis of transforming agricultural markets in the context of globalization: implications for natural resources, food prices and rural poverty in Latin America

Vivimos una época en la que el mundo se transforma aceleradamente. La globalización está siguiendo un curso imparable, la población mundial así como la población urbana siguen creciendo, y en los países emergentes los ingresos promedios aumentan, resultando en un cambio también acelerado de las dietas y hábitos alimentarios. En conjunto esos factores están causando un aumento fundamental de la demanda de alimentos. Junto con la apertura de los mercados agrícolas, estos procesos han provocado un crecimiento del comercio internacional de alimentos durante la última década. Dado que muchos países de América Latina están dotados de abundancia de recursos naturales, estas tendencias han producido un crecimiento rápido de las exportaciones de bienes primarios desde América Latina al resto del mundo. En sólo 30 años la participación en el mercado agrícola de América Latina casi se ha duplicado, desde 10% en 1980 a 18% en 2010. Este aumento del comercio agrícola ha dado lugar a un debate sobre una serie de cuestiones cruciales relacionadas con los impactos del comercio en la seguridad alimentaria mundial, en el medio ambiente o en la reducción de la pobreza rural en países en desarrollo. Esta tesis aplica un marco integrado para analizar varios impactos relacionados con la transformación de los mercados agrícolas y los mercados rurales debidos a la globalización y, en particular, al progresivo aumento del comercio internacional. En concreto, la tesis aborda los siguientes temas: En primer lugar, la producción mundial de alimentos tendrá que aumentar considerablemente para poder satisfacer la demanda de una población mundial de 9000 millones personas en 2050, lo cual plantea grandes desafíos sobre los sistemas de la producción de alimentos. Alcanzar este logro, sin comprometer la integridad del medio ambiente en regiones exportadoras, es un reto aún mayor. En este contexto, la tesis analiza los efectos de la liberalización del comercio mundial, considerando distintas tecnologías de producción agraria, sobre unos indicadores de seguridad alimentaria en diferentes regiones del mundo y sobre distintos indicadores ambientales, teniendo en cuenta escalas diferentes en América Latina y el Caribe. La tesis utiliza el modelo “International Model for Policy Analysis of Agricultural Commodities and Trade (IMPACT)” – un modelo dinámico de equilibrio parcial del sector agrícola a escala global – para modelar la apertura de los mercados agrícolas así como diferentes escenarios de la producción hasta el año 2050. Los resultados del modelo están vinculados a modelos biofísicos para poder evaluar los cambios en la huella hídrica y la calidad del agua, así como para cuantificar los impactos del cambio en el uso del suelo sobre la biodiversidad y los stocks de carbono en 2050. Los resultados indican que la apertura de los mercados agrícolas es muy importante para mejorar la seguridad alimentaria a nivel mundial, sin embargo, produce también presiones ambientales indeseables en algunas regiones de América Latina. Contrastando dos escenarios que consideran distintas modos de producción, la expansión de la tierra agrícola frente a un escenario de la producción más intensiva, se demuestra que las mejoras de productividad son generalmente superiores a la expansión de las tierras agrícolas, desde un punto de vista económico e ambiental. En cambio, los escenarios de intensificación sostenible no sólo hacen posible una mayor producción de alimentos, sino que también generan menos impactos medioambientales que los otros escenarios futuros en todas sus dimensiones: biodiversidad, carbono, emisiones de nitratos y uso del agua. El análisis muestra que hay un “trade-off” entre el objetivo de alcanzar la sostenibilidad ambiental y el objetivo de la seguridad alimentaria, independiente del manejo agrícola en el futuro. En segundo lugar, a la luz de la reciente crisis de los precios de alimentos en los años 2007/08, la tesis analiza los impactos de la apertura de los mercados agrícolas en la transmisión de precios de los alimentos en seis países de América Latina: Argentina, Brasil, Chile, Colombia, México y el Perú. Para identificar las posibles relaciones de cointegración entre los índices de precios al consumidor de alimentos y los índices de precios de agrarios internacionales, sujetos a diferentes grados de apertura de mercados agrícolas en los seis países de América Latina, se utiliza un modelo simple de corrección de error (single equation error correction). Los resultados indican que la integración global de los mercados agrícolas ha dado lugar a diferentes tasas de transmisión de precios en los países investigados. Sobre todo en el corto plazo, las tasas de transmisión dependen del grado de apertura comercial, mientras que en el largo plazo las tasas de transmisión son elevadas, pero en gran medida independientes del régimen de comercio. Por lo tanto, durante un período de shocks de precios mundiales una mayor apertura del comercio trae consigo más inestabilidad de los precios domésticos a corto plazo y la resultante persistencia en el largo plazo. Sin embargo, estos resultados no verifican necesariamente la utilidad de las políticas comerciales, aplicadas frecuentemente por los gobiernos para amortiguar los shocks de precios. Primero, porque existe un riesgo considerable de volatilidad de los precios debido a cambios bruscos de la oferta nacional si se promueve la autosuficiencia en el país; y segundo, la política de proteccionismo asume el riesgo de excluir el país de participar en las cadenas de suministro de alto valor del sector agrícola, y por lo tanto esa política podría obstaculizar el desarrollo económico. Sin embargo, es indispensable establecer políticas efectivas para reducir la vulnerabilidad de los hogares a los aumentos repentinos de precios de alimentos, lo cual requiere una planificación gubernamental precisa con el presupuesto requerido disponible. En tercer lugar, la globalización afecta a la estructura de una economía y, por medios distintos, la distribución de los ingreso en un país. Perú sirve como ejemplo para investigar más profundamente las cuestiones relacionadas con los cambios en la distribución de los ingresos en zonas rurales. Perú, que es un país que está cada vez más integrado en los mercados mundiales, consiguió importantes descensos en la pobreza extrema en sus zonas rurales, pero a la vez adolece de alta incidencia de pobreza moderada y de desigualdad de los ingresos en zonas rural al menos durante el periodo comprendido entre 2004 y 2012. Esta parte de la tesis tiene como objetivo identificar las fuerzas impulsoras detrás de estas dinámicas en el Perú mediante el uso de un modelo de microsimulación basado en modelos de generación de ingresos aplicado a nivel los hogares rurales. Los resultados indican que la fuerza principal detrás de la reducción de la pobreza ha sido el crecimiento económico general de la economía, debido a las condiciones macroeconómicas favorables durante el periodo de estudio. Estos efectos de crecimiento beneficiaron a casi todos los sectores rurales, y dieron lugar a la disminución de la pobreza rural extrema, especialmente entre los agricultores de papas y de maíz. En parte, estos agricultores probablemente se beneficiaron de la apertura de los mercados agrícolas, que es lo que podría haber provocado un aumento de los precios al productor en tiempos de altos precios mundiales de los alimentos. Sin embargo, los resultados también sugieren que para una gran parte de la población más pobre existían barreras de entrada a la hora de poder participar en el empleo asalariado fuera de la agricultura o en la producción de cultivos de alto valor. Esto podría explicarse por la falta de acceso a unos activos importantes: por ejemplo, el nivel de educación de los pobres era apenas mejor en 2012 que en 2004; y también las dotaciones de tierra y de mano de obra, sobre todo de los productores pobres de maíz y patata, disminuyeron entre 2004 y 2012. Esto lleva a la conclusión de que aún hay margen para aplicar políticas para facilitar el acceso a estos activos, que podría contribuir a la erradicación de la pobreza rural. La tesis concluye que el comercio agrícola puede ser un importante medio para abastecer una población mundial creciente y más rica con una cantidad suficiente de calorías. Para evitar adversos efectos ambientales e impactos negativos para los consumidores y de los productores pobres, el enfoque debe centrarse en las mejoras de la productividad agrícola, teniendo en cuenta los límites ambientales y ser socialmente inclusivo. En este sentido, será indispensable seguir desarrollando soluciones tecnológicas que garanticen prácticas de producción agrícola minimizando el uso de recursos naturales. Además, para los pequeños pobres agricultores será fundamental eliminar las barreras de entrada a los mercados de exportación que podría tener efectos indirectos favorables a través de la adopción de nuevas tecnologías alcanzables a través de mercados internacionales. ABSTRACT The world is in a state of rapid transition. Ongoing globalization, population growth, rising living standards and increasing urbanization, accompanied by changing dietary patterns throughout the world, are increasing the demand for food. Together with more open trade regimes, this has triggered growing international agricultural trade during the last decade. For many Latin American countries, which are gifted with relative natural resource abundance, these trends have fueled rapid export growth of primary goods. In just 30 years, the Latin American agricultural market share has almost doubled from 10% in 1980 to 18% in 2010. These market developments have given rise to a debate around a number of crucial issues related to the role of agricultural trade for global food security, for the environment or for poverty reduction in developing countries. This thesis uses an integrated framework to analyze a broad array of possible impacts related to transforming agricultural and rural markets in light of globalization, and in particular of increasing trade activity. Specifically, the following issues are approached: First, global food production will have to rise substantially by the year 2050 to meet effective demand of a nine billion people world population which poses major challenges to food production systems. Doing so without compromising environmental integrity in exporting regions is an even greater challenge. In this context, the thesis explores the effects of future global trade liberalization on food security indicators in different world regions and on a variety of environmental indicators at different scales in Latin America and the Caribbean, in due consideration of different future agricultural production practices. The International Model for Policy Analysis of Agricultural Commodities and Trade (IMPACT) –a global dynamic partial equilibrium model of the agricultural sector developed by the International Food Policy Research Institute (IFPRI)– is applied to run different future production scenarios, and agricultural trade regimes out to 2050. Model results are linked to biophysical models, used to assess changes in water footprints and water quality, as well as impacts on biodiversity and carbon stocks from land use change by 2050. Results indicate that further trade liberalization is crucial for improving food security globally, but that it would also lead to more environmental pressures in some regions across Latin America. Contrasting land expansion versus more intensified agriculture shows that productivity improvements are generally superior to agricultural land expansion, from an economic and environmental point of view. Most promising for achieving food security and environmental goals, in equal measure, is the sustainable intensification scenario. However, the analysis shows that there are trade-offs between environmental and food security goals for all agricultural development paths. Second, in light of the recent food price crisis of 2007/08, the thesis looks at the impacts of increasing agricultural market integration on food price transmission from global to domestic markets in six Latin American countries, namely Argentina, Brazil, Chile, Colombia, Mexico and Peru. To identify possible cointegrating relationships between the domestic food consumer price indices and world food price levels, subject to different degrees of agricultural market integration in the six Latin American countries, a single equation error correction model is used. Results suggest that global agricultural market integration has led to different levels of price path-through in the studied countries. Especially in the short-run, transmission rates depend on the degree of trade openness, while in the long-run transmission rates are high, but largely independent of the country-specific trade regime. Hence, under world price shocks more trade openness brings with it more price instability in the short-term and the resulting persistence in the long-term. However, these findings do not necessarily verify the usefulness of trade policies, often applied by governments to buffer such price shocks. First, because there is a considerable risk of price volatility due to domestic supply shocks if self-sufficiency is promoted. Second, protectionism bears the risk of excluding a country from participating in beneficial high-value agricultural supply chains, thereby hampering economic development. Nevertheless, to reduce households’ vulnerability to sudden and large increases of food prices, effective policies to buffer food price shocks should be put in place, but must be carefully planned with the required budget readily available. Third, globalization affects the structure of an economy and, by different means, the distribution of income in a country. Peru serves as an example to dive deeper into questions related to changes in the income distribution in rural areas. Peru, a country being increasingly integrated into global food markets, experienced large drops in extreme rural poverty, but persistently high rates of moderate rural poverty and rural income inequality between 2004 and 2012. The thesis aims at disentangling the driving forces behind these dynamics by using a microsimulation model based on rural household income generation models. Results provide evidence that the main force behind poverty reduction was overall economic growth of the economy due to generally favorable macroeconomic market conditions. These growth effects benefited almost all rural sectors, and led to declines in extreme rural poverty, especially among potato and maize farmers. In part, these farmers probably benefited from policy changes towards more open trade regimes and the resulting higher producer prices in times of elevated global food price levels. However, the results also suggest that entry barriers existed for the poorer part of the population to participate in well-paid wage-employment outside of agriculture or in high-value crop production. This could be explained by a lack of sufficient access to important rural assets. For example, poor people’s educational attainment was hardly better in 2012 than in 2004. Also land and labor endowments, especially of (poor) maize and potato growers, rather decreased than increased over time. This leads to the conclusion that there is still scope for policy action to facilitate access to these assets, which could contribute to the eradication of rural poverty. The thesis concludes that agricultural trade can be one important means to provide a growing and richer world population with sufficient amounts of calories. To avoid adverse environmental effects and negative impacts for poor food consumers and producers, the focus should lie on agricultural productivity improvements, considering environmental limits and be socially inclusive. In this sense, it will be crucial to further develop technological solutions that guarantee resource-sparing agricultural production practices, and to remove entry barriers for small poor farmers to export markets which might allow for technological spill-over effects from high-value global agricultural supply chains.

Genomic analysis of human and mouse TCL1 loci reveals a complex of tightly clustered genes

TCL1 and TCL1b genes on human chromosome 14q23.1 are activated in T cell leukemias by translocations and inversions at 14q32.1, juxtaposing them to regulatory elements of T cell receptor genes. In this report we present the cloning, mapping, and expression analysis of the human and murine TCL1/Tcl1 locus. In addition to TCL1 and TCL1b, the human locus contains two additional genes, TCL1-neighboring genes (TNG) 1 and 2, encoding proteins of 141 and 110 aa, respectively. Both genes show no homology to any known genes, but their expression profiles are very similar to those of TCL1 and TCL1b. TNG1 and TNG2 also are activated in T cell leukemias with rearrangements at 14q32.1. To aid in the development of a mouse model we also have characterized the murine Tcl1 locus and found five genes homologous to human TCL1b. Tcl1b1–Tcl1b5 proteins range from 117 to 123 aa and are 65–80% similar, but they show only a 30–40% similarity to human TCL1b. All five mouse Tcl1b and murine Tcl1 mRNAs are abundant in mouse oocytes and two-cell embryos but rare in various adult tissues and lymphoid cell lines. These data suggest a similar or complementary function of these proteins in early embryogenesis.

rSNP_Guide, a database system for analysis of transcription factor binding to target sequences: application to SNPs and site-directed mutations

rSNP_Guide is a novel curated database system for analysis of transcription factor (TF) binding to target sequences in regulatory gene regions altered by mutations. It accumulates experimental data on naturally occurring site variants in regulatory gene regions and site-directed mutations. This database system also contains the web tools for SNP analysis, i.e., active applet applying weight matrices to predict the regulatory site candidates altered by a mutation. The current version of the rSNP_Guide is supplemented by six sub-databases: (i) rSNP_DB, on DNA–protein interaction caused by mutation; (ii) SYSTEM, on experimental systems; (iii) rSNP_BIB, on citations to original publications; (iv) SAMPLES, on experimentally identified sequences of known regulatory sites; (v) MATRIX, on weight matrices of known TF sites; (vi) rSNP_Report, on characteristic examples of successful rSNP_Tools implementation. These databases are useful for the analysis of natural SNPs and site-directed mutations. The databases are available through the Web, http://wwwmgs.bionet.nsc.ru/mgs/systems/rsnp/.