Miracle-dz/UniFAR-FTUs huggingface dataset:
Generation and Characterization of B7-H4/B7S1/B7x-Deficient Mice

ABSTRACT Members of the B7 family of cosignaling molecules regulate T-cell proliferation and effector functions by engaging cognate receptors on T cells. In vitro and in vivo blockade experiments indicated that B7-H4 (also known as B7S1 or B7x) inhibits proliferation, cytokine production, and cytotoxicity of T cells. B7-H4 binds to an unknown receptor(s) that is expressed on activated T cells. However, whether B7-H4 plays nonredundant immune regulatory roles in vivo has not been tested. We generated B7-H4-deficient mice to investigate the roles of B7-H4 during various immune reactions. Consistent with its inhibitory function in vitro, B7-H4-deficient mice mounted mildly augmented T-helper 1 (Th1) responses and displayed slightly lowered parasite burdens upon Leishmania major infection compared to the wild-type mice. However, the lack of B7-H4 did not affect hypersensitive inflammatory responses in the airway or skin that are induced by either Th1 or Th2 cells. Likewise, B7-H4-deficient mice developed normal cytotoxic T-lymphocyte reactions against viral infection. Thus, B7-H4 plays a negative regulatory role in vivo but the impact of B7-H4 deficiency is minimal. These results suggest that B7-H4 is one of multiple negative cosignaling molecules that collectively provide a fine-tuning mechanism for T-cell-mediated immune responses.
Infection‐specific Prion Protein (PrP) Accumulates on Neuronal Plasmalemma in Scrapie‐infected Mice

Prion protein (PrP) is an abundant membrane-associated host protein which accumulates in abnormal, relatively protease-resistant forms in the brains of animals with scrapie and related diseases. Using correlative light and electron microscopy we determined the sites of subcellular localization of PrP in mice infected with the 87V strain of scrapie. Disease-specific accumulation of PrP was observed at light microscopy as amyloid plaques or as diffuse or granular staining within the neuropil, often clearly associated with individual neurons. Serial electron microscopical preparations were immunostained for PrP by the immunogold method. Gold particles were located on amyloid fibrils and on the plasmalemma of neurites at the periphery of plaques and in the neuropil, irrespective of the morphological form of PrP accumulation when viewed by light microscopy. This suggests the amyloid fibrils are formed following the accumulation and aggregation of sub-unit proteins at the plasmalemma and, furthermore, that normal PrP may be converted to its pathological form at this site.
Identifying and overcoming the barriers to high-quality palliative care in the intensive care unit

Initiatives to improve end-of-life care in intensive care units face several important barriers. These include inflated expectations for critical care therapies, which are shared by many clinicians and many patients and families; preoccupation with an unattainable level of prognostic certainty, delaying attention to palliative needs; and fragmentation of the healthcare team into separate “silos” of disciplines and specialties. The article reviews these barriers and relevant empirical evidence. Specific strategies to improve intensive care unit palliative care, including consultation by palliative care specialists, and palliative care quality measurement are discussed.
Soils associated with rock outcrops in the Brazilian mountain ranges Mantiqueira and Espinhaço

A Serra do Espinhaco e a Serra da Mantiqueira sao duas cadeias de grande importância para o Brasil. Nas partes mais altas destas serras encontramse ecossistemas com caracteristicas singulares, associados aos afloramentos rochosos, denominados Complexos Rupestres de Altitude. Esses ambientes apresentam caracteristicas do solo e da vegetacao distintas das areas adjacentes. Os solos sao em geral rasos, arenosos, com alta saturacao de aluminio e teores variados de materia orgânica. Neossolos Litolicos, Cambissolos e Organossolos sao as classes de solo dominantes, diretamente associadas aos afloramentos, formando um mosaico de solos. Alguns solos encontrados nestes ambientes sao endemicos, em funcao das caracteristicas peculiares da rocha matriz, da topografia e da vegetacao, e sua preservacao e estrategica por se tratar de solos raros e ameacados de extincao. A materia orgânica desses solos apresenta alto grau de humificacao, com grande quantidade de fracoes soluveis, e a presenca generalizada de fragmentos de carvao. Horizontes espodicos e rios negros estao tipicamente associados as areas de afloramento de arenito e quartzito, sendo formados pela iluviacao de compostos orgânicos, e sendo menos comuns nas areas de granito. O oligotrofismo destes solos, associado a outras limitacoes de ordem quimica e fisica, induzem o desenvolvimento de estrategias de adaptacao fisiologica e morfologica por parte da vegetacao. A maioria destes ecossistemas e instavel sob a condicao climatica atual, e a intervencao antropica e um fator de aceleracao do processo de degradacao. A descricao detalhada dos solos nestes ambientes e fundamental para um melhor entendimento do seu papel nos processos ecologicos e para o desenvolvimento de politicas de conservacao.
Predictive biomarkers for anthracycline benefit in early breast cancer : When do we act ?

Joseph ragaz, MD, FrCPC is a clinical Professor of medicine and Oncology at mcgill university and at the school of Population and Public health, university of british columbia. With cost and toxicity posing important stumbling blocks for more rapid deployment of cancer therapies, interest is growing in biomarkers that can identify which patients will and which will not likely benefit from costly and potentially toxic treatments. Estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status are well-established key biomarkers for selecting which breast cancer patients receive hormonal therapies and trastuzumab, respectively, and both have recently been associated with predictive value for chemotherapy effectiveness. Multiple biomarkers that combine signals of multiple genes (as determined by cDNA techniques) are also used to predict chemotherapy effect, for example the Oncotype 21 gene assay in North America and the 70-gene MammaPrint (Amsterdam) assay in Europe. Emerging potentially useful markers include the combination of tissue inhibitor of metalloproteinase-1 (TIMP1) and topoisomerase II-alpha (TOP2A), described recently by Danish researchers Ejlertsen et al at the 2008 San Antonio Breast Cancer Symposium (SABCS) and discussed below.
Searching for a Perceived Stare in the Crowd

Gaze direction can be represented in terms not only of local-feature information (ie the location of the pupil in the eye socket), but also of an emergent property—whether the perceived gaze direction is straight or averted. To examine whether this emergent property is preferentially accessed when searching for an oddly directed gaze, we experimentally manipulated the local-feature information and the emergent property independently, in order to investigate the influences of both types of information on visual searches for an oddly directed gaze. We found that the primary determinant of search efficiency was not the local-feature information of eye region, but the emergent property—the perceived direction of the gaze. This finding is consistent with the idea that important social signals are recognised primarily by their emergent properties.
Approaches to Ergativity in Indo-Aryan

Approaches to Ergativity in Indo-Aryan The present paper aims at giving an overview of the basic theories pertaining to the emergence and development of ergativity in Indo-Aryan. It has usually been argued that ergativity could have been derived either from the passive or the originally PIE ergative construction. In addition to these two basic approaches to ergativity in IA, other perspectives are also taken into consideration here, namely the theory which is based on the pragmatic properties of OIA, and the hypothesis of the possible borrowing from the substratum languages. The existing models of the historical scenarios of the emergence of ergativity in IA, including their later mutations, are confronted with the hypothesis of the possible active typology of PIE. The active residues in OIA and its continuants might prove that ergativity arose due to the transition from the PIE active to the nominative stage attested in the daughter languages.
What determines successful implementation of inpatient information technology systems?

OBJECTIVES To identify the factors and strategies that were associated with successful implementation of hospital-based information technology (IT) systems in US Department of Veterans Affairs (VA) hospitals, and how these might apply to other hospitals. STUDY DESIGN Qualitative analysis of 118 interviews conducted at 7 VA hospitals. The study focused on the inpatient setting, where nurses are the main patient-care providers; thus, the research emphasized the impact of Computerized Patient Record System and Bar Code Medication Administration on nurses. Hospitals were selected to represent a range of IT implementation dates, facility sizes, and geography. The subjects included nurses, pharmacists, physicians, IT staff, and managers. Interviews were guided by a semi-structured interview protocol, and a thematic analysis was conducted, with initial codes drawn from the content of the interview guides. Additional themes were proposed as the coding was conducted. RESULTS Five broad themes arose as factors which affected the process and success of implementation: (1) organizational stability and implementation team leadership, (2) implementation timelines, (3) equipment availability and reliability, (4) staff training, and (5) changes in work flow CONCLUSIONS Overall IT implementation success in the VA depended on: (1) whether there was support for change from both leaders and staff, (2) development of a gradual and flexible implementation approach, (3) allocation of adequate resources for equipment and infrastructure, hands-on support, and deployment of additional staff, and (4) how the implementation team planned for setbacks, and continued the process to achieve success. Problems that developed in the early stages of implementation tended to become persistent, and poor implementation can lead to patient harm.
From bottom-Up visual attention to robot action learning

This research addresses the challenge of developing an action learning model employing bottom-up visual attention. Although bottom-up attention enables robots to autonomously explore the environment, learn to recognize objects, and interact with humans, the instability of their attention as well as the poor quality of the information detected at the attentional location has hindered the robots from processing dynamic movements. In order to learn actions, robots have to stably attend to the relevant movement by ignoring noises while maintaining sensitivity to a new important movement. To meet these contradictory requirements, I introduce mechanisms for retinal filtering and stochastic attention selection inspired by human vision. The former reduces the complexity of the peripheral vision and thus enables robots to focus more on the currently-attended location. The latter allows robots to flexibly shift their attention to a new prominent location, which must be relevant to the demonstrated action. The signals detected at the attentional location are then enriched based on the spatial and temporal continuity so that robots can learn to recognize objects, movements, and their associations. Experimental results show that the proposed system can extract key actions from human action demonstrations.
Electrophysiological investigation of the functional overlap between semantic and equivalence relations

research using the event-related potential (ERP) technique has shown that equivalence relations have properties similar to genuine semantic relations. This study aimed to advance electrophysiological investigations of the functional overlap between semantic and equivalence relations. The N400 component, an index of semantic processing, was used to measure whether semantic relations were experimentally established between arbitrary stimuli. The stimuli became equivalent via a matching-to-sample training designed to maximize the establishment of equivalence relations and the strength of the classes. Non-equivalent pairs of stimuli elicited larger N400 responses than equivalent pairs in electrodes placed over the central and parietal scalp regions, providing additional support for the assumption that stimulus equivalence is an appropriate model of semantic relations. Latency of the N400 component was shorter than in previous studies, probably due to experimental parameters that maximized relational strength. These data raise the possibility that N400 latency may provide a continuous measure of relational strength, thus supplementing the all-or-none character of equivalence tests based on matching to sample.
EYE‐MUSCLE GEOMETRY AND COMPENSATORY EYE MOVEMENTS IN LATERAL‐EYED AND FRONTAL‐EYED ANIMALS *

Our question here has a long history and arises from the following type of observation: when a rabbit is oscillated about the naso-occipital (roll) axis, the compensatory eye movements are vertical, but when a human is oscillated about the same axis, the compensatory eye movements are torsional. What is the basis of such differences in compensatory eye movements among vertebrates with differing interocular angles? While the existence of these appropriate behavioral differences is commonly known, the origin of these differences is, currently, commonly unknown, as a search of the contemporary literature a t t e ~ t ~ . ~ * ’ ~ , ~ ~ * ~ ~ . ~ ~ This is regrettable; subsequent to arriving at our answer to the question posed above, we found that Ohm, in a rarely referenced 1919 paper, had arrived at the same answer.35 The results reported here confirm and extend Ohm’s lucid and accurate study, which had been ‘‘lost’’ to modern investigators of the vestibuloocular reflexes. To answer the question of what underlies the differences in compensatory eye movements among animals with different interocular angles, one must consider the physiological relations between the vestibular labyrinth and the extraocular muscles and also the peripheral anatomy of the labyrinth and of the extraocular muscles. Hogyes was the first to delve into these matters; he deduced a specific set of primary relations and pathways between the labyrinth of one side and the ipsilateral and contralateral eye muscles.22 Indeed, he came quite close to determining the actual arrangement, clarified much later by Szenthgothai.44-46 In the course of his studies, Hogyes also recognized the different requirements for appropriate compensatory eye movements in lateraland frontal-eyed animals, but he did not clearly resolve the question of how the requirements are met. (Hogyes’ achievements in vestibular research were fully appreciated only after his main publication, originally published in Hungarian in the 188Os, appeared in German translation in 1912.jZ3 BBr5ny accurately observed the eye movements elicited in rabbit by natural vestibular ~ t imul i . ~ However, he claimed that the actions of rabbit and human extraocular muscles were identical, and thus his description of the relations of individual vertical semicircular canals to specific eye muscles was erroneous. Why BBriny believed the actions of rabbit and human extraocular muscles to be identical is mysterious because the anatomical information about the periphery necessary to arrive at the contrary conclusion was available from his associate Rothfeld and also from W e s ~ e l y ? ~ . ~ ~ BBrAny’s viewpoint was contradicted by Ohm, who demonstrated anatomically
Ethics and Pre-exposure Prophylaxis for HIV Infection

Abstract:There is increasing evidence that the use of antiretroviral agents (ARVs) can be a safe and effective means of preventing HIV infection. In fact, a combination of ARVs, tenofovir–emtricitabine, was recently approved by the US Food and Drug Administration (FDA) for use as “pre-exposure prophylaxis”(PrEP), and the US Centers for Disease Control and other regulatory authorities have issued guidance concerning PrEP use. Clinicians and policy makers are now faced with questions about the appropriateness of prescribing ARVs to healthy persons who are at risk of becoming infected with HIV, and those at risk of being infected must decide whether to use PrEP. In addition, researcher stakeholders must grapple with determining whether and how PrEP should be included in future HIV prevention research. In addressing such issues, it is important that their ethical dimensions are identified. When using PrEP, 2 broad ethical domains are of special relevance: well-being and justice. Ethical issues related to well-being include safety, parameters of use, risk behaviors, resistance, stigma, and diversion. Those related to justice include access and competing priorities. In research involving PrEP, ethical issues include determining the appropriate control arm and whether PrEP should be included as a part of the prevention package provided to all at risk participants. Although PrEP could play an important role in HIV prevention, understanding and addressing the related ethical issues is critical to its safe, effective, and appropriate use in practice and future research.
Subhaloes gone Notts: spin across subhaloes and finders

We present a study of a comparison of spin distributions of subhaloes found associated with a host halo. The subhaloes are found within two cosmological simulation families of Milky Way-like galaxies, namely the Aquarius and GHALO simulations. These two simulations use different gravity codes and cosmologies. We employ 10 different substructure finders, which span a wide range of methodologies from simple overdensity in configuration space to full 6D phase space analysis of particles. We subject the results to a common post-processing pipeline to analyse the results in a consistent manner, recovering the dimensionless spin parameter. We find that spin distribution is an excellent indicator of how well the removal of background particles (unbinding) has been carried out. We also find that the spin distribution decreases for substructures the nearer they are to the host haloes, and that the value of the spin parameter rises with enclosed mass towards the edge of the substructure. Finally, subhaloes are less rotationally supported than field haloes, with the peak of the spin distribution having a lower spin parameter.
Deep Amino Acid Sequencing of Native Brain GABAA Receptors Using High-Resolution Mass Spectrometry

Mass spectrometric sequencing of low abundance, integral membrane proteins, particularly the transmembrane domains, presents challenges that span the multiple phases of sample preparation including solubilization, purification, enzymatic digestion, peptide extraction, and chromatographic separation. We describe a method through which we have obtained high peptide coverage for 12 γ-aminobutyric acid type A receptor (GABAA receptor) subunits from 2 picomoles of affinity-purified GABAA receptors from rat brain neocortex. Focusing on the α1 subunit, we identified peptides covering 96% of the protein sequence from fragmentation spectra (MS2) using a database searching algorithm and deduced 80% of the amino acid residues in the protein from de novo sequencing of Orbitrap spectra. The workflow combined microscale membrane protein solubilization, protein delipidation, in-solution multi-enzyme digestion, multiple stationary phases for peptide extraction, and acquisition of high-resolution full scan and fragmentation spectra. For de novo sequencing of peptides containing the transmembrane domains, timed digestions with chymotrypsin were utilized to generate peptides with overlapping sequences that were then recovered by sequential solid phase extraction using a C4 followed by a porous graphitic carbon stationary phase. The specificity of peptide identifications and amino acid residue sequences was increased by high mass accuracy and charge state assignment to parent and fragment ions. Analysis of three separate brain samples demonstrated that 78% of the sequence of the α1 subunit was observed in all three replicates with an additional 13% covered in two of the three replicates, indicating a high degree of sequence coverage reproducibility. Label-free quantitative analysis was applied to the three replicates to determine the relative abundances of 11 γ-aminobutyric acid type A receptor subunits. The deep sequence MS data also revealed two N-glycosylation sites on the α1 subunit, confirmed two splice variants of the γ2 subunit (γ2L and γ2S) and resolved a database discrepancy in the sequence of the α5 subunit.
Growth of Escherichia coli O157:H7 during sprouting of alfalfa seeds

Aims: Escherichia coli O157:H7 was monitored daily during sprouting of alfalfa seeds inoculated at high (3·92 log10 cfu g–1) and low (1·86 log10 cfu g–1) levels to assess the extent of pathogen growth during production.
Distribution and seasonality of microbial indicators and thermophilic campylobacters in two freshwater bathing sites on the River Lune in northwest England

K. OBIRI‐DANSO and K. JONES.1999. Two freshwater bathing sites, the Crook O’Lune and the University Boathouse, on the River Lune in the north‐west of England, were monitored over a 2 year period for the faecal indicators, faecal coliforms and faecal streptococci, the pathogens, Salmonella and Campylobacter, and compliance with the EU Directive on Bathing Water Quality. Faecal indicator numbers showed no seasonal variation, with numbers in the bathing season similar to those in the non‐bathing season. They were consistently above the EU Guideline and Imperative standards so that if the EU Bathing Water Quality Directive (76/160/EEC) were applied, neither site would comply. Faecal indicator numbers in the sediments were an order of magnitude higher than in the overlying water. Campylobacter numbers showed seasonal variation in the water with higher counts in winter than in the summer, although numbers were low. Higher numbers were found in the sediments but there was no seasonal variation. Analysis of various inputs showed that indicators and campylobacters came from a mixture of sources, namely a sewage treatment works, agricultural run‐off, streams and mallards. Microbial numbers in the water at the Crook O’Lune, which is closer to the sources of pollution, were twice those at the Boathouse. In the sediments they were six to eight times higher. Faecal coliforms were all identified as Escherichia coli of which 80% were a single biotype. Faecal streptococci were all enterococci of which 55% were E. avium, 38%E. faecalis and 7%E. durans. Salmonella was not isolated from either the water column or the sediments. Campylobacters were mainly Camp. jejuni, followed by Camp. coli, UPTC and Camp. lari.