Miracle-dz/UniFAR-FTUs huggingface dataset:
Site-specific DeN-glycosylation of CD 44 Can Activate Hyaluronan Binding , and CD 44 Activation States Show Distinct Threshold Densities for Hyaluronan Binding 1

CD44 is a cell surface receptor for the glycosaminoglycan hyaluronan (HA). Not all CD44-positive cells bind HA, and binding ability is strictly regulated. Three different HA binding states have been defined: inactive, inducible (by certain CD44-specific monoclonal antibodies), and constitutively active. The observation that sets of genetically related cell lines representing different HA binding states showed correlated differences in N-glycosylation of CD44, and that inhibition of N-glycosylation enhanced HA binding (Lesley et al., J. Exp. Med., 182: 431-437, 1995) led us to examine directly whether specific N-glycosylation site modifications were involved in regulating the HA binding function. CD44-negative, -active, and inducible cell lines were stably transfected with mutant constructs in which each of the five N-glycosylation sites of murine CD44 had been separately inactivated. Ability to bind soluble HA was examined over a range of CD44 expression levels. For the active cell line, AKR1, transfectants for all N-glycosylation mutants bound HA as well as did transfectants for wild type CD44. No inhibitory effects of inactivating specific N-glycosylation sites were observed. HA binding was activated when two of the mutant constructs were transfected into a novel CD44-negative inducible cell line. Inactivation of N-glycosylation sites at residues 25 or 120 converted the inducible cell line to constitutively active, whereas inactivation of other sites had little or no effect. Fusion proteins secreted from inactive, inducible, or active cell lines were purified, bound to beads, and assayed for HA binding activity by flow cytometric analysis. Fusion proteins derived from inactive, inducible, and constitutively active cells exhibited three distinguishable "threshold" densities required for HA binding ability. The results imply that the CD44 molecules produced in cells in these three activation states have intrinsic differences in HA binding function. Treatment of the fusion proteins with neuraminidase altered the HA binding state, and glycosylation mutations that affected the phenotype of the inducible cell line lowered the threshold required for HA binding of CD44-immunoglobulin fusion proteins de rived from the inducible cell line. Thus, alterations of glycosylation of CD44 itself can affect HA binding ability as manifested by a change in HA binding state.
Convergence acceleration for calculating radiated fields by a vertical electric dipole in the presence of a large sphere

The solution of the radiation of a vertical dipole in the presence of a large sphere is represented by infinite summation. It is known that the series usually has a convergence problem when both the source and the observation point are on or close to the surface. Also, the series converges slowly when the wavelength in air is much smaller than the radius of the sphere. The continuity of the field expressions on the spherical surface at r=r' in the space is discussed and we give a convergence acceleration method for the infinite summation due to a vertical electric dipole radiating in the presence of a perfectly conducting sphere.
AM last page: A guide to research paradigms relevant to medical education.

Suggestions for further reading: • Bunniss S, Kelly DR. Research paradigms in medical education research. Med Educ. 2010;44:358-366. • Carter SM, Little M. Justifying knowledge, justifying method, taking action: Epistemologies, methodologies and methods in qualitative research. Qual Health Res. 2007;17:1316-1328. • Illing J. Thinking About Research: Frameworks, Ethics and Scholarship. Edinburgh, UK: Association for the Study of Medical Education; 2007. Research Design Examples include experimental design, ethnography, case study, action research, grounded theory, phenomenology, and discourse analysis. Methods Techniques for data collection include randomized controlled trial, questionnaires, interviews, focus groups, observation, and document analysis. Paradigm
Intervening on Exercise and Nutrition in Older Adults

Presented are the basic design, methods, and baseline data analyses for the Study of Exercise and Nutrition in Older Rhode Islanders (SENIOR Project) an experimental study to investigate the relative effectiveness of a 12-month, stage of readiness to change-based multiple-behavior intervention (exercise and nutrition) compared to single-behavior interventions in a community-dwelling population of 1,277 older adults. Relationships between stage of readiness to change in the two target behaviors, as well as the relationship between stage of readiness and self-reported exercise levels and fruit and vegetable consumption, were examined using a combination of Pearson chi-squares, analyses of variance (ANOVA), and Spearman’s rank order correlations. Stage of change (SOC) for fruit and vegetable consumption was significantly associated with the dietary measure, and SOC for exercise was associated with both the three physical activity measures and servings of fruits and vegetables per day. Overall, individual older adult's readiness to change seems largely to be behavior-specific.
Recombinant Subgroup B Human Respiratory Syncytial Virus Expressing Enhanced Green Fluorescent Protein Efficiently Replicates in Primary Human Cells and Is Virulent in Cotton Rats

ABSTRACT Human respiratory syncytial virus (HRSV) is the most important viral cause of severe respiratory tract disease in infants. Two subgroups (A and B) have been identified, which cocirculate during, or alternate between, yearly epidemics and cause indistinguishable disease. Existing in vitro and in vivo models of HRSV focus almost exclusively on subgroup A viruses. Here, a recombinant (r) subgroup B virus (rHRSVB05) was generated based on a consensus genome sequence obtained directly from an unpassaged clinical specimen from a hospitalized infant. An additional transcription unit containing the gene encoding enhanced green fluorescent protein (EGFP) was introduced between the phosphoprotein and matrix genes (position 5) of the genome to generate rHRSVB05EGFP(5). The recombinant viruses replicated efficiently in both HEp-2 cells and in well-differentiated normal human bronchial cells grown at air-liquid interface. Intranasal infection of cotton rats (Sigmodon hispidus) resulted in high numbers of EGFP+ cells in epithelia of the nasal septum and conchae. When administered in a relatively large inoculum volume, the virus also replicated efficiently in bronchiolar epithelial cells and spread extensively in both the upper and lower respiratory tracts. Virus replication was not observed in ciliated epithelial cells of the trachea. This is the first virulent rHRSV strain with the genetic composition of a currently circulating wild-type virus. In vivo tracking of infected cells by means of EGFP fluorescence in the absence of cytopathic changes increases the sensitivity of virus detection in HRSV pathogenesis studies. IMPORTANCE Virology as a discipline has depended on monitoring cytopathic effects following virus culture in vitro. However, wild-type viruses isolated from patients often do not cause significant changes to infected cells, necessitating blind passage. This can lead to genetic and phenotypic changes and the generation of high-titer, laboratory-adapted viruses with diminished virulence in animal models of disease. To address this, we determined the genome sequence of an unpassaged human respiratory syncytial virus from a sample obtained directly from an infected infant, assembled a molecular clone, and recovered a wild-type recombinant virus. Addition of a gene encoding enhanced green fluorescent protein allowed this wild-type virus to be tracked in primary human cells and living animals in the absence of significant cytopathic effects. Imaging of fluorescent cells proved to be a highly valuable tool for monitoring the spread of virus and may help improve assays for evaluating novel intervention strategies.
Evaluating the morphological compositionality of polarity

Unknown words are a challenge for any NLP task, including sentiment analysis. Here, we evaluate the extent to which sentiment polarity of complex words can be predicted based on their morphological make-up. We do this on German as it has very productive processes of derivation and compounding and many German hapax words, which are likely to bear sentiment, are morphologically complex. We present results of supervised classification experiments on new datasets with morphological parses and polarity annotations.
Lymphocytes produce specific alkaline phosphatase after in vitro stimulation or after in vivo infection with HIV‐1

A unique alkaline phosphatase isoform found in the serum of HIV‐1 infected patients is thought to originate from CD4 lymphocytes. Destruction of activated CD4 lymphocytes after HIV‐1 infection is probably responsible for the appearance of this isoform in circulation. This band‐10 alkaline phosphatase isoform is thus useful as an early marker for detecting AIDS in children born to HIV‐1 infected mothers. © 1996 Wiley‐Liss, Inc.
Initial presentation with stage IV colorectal cancer: how aggressive should we be?

HYPOTHESIS The appropriate surgical treatment of patients with colorectal cancer who are found on initial presentation to have stage IV disease is controversial. With presumed limited life expectancy, the role of primary colon or rectal resection has been questioned, as has the utility of synchronous hepatic resection. DESIGN A retrospective chart review. SETTING The University of Chicago Hospitals, Chicago, Ill, a tertiary-care referral center. PATIENTS One hundred twenty patients were identified through The University of Chicago Hospitals Tumor Registry whose initial presentation showed stage IV colorectal cancer and who underwent laparotomy. MAIN OUTCOME MEASURES The primary end points of the study were perioperative morbidity and mortality and overall survival. RESULTS Median survival and 5-year survival were 14.4 months and 10%, respectively. Survival was greater for patients younger than 65 years than for those who were aged 65 years or older (18.3 vs 9.8 months; P = .007). Carcinomatosis was associated with significantly decreased survival when compared with less extensive stage IV disease (6.7 vs 18.1 months; P<.001). Patients who underwent any form of resection of hepatic metastases achieved a survival advantage over those with unresectable liver lesions (median survival, 29.6 vs 10.2 months; P<.001). Overall, 27 patients (22.5%) developed postoperative complications. Seven patients (5.8%) died during the postoperative period. CONCLUSIONS Age of 65 years or older, carcinomatosis, and extensive (bilobar) liver involvement are associated with decreased survival and increased postoperative morbidity and mortality and may negate any potential benefit patients derive from resection of the primary lesion. A substantial number of patients with synchronous hepatic metastases have protracted survival that justifies resection of the primary colorectal tumor at initial presentation. Despite the presence of stage IV disease, resection of the primary tumor and, when feasible, liver metastases is indicated.
CPC2: a fast and accurate coding potential calculator based on sequence intrinsic features

Abstract With advances in next-generation sequencing technologies, numerous novel transcripts in a large number of organisms have been identified. With the goal of fast, accurate assessment of the coding ability of RNA transcripts, we upgraded the coding potential calculator CPC1 to CPC2. CPC2 runs ∼1000 times faster than CPC1 and exhibits superior accuracy compared with CPC1, especially for long non-coding transcripts. Moreover, the model of CPC2 is species-neutral, making it feasible for ever-growing non-model organism transcriptomes. A mobile-friendly web server, as well as a downloadable standalone package, is freely available at http://cpc2.cbi. pku.edu. cn.
Agricultural Production, Agricultural Land and Rural Poverty in Madagascar

Rural areas dependent on agricultural income, are often among the poorest in developing countries. However, little distinction is generally made within the agricultural sector. This lack of distinction hinders targeting of agricultural investments towards poorer farmers. This paper illustrates, using a production function analysis with flexible marginal returns, how agricultural production activities and returns to agricultural production factors differ by poverty level in the case of Madagascar. The results show that access to primary education is relatively more beneficial for poorer agricultural households while additional secondary education has no effect on agricultural productivity. Returns to agricultural inputs are significantly higher for poorer agricultural households. Land inequality increases as land sales markets benefit the richer households and as the rich engage more in extensification while rental markets improve agricultural efficiency and may thus benefit poor and rich alike. Land titling has little effect on improved agricultural productivity. More formal land titling is therefore not sufficient to change the bad performance of agriculture of the last decades.
Raltegravir Has a Low Propensity To Cause Clinical Drug Interactions through Inhibition of Major Drug Transporters: an In Vitro Evaluation

ABSTRACT Raltegravir (RAL) is a human immunodeficiency virus type 1 (HIV-1) integrase inhibitor approved to treat HIV infection in adults in combination with other antiretrovirals. The potential of RAL to cause transporter-related drug-drug interactions (DDIs) as an inhibitor has not been well described to date. In this study, a series of in vitro experiments were conducted to assess the inhibitory effects of RAL on major human drug transporters known to be involved in clinically relevant drug interactions, including hepatic and renal uptake transporters and efflux transporters. For hepatic uptake transporters, RAL showed no inhibition of organic anion-transporting polypeptide 1B1 (OATP1B1), weak inhibition of OATP1B3 (40% inhibition at 100 μM), and no inhibition of organic cation transporter 1 (OCT1). Studies of renal uptake transporters showed that RAL inhibited organic anion transporters 1 and 3 (OAT1 and OAT3) with 50% inhibitory concentrations (IC50s) (108 μM and 18.8 μM, respectively) well above the maximum concentration of drug in plasma (Cmax) at the clinical 400-mg dose and did not inhibit organic cation transporter 2 (OCT2). As for efflux transporters, RAL did not inhibit breast cancer resistance protein (BCRP) and showed weak inhibition of multidrug and toxin extrusion protein 1 (MATE1) (52% inhibition at 100 μM) and MATE2-K (29% inhibition at 100 μM). These studies indicate that at clinically relevant exposures, RAL does not inhibit or only weakly inhibits hepatic uptake transporters OATP1B1, OATP1B3, and OCT1, renal uptake transporters OCT2, OAT1, and OAT3, as well as efflux transporters BCRP, MATE1, and MATE2-K. The propensity for RAL to cause DDIs via inhibition of these transporters is therefore considered low.
High-Resolution Cryo-Electron Microscopy Structures of Murine Norovirus 1 and Rabbit Hemorrhagic Disease Virus Reveal Marked Flexibility in the Receptor Binding Domains

ABSTRACT Our previous structural studies on intact, infectious murine norovirus 1 (MNV-1) virions demonstrated that the receptor binding protruding (P) domains are lifted off the inner shell of the virus. Here, the three-dimensional (3D) reconstructions of recombinant rabbit hemorrhagic disease virus (rRHDV) virus-like particles (VLPs) and intact MNV-1 were determined to ∼8-Å resolution. rRHDV also has a raised P domain, and therefore, this conformation is independent of infectivity and genus. The atomic structure of the MNV-1 P domain was used to interpret the MNV-1 reconstruction. Connections between the P and shell domains and between the floating P domains were modeled. This observed P-domain flexibility likely facilitates virus-host receptor interactions.
Developing an effective community conservation program for cotton‐top tamarins (Saguinus oedipus) in Colombia

Developing effective conservation programs that positively impact the survival of a species while considering the needs of local communities is challenging. Here we present an overview of the conservation program developed by Proyecto Tití to integrate local communities in the conservation of Colombia's critically endangered primate, the cotton‐top tamarin (Saguinus oedipus). Our comprehensive assessment of the threats effecting the long‐term survival of the cotton‐top tamarin allowed us to establish the primary components of our program. Proyecto Tití has three areas of emphasis: (1) scientific studies detailing the biology and long‐term survival of the cotton‐top tamarin, (2) conservation education programs to increase public awareness and conservation knowledge, and (3) community empowerment programs that demonstrate a valuable economic incentive to protecting wildlife and forested areas in Colombia. This integrated approach to conservation that involves local communities in activities that benefit individuals, as well as wildlife, has proven to be remarkably effective in protecting cotton‐top tamarins and their forested habitat. Our bindes program, which uses small cook stoves made from clay, has demonstrated a marked reduction in the number of trees that have been harvested for firewood. Developing environmental entrepreneurs, who create products made from recycled plastic for sale in national and international markets, has had a significant impact in reducing the amount of plastic that has been littering the environment and threatening the health of wildlife, while creating a stable economic income for rural communities. Proyecto Tití has provided economic alternatives to local communities that have dramatically reduced the illegal capture of cotton‐top tamarins and forest destruction in the region that has positively impacted the long‐term survival of this critically endangered primate. Am. J. Primatol. 72:379–390, 2010. © 2009 Wiley‐Liss, Inc.
SPECIAL FOCUS: THE ROLE OF TRANSMEMBRANE DOMAINS IN ADHESION

Helical membrane proteins are a major class of membrane proteins that are essentially involved in key processes including bioenergetics, signal transduction, ion transmission, catalysis and so on. This class of proteins is characterized by the presence of highly hydrophobic stretches of ∼20 amino acids, which span the membrane in an α-helical conformation. Helical membrane proteins can exist as simple structures, with just one or a few TM helices spanning a membrane, as well as large oligomeric complexes with many TM helices. The mechanisms by which helical membrane proteins fold into native structures are beginning to be understood from a confluence of structural and biochemical studies. The fold of a helical membrane protein is largely determined by interactions between membrane-embedded helices. Folding
On the mechanized validation of infinite-state and parameterized reactive and mobile systems

The growing influence of telecommunication-systems in all areas has brought with it the need for elaborate and reliable software running on concurrent and, in particular, dynamically changing systems. With the development of such systems becoming ever more complex, the outline and development of mechanized and mechanizable verification-techniques is indispensable. This overall goal can be divided into three tasks: (1) outline of a framework in which (2) complex systems can be analysed, and the (3) design and implementation of efficient proof-techniques. It is certainly beyond the scope of a thesis to provide an integrated framework dealing with these questions within one environment. This work therefore concentrates on dominant aspects of each of the three tasks in separate discussions. A major result of the thesis is that the approaches outlined for each of the three questions obviously fit together, so that they can be used as a basis for the development of an integrated framework. Often automatic verification of larger hardware- and software-applications is impossible, because the systems are too large or even infinite. This thesis focusses on infinite-state and parameterized systems, and builds tool-support on interactive theorem-proving. Further, it concentrates on the validation of correct implementations by exploiting behavioural reasoning. It demonstrates how to apply various techniques to tackle proofs about infinite-state and parameterized systems with large descriptions, discusses the support that theorem-provers can offer, and presents a foundational platform for reasoning about mobile systems in a general-purpose theorem-prover. Several design-decisions have to be taken. This thesis uses process-algebra as a framework, in particular CCS for the description and analysis of infinite-state reactive systems, and the pi-calculus for the discussion of mobile and higher-order systems. For a validation, it applies observation-equivalence, exploiting a range of proof-techniques that have been developed for the two calculi. For all mechanizations, the general-purpose theorem-prover Isabelle/HOL is used.
Parental Stress in Families of Children With Autism and Other Developmental Disabilities

The level of parental stress in families of children with autism and other developmental disabilities and its association with child comorbid symptoms was studied in an ethnically diverse population, in a cross-sectional study with structured interview. The sample included 50 families of children with autism and 50 families of children with other developmental disabilities, matched by age/gender. Interview included Parenting Stress Index–Short Form, Gastrointestinal Questionnaire, Child Sleep Habits Questionnaire, and Aberrant Behavior Checklist. In this ethnically diverse sample, parental stress was significantly higher for the autism group and for non-Hispanic and US-born mothers. In both study groups, parental stress was related to child irritability. Parental stress was also related to gastrointestinal problems in the autism group and to sleep difficulties in the developmental disabilities group. Targeting child irritability may be particularly important in reducing parental stress for families of children with autism and other developmental disabilities.