gebhart/patrepeval huggingface dataset:
Characterization of cDNAs encoding the murine interleukin 2 receptor (IL-2R) gamma chain: chromosomal mapping and tissue specificity of IL-2R gamma chain expression. (1993)

The IL-2R gamma chain (IL-2R gamma) is an essential component of high- and intermediate-affinity IL-2Rs, playing critical roles for ligand binding and internalization. Recently, our laboratory has demonstrated that IL-2R gamma mutation results in X chromosome-linked severe combined immunodeficiency in humans, suggesting that IL-2R gamma plays a vital role in thymic maturation of human T cells. We now report the isolation and characterization of cDNAs encoding murine IL-2R gamma. The open reading frame encodes 369 aa, identical in length to that encoded by the human IL-2R gamma cDNA. Murine IL-2R gamma and human IL-2R gamma have 69% and 70% identity at the nucleotide and amino acid levels, respectively. As expected, the murine IL-2R gamma retains the WSXWS motif and four cysteine residues characteristic of cytokine receptor superfamily members. IL-2R gamma mRNA distribution shows significant tissue specificity, with particularly high-level expression in spleen and thymus, and higher expression in single-positive (CD4+8- or CD4-8+)-enriched thymocytes than in double-negative (CD4-8-) thymocytes. Finally, we have localized the murine IL-2R gamma gene, Il2rg, to the X chromosome between Rsvp and Plp and demonstrated that a defect in IL-2R gamma is not responsible for the X chromosome-linked xid mutation, which maps to this same region. The cloning of the murine IL-2R gamma cDNA will facilitate the investigation of the role of this protein in lymphocyte function and thymic development.
Regulation of constitutive and alternative splicing by PRMT5 reveals a role for Mdm4 pre-mRNA in sensing defects in the spliceosomal machinery (2013)

The tight control of gene expression at the level of both transcription and post-transcriptional RNA processing is essential for mammalian development. We here investigate the role of protein arginine methyltransferase 5 (PRMT5), a putative splicing regulator and transcriptional cofactor, in mammalian development. We demonstrate that selective deletion of PRMT5 in neural stem/progenitor cells (NPCs) leads to postnatal death in mice. At the molecular level, the absence of PRMT5 results in reduced methylation of Sm proteins, aberrant constitutive splicing, and the alternative splicing of specific mRNAs with weak 5' donor sites. Intriguingly, the products of these mRNAs are, among others, several proteins regulating cell cycle progression. We identify Mdm4 as one of these key mRNAs that senses the defects in the spliceosomal machinery and transduces the signal to activate the p53 response, providing a mechanistic explanation of the phenotype observed in vivo. Our data demonstrate that PRMT5 is a master regulator of splicing in mammals and uncover a new role for the Mdm4 pre-mRNA, which could be exploited for anti-cancer therapy.
Maturation of human monocyte-derived dendritic cells (MoDCs) in the presence of prostaglandin E2 optimizes CD4 and CD8 T cell-mediated responses to protein antigens: role of PGE2 in chemokine and cytokine expression by MoDCs (2005)

Prostaglandin E2 (PGE2) acts in synergy with other inflammatory stimuli such as tumor necrosis factor (TNF) to induce the maturation of migratory-type monocyte-derived dendritic cells (MoDCs). However, PGE2 has been reported to inhibit IL-12p70 production by MoDCs and to promote the generation of Th2 T cell responses. We demonstrate here that the addition of PGE2 to TNF for the maturation of MoDCs enhanced CD4 and CD8 T cell proliferative responses to neoantigen and recall antigen, and enhanced Th1-type responses. The increased stimulatory capacity of MoDCs matured with PGE2 was associated with a fully mature, migratory-type MoDC phenotype and more rapid down-regulation of the expression of inflammatory chemokines, with up-regulated expression of the constitutive chemokines TARC and MDC. In addition, although MoDCs matured with TNF and PGE2 selectively produced the inhibitory IL-12p40 subunit at steady state, they were able to produce the bioactive IL-12p70 heterodimer after stimulation with CD40 ligand and/or IFN-gamma. Despite increased IL-6 mRNA expression, MoDCs matured with PGE2 did not overcome the suppressive effects of CD4+ CD25+ T cells in allogeneic mixed lymphocyte reactions. In conclusion, MoDCs matured in the presence of PGE2 display characteristics of more efficient antigen-presenting cells that might be optimal for use in cancer vaccine-based clinical trials.
Characterization of Detergent-Insoluble Proteins in ALS Indicates a Causal Link between Nitrative Stress and Aggregation in Pathogenesis (2009)

Analysis of the insoluble fractions from cellular/mouse models and human tissues revealed novel aggregation-prone proteins and suggests that nitrative stress contribute to protein aggregate formation in ALS.
Rapid changes in circulating tumor cells following anti-angiogenic therapy (2015)

Angiogenesis is essential for tumor growth and metastasis. Bevacizumab (Avastin™) is a humanized monoclonal antibody directed against vascular endothelial growth factor (VEGF). Prior studies suggest that bevacizumab causes transient changes in tumor perfusion and oncostatic pressure. However, it has been difficult to directly demonstrate immediate effects in living patients. The high-definition circulating tumor cell (HD-CTC) assay allows for enumeration and cytologic analysis of CTCs without reliance on immunologic or physical separation methods. Here, we assess rapid changes in HD-CTCs immediately following bevacizumab administration in patients with metastatic castration resistant prostate cancer (CRPC). Peripheral blood was obtained in 8 subjects with CRPC before and within 2 h following bevacizumab. The median (range) of HD-CTCs observed immediately pre- and post- bevacizumab was 2.4 (0–352) and 40 (0–352) cells ml−1, respectively. Changes in apoptotic HD-CTCs were observed following bevacizumab in most patients. The HD-CTC assay can also be used to monitor androgen receptor (AR) expression, a therapeutic target particularly important for some prostate cancer treatments. As bevacizumab is not expected to directly interact with AR, we observed no change in the AR expression or sub-cellular localization in these patients. Following the bevacizumab administration, all subjects subsequently received docetaxel and everolimus along with bevacizumab over additional cycles in the context of a therapeutic clinical trial. Interestingly, the two subjects with the smallest variation in HD-CTCs following bevacizumab demonstrated the least response to subsequent treatment. These pilot data suggest CTC-based assays may be used to measure immediate effects associated with bevacizumab treatment at an individual patient level. Additional subjects and longer follow-up will be required to determine if immediate changes in HD-CTCs relate to therapeutic response and overall clinical outcome for patients with metastatic prostate cancer and other malignancies.
Identification of a cytotoxic T lymphocyte response to the apoptosis inhibitor protein survivin in cancer patients. (2001)

During the last decade, a large number of human tumor-associated antigens have been identified that are recognized by CTLs in a MHC-restricted fashion. The apoptosis inhibitor protein survivin is overexpressed in most human cancers, and inhibition of its function results in increased apoptosis. Therefore, this protein may serve as a target for therapeutic CTL responses. Here, using CTL epitopes deduced from survivin, we describe specific T-cell reactivity against this antigen in peripheral blood from chronic lymphatic leukemia patients and in tumor-infiltrated lymph nodes from melanoma patients by ELISPOT analysis. CTL responses against two survivin-deduced peptide epitopes were detected in three of six melanoma patients and three of four chronic lymphatic leukemia patients. No T-cell reactivity was detected in peripheral blood lymphocytes from six healthy controls. Thus, survivin may serve as an important and widely applicable target for anticancer immunotherapeutic strategies.
Column: Polymer Supports in Synthesis (2005)

Synthetic polymers have often been employed as the backbones of artificial enzymes because such enzyme-like catalysts could possess thermal, chemical, and mechanical stability not available in the native enzyme. Usually, organic functional groups are present in amino acid side chains. They play the key role in the enzymatic activity of these artifical enzymes by acting as general acids, bases, or nucleophiles (R. B. Silverman, The Organic Chemistry of Drug Design and Drug Action, Academic Press, San Diego, 1992; P. Hodge, Chem. Soc. Rev., 1997, 26, 417). Metal ions or metal-bound hydroxide ions (or water molecules) are often more effective at catalyzing protein cleavage reactions (J. Chin, Acc. Chem. Res., 1991, 24, 145–152; J. Suh, Acc. Chem. Res., 1992, 25, 273–279).
Multi-speaker modeling and speaker adaptation for DNN-based TTS synthesis (2015)

In DNN-based TTS synthesis, DNNs hidden layers can be viewed as deep transformation for linguistic features and the output layers as representation of acoustic space to regress the transformed linguistic features to acoustic parameters. The deep-layered architectures of DNN can not only represent highly-complex transformation compactly, but also take advantage of huge amount of training data. In this paper, we propose an approach to model multiple speakers TTS with a general DNN, where the same hidden layers are shared among different speakers while the output layers are composed of speaker-dependent nodes explaining the target of each speaker. The experimental results show that our approach can significantly improve the quality of synthesized speech objectively and subjectively, comparing with speech synthesized from the individual, speaker-dependent DNN-based TTS. We further transfer the hidden layers for a new speaker with limited training data and the resultant synthesized speech of the new speaker can also achieve a good quality in term of naturalness and speaker similarity.
Chilled ammonia process for CO2 capture (2009)

The Chilled Ammonia Process (CAP) can be applied to capture CO2 from flue gases exhausted from coal-fired boilers and natural gas combined cycle (NGCC) systems, as well as a wide variety of industrial applications. Initial tests conducted at the We Energies Pleasant Prairie Power Plant indicate that CAP can absorb CO2 using regenerated ionic solution on a continuous basis. The We Energies facility is designed to capture over 35 tonnes/day of CO2 at design rates. The facility was engineered, installed, and is being operated as a co-operative effort between Alstom (the process supplier) who engineered and constructed the pilot; EPRI (including 37 funders) who is conducting data collection and process evaluation; and We Energies who is providing operating utilities and is serving as the site host. The CAP is a solvent-based regenerable process that uses an aqueous ammonium solution to capture CO2 by forming ammonium bicarbonate. The bicarbonate is subsequently heated to drive off the CO2 with the resulting carbonate returned to the CO2 absorption system for re-use. Anticipated advantages of the CAP over an amine-based process include: Lower energy for regeneration Regeneration at pressure Ability to offset LP steam consumption with reject heat (Not tested at We Energies) Cooling to minimize ammonia penetration from the absorber. Results from the initial operation of the CAP process at the We Energies site are presented in this paper.
Issues for meteorological and oceanographic data web services (2009)

Web Services are becoming the standard technology used to share data for many Navy and other DoD operations. These enable an automated capability to obtain and integrate data for data fusion. This paper will address issues that are involved in coordination and collaboration for MetOc data access and exchange across enterprise boundaries. This includes issues of JMBL, JMBL-OGC compatibility and UCore messaging.
TDP-43 Is Not a Common Cause of Sporadic Amyotrophic Lateral Sclerosis (2008)

Our data indicate that genetic variation in TARDBP is not a common cause of sporadic ALS in North American.
Intracerebral transplantation of mesenchymal stem cells into acid sphingomyelinase–deficient mice delays the onset of neurological abnormalities and extends their life span (2002)

Types A and B Niemann-Pick disease (NPD) are lysosomal storage disorders resulting from loss of acid sphingomyelinase (ASM) activity. We have used a knockout mouse model of NPD (ASMKO mice) to evaluate the effects of direct intracerebral transplantation of bone marrow-derived mesenchymal stem cells (MSCs) on the progression of neurological disease in this disorder. MSCs were transduced with a retroviral vector to overexpress ASM and were injected into the hippocampus and cerebellum of 3-week-old ASMKO pups. Transplanted cells migrated away from the injection sites and survived at least 6 months after transplantation. Seven of 8 treated mice, but none of the untreated controls, survived for > or = 7 months after transplant. Survival times were greater in sex-matched than in sex-mismatched transplants. Transplantation significantly delayed the Purkinje cell loss that is characteristic of NPD, although the protective effect declined with distance from the injection site. Overall ASM activity in brain homogenates was low, but surviving Purkinje cells contained the retrovirally expressed human enzyme, and transplanted animals showed a reduction in cerebral sphingomyelin. These results reveal the potential of treating neurodegenerative lysosomal storage disorders by intracerebral transplantation of bone marrow-derived MSCs.
M. Levator Ani in the rat: Does it really lift the anus? (1998)

The M. pubococcygeus and the M. iliococcygeus share similarities with their homologues in the human. The M. levator ani, which is present only in the male rat, reveals some anatomical resemblance with the human M. puborectalis but has a different insertion and function. Because it does not lift the anus during contraction, its denomination as M. levator ani seems unjustified. Because of its principal sexual function, its fixation to the bulbus, and its sensitivity to testosterone, naming this muscle M. bulbocavernosus dorsalis would indeed seem more logical.
Dy‐DTPA derivatives as relaxation agents for very high field MRI: The beneficial effect of slow water exchange on the transverse relaxivities (2002)

Proton longitudinal and transverse relaxivities of Dy(DTPA)(2-) and Dy-DTPA bisamide derivatives (Dy(DTPA-BA): Dy-DTPA bisamide, Dy(DTPA-BEA): Dy-DTPA bisethylamide, Dy(DTPA-BnBA): Dy-DTPA bis-n-butylamide, and Dy(DTPA-BBMA): Dy-DTPA bisbismethylamide) were analyzed between 0.47 T and 18.8 T. Curie longitudinal relaxation was clearly observed at magnetic fields larger than 2.4 T, but the longitudinal relaxivities are limited by the fast rotation of the complexes. Rotational correlation times were separately assessed by deuterium relaxometry of the diamagnetic deuterated lanthanum analogs. Transverse relaxivity, which depends on the square of the magnetic field and on the residence time of the coordinated water molecule (tau(M)), was more than 7.5 times larger at 18.8 T and 310 K for Dy(DTPA-BA) and Dy(DTPA-BEA) as compared to Dy(DTPA)(2-). This difference is mainly related to the slower water exchange of the bisamide complexes, as confirmed by the values of tau(M) measured by oxygen-17 relaxometry. Such Dy-complexes, characterized by relatively long tau(M) values (tauM310 larger than 100 ns but smaller than 1 micros), thus appear to be useful as negative T(2) (or transverse) contrast agents for high-field imaging. This was demonstrated by the spin-echo images of phantoms obtained at 4.7 T on samples containing Dy(DTPA)(2-) and Dy(DTPA-BEA).
The movable filter as a user interface tool (1994)

Magic LensT'l filters area new user interface tool that combine an arbitrarily-shaped region with an operator that changes the view of objects viewed through that region.
Resistance to Selective BRAF Inhibition Can Be Mediated by Modest Upstream Pathway Activation (2011)

A high percentage of patients with BRAF(V600E) mutant melanomas respond to the selective RAF inhibitor vemurafenib (RG7204, PLX4032) but resistance eventually emerges. To better understand the mechanisms of resistance, we used chronic selection to establish BRAF(V600E) melanoma clones with acquired resistance to vemurafenib. These clones retained the V600E mutation and no second-site mutations were identified in the BRAF coding sequence. Further characterization showed that vemurafenib was not able to inhibit extracellular signal-regulated kinase phosphorylation, suggesting pathway reactivation. Importantly, resistance also correlated with increased levels of RAS-GTP, and sequencing of RAS genes revealed a rare activating mutation in KRAS, resulting in a K117N change in the KRAS protein. Elevated levels of CRAF and phosphorylated AKT were also observed. In addition, combination treatment with vemurafenib and either a MAP/ERK kinase (MEK) inhibitor or an AKT inhibitor synergistically inhibited proliferation of resistant cells. These findings suggest that resistance to BRAF(V600E) inhibition could occur through several mechanisms, including elevated RAS-GTP levels and increased levels of AKT phosphorylation. Together, our data implicate reactivation of the RAS/RAF pathway by upstream signaling activation as a key mechanism of acquired resistance to vemurafenib, in support of clinical studies in which combination therapy with other targeted agents are being strategized to combat resistance.
Autologous fibrin tissue adhesive (1985)

Various methods of making fibrin tissue adhesive from a patient's own blood were evaluated. The method using ammonium sulfate for fibrinogen preparation produced the greatest bonding strength. The average bonding strength of the commercially manufactured adhesive and of the autologous fibrin tissue adhesive were compared at 10 minutes and 30 minutes after glueing together 1 X 1 cm samples of fresh human dura. Results indicate the commercial glue holding 57 gms/cm2 at 10 minutes and 123 gms/cm2 at 30 minutes, while autologous glue prepared with the "ammonium sulfate method" has a bonding strength of 41 gms/cm2 at 10 minutes and 217 gms/cm2 at 30 minutes.
Challenges and Technologies in Reservoir Modeling (2009)

Reservoir modeling is playing an increasingly important role in developing and producing hydrocarbon reserves. In this paper, we provide a brief overview of some main challenges in reservoir modeling, i.e., accurate and efficient modeling of complex reservoir geometry and heterogeneous reservoir properties. We then present modeling techniques we recently developed in addressing these challenges, including a method for generating constrained Voronoi grids and a generic global scale-up method. We focus on the Voronoi gridding method, which is based on a new constrained Delaunay triangulation algorithm and a rigorous method of adapting Voronoi grids to piecewise linear constraints. The global scale-up method based on generic flows is briefly described. Numerical examples are provided to demonstrate the techniques and the advantage of combining them in constructing accurate and efficient reservoir models. AMS subject classifications: 37M05, 76S05, 86A60, 65M50, 65N50
The role of B cells in lpr/lpr-induced autoimmunity. (1994)

The primary roles of T cells and B cells in the initiation of systemic autoimmunity are unclear. To investigate the role of B cells, we crossed the "Jh knockout" mutation onto the autoimmune lpr/lpr background. Animals homozygous for both traits were obtained. As expected, these animals lack B cells. These animals also show no signs of autoimmune kidney destruction nor vasculitis, in spite of carrying the lpr/lpr mutation. In contrast, lpr/lpr littermates that had B cells had severe nephritis and vasculitis, as well as autoantibodies. These results demonstrate a primary role for B cells and/or (auto)antibodies in initiating several types of autoimmune-mediated tissue destruction. The implications of this finding for models and therapy of autoimmunity are discussed.
Laser Photocoagulation of Senile Macular Degeneration (1982)

The first report of the Macular Photocoagulation Study in this issue is an important event. For the first time, a method of treatment of certain types of senile macular degeneration has been proved. Ophthalmologists and their patients will be heartened to hear of the positive results of this prospective randomized cooperative clinical trial. <h3>See p 912.</h3> There are certain caveats. Laser treatment to all types of senile macular degeneration was not tested or proved to be of benefit. It would be a distortion of the careful design of this study and a disservice to patients with this disease if we do not apply the study's results carefully and precisely. The positive results are limited to patients older than 50 years who have a visual acuity of 20/100 or better and with a subretinal neovascular membrane at least 200 μm from the center of the fovea. Practically, this means a subretinal
Human Coronavirus: Host-Pathogen Interaction (2019)

Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Replication of HCoV is regulated by a diversity of host factors and induces drastic alterations in cellular structure and physiology. Activation of critical signaling pathways during HCoV infection modulates the induction of antiviral immune response and contributes to the pathogenesis of HCoV. Recent studies have begun to reveal some fundamental aspects of the intricate HCoV-host interaction in mechanistic detail. In this review, we summarize the current knowledge of host factors co-opted and signaling pathways activated during HCoV infection, with an emphasis on HCoV-infection-induced stress response, autophagy, apoptosis, and innate immunity. The cross talk among these pathways, as well as the modulatory strategies utilized by HCoV, is also discussed.