gebhart/patrepeval huggingface dataset:
Role of Fatty Acids in the Pathogenesis of Insulin Resistance and NIDDM (1997)

Evidence is reviewed that free fatty acids (FFAs) are one important link between obesity and insulin resistance and NIDDM. First, plasma FFA levels are elevated in most obese subjects. Second, physiological elevations in plasma FFA concentrations inhibit insulin stimulated peripheral glucose uptake in a dose-dependent manner in normal controls and in patients with NIDDM. Two possible mechanisms are identified: 1) a fat-related inhibition of glucose transport or phosphorylation, which appears after 3-4 h of fat infusion, and 2) a decrease in muscle glycogen synthase activity, which appears after 4-6 h of fat infusion. Third, FFAs stimulate insulin secretion in nondiabetic individuals. Some of this insulin is transmitted in the peripheral circulation and is able to compensate for FFA-mediated peripheral insulin resistance. FFA-mediated portal hyperinsulinemia counteracts the stimulation of FFAs on hepatic glucose production (HGP) and thus prevents hepatic glucose overproduction. We speculate that, in obese individuals who are genetically predisposed to develop NIDDM, FFAs will eventually fail to promote insulin secretion. The stimulatory effect of FFAs on HGP would then become unchecked, resulting in hyperglycemia. Hence, continuously elevated levels of plasma FFAs may play a key role in the pathogenesis of NIDDM in predisposed individuals by impairing peripheral glucose utilization and by promoting hepatic glucose overproduction.
Association of the FAM167A–BLK region with systemic sclerosis (2010)

Our findings indicate that the rs13277113A allele is associated not only with SLE but also with SSc and that the FAM167A-BLK region is a common genetic risk factor for both SLE and SSc.
Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01 (2010)

During HIV-1 infection, antibodies are generated against the region of the viral gp120 envelope glycoprotein that binds CD4, the primary receptor for HIV-1. Among these antibodies, VRC01 achieves broad neutralization of diverse viral strains. We determined the crystal structure of VRC01 in complex with a human immunodeficiency virus HIV-1 gp120 core. VRC01 partially mimics CD4 interaction with gp120. A shift from the CD4-defined orientation, however, focuses VRC01 onto the vulnerable site of initial CD4 attachment, allowing it to overcome the glycan and conformational masking that diminishes the neutralization potency of most CD4-binding-site antibodies. To achieve this recognition, VRC01 contacts gp120 mainly through immunoglobulin V-gene regions substantially altered from their genomic precursors. Partial receptor mimicry and extensive affinity maturation thus facilitate neutralization of HIV-1 by natural human antibodies.
Multianalyte Quantification of Vitamin B6 and B2 Species in the Nanomolar Range in Human Plasma by Liquid Chromatography–Tandem Mass Spectrometry (2005)

This method based on liquid chromatography-tandem mass spectrometry measures all known plasma forms of vitamins B(6) and B(2), which span a wide range of polarity. The assay is characterized by simple sample processing with no derivatization, low sample volume requirement, and a short run time.
Dual Effects of Ketamine (2013)

Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is widely used in pediatric anesthesia. Recently, a series of animal studies have shown that ketamine may have neurotoxic effects on the developing brain and that these effects can later cause neurofunctional impairment. However, other studies have also shown that ketamine protects the central nervous system by inhibiting inflammation in the developing brain. The present study offers a review of the existing preclinical and clinical studies. We concluded that the role of ketamine varies not only on the basis of the dose and frequency of exposure but also the intensity of the noxious stimuli. Moreover, the repeated ketamine usage may be neurotoxic to immature brains in the absence of noxious stimuli, whereas it may be neuroprotective in the same brains in the presence of strong painful stimuli. Balancing the neurotoxic and neuroprotective effects of ketamine on the developing brain may be possible, but further study is required. The therapeutic window during which precritical surgeries can be performed remains undefined.
Plasma Lipoproteins and Regulation of Hepatic Metabolism of Fatty Acids in Altered Thyroid States* (1985)

This article reviews our understanding of effects of thyroid hormone excess and deficiency on hepatic metabolism of FFA, and consequent effects on production, secretion, and metabolism of plasma lipoproteins. In the hyperthyroid state the following alterations are observed. Fatty acid oxidation and ketogenesis are stimulated simultaneously with a paradoxical stimulation of fatty acid synthesis, which may be linked by virtue of a blunted response of mitochondrial carnitine palmitoyltransferase I (CPT-I) to malonyl coenzyme A (CoA). Esterification of fatty acid to triglyceride (TG) is reduced, as is the secretion of the very low density lipoprotein (VLDL) (including VLDL TG, cholesterol, and apoprotein); this may be due, in part, to decreased concentrations of glycerol-3-phosphate (G3P) in the hepatic cell. In the intact animal or patient, however, serum TG concentration is variable, which may reflect increased adipose tissue lipolysis and elevated concentrations of plasma FFA, which would tend to drive VLDL secretion by the liver. Clearance of the VLDL and its metabolic product, the low density lipoprotein (LDL), is increased, resulting in decreased plasma total and LDL cholesterol. Although high density lipoprotein (HDL) cholesterol may also be reduced, the ratio of LDL/HDL cholesterol is further decreased. The regulatory role of the lipoprotein apoproteins is less clear, but hepatic apolipoprotein (apo) B secretion (required for VLDL) is diminished, while apo-AI secretion (required for HDL) is stimulated, perhaps both reflecting rates of synthesis. Plasma concentrations of apo-AI are variable, dependent on relative rates of secretion and clearance. In the hypothyroid, many of these effects are reversed, which results in hyperlipoproteinemias and greater risk for the development of atherosclerotic cardiovascular disease.
Correction of glycogen storage disease type II by an adeno-associated virus vector containing a muscle-specific promoter (2005)

Glycogen storage disease type II (Pompe disease) causes death in infancy from cardiorespiratory failure due to acid alpha-glucosidase (GAA; acid maltase) deficiency. An AAV2 vector pseudotyped as AAV6 (AAV2/6 vector) transiently expressed high-level human GAA in GAA-knockout (GAA-KO) mice without reducing glycogen storage; however, in immunodeficient GAA-KO/SCID mice the AAV2/6 vector expressed high-level GAA and reduced the glycogen content of the injected muscle for 24 weeks. A CD4+/CD8+ lymphocytic infiltrate was observed in response to the AAV2/6 vector in immunocompetent GAA-KO mice. When a muscle-specific creatine kinase promoter was substituted for the CB promoter (AAV-MCKhGAApA), that AAV2/6 vector expressed high-level GAA and reduced glycogen content in immunocompetent GAA-KO mice. Muscle-restricted expression of hGAA provoked only a humoral (not cellular) immune response. Intravenous administration of a high number of particles of AAV-MCKhGAApA as AAV2/7 reduced the glycogen content of the heart and skeletal muscle and corrected individual myofibers in immunocompetent GAA-KO mice 24 weeks postinjection. In summary, persistent correction of muscle glycogen content was achieved with an AAV vector containing a muscle-specific promoter in GAA-KO mice, and this approach should be considered for muscle-targeted gene therapy in Pompe disease.
Dithiochelates of the Bis(η-cyclopentadienyl)vanadium(IV) moiety. II. N,N-Dialkyldithiocarbamate and O,O'-dialkyldithiophosphate complexes (1974)

Two series of complexes, believed to be of the forms (R1 = R2 = Me, Et, Pri, Bu and R1 = H, R2 = Me) and (R = Me, Et, C2H4Cl, Pr, Bu, n-C8H17) have been prepared. A large anion X was used to precipitate the green compounds, which are monomeric and 1 : 1 electrolytes in solution. Infrared, electronic and e.s.r. spectra are reported together with magnetic susceptibility measurements. The phosphorus hyperfine coupling observed in the dithiophosphates is discussed in the light of current models.
A Meta-Analysis of Thromboembolic Prophylaxis Following Elective Total Hip Arthroplasty* (2000)

The best prophylactic agent in terms of both efficacy and safety was warfarin, followed by pneumatic compression, and the least effective and safe was low-dose heparin. Warfarin provided the lowest risk of both proximal deep venous thrombosis and symptomatic pulmonary embolism. However, there were no identifiable significant differences in the rates of fatal pulmonary embolism or death among the agents. Significant risks of minor and major bleeding complications were observed with greater frequency with certain prophylactic agents, particularly low-molecular-weight heparin (minor bleeding) and low-dose heparin (both major and minor bleeding).
Abnormal Reaction to Central Nervous System Injury in Mice Lacking Glial Fibrillary Acidic Protein and Vimentin (1999)

In response to injury of the central nervous system, astrocytes become reactive and express high levels of the intermediate filament (IF) proteins glial fibrillary acidic protein (GFAP), vimentin, and nestin. We have shown that astrocytes in mice deficient for both GFAP and vimentin (GFAP-/-vim-/-) cannot form IFs even when nestin is expressed and are thus devoid of IFs in their reactive state. Here, we have studied the reaction to injury in the central nervous system in GFAP-/-, vimentin-/-, or GFAP-/-vim-/- mice. Glial scar formation appeared normal after spinal cord or brain lesions in GFAP-/- or vimentin-/- mice, but was impaired in GFAP-/-vim-/- mice that developed less dense scars frequently accompanied by bleeding. These results show that GFAP and vimentin are required for proper glial scar formation in the injured central nervous system and that some degree of functional overlap exists between these IF proteins.
Surface Acoustic Wave Devices for Sensor Applications (2001)

Identification and sensor systems based on surface acoustic waves exhibit intriguing properties which have hitherto remained unexploited by semiconductor-based systems. They offer a long readout distance of up to more than 20 m with purely passive surface acoustic wave (SAW) devices. SAW devices operate with no battery or wiring, withstand extreme temperatures and work reliably and maintenance-free over many decades even in harsh industrial environments. Because they operate at frequencies in the GHz range, SAW identification and sensor systems are well protected from the electromagnetic interference that often occurs in the vicinity of industrial equipment such as motors and high-voltage lines. The fundamentals and design rules of numerous passive wireless SAW sensor and identification systems for industrial and domestic applications as well as relevant practical work will be presented.
Extended Dose Ipilimumab with a Peptide Vaccine: Immune Correlates Associated with Clinical Benefit in Patients with Resected High-Risk Stage IIIc/IV Melanoma (2010)

Adjuvant ipilimumab following resection of melanoma at high risk for relapse appeared to be associated with improved outcome compared to historical reports. Significant immune-related adverse events were generally reversible and appeared to be associated with improved relapse-free survival. Although vaccination failed to induce a consistent in vitro measurable response, a higher change in Th-17 inducible cells and higher baseline CRP levels were positively associated with freedom from relapse.
Targeting Apoptotic Tumor Cells to FcγR Provides Efficient and Versatile Vaccination Against Tumors by Dendritic Cells (2003)

Dendritic cells (DCs) loaded with tumor-associated Ags (TAAs) act as potent adjuvant that initiates antitumor immune responses in vivo. However, TAA-based DC vaccination requires prior identification of TAAs. Apoptotic tumor cells (ATCs) can be an excellent source for DC loading because their potential uncharacterized Ags would be efficiently presented to T cells without any prior characterization and isolation of these Ags. However, ATCs alone are considered to be inefficient for activating antitumor immunity, possibly because of their inability to induce DC maturation. In this study, the aim was to enhance antitumor immune response by taking advantage of ATCs that have been opsonized with IgG (ATC-immune complexes, ATC-ICs) so as to target them to FcR for IgG (FcgammaRs) on DCs. It was found that when compared with ATCs, ATC-ICs were efficiently internalized by DCs via FcgammaRs, and this process induced maturation of DCs, which was more efficient than that of ATCs. Importantly, ATC-IC loading was shown to be more efficient than ATCs alone in its capacity for inducing antitumor immunity in vivo, in terms of cytotoxic T cell induction and tumor rejection. These results show that using ATC-ICs may overcome the limitations and may enhance the immune response of current ATC-based DC vaccination therapy.
Noncanonical Self-Assembly of Highly Asymmetric Genetically Encoded Polypeptide Amphiphiles into Cylindrical Micelles (2014)

Elastin-like polypeptides (ELPs) are a class of biopolymers consisting of the pentameric repeat (VPGαG)n based on the sequence of mammalian tropoelastin that display a thermally induced soluble-to-insoluble phase transition in aqueous solution. We have discovered a remarkably simple approach to driving the spontaneous self-assembly of high molecular weight ELPs into nanostructures by genetically fusing a short 1.5 kDa (XGy)z assembly domain to one end of the ELP. Classical theories of self-assembly based on the geometric mass balance of hydrophilic and hydrophobic block copolymers suggest that these highly asymmetric polypeptides should form spherical micelles. Surprisingly, when sufficiently hydrophobic amino acids (X) are presented in a periodic sequence such as (FGG)8 or (YG)8, these highly asymmetric polypeptides self-assemble into cylindrical micelles whose length can be tuned by the sequence of the morphogenic tag. These nanostructures were characterized by light scattering, tunable resistive pulse sensing, fluorescence spectrophotometry, and thermal turbidimetry, as well as by cryogenic transmission electron microscopy (cryo-TEM) and small-angle neutron scattering (SANS). These short assembly domains provide a facile strategy to control the size, shape, and stability of stimuli responsive polypeptide nanostructures.
Models of groundwater flow in statistically homogeneous porous formations (1979)

Most natural porous formations display significant variations in space of permeability K and storativity S . Such formations are regarded as random structures characterized by the permeability frequency distribution and its autocorrelation. With the aid of three basic length scales ( l , microscale; £, integral scale of K autocorrelation; and L , length scale of space change of average K ) a classification of aquifers is suggested. A similar classification is proposed for the flow regimes. The study is limited to statistically homogeneous or slowly varying formations (£ ≪ L ) and to uniform or slowly varying (in space and time) flows. In the section dealing with steady flows, effective permeability, as well as variances of head gradient, specific discharge, and head, is computed for one‐, two‐, and three‐dimensional flows. Bounds and an estimate of the effective permeability in terms of a log normal permeability distribution are given. The computations are based on physical, simplified models of formation structure. It is shown that the head variance is grossly overestimated for one‐dimensional flow through blocks ‘in series,’ and the same is true for specific discharge for layers ‘in parallel.’ The two‐ and three‐dimensional variances are much lower and are close to each other. The unsteady flow is analyzed with the aid of the relaxation time needed for blocks of different K, S to adapt to the environment. For flows which change slowly and uniformly the effective permeability is that derived for steady uniform flows, and the effective storativity is equal to the S arithmetic mean. The head gradient variance computed with the aid of some physical models is compared with that of steady uniform flow, and it is shown that for sufficiently slow time changes the flow field can be considered momentarily uniform. The various results are employed to estimate effective properties, as well as fluctuations of the head and specific discharge, in aquifers, with possible applications to prediction, the inverse problem, and hydrodynamic dispersion.
Tumor microenvironment can restrict the effectiveness of activated antitumor lymphocytes. (1998)

Transgenic mice expressing the oncogene SV40 T antigen (Tag) in the insulin-producing beta cells of the pancreas develop islet cell carcinomas. Expression of the oncogene beginning in adult life leads to autoimmunity and lymphocytic infiltration of premalignant lesions. Nevertheless, Tag-expressing solid tumors escape the immune surveillance and are devoid of infiltrating lymphocytes. Attempting to elicit a tumor inflammatory response, we have both expressed a potent costimulator in oncogene-expressing beta cells and increased the abundance of reactive T cells. Coexpression of the costimulator B7.1 and the Tag oncoprotein leads to destruction of normal and premalignant islets and severe diabetes. Nevertheless, Tag+ tumors eventually develop, evidencing significantly reduced B7.1 expression and no infiltration. Another approach, whereby the abundance of reactive T cells was increased in double transgenic mice expressing Tag and a Tag-specific, CD4+-restricted T-cell receptor, was similarly unable to elicit tumor infiltration and destruction. Thus, neither costimulatory tumor cells nor hyperactivated antitumor lymphocytes were sufficient to produce an effective tumor immune response. In contrast, adoptive transfer of lymphocytes activated ex vivo did result in modest tumor infiltration with a limited induction of high endothelial venules on tumor vasculature, provided that T cells were transferred into irradiated recipients. However, adoptive transfer of ex vivo activated lymphocytes did not produce the dramatic inflammation seen in premalignant lesions. Thus, in addition to the parameters of activation and abundance of antitumor lymphocytes, the tumor microenvironment is evidently a critical parameter that can suppress lymphocyte extravasation and/or function inside tumors, likely in part via distinctive properties of the tumor vasculature.
Rapid cytoplasmic turnover of c-myc mRNA: requirement of the 3' untranslated sequences. (1987)

Expression of the c-myc gene can be controlled by transcriptional or posttranscriptional mechanisms (or both), depending on the cell type and the growth conditions. An important mechanism of posttranscriptional regulation is modulation of cytoplasmic c-myc mRNA stability; normal human and murine c-myc mRNAs have cytoplasmic half-lives of 30 min or less. To elucidate the c-myc sequences which impart this unusually high rate of cytoplasmic transcript turnover, we have constructed various deletion and hybrid c-myc genes and analyzed the cytoplasmic stability of the mRNAs produced from them in stably transfected murine fibroblasts. The results indicate that sequences contained within the 5' and 3' ends of the c-myc transcript can affect cytoplasmic stability. Specifically, the 3' untranslated sequences of c-myc exon 3 are required for, but do not ensure, a high rate of transcript turnover in the cytoplasm. Exon 2 coding sequences do not seem to be involved, and exon 1 sequences at the 5' end of the transcript have only a small effect on cytoplasmic transcript stability. The sequences that are primarily responsible for the short c-myc RNA half-life were localized to a region of 140 bases in the 3' untranslated region.
Transient Receptor Potential Channels in Cardiovascular Function and Disease (2006)

Sustained elevation in the intracellular Ca2+ concentration via Ca2+ influx, which is activated by a variety of mechanisms, plays a central regulatory role for cardiovascular functions. Recent molecular biological research has disclosed an unexpectedly diverse array of Ca(2+-entry channel molecules involved in this Ca2+ influx. These include more than ten transient receptor potential (TRP) superfamily members such as TRPC1, TRPC3-6, TRPV1, TRPV2, TRPV4, TRPM4, TRPM7, and polycystin (TRPP2). Most of them appear to be multimodally activated or modulated and show relevant features to both acute hemodynamic control and long-term remodeling of the cardiovascular system, and many of them have been found to respond not only to receptor stimulation but also to various forms of stimuli. There is good evidence to implicate TRPC1 in neointimal hyperplasia after vascular injury via store-depletion-operated Ca2+ entry. TRPC6 likely contributes to receptor-operated and mechanosensitive Ca2+ mobilizations, being involved in vasoconstrictor and myogenic responses and pulmonary arterial proliferation and its associated disease (idiopathic pulmonary arterial hypertension). Considerable evidence has also been accumulated for unique involvement of TRPV1 in blood flow/pressure regulation via sensory vasoactive neuropeptide release. New lines of evidence suggest that TRPV2 may act as a Ca2+-overloading pathway associated with dystrophic cardiomyopathy, TRPV4 as a mediator of endothelium-dependent hyperpolarization, TRPM7 as a proproliferative vascular Mg2+ entry channel, and TRPP2 as a Ca2+-entry channel requisite for vascular integrity. This review attempts to provide an overview of the current knowledge on TRP proteins and discuss their possible roles in cardiovascular functions and diseases.
The NASA Optical Communication and Sensor Demonstration Program (2013)

The Aerospace Corporation was selected by the NASA Small Spacecraft Technology Program in 2012 to conduct a subsystem flight validation mission to test commercial-of-the-shelf (COTS) components and subsystems that will enable new communications and proximity operations capabilities for CubeSats and other spacecraft. We proposed optical communications using milliradian beam spreads that are compatible with near-term CubeSat pointing capabilities. Our baseline mission will use a ~10-W modulated fiber laser with a 1.4o angular beam-width on a 1.5-U CubeSat (AeroCube-OCSD) and a 30-cm diameter telescope located on Mt. Wilson in southern California to receive optical pulses. We plan on demonstrating the baseline 5-Mbps optical link with a stretch goal of 50-Mbps. We also proposed integrating an automotive anti-collision radar system and an enhanced optical mouse sensor into these CubeSats to enable future proximity operations. In late 2014 or early 2015, two 1.5-U AeroCube-OCSD CubeSats will be ejected from the same P-POD and brought within 200-meters of each other using on-board GPS for position and velocity determination, variable drag for cooperative orbit rephasing, and cold gas thrusters for proximity maneuvering. Each satellite has deployed wings that allow varying the ballistic coefficient by at least a factor of 4 by changing spacecraft orientation with respect to the flight direction. We plan on characterizing the on-orbit performance of the radar and optical flow sensors as a function of distance between AeroCubes and their orientation.