gebhart/patrepeval huggingface dataset:
Insulin Resistance and the Polycystic Ovary Syndrome: Mechanism and Implications for Pathogenesis* (1997)

It is now clear that PCOS is often associated with profound insulin resistance as well as with defects in insulin secretion. These abnormalities, together with obesity, explain the substantially increased prevalence of glucose intolerance in PCOS. Moreover, since PCOS is an extremely common disorder, PCOS-related insulin resistance is an important cause of NIDDM in women (Table 3). The insulin resistance in at least 50% of PCOS women appears to be related to excessive serine phosphorylation of the insulin receptor. A factor extrinsic to the insulin receptor, presumably a serine/threonine kinase, causes this abnormality and is an example of an important new mechanism for human insulin resistance related to factors controlling insulin receptor signaling. Serine phosphorylation appears to modulate the activity of the key regulatory enzyme of androgen biosynthesis, P450c17. It is thus possible that a single defect produces both the insulin resistance and the hyperandrogenism in some PCOS women (Fig. 19). Recent studies strongly suggest that insulin is acting through its own receptor (rather than the IGF-I receptor) in PCOS to augment not only ovarian and adrenal steroidogenesis but also pituitary LH release. Indeed, the defect in insulin action appears to be selective, affecting glucose metabolism but not cell growth. Since PCOS usually has a menarchal age of onset, this makes it a particularly appropriate disorder in which to examine the ontogeny of defects in carbohydrate metabolism and for ascertaining large three-generation kindreds for positional cloning studies to identify NIDDM genes. Although the presence of lipid abnormalities, dysfibrinolysis, and insulin resistance would be predicted to place PCOS women at high risk for cardiovascular disease, appropriate prospective studies are necessary to directly assess this.
IL-22 is required for Th17 cell–mediated pathology in a mouse model of psoriasis-like skin inflammation (2008)

Psoriasis is a chronic skin disease resulting from the dysregulated interplay between keratinocytes and infiltrating immune cells. We report on a psoriasis-like disease model, which is induced by the transfer of CD4(+)CD45RB(hi)CD25(-) cells to pathogen-free scid/scid mice. Psoriasis-like lesions had elevated levels of antimicrobial peptide and proinflammatory cytokine mRNA. Also, similar to psoriasis, disease progression in this model was dependent on the p40 common to IL-12 and IL-23. To investigate the role of IL-22, a Th17 cytokine, in disease progression, mice were treated with IL-22-neutralizing antibodies. Neutralization of IL-22 prevented the development of disease, reducing acanthosis (thickening of the skin), inflammatory infiltrates, and expression of Th17 cytokines. Direct administration of IL-22 into the skin of normal mice induced both antimicrobial peptide and proinflammatory cytokine gene expression. Our data suggest that IL-22, which acts on keratinocytes and other nonhematopoietic cells, is required for development of the autoreactive Th17 cell-dependent disease in this model of skin inflammation. We propose that IL-22 antagonism might be a promising therapy for the treatment of human psoriasis.
Genetic analysis of methicillin-resistant Staphylococcus aureus expressing high- and low-level mupirocin resistance (2001)

Clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) expressing high- and low-level mupirocin resistance were studied to determine the genetic location of mupirocin and other resistance determinants. Mupirocin resistance was confirmed by MIC determination with E-test strips. Curing and transfer experiments were used to establish the genetic location of the resistance determinants and the PCR with mupA-specific primers was used to detect the presence of mupA genes. High-level mupirocin-resistant isolates had MICs >1024 mg/L, whereas the low-level resistant isolates had MICs of 32-128 mg/L. The isolates carried plasmids ranging from 2.8 to 38 kb in size. All of them carried 26- and 3.0-kb plasmids, but only the high-level mupirocin-resistant isolates carried a 38-kb plasmid. Curing and transfer experiments revealed that the 26-kb plasmid encoded resistance to cadmium, mercuric chloride, propamidine isethionate and ethidium bromide and the 38-kb plasmid was a conjugative plasmid encoding high-level mupirocin resistance. One isolate, IBN287, carried both plasmid-borne high-level and chromosomal low-level mupirocin resistance. The mupA gene was detected on the 38-kb plasmid DNA but not in the genomic DNA of the low-level mupirocin-resistant isolates. The genomic DNA of strain IBN287 cured of the 38-kb mupirocin resistance plasmid did not contain mupA. The results suggest that different genes encoded low- and high-level mupirocin resistance in these isolates.
NMR Detection and Study of Hydrolysis of HNO-Derived Sulfinamides (2013)

Nitroxyl (HNO), a potential heart failure therapeutic, is known to post-translationally modify cysteine residues. Among reactive nitrogen oxide species, the modification of cysteine residues to sulfinamides [RS(O)NH2] is unique to HNO. We have applied (15)N-edited (1)H NMR techniques to detect the HNO-induced thiol to sulfinamide modification in several small organic molecules, peptides, and the cysteine protease, papain. Relevant reactions of sulfinamides involve reduction to free thiols in the presence of excess thiol and hydrolysis to form sulfinic acids [RS(O)OH]. We have investigated sulfinamide hydrolysis at physiological pH and temperature. Studies with papain and a related model peptide containing the active site thiol suggest that sulfinamide hydrolysis can be enhanced in a protein environment. These findings are also supported by modeling studies. In addition, analysis of peptide sulfinamides at various pH values suggests that hydrolysis becomes more facile under acidic conditions.
Cyclic GMP-dependent protein kinase is required for thrombospondin and tenascin mediated focal adhesion disassembly (1996)

Focal adhesions are specialized regions of cell membranes that are foci for the transmission of signals between the outside and the inside of the cell. Intracellular signaling events are important in the organization and stability of these structures. In previous work, we showed that the counter-adhesive extracellular matrix proteins, thrombospondin, tenascin, and SPARC, induce the disassembly of focal adhesion plaques and we identified the active regions of these proteins. In order to determine the mechanisms whereby the anti-adhesive matrix proteins modulate cytoskeletal organization and focal adhesion integrity, we examined the role of protein kinases in mediating the loss of focal adhesions by these proteins. Data from these studies show that cGMP-dependent protein kinase is necessary to mediate focal adhesion disassembly triggered by either thrombospondin or tenascin, but not by SPARC. In experiments using various protein kinase inhibitors, we observed that selective inhibitors of cyclic GMP-dependent protein kinase, KT5823 and Rp-8-Br-cGMPS, blocked the effects of both the active sequence of thrombospondin 1 (hep I) and the alternatively-spliced segment (TNfnA-D) of tenascin-C on focal adhesion disassembly. Moreover, early passage rat aortic smooth muscle cells which have high levels of cGMP-dependent protein kinase were sensitive to hep I treatment, in contrast to passaged cGMP-dependent protein kinase deficient cells which were refractory to hep I or TNfnA-D treatment, but were sensitive to SPARC. Transfection of passaged smooth muscle cells with the catalytic domain of PKG I alpha restored responsiveness to hep I and TNfnA-D. While these studies show that cGMP-dependent protein kinase activity is necessary for thrombospondin and tenascin-mediated focal adhesion disassembly, kinase activity alone is not sufficient to induce disassembly as transfection of the catalytic domain of the kinase in the absence of additional stimuli does not result in loss of focal adhesions.
INHIBITION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR INDUCED CELL-GROWTH BY AN ANGIOGENESIS INHIBITOR AGM-1470 IN CAPILLARY ENDOTHELIAL-CELLS (1994)

It is known that an anti-angiogenic compound AGM-1470 inhibits cells in vitro and in vivo, on mitogen-induced cell growth in capillary endothelial cells. In monolayer cultures, 1 ng/ml AGM-1470 completely inhibited both basic fibroblast growth factor (bFGF) induced cell growth and vascular endothelial growth factor (VEGF) induced cell growth in a cytostatic manner. IC50 was 85 pg/ml and 55 pg/ml for bFGF and VEGF induced cell growth, respectively. Moreover, in collagen gels, AGM-1470 suppressed the colony formation induced by bFGF and by VEGF in a dose dependent manner. Few colonies appeared 25 days after co-culuture with I ng/ml AGM-1470 and either 1 ng/ml bFGF or 5 ng/ml VEGF. It is suggested that a potent; inhibition of growth signals of more than one growth factor for endothelial cells might be involved in anti-angiogenic activity of AGM-1470.
Staged-fault testing for high impedance fault data collection (2005)

Faulted lines must be repaired and returned to service in the shortest possible time to provide reliable service to the customers. Fault detection is an important aspect of system protection, as it involves personnel as well as equipment safety. The research on high impedance fault (HTF) detection techniques is mainly based on conventional methods, familiar to the power system engineers. TXU Electric Delivery (TXUED) and ABB have initiated a project to collect HIF data from staged-fault testing, to assist ABB in the research and development of suitable techniques for detecting high impedance faults. Since most protective relay engineers have spent their careers avoiding faults on the electric system, they are not usually comfortable with the process of staging faults on a system in service. The purpose of this paper is to describe one method of staging faults that is both safe for utility personnel performing the tests and results in no interruption or break in service to the utility consumers connected to the distribution feeder. Also, the analysis of the resulting HIF test data is discussed. These staged fault tests occurred on January 27-29, 2004 and also on September 27-28, 2004 on a distribution feeder at the TXU Huntington Substation near Lufkin, Texas.
Structure-function relationships of lipoprotein lipase: mutation analysis and mutagenesis of the loop region (1993)

The molecular models of two microbial lipases and human pancreatic lipase (PL) have suggested the existence of common structural motifs including a buried active site shielded by an amphipathic surface loop. In an effort to explore the role of residues comprising the loop of lipoprotein lipase (LPL), we have used site-directed mutagenesis to generate three new LPL variants. In variant LPLM1 we deleted 18 amino acids leaving a loop of only 4 residues which resulted in an LPL protein inactive against triolein substrates. In contrast, two other LPL variants with only partial deletions, involving the apical section of the loop [LPLM2 (-8 amino acids) and LPLM3 (-2 amino acids)] manifested normal lipolytic activity. These findings indicate a critical requirement for the maintenance of charge and periodicity in the proximal and distal segments of the LPL loop in normal catalytic function. This is further highlighted by the detection of a mutation in the proximal section of the loop in a patient with LPL deficiency at position 225 which results in a substitution of threonine for isoleucine. The intact catalytic activity of the partial deletion variants (LPLM2 and LPLM3) further suggests that the apical residues of the loop contribute minimally to the functional motifs of the active site. We support this postulate by showing that the conserved glycine in the apical turn section (G229) can be substituted by glutamine, lysine, proline, or threonine without significantly affecting catalytic activity.
Mutagenesis of Escherichia coli: a method for determining mutagenic specificity by analysis of tRNA suppressors (1992)

A method for estimating mutagenic specificity in Escherichia coli (argE3, hisG4, thr-1, supE44), based upon the isolation of Arg+ or His+ revertants and identification of tRNA suppressors, is described. The method gives an insight not only into mutagenic pathways but also into the functioning of tRNA. With N-methyl-N'-nitro-N-nitrosoguanidine, 98% of mutations are GC----AT transitions. With N4-hydroxycytidine, 100% are AT----GC transitions. With hydroxylamine, apart from GC----AT transitions, approximately 30% of Arg+ revertants are formed by GC (or AT)----TA transversions. When the chemistry of the mutagenic attack is known, the method allows us to discriminate whether mutations occur on the transcribed or non-transcribed strands of DNA. It has been found that reversion of argE3 to Arg+ is a better monitor of mutagenic pathways than reversion of hisG4 to His+.
The Reaction of Active Zinc with Organic Bromides (1999)

The oxidative addition of highly reactive zinc to organic bromides shows a pronounced structure−reactivity dependence, in contrast to that shown by other metals. The kinetic and LFER studies suggest a mechanism in which electron transfer (ET) is the rate-determining step of the reaction. Experiments carried out with radical clocks as well as the stereochemical outcome of the reaction support the presence of radicals. The reactivity profiles suggest that the ET has an important component of inner-sphere process in the reaction with alkyl bromides. In the case of aryl halides, Hammet plots are consistent with the participation of aryl halide radical anions as intermediates. The reaction contemplated here can be ascribed as another example of radical-mediated selective reaction, and it has straightforward synthetic applications. Some synthetic work was done in this direction, to demonstrate how this structure−reactivity dependence can be used to obtain selective organozinc formation in unsymmetrical dibromides.
Neuronal pp60 c- src Contains a Six-Amino Acid Insertion Relative to Its Non-Neuronal Counterpart (1987)

Neuronal cells express a pp60c-src variant that displays an altered electrophoretic mobility and a different V8 peptide pattern relative to pp60c-src expressed in tissues of non-neuronal origin. To determine whether the neuronal form of pp60c-src is encoded by a brain-specific messenger RNA, a mouse brain complementary DNA (cDNA) library was screened with a chicken c-src probe and a 3.8-kilobase c-src cDNA clone was isolated. This clone encodes a 60-kilodalton protein that differs from chicken or human pp60c-src primarily in having six extra amino acids (Arg-Lys-Val-Asp-Val-Arg) within the NH2-terminal 16 kilodaltons of the molecule. S1 nuclease protection analysis confirmed that brain c-src RNA contains an 18-nucleotide insertion at the position of the extra six amino acids. This insertion occurs at a position that corresponds to a splice junction in the chicken and human c-src genes. The isolated c-src cDNA clone encodes a protein that displays an identical V8 peptide pattern to that observed in pp60c-src isolated from tissues of neuronal origin.
Nuclear Accumulation of p21 Cip1 at the Onset of Mitosis: a Role at the G 2 /M-Phase Transition (1998)

Cell cycle arrest in G1 in response to ionizing radiation or senescence is believed to be provoked by inactivation of G1 cyclin-cyclin-dependent kinases (Cdks) by the Cdk inhibitor p21(Cip1/Waf1/Sdi1). We provide evidence that in addition to exerting negative control of the G1/S phase transition, p21 may play a role at the onset of mitosis. In nontransformed fibroblasts, p21 transiently reaccumulates in the nucleus near the G2/M-phase boundary, concomitant with cyclin B1 nuclear translocation, and associates with a fraction of cyclin A-Cdk and cyclin B1-Cdk complexes. Premitotic nuclear accumulation of cyclin B1 is not detectable in cells with low p21 levels, such as fibroblasts expressing the viral human papillomavirus type 16 E6 oncoprotein, which functionally inactivates p53, or in tumor-derived cells. Moreover, synchronized E6-expressing fibroblasts show accelerated entry into mitosis compared to wild-type cells and exhibit higher cyclin A- and cyclin B1-associated kinase activities. Finally, primary embryonic fibroblasts derived from p21-/- mice have significantly reduced numbers of premitotic cells with nuclear cyclin B1. These data suggest that p21 promotes a transient pause late in G2 that may contribute to the implementation of late cell cycle checkpoint controls.
Comprehensive view of a live network coding P2P system (2006)

In this paper we present the first implementation of a P2P content distribution system that uses Network Coding. Using results from live trials with several hundred nodes, we provide a detailed performance analysis of such P2P system. In contrast to prior work, which mainly relies on monitoring P2P systems at particular locations, we are able to provide performance results from a variety of novel angles by monitoring all components in the P2P distribution.In particular, we show that Network Coding is practical in a P2P setting since it incurs little overhead, both in terms of CPU processing and IO activity, and it results in smooth, fast downloads, and efficient server utilization. We also study the importance of topology construction algorithms in real scenarios and study the effect of peers behind NATs and firewalls, showing that the system is surprisingly robust to large number of unreachable peers. Finally, we present performance results related to verifying network encoded blocks on-the-fly using special security primitives called Secure-Random-Checksums.
Cdma Mobile Radio Design (2000)

From the Publisher:
This new book presents the complete design background of a CDMA mobile radio, including hardware and software, digital, analog and RF, in one complete, convenient volume. You get an integral understanding of where this essential piece of communications technology fits into the CDMA big picture and what the basic parts are that make it work. Such an approach provides you with a complete understanding of how mobile radio hardware and software design affect system performance.

CDMA Mobile Radio Design includes an overview of mobile communications principles and covers the basics of direct sequence spread spectrum communications systems before delivering a comprehensive look at the digital signal processing and software functions of a typical CDMA mobile radio. By examining the vital link between hardware performance and system specifications, you get insight into the tradeoffs to be made during design, simulation, and production.

The book...

> Details the DSP algorithms and the RF circuits included in the mobile radio

> Investigates third generation (WCMDA) wireless standards and their impact 

> Examines advances that are certain to occur in future mobile radio design

In addition, this book presents the full impact that key circuit and device approaches have on typical CDMA system operation by examining the individual building blocks of the CDMA mobile radio. A detailed discussion of modulation techniques, analog-to-digital and digital-to-analog conversion, and the radio frequency portion of the mobile radio are included.
Successful Allogeneic Hematopoietic Stem Cell Transplantation in a Young Patient with Richter Syndrome Presenting with Chronic Lymphocytic Leukemia and Diffuse Large B-Cell Lymphoma with Different Cell Origins (2013)

A 32-year-old woman was referred to our hospital due to systemic lymphadenopathy. The patient's peripheral blood showed expansion of CD5+CD20+ CD38+ CD23- mature lymphocytes. However, the axillary lymph nodes were infiltrated by both CD23+ large lymphocytes and CD23- small lymphocytes. Because the pattern of the rearranged immunoglobulin heavy chain gene was different between the peripheral blood and lymph node samples in a Southern blot analysis, the patient was diagnosed with Richter syndrome, in which diffuse large B-cell lymphoma develops from a clone distinct from B-cell chronic lymphocytic leukemia. After undergoing rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) therapy, the patient was successfully treated with allogeneic hematopoietic transplantation, and no relapse was observed for three years.
Therapeutic Antibody Targeting of CD47 Synergizes with Rituximab to Completely Eradicate Human B-Cell Lymphoma Xenografts. (2009)

Abstract Abstract 2716 Poster Board II-692 The anti-CD20 antibody, rituximab, is standard therapy for many CD20 positive B-cell lymphomas, significantly improving long-term survival in combination with chemotherapy. However, rituximab alone is not curative in many non-Hodgkin lymphoma (NHL) patients with observation of primary and acquired resistance, arguing for a need for additional targeted therapies. We identified the cell surface protein CD47 as a potential therapeutic antibody target in human NHL. A major function of CD47 is to inhibit phagocytosis through binding its receptor SIRPα, on phagocytes. We hypothesize that NHL cells over-express CD47 to evade immune phagocytosis and that blockade of CD47 signaling with a monoclonal antibody can eliminate NHL cells by enabling phagocytic engulfment. We have previously shown that an anti-CD47 antibody enables phagocytosis of acute myeloid leukemia (AML) stem cells and eliminates AML in vivo. Here we investigate the therapeutic potential of an anti-CD47 antibody alone and in combination with rituximab for the treatment of NHL. We predict that the combination of anti-CD47 antibody and rituximab will result in synergistic elimination of NHL cells by both blocking an inhibitory signal and delivering a positive signal for phagocytosis. We found that CD47 protein is highly expressed on primary human B-cell NHL cells compared to normal peripheral blood B-cells. Higher CD47 gene expression independently predicted a worse clinical outcome in several cohorts of NHL patients including diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, and chronic lymphocytic leukemia. Blocking anti-CD47 antibodies preferentially enabled phagocytosis of NHL cells but not normal cell counterparts in vitro. Using isobologram analyses, the combination of anti-CD47 antibody and rituximab resulted in synergistic phagocytosis of NHL cells at higher levels compared to either anti-CD47 antibody or rituximab alone. In addition, anti-CD47 antibody and rituximab mediated their therapeutic effects through Fc-receptor-independent and Fc-receptor-dependent effector mechanisms, respectively. In vivo, anti-CD47 antibody treatment of NHL-engrafted mice reduced lymphoma burden and prolonged survival compared to IgG control. Furthermore, combination treatment with anti-CD47 antibody and rituximab led to elimination of lymphoma and cure of NHL-engrafted mice. These in vivo results were observed in both a disseminated and localized human NHL cell line mouse model as well as in primary human DLBCL mouse xenotransplants. Together, these data provide the rationale for utilizing an anti-CD47 antibody either alone or in combination with rituximab in treating human NHL. Disclosures: Weissman: U.S. Patent Application 11/528,890 entitled “Methods for Diagnosing and Evaluating Treatment of Blood Disorders.”: Patents &amp; Royalties; Stem Cells Inc.: Cofounder and director; Cellerant Inc.: cofounder; Amgen: Equity Ownership.