A statistical physics perspective on alignment-independent protein sequence comparison.

Motivation: Within bioinformatics, the textual alignment of amino acid sequences has long dominated the determination of similarity between proteins, with all that implies for shared structure, function, and evolutionary descent. Despite the relative success of modern-day sequence alignment algorithms, so-called alignment-free approaches offer a complementary means of determining and expressing similarity, with potential benefits in certain key applications, such as regression analysis of protein structure-function studies, where alignment-base similarity has performed poorly. Results: Here, we offer a fresh, statistical physics-based perspective focusing on the question of alignment-free comparison, in the process adapting results from “first passage probability distribution” to summarize statistics of ensemble averaged amino acid propensity values. In this paper, we introduce and elaborate this approach.

Blurring the lines between public and private spaces in residential design

This thesis explores the role of public space as an integral part of residential design to promote a sense of community, where neighbors can congregate and children can play in safety. ^ Through research and analysis of successful public spaces, I evaluated relationships between dwellings and public spaces that offer progressive levels of privacy, and between indoor and outdoor spaces. Further research of published studies on child development, human behavior and relationships with nature identified a human preference for natural environments, a need for adequate recreation space for children's development and the potential of open spaces to build a strong sense of community. ^ My project develops multiple transitional spaces between the street and the interior of dwellings that provide varying degrees of privacy closely related to the community's green spaces. The result is a community-oriented pedestrian environment that encourages family and community values and contributes to the healthy living of its residents without depriving them of their privacy. ^

The Five Essentials of Private Club Leadership

The authors examine underlying dimensions of private club leadership using principal components analysis. The data were collected between 1996 and 2003 from 702 club managers or club chief operating officers who are members of the Club Managers Association of America (CMAA). Five factors - innovation, vision, inner values, stewardship, and communication - were identified as essentials of private club leadership.

THE IMPORTANCE OF MHC-INDEPENDENT NATURAL KILLER CELL RECEPTORS IN THE IMMUNOREGULATION OF MURINE PREGNANCY

Numerous leukocyte populations are essential for pregnancy success. Uterine natural killer (uNK) cells are chief amongst these leukocytes and represent a unique lineage with limited cytotoxicity but abundant angiokine production. They possess a distinct phenotype of activating and inhibitory receptors that recognize major histocompatibility complex (MHC) molecules, such as the killer immunoglobulin like receptors (KIRs; mouse Ly49), and MHC-independent activating receptors, including the aryl hydrocarbon receptor (AHR) and natural cytotoxicity receptor 1 (NCR1). While the roles of MHC-dependent receptors are widely addressed in pregnancy, MHC-independent receptors are relatively unstudied. This thesis investigated the roles of MHC-independent receptors in promotion of mouse pregnancy and characterized early leukocyte interactions in the presence and absence of NCR1. It was hypothesized that loss of MHC-independent receptors impairs uNK cell development resulting in aberrations in leukocyte function and decidual vasculature. Implantation sites from Ahr-/- and Ncr1Gfp/Gfp mice were assessed using whole mount in situ immunohistochemistry (WM-IHC) and histochemical techniques. Leukocyte interactions identified during preliminary WM-IHC studies were confirmed as immune synapses. The novel identification of immune synapses in early mouse pregnancy compelled further examination of leukocyte conjugates in wildtype C57BL/6 and Ncr1Gfp/Gfp mice. In Ahr-/- and Ncr1Gfp/Gfp mice, receptor loss resulted in reduced uNK cell diameters, impaired decidual vasculature, and failures in spiral artery remodeling. Ahr-/- mice had severe fertility deficits whereas Ncr1Gfp/Gfp mice had increased fetal resorption indicating differing receptor requirements in pregnancy success. NCR1 loss primarily affected uNK cell maturation and function as identified by alterations in granule ultrastructure, lytic protein expression, and angiokine production. Leukocyte conjugates were frequent in early C57BL/6 decidua basalis and included uNK cells conjugating first with antigen presenting cells and then with T cells. Overall conjugate formation was reduced in the absence of NCR1, but specific uNK cell conjugations were unaffected by receptor loss. While KIR-MHC interactions are associated with numerous pregnancy complications in humans, the role of other uNK cell receptors are not well characterized. These results illustrate the importance of MHC-independent receptors in uNK cell activation during early pregnancy in mice and encourage further studies of pregnancy complications that may occur independently of maternal KIR-MHC contributions.

Communication-efficient decentralized sequential detection

The problem of decentralized sequential detection is studied in this thesis, where local sensors are memoryless, receive independent observations, and no feedback from the fusion center. In addition to traditional criteria of detection delay and error probability, we introduce a new constraint: the number of communications between local sensors and the fusion center. This metric is able to reflect both the cost of establishing communication links as well as overall energy consumption over time. A new formulation for communication-efficient decentralized sequential detection is proposed where the overall detection delay is minimized with constraints on both error probabilities and the communication cost. Two types of problems are investigated based on the communication-efficient formulation: decentralized hypothesis testing and decentralized change detection. In the former case, an asymptotically person-by-person optimum detection framework is developed, where the fusion center performs a sequential probability ratio test based on dependent observations. The proposed algorithm utilizes not only reported statistics from local sensors, but also the reporting times. The asymptotically relative efficiency of proposed algorithm with respect to the centralized strategy is expressed in closed form. When the probabilities of false alarm and missed detection are close to one another, a reduced-complexity algorithm is proposed based on a Poisson arrival approximation. In addition, decentralized change detection with a communication cost constraint is also investigated. A person-by-person optimum change detection algorithm is proposed, where transmissions of sensing reports are modeled as a Poisson process. The optimum threshold value is obtained through dynamic programming. An alternative method with a simpler fusion rule is also proposed, where the threshold values in the algorithm are determined by a combination of sequential detection analysis and constrained optimization. In both decentralized hypothesis testing and change detection problems, tradeoffs in parameter choices are investigated through Monte Carlo simulations.

Of Marx and Makers: an Historical Perspective on Generative Justice

In Marxist frameworks “distributive justice” depends on extracting value through a centralized state. Many new social movements—peer to peer economy, maker activism, community agriculture, queer ecology, etc.—take the opposite approach, keeping value in its unalienated form and allowing it to freely circulate from the bottom up. Unlike Marxism, there is no general theory for bottom-up, unalienated value circulation. This paper examines the concept of “generative justice” through an historical contrast between Marx’s writings and the indigenous cultures that he drew upon. Marx erroneously concluded that while indigenous cultures had unalienated forms of production, only centralized value extraction could allow the productivity needed for a high quality of life. To the contrary, indigenous cultures now provide a robust model for the “gift economy” that underpins open source technological production, agroecology, and restorative approaches to civil rights. Expanding Marx’s concept of unalienated labor value to include unalienated ecological (nonhuman) value, as well as the domain of freedom in speech, sexual orientation, spirituality and other forms of “expressive” value, we arrive at an historically informed perspective for generative justice. 

(Des)igualdades de Género nas Organizações de Trabalho: o caso de uma autarquia local

Em Portugal, cerca de duas centenas de organizações estão empenhadas a criar e implementar Planos para a igualdade de homens e mulheres. Entre elas estão empresas públicas e privadas, autarquias, associações empresariais, organizações do setor terciário, associações de desenvolvimento, universidades, ministérios e outros departamentos governativos. A pesquisa que aqui se expõe inscreveu-se num projeto mais amplo de diagnóstico em realização na Câmara Municipal da Lousã, que se encontra a promover um Plano Municipal para a Igualdade. Nesse âmbito mostrou-se necessário fazer um diagnóstico interno à organização com uma perspetiva de género, quer em termos de desigualdades de género na composição e situação dos seus efetivos quer de forma a conhecer as representações das pessoas que trabalham na autarquia, em torno do fenómeno da (des)igualdade de mulheres e homens. Para a sua realização foi feita análise estatística a dados fornecidos pela organização, e aplicou-se um inquérito por questionário ao pessoal ao serviço da autarquia. Concluiu-se que estamos na presença do fenómeno da desigualdade em função do sexo na estrutura da organização traduzida pela segregação ocupacional e segregação vertical, sendo os homens que apresentam os maiores níveis de antiguidade, que justificarão, de certa forma, as disparidades salariais existentes. Confirmamos uma dualidade entre o ideal de mulher como mãe e dona-de-casa e o de mulher como pessoa independente, especialmente quando são evocadas as consequências da sua atividade profissional sobre os/as filhos/as e a vida familiar. O papel de cuidar surge assim como o obstáculo a conceções menos tradicionalistas e individualizadoras da identidade feminina que nos remete para uma mudança na atribuição do lugar social de homens e mulheres dentro e fora da família. Sobressai a valorização e enfatização da maternidade e do cuidado das crianças na identidade feminina; ao passo que aos homens se atribui uma maior valorização da atividade profissional. Esta constatação comprova a ambivalência e dicotomia de valores e atitudes entre uma fuga à convencional polarização entre papéis “masculinos” e “femininos” rígida e estereotipadamente definidos. / In Portugal, about two hundred organizations are committed to create and implement plans for men and women’s equality. These include public and private companies, local authorities, business associations, third sector organizations, development associations, universities, ministries and other governmental departments. The research exposed here is part of a broader diagnostic project taking placa in the City Hall, of Lousã which is promoting a Municipal Plan for Equality. In this context it was necessary to make an internal diagnosis to the organization from a perspective of gender, either in terms of gender inequalities in the composition and status of their workers or in order to know the workers representations around the phenomenon of women and men’s equality. To make it passible the organization provided statistical data which was analysed and subsequentaly a questionnaire was applied to the municipality staff. We concluded that there is the phenomenon of gender inequality in the structure of the organization namely occupational/professional segregation and vertical segregation, - men having the highest levels of seniority, which may justify in some way the existing wage gap. The study confirms a duality between the ideal of woman as a mother and housewife and the woman as an independent person, especially when the consequences suggested are related to their professional activity on their children and life family. The role of caring emerges as the obstacle to less traditionalist conceptions of female identity and individualization, which leads us to talk about a change of the social position of men and women within and outside the family. It points out the valuation and emphasizing of motherhood and care in female identity, whereas men are given a greater appreciation of the professional activity. This conclusion confirms the ambivalence and dichotomy of values and attitudes between escape from the conventional polarization between rigid and stereotypically defined roles of "male" and "female".

Review into the Proposed Registration of Teachers and Others who Support Learning in the Independent Sector with the Education Workforce Council

During the passage of the Education (Wales) Bill, Assembly Members called for parity in the way the behaviour of practitioners within maintained schools and the independent sector are regulated. This study was therefore commissioned to gather the views of groups and individuals who work in the education sector in Wales, on whether: i) there should be a requirement for practitioners (both teaching and learning support staff) within independent schools and private FE institutions to register with the Council ii) employers should be legally required to refer cases of unacceptable professional conduct and serious professional incompetence to the Council It was also intended, through this process, to gather views on the potential implications associated with any such registration so that the resulting impact could be identified. The individuals and organisations consulted included head teachers, college principals, governing bodies, teaching staff, learning support staff, trade unions, registration bodies, independent sector representative bodies, inspectorates and teaching councils. Consultations took place between August and November 2015, with data gathered through an online survey, face-to-face interviews, telephone interviews and via email.

Friendships of High-Achieving African American Adolescents: Relation to Ethnic Identity and Achievement Values

The academic achievement of African American adolescents is a national concern for educators and researchers especially since current reports depict the underachievement of African American students as continuing to lag behind their European American peers. Determining what factors within the school environment that contributes to the achievement gap and how it can be reduced remains an important issue in alleviating disparities seen in educational achievement and attainment. This study examined the relation between characteristics of the close friendships of high-achieving African American adolescents and students’ identity development and motivation in school. Data were collected from 217 high-achieving African American students within 10th to 12th grade from 5 public and private high schools. Each student self-reported on their ethnicity, gender, parents’ education level, grade, FARMs, GPA, perceived teacher support (emotional, academic, and instrumental support), their perception of their ethnic identity, and their perception of their achievement values. Through the use of nomination procedures, students also identified their close friends and responded to questions concerning how supportive (emotional, academic, and instrumental support) they each were. Results from multiple regression analyses showed that the provision of instrumental support from close friends related to the exploration process of the high-achieving students’ ethnic identity. In addition, there was a strong relation between the ethnic identity of close friends and that of the individual. Furthermore, although friend support was not a significant predictor of achievement values, demographic (mother’s education level, grade, and FARMS) and control (teacher support) variables predicted students’ importance and utility of school respectively. These findings add to the literature on age and socioeconomic status as they relate to student’s motivation to achieve. Overall, this study provides some evidence highlighting ways in which close friendships might relate to the self-development of high-achieving African American adolescents. This study provides a starting point for additional ways in which to explore how peer processes relate to the academic behaviors of high-achieving African American adolescents.

Review of Abuse, Neglect, and Exploitation Allegations Involving SC Mentor, a Private Provider for the South Carolina Department of Disabilities and Special Needs

This review was requested by the Department of Disabilities and Special Needs for an independent review of allegations of abuse, neglect, and exploitation at SC Mentor, a private provider of residential services for DDSN consumers. An analysis of incidents did not indicate systemic abuse towards consumers inasmuch as the majority of the ANE reporting system contained allegations more akin to staff/facility performance issues and the vast majority of all allegations were unsustained by independent investigations. In the future, DDSN should expand the level of detail in its ANE reporting, which currently only reports total allegations and sustained criminal incidents.

Normative reference values for the 20-meter shuttlerun test in a population-based sample of schoolchildren in Bogota, Colombia: The FUPRECOL Study

Our aim was to determine the normative reference values of cardiorespiratory fitness (CRF) and to establish the proportion of subjects with low CRF suggestive of future cardio-metabolic risk.

Private sensors and crowdsourced rainfall data: accuracy and effectiveness for monitoring severe events and mapping pluvial flooding in urban areas

The increasing number of extreme rainfall events, combined with the high population density and the imperviousness of the land surface, makes urban areas particularly vulnerable to pluvial flooding. In order to design and manage cities to be able to deal with this issue, the reconstruction of weather phenomena is essential. Among the most interesting data sources which show great potential are the observational networks of private sensors managed by citizens (crowdsourcing). The number of these personal weather stations is consistently increasing, and the spatial distribution roughly follows population density. Precisely for this reason, they perfectly suit this detailed study on the modelling of pluvial flood in urban environments. The uncertainty associated with these measurements of precipitation is still a matter of research. In order to characterise the accuracy and precision of the crowdsourced data, we carried out exploratory data analyses. A comparison between Netatmo hourly precipitation amounts and observations of the same quantity from weather stations managed by national weather services is presented. The crowdsourced stations have very good skills in rain detection but tend to underestimate the reference value. In detail, the accuracy and precision of crowd- sourced data change as precipitation increases, improving the spread going to the extreme values. Then, the ability of this kind of observation to improve the prediction of pluvial flooding is tested. To this aim, the simplified raster-based inundation model incorporated in the Saferplaces web platform is used for simulating pluvial flooding. Different precipitation fields have been produced and tested as input in the model. Two different case studies are analysed over the most densely populated Norwegian city: Oslo. The crowdsourced weather station observations, bias-corrected (i.e. increased by 25%), showed very good skills in detecting flooded areas.

Effects Of Therapeutic Approach On The Neonatal Evolution Of Very Low Birth Weight Infants With Patent Ductus Arteriosus.

To analyze the effects of treatment approach on the outcomes of newborns (birth weight [BW] < 1,000 g) with patent ductus arteriosus (PDA), from the Brazilian Neonatal Research Network (BNRN) on: death, bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage (IVH III/IV), retinopathy of prematurity requiring surgical (ROPsur), necrotizing enterocolitis requiring surgery (NECsur), and death/BPD. This was a multicentric, cohort study, retrospective data collection, including newborns (BW < 1000 g) with gestational age (GA) < 33 weeks and echocardiographic diagnosis of PDA, from 16 neonatal units of the BNRN from January 1, 2010 to Dec 31, 2011. Newborns who died or were transferred until the third day of life, and those with presence of congenital malformation or infection were excluded. Groups: G1 - conservative approach (without treatment), G2 - pharmacologic (indomethacin or ibuprofen), G3 - surgical ligation (independent of previous treatment). Factors analyzed: antenatal corticosteroid, cesarean section, BW, GA, 5 min. Apgar score < 4, male gender, Score for Neonatal Acute Physiology Perinatal Extension (SNAPPE II), respiratory distress syndrome (RDS), late sepsis (LS), mechanical ventilation (MV), surfactant (< 2 h of life), and time of MV. death, O2 dependence at 36 weeks (BPD36wks), IVH III/IV, ROPsur, NECsur, and death/BPD36wks. Student's t-test, chi-squared test, or Fisher's exact test; Odds ratio (95% CI); logistic binary regression and backward stepwise multiple regression. Software: MedCalc (Medical Calculator) software, version 12.1.4.0. p-values < 0.05 were considered statistically significant. 1,097 newborns were selected and 494 newborns were included: G1 - 187 (37.8%), G2 - 205 (41.5%), and G3 - 102 (20.6%). The highest mortality was observed in G1 (51.3%) and the lowest in G3 (14.7%). The highest frequencies of BPD36wks (70.6%) and ROPsur were observed in G3 (23.5%). The lowest occurrence of death/BPD36wks occurred in G2 (58.0%). Pharmacological (OR 0.29; 95% CI: 0.14-0.62) and conservative (OR 0.34; 95% CI: 0.14-0.79) treatments were protective for the outcome death/BPD36wks. The conservative approach of PDA was associated to high mortality, the surgical approach to the occurrence of BPD36wks and ROPsur, and the pharmacological treatment was protective for the outcome death/BPD36wks.

Toll-like Receptor 4 Activation Promotes Cardiac Arrhythmias By Decreasing The Transient Outward Potassium Current (ito) Through An Irf3-dependent And Myd88-independent Pathway.

Cardiac arrhythmias are one of the main causes of death worldwide. Several studies have shown that inflammation plays a key role in different cardiac diseases and Toll-like receptors (TLRs) seem to be involved in cardiac complications. In the present study, we investigated whether the activation of TLR4 induces cardiac electrical remodeling and arrhythmias, and the signaling pathway involved in these effects. Membrane potential was recorded in Wistar rat ventricle. Ca(2+) transients, as well as the L-type Ca(2+) current (ICaL) and the transient outward K(+) current (Ito), were recorded in isolated myocytes after 24 h exposure to the TLR4 agonist, lipopolysaccharide (LPS, 1 μg/ml). TLR4 stimulation in vitro promoted a cardiac electrical remodeling that leads to action potential prolongation associated with arrhythmic events, such as delayed afterdepolarization and triggered activity. After 24 h LPS incubation, Ito amplitude, as well as Kv4.3 and KChIP2 mRNA levels were reduced. The Ito decrease by LPS was prevented by inhibition of interferon regulatory factor 3 (IRF3), but not by inhibition of interleukin-1 receptor-associated kinase 4 (IRAK4) or nuclear factor kappa B (NF-κB). Extrasystolic activity was present in 25% of the cells, but apart from that, Ca(2+) transients and ICaL were not affected by LPS; however, Na(+)/Ca(2+) exchanger (NCX) activity was apparently increased. We conclude that TLR4 activation decreased Ito, which increased AP duration via a MyD88-independent, IRF3-dependent pathway. The longer action potential, associated with enhanced Ca(2+) efflux via NCX, could explain the presence of arrhythmias in the LPS group.

Bay 41-2272, A Soluble Guanylate Cyclase Stimulator, Relaxes Isolated Human Ureter In A Standardized In Vitro Model.

To characterize the relaxation induced by BAY 41-2272 in human ureteral segments. Ureter specimens (n = 17) from multiple organ human deceased donors (mean age 40 ± 3.2 years, male/female ratio 2:1) were used to characterize the relaxing response of BAY 41-2272. Immunohistochemical analysis for endothelial and neuronal nitric oxide synthase, guanylate cyclase stimulator (sGC) and type 5 phosphodiesterase was also performed. The potency values were determined as the negative log of the molar to produce 50% of the maximal relaxation in potassium chloride-precontracted specimens. The unpaired Student t test was used for the comparisons. Immunohistochemistry revealed the presence of endothelial nitric oxide synthase in vessel endothelia and neuronal nitric oxide synthase in urothelium and nerve structures. sGC was expressed in the smooth muscle and urothelium layer, and type 5 phosphodiesterase was present in the smooth muscle only. BAY 41-2272 (0.001-100 μM) relaxed the isolated ureter in a concentration dependent manner, with a potency and maximal relaxation value of 5.82 ± 0.14 and 84% ± 5%, respectively. The addition of nitric oxide synthase and sGC inhibitors reduced the maximal relaxation values by 21% and 45%, respectively. However, the presence of sildenafil (100 nM) significantly potentiated (6.47 ± 0.10, P <.05) this response. Neither glibenclamide or tetraethylammonium nor ureteral urothelium removal influenced the relaxation response by BAY 41-2272. BAY 41-2272 relaxes the human isolated ureter in a concentration-dependent manner, mainly by activating the sGC enzyme in smooth muscle cells rather than in the urothelium, although a cyclic guanosine monophosphate-independent mechanism might have a role. The potassium channels do not seem to be involved.