gebhart/patrepeval huggingface dataset:
GAD-alum immunotherapy in type 1 diabetes expands bifunctional Th1/Th2 autoreactive CD4 T cells (2020)

GAD-alum immunisation activates and propagates GAD-specific CD4 T cells with a distinctive bifunctional phenotype, the functional analysis of which might be important in understanding therapeutic responses.
A Mixed Friction Hydrostatic Face Seal Model With Phase Change (1980)

A mixed friction hydrostatic mechanical face seal model is presented. Load support and friction due to mechanical contact and the effect of a phase change are considered. The results show that a phase change within the seal interface leads to a greater fraction of the load being supported by fluid film pressure than for an all liquid or all gas phase seal. As seal operating temperature approaches the boiling point of the sealed fluid, very high leakage is predicted. An explanation for puffing is offered. The effect of various design parameters on two phase seal operation is examined. On a theoretical basis, operation at a higher temperature reduces seal wear rate and friction. The model can be used by seal designers to predict instability and performance for a two phase seal.
Clinical Pharmacogenetics Implementation Consortium Guidelines for Cytochrome P450 2D6 Genotype and Codeine Therapy: 2014 Update (2014)

Codeine is bioactivated to morphine, a strong opioid agonist, by the hepatic cytochrome P450 2D6 (CYP2D6); hence, the efficacy and safety of codeine are governed by CYP2D6 activity. Polymorphisms are a major cause of CYP2D6 variability. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for codeine based on CYP2D6 genotype. This document is an update to the 2012 Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for CYP2D6 genotype and codeine therapy.
Towards Resolving the Interordinal Relationships of Placental Mammals (1999)

Here we show that progress towards a reliable phylogeny for placental mammals at the ordinal level continues apace. We draw especially upon insights from the recent “International Symposium on the Origin of Mammalian Orders” held at The Graduate University of Advanced Study, Hayama, Japan (21–25 July 1998), particularly work not incorporated in the remainder of this issue or published elsewhere. Abstracts to talks and posters presented at this meeting can be found at www.utexas.edu/ftp/depts/systbiol/. The talks fell into three main sections, which we will now consider, followed by a summary where we present our current best estimate of the tree for placental mammals.
IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses (2011)

Polymorphisms in the gene encoding the transcription factor IRF5 that lead to higher mRNA expression are associated with many autoimmune diseases. Here we show that IRF5 expression in macrophages was reversibly induced by inflammatory stimuli and contributed to the plasticity of macrophage polarization. High expression of IRF5 was characteristic of M1 macrophages, in which it directly activated transcription of the genes encoding interleukin 12 subunit p40 (IL-12p40), IL-12p35 and IL-23p19 and repressed the gene encoding IL-10. Consequently, those macrophages set up the environment for a potent T helper type 1 (T(H)1)-T(H)17 response. Global gene expression analysis demonstrated that exogenous IRF5 upregulated or downregulated expression of established phenotypic markers of M1 or M2 macrophages, respectively. Our data suggest a critical role for IRF5 in M1 macrophage polarization and define a previously unknown function for IRF5 as a transcriptional repressor.
Fat Augmentation for Glottic Insufficiency (2000)

Fat injection is a good autogenous implant and may be considered as an option in management of patients with vocal fold scar, defect, or atrophy. Reabsorption of fat is a problem, but the procedure may be repeated.
Synthetic approaches to biologically active peptides and proteins including enzymes (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthetic approaches to biologically active peptides and proteins including enzymesE. T. KaiserCite this: Acc. Chem. Res. 1989, 22, 2, 47–54Publication Date (Print):February 1, 1989Publication History Published online1 May 2002Published inissue 1 February 1989https://doi.org/10.1021/ar00158a001Request reuse permissionsArticle Views258Altmetric-Citations51LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (856 KB) Get e-Alertsclose Get e-Alerts
An Implantable Multichannel Digital Neural Recording System For A Micromachined Sieve Electrode (2005)

This paper reports the development of an implantable, fully integrated, single-chip, multichannel neural recording system, which is powered and communicated with using an RF telemetry link. The system allows recording of /spl plusmn/500/spl mu/V neural signals from axons regenerated through a micromachined silicon sieve electrode. These signals are amplified using on-chip 100Hz to 3.IkHz bandlimited amplifiers, multiplexed, and digitized with a low-power, high speed current-mode 8-bit ADC, and then transmitted out using a passive RF telemetry link. The overall system dissipates 90mW of power from a 5V supply, and occupies 4x4mm/sup 2/ of area.
Nondestructive Sampling of Living Systems Using in Vivo Solid-Phase Microextraction (2011)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTNondestructive Sampling of Living Systems Using in Vivo Solid-Phase MicroextractionGangfeng Ouyang*†, Dajana Vuckovic‡, and Janusz Pawliszyn*‡View Author Information† MOE Key Laboratory of Aquatic Product Safety/KLGHEI of Environment and Energy Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China‡ Department of Chemistry, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada*E-mail addresses: [email protected] (G. Ouyang); [email protected] (J. Pawliszyn).Cite this: Chem. Rev. 2011, 111, 4, 2784–2814Publication Date (Web):January 27, 2011Publication History Received1 July 2010Published online27 January 2011Published inissue 13 April 2011https://pubs.acs.org/doi/10.1021/cr100203thttps://doi.org/10.1021/cr100203treview-articleACS PublicationsCopyright © 2011 American Chemical SocietyRequest reuse permissionsArticle Views7038Altmetric-Citations395LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Anatomy,Coating materials,Computer simulations,Extraction,Fibers Get e-Alerts
In vivoInhibition of Human CD19-Targeted Effector T Cells by Natural T Regulatory Cells in a Xenotransplant Murine Model of B Cell Malignancy (2011)

Human T cells genetically modified to express chimeric antigen receptors (CAR) specific to the B cell tumor antigen CD19 can successfully eradicate systemic human CD19(+) tumors in immunocompromised SCID (severe combined immunodeficient)-Beige mice. However, in the clinical setting, CD4(+) CD25(hi) T regulatory cells (Treg) present within the tumor microenvironment may be potent suppressors of tumor-targeted effector T cells. In order to assess the impact of Tregs on CAR-modified T cells in the SCID-Beige xenotransplant model, we isolated, genetically targeted and expanded natural T regulatory cells (nTreg). In vitro nTregs modified to express CD19-targeted CARs efficiently inhibited the proliferation of activated human T cells, as well as the capacity of CD19-targeted 19-28z(+) effector T cells to lyse CD19(+) Raji tumor cells. Intravenous infusion of CD19-targeted nTregs into SCID-Beige mice with systemic Raji tumors traffic to sites of tumor and recapitulate a clinically relevant hostile tumor microenvironment. Antitumor efficacy of subsequently infused 19-28z(+) effector T cells was fully abrogated as assessed by long-term survival of treated mice. Optimal suppression by genetically targeted nTregs was dependent on nTreg to effector T-cell ratios and in vivo nTreg activation. Prior infusion of cyclophosphamide in the setting of this nTreg-mediated hostile microenvironment was able to restore the antitumor activity of subsequently infused 19-28z(+) effector T cells through the eradication of tumor-targeted nTregs. These findings have significant implications for the design of future clinical trials utilizing CAR-based adoptive T-cell therapies of cancer.
All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation (2007)

We demonstrate that all-trans retinoic acid (RA) induces FoxP3(+) adaptive T regulatory cells (A-Tregs) to acquire a gut-homing phenotype (alpha 4 beta 7(+) CC chemokine receptor 9(+)) and the capacity to home to the lamina propria of the small intestine. Under conditions that favor the differentiation of A-Tregs (transforming growth factor-beta1 and interleukin 2) in vitro, the inclusion of RA induces nearly all activated CD4(+) T cells to express FoxP3 and greatly increases the accumulation of these cells. In the absence of RA, A-Treg differentiation is abruptly impaired by proficient antigen presenting cells or through direct co-stimulation. In the presence of RA, A-Treg generation occurs even in the presence of high levels of co-stimulation, with RA attenuating co-stimulation from interfering from FoxP3 induction. The recognition that RA induces gut imprinting, together with our finding that it enhances A-Treg conversion, differentiation, and expansion, indicates that RA production in vivo may drive both the imprinting and A-Treg development in the face of overt inflammation.
Dextran Hydrogels Containing Poly(N‐isopropylacrylamide) as Grafts and Cross‐Linkers Exhibiting Enzymatic Regulation in a Specific Temperature Range (2004)

Abstract Summary: Specific temperature‐responsive biodegradable hydrogels were synthesized and characterized in terms of their regulation of enzymatic accessibility based on the physical properties of the temperature‐responsive polymers. The hydrogels consist of glycidyl methacrylate‐modified dextran grafted with the poly( N ‐isopropylacrylamide) (PNIPAAm) homopolymer, and cross‐linked by co‐polymerization with NIPAAm and N , N ‐dimethylacrylamide (DMAAm). The coil‐globule change in the grafted poly(NIPAAm) chains and only a slight dehydration of the poly(NIPAAm‐co‐DMAAm) cross‐linkers are effective in controlling the enzymatic degradation over a specific temperature range. The thermo‐responses of the graft chains (steric hindrance) and the crosslinkers (slight deswelling of the hydrogel networks) control the enzymatic degradation of the hydrogel. image The thermo‐responses of the graft chains (steric hindrance) and the crosslinkers (slight deswelling of the hydrogel networks) control the enzymatic degradation of the hydrogel.
Whispering to horses: Childhood sexual abuse, depression and the efficacy of Equine Facilitated Therapy (2013)

Experience of childhood sexual abuse (CSA) is bothprevalent and under-reported in Australia as it is elsewherein the world. The negative psychosocial and behavioural sequelae of such abuse may be severe and can often last for the lifetime of the individual if therapeutic intervention is not successful. Meta-analyses of treatment outcome evaluations suggest that Cognitive Behavioural Therapy based approaches tend to be the most successful in reducing psychological symptoms (such as PTSD, internalising and externalising disorders), however for some clients these approaches may not be appropriate or as efficacious due to variables such as cognitive maturity or ethnicity. The use of animals within therapy situations to help develop an effective therapeutic alliance is not new but methodologically strong evaluations of Animal Assisted Therapies (AAT) generally and Equine Facilitated Therapy (EFT) specifically are needed in order to provide a solid evidence base regarding for whom, and in what situations, these approaches are the most effective. The current study aimed to evaluate and compare the efficacy of an adjunct EFT program run by Phoenix House (a sexual assault referral centre in Queensland, Australia) for the reduction of depressive symptoms across three age cohorts of CSA victims (children, adolescents and adults). Participants included 15 children (aged 8-11 years), 15adolescents (aged 12-17 years) and 14 adults (aged 19-50 years) with 10 of the 44 participants identifying as Indigenous Australians. A quasi-experimental, repeated measures design was used to evaluate changes in depressive symptoms with all participants responding onthe Child Depression Index or Beck Depression Inventory (as appropriate) at three points in time. Comparisons of change scores between Time 1 (intake to service) and Time 2 (post in-clinic counselling) and Time 2 and Time 3 (post-EFT) indicated that regardless of age or ethnicity, EFT proved to result in a greater decrement in depressive scores than that seen between Times 1 and 2. Implications of this and directions for future research are discussed.
Interim Analysis of a Phase 2 Open-Label Trial Assessing Burosumab Efficacy and Safety in Patients With Tumor-Induced Osteomalacia (2020)

Patients with tumor-induced osteomalacia (TIO), an acquired paraneoplastic condition characterized by osteomalacia due to hypophosphatemia, exhibit a similar clinical picture to those with X-linked hypophosphatemic rickets/osteomalacia (XLH). The human monoclonal anti-fibroblast growth factor 23 (FGF23) antibody burosumab (KRN23) increases serum phosphate and improves bone turnover, fracture healing, pain, and physical function in XLH patients by inhibiting circulating FGF23; thus, burosumab is expected to be an effective treatment for TIO. We report here an interim analysis of a multicenter, open-label, intraindividual dose-adjustment study of burosumab (0.3 to 2.0 mg/kg every 4 weeks) in Japanese and Korean TIO patients. The primary endpoint was the fasting serum phosphate level at each visit. Key secondary endpoints were changes over time in bone biomarkers, pharmacodynamic markers, bone histomorphometric parameters, motor function, and patient-reported outcomes. Safety was assessed based on treatment-emergent adverse events (TEAEs). Thirteen patients received burosumab treatment, of whom 4 underwent bone biopsy. The mean dose after week 112 was approximately 1.0 mg/kg. After the first burosumab administration, mean serum phosphate levels increased and remained above the lower limit of normal and in the normal range from weeks 14 to 112. Bone biomarkers initially increased, reaching maximum values at week 16 or 24, and then gradually decreased. After burosumab treatment, patients were able to walk further (evaluated by the 6-minute walk test), reported decreased pain levels, and showed a tendency toward healing of baseline fractures and pseudofractures. Two patients discontinued, one each due to disease progression and consent withdrawal. Burosumab was generally well tolerated, with no treatment-related TEAEs of grade ≥3 and no treatment-related serious AEs. In conclusion, the interim results of this first study of burosumab to treat TIO patients indicate that this drug has the potential to provide clinical benefit for patients with unresectable tumors. The full study results are eagerly anticipated. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..
Glycoprotein D Receptor-Dependent, Low-pH-Independent Endocytic Entry of Herpes Simplex Virus Type 1 (2005)

Two herpes simplex virus type 1 (HSV-1) entry pathways have been described: direct fusion between the virion envelope and the plasma membrane, as seen on Vero cells, and low-pH-dependent endocytosis, as seen on CHO nectin-1 and HeLa cells. In this paper, we studied HSV entry into C10 murine melanoma cells and identified a third entry pathway for this virus. During entry into C10 cells, virion envelope glycoproteins rapidly became protected from the membrane-impermeable chemical cross-linker BS3 and from proteinase K. Protection was gD receptor dependent, and the time taken to detect protected protein was proportional to the rate of virus entry. Ultrastructural examination revealed that virions attached to the surface of C10 cells were localized to membrane invaginations, whereas those on the surface of receptor-negative B78 cells were peripherally attached. Virus entry into C10 cells was energy dependent, and intracellular enveloped virions were seen within membrane-bound vesicles consistent with endocytic entry. Entry was not inhibited by bafilomycin A1 or ammonium chloride, showing that passage of the virion through a low-pH environment was not required for infection. Resistance to similar reagents should therefore not be taken as proof of HSV entry by a nonendosomal pathway. These data define a novel gD receptor-dependent acid-independent endocytic entry pathway for HSV.
Context-aware, adaptive wearable computers as remote interfaces to 'intelligent' environments (2002)

This paper describes a wearable computing system for monitoring and controlling of 'intelligent' environments. The main components of the system are (1) an open, expandable service model for the description of functionality provided by environments; (2) a self-adapting wearable computer that can function as remote interface to a wide variety of services.
Structural origins of substrate discrimination in trypsin and chymotrypsin (1995)

Converting the specificity of trypsin to that of chymotrypsin has been shown to require the exchange of amino acids in multiple portions of the protein, including two surface loops which do not directly contact the substrate. Crystallographic analysis of two mutant trypsins possessing chymotrypsin-like specificity now reveals that these distal surface loops alter function by directly determining the structure of the primary binding site. Efficient acylation of cognate substrates correlates with a distinct backbone conformation of the conserved Gly216 residue. This amino acid is located on the surface of the specificity pocket and forms two main-chain hydrogen bonds with a nonspecific portion of substrate. By contrast, the improvement in substrate binding affinity effect by the substitution of the distal Tyr172 residue with Trp derives from structural rearrangements at the extreme base of the pocket. Together, the kinetic and crystallographic data strongly suggest that both Asp189 and Gly216 must be considered as primary determinants of substrate specificity in trypsin.
The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen (2005)

Current dosing algorithms do not account for genetic and environmental factors for warfarin dose determinations. This study investigated the contribution of age, CYP2C9 and VKORC1 genotype, and body size to warfarin-dose requirements. Studied were 297 patients with stable anticoagulation with a target international normalized ratio (INR) of 2.0 to 3.0. Genetic analyses for CYP2C9 (*2 and *3 alleles) and VKORC1 (-1639 polymorphism) were performed and venous INR and plasma R- and S-warfarin concentrations determined. The mean warfarin daily dose requirement was highest in CYP2C9 homozygous wild-type patients, compared with those with the variant *2 and *3 alleles (P < .001) and highest in patients with the VKORC1 (position -1639) GG genotype compared with those with the GA genotype and the AA genotype (P < .001). Mean warfarin daily dose requirements fell by 0.5 to 0.7 mg per decade between the ages of 20 to 90 years. Age, height, and CYP2C9 genotype significantly contributed to S-warfarin and total warfarin clearance, whereas only age and body size significantly contributed to R-warfarin clearance. The multivariate regression model including the variables of age, CYP2C9 and VKORC1 genotype, and height produced the best model for estimating warfarin dose (R2 = 55%). Based upon the data, a new warfarin dosing regimen has been developed. The validity of the dosing regimen was confirmed in a second cohort of patients on warfarin therapy.
Bone cancer pain (2010)

In the United States, cancer is the second most common cause of death and it is expected that about 562,340 Americans will have died of cancer in 2009. Bone cancer pain is common in patients with advanced breast, prostate, and lung cancer as these tumors have a remarkable affinity to metastasize to bone. Once tumors metastasize to bone, they are a major cause of morbidity and mortality as the tumor induces significant skeletal remodeling, fractures, pain, and anemia. Currently, the factors that drive cancer pain are poorly understood. However, several recently introduced models of bone cancer pain, which closely mirror the human condition, are providing insight into the mechanisms that drive bone cancer pain and guide the development of mechanism-based therapies to treat the cancer pain. Several of these mechanism-based therapies have now entered human clinical trials. If successful, these therapies have the potential to significantly enlarge the repertoire of modalities that can be used to treat bone cancer pain and improve the quality of life, functional status, and survival of patients with bone cancer.