gebhart/patrepeval huggingface dataset:
Mice lacking the CCR9 CC-chemokine receptor show a mild impairment of early T- and B-cell development and a reduction in T-cell receptor γδ+ gut intraepithelial lymphocytes (2001)

CC chemokine receptor (CCR) 9, the receptor for the CC-chemokine CCL25/thymus-expressed chemokine (TECK), is mainly expressed by thymocytes and by intraepithelial (IEL) and lamina propria lymphocytes of the small intestine. To study the biologic role of CCR9, a mouse strain was generated in which the CCR9 gene was deleted. In spite of the high level of CCR9 found in double- and single-positive thymocytes and of the expression of its corresponding ligand on thymic stromal cells, CCR9 deletion had no major effect on intrathymic T-cell development. It was noted that there was only a one-day lag in the appearance of double-positive cells during fetal ontogeny in CCR9(-/-) thymi. When tested in chemotaxis assay, thymocytes isolated from CCR9(-/-) mice failed to respond to TECK/CCL25. Taken together, these results suggest that in thymocytes, CCR9 is the only physiologic receptor for TECK/CCL25, and that it is dispensable for proper T-cell development. Bone marrow pre-pro-B cells migrate in response to TECK/CCL25, but more mature B cells do not. Consistent with this observation, it was shown that there are fewer pre-pro-B cells in CCR9(-/-) mice than in wild-type mice. However, this diminution does not appear to have a detectable effect on the generation of a normal complement of mature B cells. Finally, it was shown that in the small intestine of CCR9-deficient mice, the intraepithelial T-cell-to-epithelial cell ratio is decreased, an observation that can be accounted for by a marked diminution of the T-cell receptor gammadelta(+) compartment.
Object-based Visual Attention: a Model for a Behaving Robot (2006)

One of the first steps of any visual system is that of locating suitable interest points, "salient regions", in the scene, to detect events, and eventually to direct gaze toward these locations. In the last few years, object-based visual attention models have received an increasing interest in the literature, the problem, in this case, being that of creating a model of "objecthood" that eventually guides a saliency mechanism. We propose here an object-based model of visual attention and show its instantiation on a humanoid robot. The robot employs action to learn and define its own concept of objecthood.
Down-regulation of the chicken α5β1 integrin fibronectin receptor during development (1991)

We have characterized the diversity of the chicken beta 1 integrin family and studied the expression of individual receptors during development. The diversity of the beta 1 integrin family was investigated by affinity purifying the beta 1 integrins from a variety of adult and embryonic tissues. These purifications reveal the relative levels of expression and also the differential expression of the alpha subunits in those tissues. Monoclonal antibodies were generated against the prominent 'band 1' of the embryonic chicken integrins and used to characterize the expression of this alpha subunit in embryonic and adult tissues. This alpha subunit is shown to be the chicken homologue of human alpha 5 fibronectin receptor. The chicken alpha 5 beta 1 integrin is the most prominent beta 1 integrin in the embryo and is expressed on the majority of cell types through the day 17 stage. The distribution of this receptor in the embryo closely parallels the distribution of its ligand, fibronectin. In adult tissues, expression of this receptor is greatly diminished relative to the expression of other alpha subunits. The cell type distribution is highly restricted: limited primarily to the vasculature and to connective tissue regions. These studies reveal a prominent role for the alpha 5 beta 1 integrin in embryonic cell types and a down-regulation of this receptor on many cell types during development.
Expression of manganese superoxide dismutase reduces tumor control radiation dose: gene-radiotherapy. (1995)

This study investigated the in vitro and in vivo radiation response of tumor cells transfected with human manganese superoxide dismutase (MnSOD) cDNA. A major objective was to test the potential tumor suppressive effect of MnSOD in vivo. Tumor cells studied were an in vitro line derived from a murine spontaneous fibrosarcoma, FSa-II, which expressed an undetectable MnSOD activity. These cells were transfected with pSV2-NEO plasmid (NEO line) or cotransfected with MnSOD plasmid plus pSV2-NEO plasmid (SOD lines) as described previously. The cell lines used were SOD-L and SOD-H, which expressed, respectively, low and high MnSOD activities after transfection, and NEO and parental FSa-II controls. Both SOD-L and SOD-H cell lines were slightly more resistant to ionizing radiation than were the two control cell lines when irradiated in vitro in the presence of oxygen. The dose-modifying factors calculated at the survival level of 0.01 were 1.13 and 1.15 for the SOD-L and SOD-H cells, respectively. To investigate potential tumor suppressive effects, animal tumors of 4 mm diameter were irradiated in vivo under hypoxic conditions, and the radiation dose to control one-half of the irradiated tumors (TCD50) was determined for each tumor. The TCD50S obtained on the basis of the tumor control rate in 120 days after irradiation were substantially lower for the SOD-H and SOD-L tumors compared to the NEO tumors. They were 22.9, 28.6, and 47.5 Gy for SOD-H, SOD-L and NEO tumors, respectively. To analyze these data, survival curves were obtained for hypoxic cells by irradiating NEO and SOD-H tumors under hypoxic conditions in vivo and assaying in vitro. Analysis of these curves suggests that the decrease in the TCD50S of SOD tumors is attributable to the reduced tumorigenicity in these tumors. The hypoxic cell survival curves also showed that SOD did not protect cells from radiation in the absence of oxygen. Electron microscopy showed no morphological differences between these cells. These results suggest that the fraction of tumorigenic cells could be reduced by expression of MnSOD, resulting in a substantial decrease in the TCD50.
Recombinant Human Hyaluronidase-Enabled Subcutaneous Pediatric Rehydration (2009)

rHuPH20-facilitated subcutaneous hydration seems to be safe and effective for young children with mild/moderate dehydration. Subcutaneous access is achieved easily, and the procedure is well accepted by clinicians and parents.
Modified- versus immediate-release tofacitinib in Japanese rheumatoid arthritis patients: a randomized, phase III, non-inferiority study (2018)

ClinicalTrials.gov, http://clinicaltrials.gov, NCT02281552.
Inhibition of p38 Mitogen-activated Protein Kinase Impairs Influenza Virus-induced Primary and Secondary Host Gene Responses and Protects Mice from Lethal H5N1 Infection (2013)

Highly pathogenic avian influenza viruses (HPAIV) induce severe inflammation in poultry and men. One characteristic of HPAIV infections is the induction of a cytokine burst that strongly contributes to viral pathogenicity. This cell-intrinsic hypercytokinemia seems to involve hyperinduction of p38 mitogen-activated protein kinase. Here we investigate the role of p38 MAPK signaling in the antiviral response against HPAIV in mice as well as in human endothelial cells, the latter being a primary source of cytokines during systemic infections. Global gene expression profiling of HPAIV-infected endothelial cells in the presence of the p38-specific inhibitor SB 202190 revealed that inhibition of p38 MAPK leads to reduced expression of IFNβ and other cytokines after H5N1 and H7N7 infection. More than 90% of all virus-induced genes were either partially or fully dependent on p38 signaling. Moreover, promoter analysis confirmed a direct impact of p38 on the IFNβ promoter activity. Furthermore, upon treatment with IFN or conditioned media from HPAIV-infected cells, p38 controls interferon-stimulated gene expression by coregulating STAT1 by phosphorylation at serine 727. In vivo inhibition of p38 MAPK greatly diminishes virus-induced cytokine expression concomitant with reduced viral titers, thereby protecting mice from lethal infection. These observations show that p38 MAPK acts on two levels of the antiviral IFN response. Initially the kinase regulates IFN induction and, at a later stage, p38 controls IFN signaling and thereby expression of IFN-stimulated genes. Thus, inhibition of MAP kinase p38 may be an antiviral strategy that protects mice from lethal influenza by suppressing excessive cytokine expression.
Isolation and Characterization of Human μ-Defensin-3, a Novel Human Inducible Peptide Antibiotic (2001)

The growing public health problem of infections caused by multiresistant Gram-positive bacteria, in particular Staphylococcus aureus, prompted us to screen human epithelia for endogenous S. aureus-killing factors. A novel 5-kDa, nonhemolytic antimicrobial peptide (human beta-defensin-3, hBD-3) was isolated from human lesional psoriatic scales and cloned from keratinocytes. hBD-3 demonstrated a salt-insensitive broad spectrum of potent antimicrobial activity against many potentially pathogenic microbes including multiresistant S. aureus and vancomycin-resistant Enterococcus faecium. Ultrastructural analyses of hBD-3-treated S. aureus revealed signs of cell wall perforation. Recombinant hBD-3 (expressed as a His-Tag-fusion protein in Escherichia coli) and chemically synthesized hBD-3 were indistinguishable from naturally occurring peptide with respect to their antimicrobial activity and biochemical properties. Investigation of different tissues revealed skin and tonsils to be major hBD-3 mRNA-expressing tissues. Molecular cloning and biochemical analyses of antimicrobial peptides in cell culture supernatants revealed keratinocytes and airway epithelial cells as cellular sources of hBD-3. Tumor necrosis factor alpha and contact with bacteria were found to induce hBD-3 mRNA expression. hBD-3 therefore might be important in the innate epithelial defense of infections by various microorganisms seen in skin and lung, such as cystic fibrosis.
Design and Implementation of a Standard Cell Library for Building Asynchronous ASICs (2011)

Asynchronous ASIC design automation tools and standard cell libraries development lag behind their synchronous counterpart. Therefore, most asynchronous designs still make use of full-custom design approaches, which contributes to make asynchronous circuits less used. To help in solving this problem this work presents the design and implementation of a standard cell library for building asynchronous application specific integrated circuits (ASICs), called ASCEnD-ST65 (currently at version 0.1), developed for a 65nm gate length STMicroelectronics CMOS process. An abridged version of this library was designed to implement an asynchronous network on chip (NoC) router. Nevertheless, those cells presented elevated leakage power consumption. This characteristic was treated in ASCEnD-ST65, by proposing a new, robust design flow. This flow contains a novel method to determine the dimension of transistors in the CMOS implementation of C-Element gates, fundamental elements in asynchronous design. This work presents the details of the method and adopts it throughout the specification of the library cells. The designed standard cells count with several views: layout, schematic, symbol, Verilog and abstract. LEF and LIB files describe the physical and electrical characteristics for each cell, and the cells have been characterized for three different process corners, worst, typical and best cases. A total of 251 cells were designed. Among these are a large amount of implementations and variations of C-Elements, the main gate used in many asynchronous design styles. A tradeoff between three different C-Element CMOS implementations – Conventional, Symmetric and Weak Feedback – is presented in this work. Also, the library contains other cells, such as metastability filters. To validate the library, two different IC design flows were adopted. First, a typical flow consisting of VHDL sources synthesized and implemented through the Cadence Framework was used to generate and simulate an asynchronous NoC router. Next, a novel design flow, consisting of a Balsa description synthesized through the Teak System was used to generate the netlist of an asynchronous RSA based cryptography circuit. The layout of this circuit was obtained through Cadence Encounter and simulated through Spectre. The results prove the successful integration of this library and Teak System.
Structure of the toxic domain of Escherichia coli heat-stable enterotoxin ST I (1986)

Active fragments of the heat-stable enterotoxin ST I of Escherichia coli were chemically synthesized with the sequence Cys-Cys-Glu-Leu-Cys-Cys-Asn-Pro-Ala-Cys-Thr-Gly-Cys-(Tyr) and studied by proton (1H NMR) and carbon-13 (13C NMR) nuclear magnetic resonance spectroscopy as a function of pH and temperature. All of the nonexchangeable protons in the 1H NMR spectrum were assigned. Although all amide protons were present at temperatures below 25 degrees C and and pH values below 6, some of the resonances are broad and could not be assigned. The temperature dependence of these broad resonances indicates a change in conformation that is localized in the N-terminus. Other amide protons disappear at higher temperatures owing to chemical exchange with the solvent. Sufficient resonance assignments can be made at high and low temperatures to permit structural conclusions to be made. The chemical shifts of the alpha-carbon protons indicate the presence of substantial structure, which was further defined with the observed pattern of nuclear Overhauser enhancements (NOEs), coupling constants, and exchange rates. The NMR data identify a turn from Ala-14 to Cys-18. A second likely turn is centered around the proline residue. An interresidue NOE between the alpha-carbon protons of Asn-12 and Gly-17 indicates that the molecule folds back on itself. The NMR information is sufficient to define the structure of the C-terminal region of ST I. Manual model building then indicated that one arrangement of the three disulfides is particularly compatible with the NMR data and van der Waals constraints. A model incorporating the disulfide arrangement proposed by Houghten and his co-workers [Houghten, R.A., Ostresh, J.M., & Klipstein, F.A. (1984) Eur. J. Biochem. 145, 157-162] and the NMR constraints was derived with the programs PROTO [Frayman, F. (1985) Ph.D. Thesis, Northwestern University] and NOEMOT [Lane, A.N., Lefévre, J.-F., & Jardetsky, O. (1986) Biochim. Biophys. Acta 867, 45-56].
A PHYSIOLOGIST'S PERSPECTIVE ON ROBOTIC EXOSKELETONS FOR HUMAN LOCOMOTION (2007)

Technological advances in robotic hardware and software have enabled powered exoskeletons to move from science fiction to the real world. The objective of this article is to emphasize two main points for future research. First, the design of future devices could be improved by exploiting biomechanical principles of animal locomotion. Two goals in exoskeleton research could particularly benefit from additional physiological perspective: 1) reduction in the metabolic energy expenditure of the user while wearing the device, and 2) minimization of the power requirements for actuating the exoskeleton. Second, a reciprocal potential exists for robotic exoskeletons to advance our understanding of human locomotor physiology. Experimental data from humans walking and running with robotic exoskeletons could provide important insight into the metabolic cost of locomotion that is impossible to gain with other methods. Given the mutual benefits of collaboration, it is imperative that engineers and physiologists work together in future studies on robotic exoskeletons for human locomotion.
Formulation and <i>In Vitro</i> Evaluation of <i>In Situ</i> Gels Containing Secnidazole for Vaginitis (2009)

Gel dosage forms are successfully used as drug delivery systems considering their ability to prolong the drug release. The main objective is to formulate and evaluate in situ vaginal gels of secnidazole, based on ion activated systems. The system utilizes polymers that exhibit sol-to-gel phase transition due to change in specific physico chemical parameters. Ion triggered system using gellan gum (0.1-0.75% w/v) along with sodium carboxymethylcelluose was used to prolong the release of secnidazole (1% w/v). Formulations were evaluated for gelling capacity, viscosity, gel strength, mucoadhesive force, spreadability, microbiological studies and in vitro release studies. The transformation of sols occur in the presence of monovalent/divalent cations in the dissolution medium. Effect of calcium carbonate and other process parameters were optimized and found that increase in calcium ions produce stronger gels. The drug content, clarity, and pH of formulation were found to be satisfactory. The viscosity was found to be in the range of 0.005 to 0.085 for sols, whereas for the gels 16 Pa.s. Formulation showed pseudoplastic flow with thixotrophy. The gel strength (using texture analyzer) and mucoadhesion was found to be up to 6.5 g and 4 g respectively. The optimized formulations were able to release the drug for 360 min. The gels are expected to improve the administration at the site of infection and decrease frequency.
Identification of Amino Acids in the Hormone Binding Domain of the Human Estrogen Receptor Important in Estrogen Binding (1996)

The initial step in the regulation of the transcriptional activity of the estrogen receptor (ER) is the binding of hormone. Previous studies have suggested that the region between amino acids 515 and 535 near the C terminus of the human ER is likely to be important in ligand binding. In order to explicitly define which amino acids in this region are critical for ligand recognition and binding, we have utilized alanine-scanning mutagenesis over the complete 515-535 region. The ability of these 21 mutants to activate transcription in response to the natural estrogen, 17beta-estradiol (E2), was evaluated in cell co-transfection assays with estrogen-responsive reporter genes. In addition, their ability to bind E2 was also tested. Mutations at four sites in the 521-528 region had the greatest effects on E2-induced transcription, with L525A reducing responsiveness 250-fold, G521A and H524A 35-fold, and M528A 11-fold. Mutations at other sites had either no effect or a 4-fold or lesser reduction in sensitivity to E2 (M517A, Y526A, N532A, and P535A). Three of the mutants most affected in their transcriptional response, G521A, H524A, and M528A, showed a coordinate reduction in E2 binding affinity. E2 binding by the most affected mutant, L525A, could not be detected. Thus, the altered transcriptional response of these ER mutants appears to derive solely from an alteration in their affinity for the ligand E2. The four sites most affected by alanine substitution, 521, 524, 525, and 528, follow an alpha-helical periodicity, such that they would be positioned on one face of an alpha-helix. Furthermore, they correspond precisely to residues in an alpha-helix shown to be in contact with ligand in the recently described x-ray crystal structures of two other members of the nuclear hormone receptor superfamily, namely the retinoic acid receptor- and thyroid hormone receptor-ligand complexes. Our findings, which broaden observations to the steroid receptor family within the superfamily of nuclear receptors, suggest that this region of the estrogen receptor is in contact with its cognate ligand in a similar fashion.
Hepatology Highlights – August 2017 (2017)

Treatment of chronic hepatitis B virus (HBV) has the potential to decrease the incidence of hepatocellular carcinoma (HCC). Some patients on therapy may develop persistent or intermittent low-level (<2,000 IU/mL) HBV viremia (LLV), but its significance is not well understood. Kim et al. conducted a retrospective cohort study to evaluate the clinical significance of LLV after achieving a negative viral load. A retrospective cohort of 875 treatment-na ve patients on entecavir monotherapy were followed for the development of HCC. HCC developed more frequently in those with LLV, compared to those with persistently undetectable HBV DNA. This difference was over 2-fold higher and was significant in patients with cirrhosis, but not in patients without cirrhosis. This suggests that LLV may have clinical implications, and more data are needed to guide clinical practice. (
Comparison of Knowledge-Based and Distance Geometry Approaches for Generation of Molecular Conformations (2001)

A knowledge-based approach for generating conformations of molecules has been developed. The method described here provides a good sampling of the molecule's conformational space by restricting the generated conformations to those consistent with the reference database. The present approach, internally named et for enumerate torsions, differs from previous database-mining approaches by employing a library of much larger substructures while treating open chains, rings, and combinations of chains and rings in the same manner. In addition to knowledge in the form of observed torsion angles, some knowledge from the medicinal chemist is captured in the form of which substructures are identified. The knowledge-based approach is compared to Blaney et al.'s distance geometry (DG) algorithm for sampling the conformational space of molecules. The structures of 113 protein-bound molecules, determined by X-ray crystallography, were used to compare the methods. The present knowledge-based approach (i) generates conformations closer to the experimentally determined conformation, (ii) generates them sooner, and (iii) is significantly faster than the DG method.
Burkholderia vaccines: are we moving forward? (2013)

The genus Burkholderia consists of diverse species which includes both "friends" and "foes." Some of the "friendly" Burkholderia spp. are extensively used in the biotechnological and agricultural industry for bioremediation and biocontrol. However, several members of the genus including B. pseudomallei, B. mallei, and B. cepacia, are known to cause fatal disease in both humans and animals. B. pseudomallei and B. mallei are the causative agents of melioidosis and glanders, respectively, while B. cepacia infection is lethal to cystic fibrosis (CF) patients. Due to the high rate of infectivity and intrinsic resistance to many commonly used antibiotics, together with high mortality rate, B. mallei and B. pseudomallei are considered to be potential biological warfare agents. Treatments of the infections caused by these bacteria are often unsuccessful with frequent relapse of the infection. Thus, we are at a crucial stage of the need for Burkholderia vaccines. Although the search for a prophylactic therapy candidate continues, to date development of vaccines has not advanced beyond research to human clinical trials. In this article, we review the current research on development of safe vaccines with high efficacy against B. pseudomallei, B. mallei, and B. cepacia. It can be concluded that further research will enable elucidation of the potential benefits and risks of Burkholderia vaccines.