gebhart/patrepeval huggingface dataset:
In vitro evaluation of the genotoxicity of a naturally occurring crosslinking agent (genipin) for biologic tissue fixation (2000)

The objective of the present study was to evaluate in vitro, using Chinese hamster ovary (CHO-K1) cells, the genotoxicity of genipin, a naturally occurring crosslinking agent. Glutaraldehyde, the most commonly used crosslinking agent for biologic tissue fixation, was employed as a reference chemical. The selected procedures for this evaluation were the micronucleus (MN) and sister chromatid exchange (SCE) assays with or without the addition of a metabolic activation system (S9 mix). Before starting the genotoxicity assays, the maximum noncytotoxic amounts of glutaraldehyde and genipin were determined using the MTT assay. The results obtained in the MTT assay revealed that the cytotoxicity of genipin was significantly lower than that of glutaraldehyde with or without S9 mix. The frequencies of MN observed in the cases drugged with varying concentrations of glutaraldehyde or genipin were not statistically different from those seen in the negative controls (blank) in the presence or absence of S9 mix. However, it was noted that glutaraldehyde significantly inhibited the cell-cycle progression while the cells drugged with genipin did not result in cell-cycle delay. In the SCE assay, the numbers of SCE per cell observed in the cases drugged with varying concentrations of glutaraldehyde were significantly greater than those found in the negative controls with or without S9 mix. Nevertheless, these numbers were still low compared to the numbers of SCE induced by the strong mutagens used as our positive control substances. This suggests that glutaraldehyde may produce a weakly clastogenic response in CHO-K1 cells. In contrast, the numbers of SCE per cell obtained in the cases drugged with genipin were comparable to those observed in the negative controls in those that were except drugged with the highest dose (50 ppm). This suggests that genipin does not cause clastogenic response in CHO-K1 cells provided its concentration is lower than 50 ppm. In conclusion, as far as cytotoxicity and genotoxicity are concerned, genipin is a promising crosslinking agent for biologic tissue fixation.
Mapping the Active Site of CD59 (1997)

CD59 is a widely distributed membrane-bound inhibitor of the cytolytic membrane attack complex (MAC) of complement. This small (77 amino acid) glycoprotein is a member of the Ly6 superfamily of proteins and is important in protecting host cells from the lytic and proinflammatory activity of the MAC. CD59 functions by binding to C8 and/or C9 in the nascent MAC and interfering with C9 membrane insertion and polymerization. We present data obtained from a combination of molecular modeling and mutagenesis techniques, which together indicate that the active site of CD59 is located in the vicinity of a hydrophobic groove on the face of the molecule opposite to a “hydrophobic strip” suggested earlier. In addition, removal of the single N-linked glycosylation site at Asn18 of CD59 resulted in an enhancement of complement inhibitory activity.
D2 dopamine receptor gene and obesity (1994)

The prevalence of Taql A D2 dopamine receptor (DRD2) alleles was determined in 73 obese women and men. In this sample with a mean body mass index of 35.1, the A1 (minor) allele of the DRD2 gene was present in 45.2% of these nonalcohol, nondrug abusing subjects. The DRD2 A1 allele was not associated with a number of cardiovascular risk factors examined, including blood lipids (cholesterol, high-density lipoprotein [HDL]- and low-density lipoprotein [LDL]-cholesterol, and triglycerides). However, phenotypic factors characterized by the presence of parental history and postpuberty onset of obesity as well as carbohydrate preference were associated with obese subjects carrying the A1 allele. The cumulative number of these three factors was positively and significantly (p < .0002) related to A1 allelic prevalence. The data showing an association of the minor allele of the DRD2 gene with phenotypic characteristics suggest that this gene, located on q22-q23 region of chromosome 11, confers susceptibility to a subtype of this disorder.
Implicating a role for immune recognition of self in tumor rejection: passive immunization against the brown locus protein. (1995)

The immune system can recognize differentiation antigens that are selectively expressed on malignant cells and their normal cell counterparts. However, it is uncertain whether immunity to differentiation antigens can effectively lead to tumor rejection. The mouse brown locus protein, gp75 or tyrosinase-related protein 1, is a melanocyte differentiation antigen expressed by melanomas and normal melanocytes. The gp75 antigen is recognized by autoantibodies and autoreactive T cells in persons with melanoma. To model autoimmunity against a melanocyte differentiation antigen, mouse antibodies against gp75 were passively transferred into tumor-bearing mice. Passive immunization with a mouse monoclonal antibody against gp75 induced protection and rejection of both subcutaneous tumors and lung metastases in syngeneic C57BL/6 mice, including established tumors. Passive immunity produced coat color alterations but only in regenerating hairs. This system provides a model for autoimmune vitiligo and shows that immune responses to melanocyte differentiation antigens can influence mouse coat color. Immune recognition of a melanocyte differentiation antigen can reject tumors, providing a basis for targeting tissue autoantigens expressed on cancer.
Antiinflammatory 4,5-Diarylpyrroles: Synthesis and QSAR (1994)

A series of 2-substituted- and 2,3-disubstituted-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-1H- pyrroles was synthesized and found to be active in the rat adjuvant arthritis model of inflammation. The most active compounds were the 2-halo derivatives in the order of chloro > bromo > iodo. The same pattern of activity was observed for the 2,3-dihalopyrroles. Quantitative structure-activity relationship studies suggested that the activity could be correlated with the molar refractivity and the inductive field effect of the 2-substituent and the lipophilicity of the 3-substituent.
Individual Correlates of Health Service Utilization and the Cost of Poor Adjustment to Chronic Illness (1990)

It was conjectured that a small group of chronically ill in tertiary ambulatory clinics consume a large amount of health resources and that, from the perspective of the patient, psychosocial rather than disease variables would most explain their health service utilization and subsequent cost. New referrals with a chronic illness (N = 215) to one of three clinics (oncology, rheumatology, and gastroenterology) consented to participate in a subsequent trial of a psychosocial intervention designed to promote their adjustment to illness and, conceivably, to reduce their health service utilization. At baseline an inventory to describe the disease, treatment, functional capacity, prognosis, and socioeconomic situation of consenting subjects was completed. In addition, subjects completed the Psychosocial Adjustment to Illness Inventory (PAIS-SR), the Family Assessment Device (FAD), the Meaning of Illness Questionnaire (MIQ), and a Health Service Utilization Inventory designed to assess direct and indirect costs of health resources. These data were entered into a concurrent analytic survey design. Participating subjects represented a more socioeconomically advantaged and better-adjusted group of chronically ill patients compared with others referred to the tertiary clinics. They were representative of all new referrals in their use of the majority of health services. However, once hospitalized, participating subjects stayed longer and used specialists less. There was no important relationship between disease severity or prognosis and any type of service utilization, including hospitalization. Because the strongest correlate of all types of health services consumed was psychosocial adjustment to illness (r = 0.28 to 0.33), patients were partitioned into one of three categories of adjustment to illness: good, fair, and poor. The total annual cost per patient was $23,883, if poorly adjusted, compared with $9,791 if well adjusted. If cash transfers (benefits paid by different types of insurance) are added, the average 1987 annual cost per poorly adjusted subject was $31,291 per patient, compared with $13,771 for a patient well adjusted to the illness. There was a statistically significant and economically important linear gradient in 1987 treatment costs per category of adjustment. The possible economic implications for psychosocial intervention are highlighted.
Rational Design of Intrinsically Ultramicroporous Polyimides Containing Bridgehead-Substituted Triptycene for Highly Selective and Permeable Gas Separation Membranes (2014)

Highly ultramicroporous, solution-processable polyimides bearing 9,10-bridgehead-substituted triptycene demonstrated the highest BET surface area reported for polyimides (840 m2 g-1) and several new highs in gas selectivity and permeability for hydrogen (1630-3980 barrers, H2/CH4 ∼ 38) and air (230-630 barrers, O 2/N2 = 5.5-5.9) separations. Two new dianhydrides bearing 9,10-diethyl- and 9,10-dipropyltriptycenes indicate that the ultramicroporosity is optimized for fast polymeric sieving with the use of short, bulky isopropyl bridgeheads and methyl-substituted diamines (TrMPD, TMPD, and TMBZ) that increase intrachain rigidity. Mechanically, the triptycene-based analogue of a spirobisindane-based polyimide exhibited 50% increases in both tensile strength at break (94 MPa) and elastic modulus (2460 MPa) with corresponding 90% lower elongations at break (6%) likely due to the ability of highly entangled spiro-based chains to unwind. To guide future polyimide design, structure/property relationships are suggested between the geometry of the contortion center, the diamine and bridgehead substituent, and the mechanical, microstructural, and gas transport properties. © 2014 American Chemical Society.
Biomolecular modification of p(AAm-co-EG/AA) IPNs supports osteoblast adhesion and phenotypic expression (1998)

Interpenetrating polymer networks (IPNs) were designed to resist materials fouling caused by non-specific protein adsorption, and indiscriminate cell or bacterial adhesion. These IPNs were thin adherent films (approximately 20 nm) comprised of acrylamide (AAm), ethylene glycol (EG), and acrylic acid (AA) grafted to either silicon waters or quartz substrates via photoinitiated free radical polymerization. These networks were further modified to promote specific cell adhesion by tethering bioactive groups such as peptides that mimic cell-binding domains found on extracellular matrix molecules. As a specific example of biomolecular surface engineering, peptides from the cell-binding domain of bone sialoprotein were tethered to a p(AAm-co-EG/AA) IPN to control cell behavior at the surface. The networks were characterized by contact angle measurements, spectroscopic ellipsometry, and X-ray photoelectron spectroscopy to convey information on IPN wettability, thickness, and chemistry. The surface characterization data supported the theory that the PEG/AA layer formed an IPN with the underlying p(AAm) network, and after graft modification of this IPN with diamino PEG (PEG(NH2)2), the PEG(NH2)2 chains were enriched at the surface. Rat calvarial osteoblasts attached to Arg-Gly-Asp (RGD) modified IPNs at levels significantly greater than on clean quartz, Arg-Gly-Glu (RGE) modified, or the PEG(NH2)2 modified IPN, with or without serum in the media. Cells maintained in media containing 15% fetal bovine serum (FBS) proliferated, exhibited nodule formation, and generated sheets of mineralized extracellular matrix (ECM) with the addition on beta-glycerophosphate to the media. Cell adhesion and mineralized ECM formation were specifically dependent on the peptide sequence present at the surface.
Validation of a remote monitoring system for the elderly: Application to mobility measurements (2002)

The aim of this paper is to introduce a smart tool for the assessment of the mobility of patient with motor disorders and to evaluate its performance through some initial experiments. These experiments are based on a system which is composed of sensors connected to a Personal Computer (PC) using data acquisition cards and a communication network. The PC includes a data acquisition and processing software. This system has been installed in a patient's housing (a bedroom and a washroom) in a long-stay setting. Pre-established travel and activity (going to bed, getting up, visiting the washroom em leader ) patterns of patient in the housing including their duration have been defined by physicians for the experiments. A volunteer participated in the experiments and the results of his mobility obtained by the data processing software were compared with his real mobility. An agreement was found between the proposed assessment system and the experiments, thereby validating functioning of the whole system. Then, the system has been used to monitor a patient over a period of 39 nights. Again there is a good agreement between the characteristics derived from the system and the findings of the caring staff in charge of the patient's routine night monitoring. Data collected during 24 consecutive hours have been used to identify and characterise the patient's whole day mobility. This study paves the way for a new assessment system of the mobility of patient thus allowing the follow up of patients suffering from dementia and to study their significant mobility changes over time by introducing an indicator of mobility which can be used to assess their motor behavioural disorders.
Peginterferon Alfa-2a in Patients with Chronic Hepatitis C and Cirrhosis (2000)

In patients with chronic hepatitis C and cirrhosis or bridging fibrosis, 180 microg of peginterferon alfa-2a administered once weekly is significantly more effective than 3 million units of standard interferon alfa-2a administered three times weekly.
Tetrabenazine Treatment for Tardive Dyskinesia: Assessment by Randomized Videotape Protocol (1999)

Tetrabenazine was well tolerated and resulted in significant improvements in AIMS scores for patients with refractory tardive dyskinesia.
A Single Amino Acid Change in the Newcastle Disease Virus Fusion Protein Alters the Requirement for HN Protein in Fusion (2000)

The role of a leucine heptad repeat motif between amino acids 268 and 289 in the structure and function of the Newcastle disease virus (NDV) F protein was explored by introducing single point mutations into the F gene cDNA. The mutations affected either folding of the protein or the fusion activity of the protein. Two mutations, L275A and L282A, likely interfered with folding of the molecule since these proteins were not proteolytically cleaved, were minimally expressed at the cell surface, and formed aggregates. L268A mutant protein was cleaved and expressed at the cell surface although the protein migrated slightly slower than wild type on polyacrylamide gels, suggesting an alteration in conformation or processing. L268A protein was fusion inactive in the presence or absence of HN protein expression. Mutant L289A protein was expressed at the cell surface and proteolytically cleaved at better than wild-type levels. Most importantly, this protein mediated syncytium formation in the absence of HN protein expression although HN protein enhanced fusion activity. These results show that a single amino acid change in the F(1) portion of the NDV F protein can alter the stringent requirement for HN protein expression in syncytium formation.
Peripheral and Thymic Foxp3+ Regulatory T Cells in Search of Origin, Distinction, and Function (2013)

Over the past decade, much has been learnt and much more to discover about Foxp3(+) regulatory T cells (Tregs). Initially, it was thought that Tregs were a unique entity that originates in the thymus. It is now recognized that there is a fraternal twin sibling that is generated in the periphery. The difficulty is in the distinction between these two subsets. The ability to detect, monitor, and analyze these two subsets in health and disease will provide invaluable insights into their functions and purposes. The plasticity and mechanisms of action can be unique and not overlapping within these subsets. Therefore, the therapeutic targeting of a particular subset of Tregs might be more efficacious. In the past couple of years, a vast amount of data have provided a better understanding of the cellular and molecular components essential for their development and stability. Many studies are implicating their preferential involvement in certain diseases and immunologic tolerance. However, it remains controversial as to whether any phenotypic markers have been identified that can differentiate thymic versus peripheral Tregs. This review will address the validity and controversy regarding Helios, Lap/Garp and Neuropilin-1 as markers of thymic Tregs. It also will discuss updated information on distinguishing features of these two subsets and their critical roles in maternal-fetal tolerance and transplantation.
RhoB Alteration Is Necessary for Apoptotic and Antineoplastic Responses to Farnesyltransferase Inhibitors (2000)

Farnesyltransferase inhibitors (FTIs) are in clinical trials, but how they selectively inhibit malignant cell growth remains uncertain. One important player in this process appears to be RhoB, an endosomal Rho protein that regulates receptor trafficking. FTI treatment elicits a gain of the geranylgeranylated RhoB isoform (RhoB-GG) that occurs due to modification of RhoB by geranylgeranyltransferase I in drug-treated cells. Notably, this event is sufficient to mediate antineoplastic effects in murine models and human carcinoma cells. To further assess this gain-of-function mechanism and determine whether RhoB-GG has a necessary role in drug action, we examined the FTI response of murine fibroblasts that cannot express RhoB-GG due to homozygous deletion of the rhoB gene. Nullizygous (-/-) cells were susceptible to cotransformation by adenovirus E1A plus activated H-Ras but defective in their FTI response, despite complete inhibition of H-Ras prenylation. Actin cytoskeletal and phenotypic events were disrupted in -/- cells, implicating RhoB-GG in these effects. Interestingly, -/- cells were resistant to FTI-induced growth inhibition under anchorage-dependent but not anchorage-independent conditions, indicating that, while RhoB-GG is sufficient, it is not necessary for growth inhibition under all conditions. In contrast, -/- cells were resistant to FTI-induced apoptosis in vitro and in vivo. Significantly, the apoptotic defect of -/- cells compromised the antitumor efficacy of FTI in xenograft assays. This study offers genetic proof of the hypothesis that RhoB-GG is a crucial mediator of the antineoplastic effects of FTIs.
Novel Osteoinductive Biomimetic Scaffolds Stimulate Human Osteoprogenitor Activity--Implications for Skeletal Repair (2003)

The development of new bone formation strategies offers tremendous therapeutic implications in a variety of musculoskeletal diseases. One approach involves harnessing the regenerative capacity of osteoprogenitor bone cells in combination with biomimetic scaffolds generated from appropriate scaffold matrices and osteoinductive factors. The aims of our study were to test the efficacy of two innovative osteoinductive agents: the osteoblast stimulating factor-1 (osf-1), an extracellular matrix-associated protein, and osteoinductive extracts of Saos-2 cells on human osteoprogenitor cells. Saos-2 extracted osteoinductive factors significantly stimulated alkaline phosphatase specific activity in basal and osteogenic conditions. Osf-1 significantly stimulated chemotaxis, total colony formation, alkaline phosphatase-positive colony formation, and alkaline phosphatase specific activity at concentrations as low as 10 pg/ml compared with control cultures. Osteoinductive factors present in Saos-2 cell extracts and osf-1 promoted adhesion, migration, expansion, and differentiation of human osteoprogenitor cells on 3-D scaffolds. The successful generation of 3-D biomimetic structures incorporating osf-1 or osteoinductive factors from Saos-2 cells indicates their potential for de novo bone formation that exploits cell-matrix interactions.
Oral administration of a streptococcal antigen coupled to cholera toxin B subunit evokes strong antibody responses in salivary glands and extramucosal tissues (1989)

Generation of local and systemic immune responses by the oral administration of antigens is frequently inefficient, requiring large quantities of immunogens and yielding only modest antibody responses. In this study, we have demonstrated that oral administration of microgram amounts of Streptococcus mutans protein antigen I/II covalently coupled to the B subunit of cholera toxin elicits vigorous mucosal as well as extramucosal immunoglobulin A and G antistreptococcal antibody responses in mice. These responses were manifested by the presence of large numbers of antibody-secreting cells in salivary glands, mesenteric lymph nodes, and spleens and by the development of high levels of circulating antibodies. This novel immunization strategy may find broad application in the construction of oral vaccines for the control of infectious diseases caused by pathogens encountered at mucosal and extramucosal sites.
Morphometric aspects of the human hypoglossal nerve in adults and the elderly (2005)

The intraperineural area and the total number of myelinic fibers of the right hypoglossal nerve are similar in both age groups.
The mitochondria-targeted anti-oxidant MitoQ decreases ischemia-reperfusion injury in a murine syngeneic heart transplant model (2015)

IR after heart transplantation results in mitochondrial oxidative damage that is potentiated by cold ischemia. Supplementing donor graft perfusion with the anti-oxidant MitoQ before transplantation should be studied further to reduce IR-related free radical production, the innate immune response to IR injury, and subsequent donor cardiac injury.
Critical evaluation of parameter consistency and predictive uncertainty in hydrological modeling: A case study using Bayesian total error analysis (2009)

The lack of a robust framework for quantifying the parametric and predictive uncertainty of conceptual rainfall‐runoff (CRR) models remains a key challenge in hydrology. The Bayesian total error analysis (BATEA) methodology provides a comprehensive framework to hypothesize, infer, and evaluate probability models describing input, output, and model structural error. This paper assesses the ability of BATEA and standard calibration approaches (standard least squares (SLS) and weighted least squares (WLS)) to address two key requirements of uncertainty assessment: (1) reliable quantification of predictive uncertainty and (2) reliable estimation of parameter uncertainty. The case study presents a challenging calibration of the lumped GR4J model to a catchment with ephemeral responses and large rainfall gradients. Postcalibration diagnostics, including checks of predictive distributions using quantile‐quantile analysis, suggest that while still far from perfect, BATEA satisfied its assumed probability models better than SLS and WLS. In addition, WLS/SLS parameter estimates were highly dependent on the selected rain gauge and calibration period. This will obscure potential relationships between CRR parameters and catchment attributes and prevent the development of meaningful regional relationships. Conversely, BATEA provided consistent, albeit more uncertain, parameter estimates and thus overcomes one of the obstacles to parameter regionalization. However, significant departures from the calibration assumptions remained even in BATEA, e.g., systematic overestimation of predictive uncertainty, especially in validation. This is likely due to the inferred rainfall errors compensating for simplified treatment of model structural error.