gebhart/patrepeval huggingface dataset:
α-Synuclein fate is determined by USP9X-regulated monoubiquitination (2011)

α-Synuclein is central to the pathogenesis of Parkinson disease (PD). Mutations as well as accumulation of α-synuclein promote the death of dopaminergic neurons and the formation of Lewy bodies. α-Synuclein is monoubiquitinated by SIAH, but the regulation and roles of monoubiquitination in α-synuclein biology are poorly understood. We now report that the deubiquitinase USP9X interacts in vivo with and deubiquitinates α-synuclein. USP9X levels are significantly lower in cytosolic fractions of PD substantia nigra and Diffuse Lewy Body disease (DLBD) cortices compared to controls. This was associated to lower deubiquitinase activity toward monoubiquitinated α-synuclein in DLBD cortical extracts. A fraction of USP9X seems to be aggregated in PD and DLBD, as USP9X immunoreactivity is detected in Lewy bodies. Knockdown of USP9X expression promotes accumulation of monoubiquitinated α-synuclein species and enhances the formation of toxic α-synuclein inclusions upon proteolytic inhibition. On the other hand, by manipulating USP9X expression levels in the absence of proteolytic impairment, we demonstrate that monoubiquitination controls the partition of α-synuclein between different protein degradation systems. Deubiquitinated α-synuclein is mostly degraded by autophagy, while monoubiquitinated α-synuclein is preferentially degraded by the proteasome. Moreover, monoubiquitination promotes the degradation of α-synuclein, whereas deubiquitination leads to its accumulation, suggesting that the degradation of deubiquitinated α-synuclein by the autophagy pathway is less efficient than the proteasomal one. Lower levels of cytosolic USP9X and deubiquitinase activity in α-synucleinopathies may contribute to the accumulation and aggregation of monoubiquitinated α-synuclein in Lewy bodies. Our data indicate that monoubiquitination is a key determinant of α-synuclein fate.
Oxygen Tension Changes Evoked in the Brain by Visual Stimulation (1967)

Localized changes in oxygen tension were recorded with platinum cathodes placed in the lateral geniculate nucleus in both anesthetized and awake cats. The amplitude of the responses increased with increasing stimulus intensity, but decreased with increasing flash rate. Both increases and decreases in cathode current were produced by steady illumination. The characteristics of the responses suggest that the responses reflect localized variations in blood flow, produced in turn by changes evoked in the tonic neural activity of the lateral geniculate nucleus.
Untersuchungen an Spiroorthoester‐Copolymeren (1989)

Abstract Monofunktionelle Spiroorthoester werden in Gegenwart eines Bisspiroorthoesters oder Bisepoxides mit Et 3 O + SbCl 6 ‐als Initiator thermisch copolymerisiert. Aus den Dichten der Monomermischungen und der entstandenen Polymerkörper wird die Gesamtvolumenschrumpfung der Polymerisation berechnet. Die resultierenden Copolymere werden hinsichtlich extrahierbarer Anteile, Glastemperatur und thermischem Abbau untersucht. Durch Variation der Zusammensetzung der Monomermischungen entstehen Copolymere mit unterschiedlichen mechanischen Eigenschaften, die als Bestandteil neuartiger Werkstoffe geeignet sind.
Responsabilidad del estado por el obrar irregular de sus funcionarios (2007)

1. En el estadio actual del derecho de danos en Argentina, es indudable que el Estado debe reparar todo dano que cause por su accionar, inclusive, en algunas circunstancias, por su accionar licito.1 Por tanto debe asumir tambien la reparacion de los perjuicios ocasionados por sus funcionarios, aunque cabe aclarar, de entrada, que el primer obligado al resarcimiento deberia ser el propio funcionario. La experiencia muestra que, en general, los ciudadanos no reclaman al obligado principal y generalmente se acciona solo contra el Estado, el que a su vez tampoco repite contra el funcionario. De manera tal que los danos por el irregular obrar de los funcionarios son pagados exclusivamente por el Estado, lo que supone una notoria injusticia en la practica de nuestro pais. Dice Gordillo:
An Endothelial Cell Growth Factor from the Mouse Neuroblastoma Cell Line NB41 (1989)

A growth factor that stimulates the proliferation of endothelial cells from human umbilical vein but is not mitogenic for fibroblastic cells is present in medium conditioned by the mouse neuroblastoma cell line NB41. In a partially purified preparation, factor activity coeluted from a reverse-phase high-pressure liquid chromatography (HPLC) column with a reduced protein of about 24 kd. Activity recovered following electrophoresis of HPLC fractions corresponded to protein of 43-51 kd in the absence of reducing agent and to protein of 23-29 kd after reduction. Antiserum raised against a peptide corresponding to the putative N-terminal amino acid sequence of the 24-kd protein reacted with the 24-kd protein and with a protein of about 47 kd in the nonreduced preparation. After N-glycanase treatment, the immunoreactive 24-kd protein had a mobility corresponding to 19 kd. We infer that the native NB41 factor is a glycosylated dimer whose biochemical and biological properties distinguish if from other endothelial cell growth factors.
Comparison of the Effects of Synthetic Human Parathyroid Hormone (PTH)-(l–34)-Related Peptide of Malignancy and Bovine PTH-(l–34) on Bone Formation and Resorption in Organ Culture* (1990)

We have compared the effects of synthetic amino-terminal human PTH-(1-34)-related peptide (PTHrP) of malignancy with those of synthetic bovine PTH-(1-34) in cultures of half-calvariae from 21-day-old fetal rats and of parietal bones from 7-day neonatal mice. Incorporation of [3H] proline into collagenase-digestible protein (CDP) and noncollagen protein (NCP), and percent collagen synthesis (PCS) were measured in both systems. Incorporation of [3H]thymidine and cAMP production were measured in fetal rat calvariae. Production of prostaglandin E2 and I2 and bone resorption, as assessed by release of previously incorporated 45Ca, were measured in mouse parietal bones. The effects of PTHrP and PTH were qualitatively similar. At 96 h CDP in rat calvariae was decreased by PTH at a concentration as low as 0.01 nM, while similar effects were seen with PTHrP at 0.1 nM. Effects on NCP were small, so PCS was reduced. At 24 h [3H]thymidine was not altered, but CDP and PCS were decreased by both PTH and PTHrP. cAMP production was increased in fetal rat calvariae at 30 min. Both PTH and PTHrP increased 45Ca release at low concentrations and prostaglandin production at high concentrations in mouse parietal bones. While PTH was about 10-fold more potent than PTHrP, there was no qualitative difference in the responses. These studies further suggest that PTHrP affects bone through the PTH receptor.
Relationships among Isoprene Emission Rate, Photosynthesis, and Isoprene Synthase Activity as Influenced by Temperature (1992)

Isoprene emissions from the leaves of velvet bean (Mucuna pruriens L. var utilis) plants exhibited temperature response patterns that were dependent on the plant's growth temperature. Plants grown in a warm regimen (34/28 degrees C, day/night) exhibited a temperature optimum for emissions of 45 degrees C, whereas those grown in a cooler regimen (26/20 degrees C, day/night) exhibited an optimum of 40 degrees C. Several previous studies have provided evidence of a linkage between isoprene emissions and photosynthesis, and more recent studies have demonstrated that isoprene emissions are linked to the activity of isoprene synthase in plant leaves. To further explore this linkage within the context of the temperature dependence of isoprene emissions, we determined the relative temperature dependencies of photosynthetic electron transport, CO(2) assimilation, and isoprene synthase activity. When measured over a broad range of temperatures, the temperature dependence of isoprene emission rate was not closely correlated with either the electron transport rate or the CO(2) assimilation rate. The temperature optima for electron transport rate and CO(2) assimilation rate were 5 to 10 degrees C lower than that for the isoprene emission rate. The dependence of isoprene emissions on photon flux density was also affected by measurement temperature in a pattern independent of those exhibited for electron transport rate and CO(2) assimilation rate. Thus, despite no change in the electron transport rate or CO(2) assimilation rate at 26 and 34 degrees C, the isoprene emission rate changed markedly. The quantum yield of isoprene emissions was stimulated by a temperature increase from 26 to 34 degrees C, whereas the quantum yield for CO(2) assimilation was inhibited. In greenhouse-grown aspen leaves (Populus tremuloides Michaux.), the high temperature threshold for inhibition of isoprene emissions was closely correlated with the high temperature-induced decrease in the in vitro activity of isoprene synthase. When taken together, the results indicate that although there may be a linkage between isoprene emission rate and photosynthesis, the temperature dependence of isoprene emission is not determined solely by the rates of CO(2) assimilation or electron transport. Rather, we propose that regulation is accomplished primarily through the enzyme isoprene synthase.
Parallel Synthesis and Antimalarial Screening of a 4-Aminoquinoline Library (2004)

Due to growing problems with drug resistance, there is an outstanding need for new, cost-effective drugs for the treatment of malaria. The 4-aminoquinolines have provided a number of useful antimalarials, and Plasmodium falciparum, the causative organism for the most deadly form of human malaria, is generally slow to develop resistance to these drugs. Therefore, diverse screening libraries of quinolines continue to be useful for antimalarial drug discovery. We report herein the development of an efficient method for producing libraries of 4-aminoquinolines variant in the side chain portion of the molecule. The effects of these substitutions were evaluated by screening this library for activity against P. falciparum, revealing four potent compounds active against drug-resistant strains.
Purification and NH2-terminal amino acid sequence of a T-cell-derived lymphokine with growth factor activity for B-cell hybridomas. (1986)

A T-cell-derived lymphokine was identified by its ability to support the growth of a subset of B-cell hybridomas. Hybrids that failed to survive in the absence of this molecule represented a major proportion of rat-mouse hybridomas but were very rare among mouse-mouse B-cell hybrids. Stable factor-dependent B-cell hybridomas were used to monitor the purification of the growth factor from the supernatant of a clonotypically stimulated mouse helper T-cell clone. Sequential fractionation using gel filtration, anion-exchange chromatography, and reversed-phase HPLC resolved the factor from other B-cell growth factors and yielded a single-chain protein characterized by a major charge (pI = 5-7) and molecular mass (22- to 29-kDa) heterogeneity, probably due to variations in glycosylation. The NH2-terminal amino acid sequence of this protein, which is active on B-cell hybridomas in the 0.1 pM range, showed no significant homology with that of known lymphokines. Because the purified factor also supported the growth and survival in vitro of murine plasmacytomas (to be published elsewhere), it was provisionally designated interleukin-HP1 (where H stands for hybridoma and P stands for plasmacytoma).
Active objects in hybrid (1987)

Most object-oriented languages are strong on reusability or on strong-typing, but weak on concurrency. In response to this gap, we are developing Hybrid , an object-oriented language in which objects are the active entities. Objects in Hybrid are organized into domains , and concurrent executions into activities . All object communications are based on remote procedure-calls. Unstructured sends and accepts are forbidden. To this the mechanisms of delegation and delay queues are added to enable switching and triggering of activities. Concurrent subactivities and atomic actions provided for compactness and simplicity. We show how solutions to many important concurrent problems, such a pipelining, constraint management and “administration” can be compactly expressed using these mechanisms.
Safety and Immunogenicity of CVD 1208S, a Live, OralΔguaBA Δsen Δset Shigella flexneri2a Vaccine Grown on Animal-Free Media (2007)

A previous Phase 1 trial demonstrated that Shigella flexneri 2a deleted in guaBA, sen and set (strain CVD 1208) is well-tolerated and immunogenic after a single oral dose of 10(8) or 10(9) CFU. To facilitate further clinical development, the strain was reconstructed using animal-free media to conform to regulatory guidelines, and designated CVD1208S. Healthy inpatient volunteers were randomized (double-blind) to receive a single oral dose of either CVD 1208S (10(8) [n = 7] or 10(9) [n = 7] CFU) or placebo (n = 2). Both vaccine dosage levels were generally well-tolerated. Anti-lipopolysaccharide responses, measured as IgA antibody secreting cells, serum IgG, or fecal IgA levels, occurred in 7 (100%), three (43%) and two (29%) subjects following inoculation with 10(9) CFU, respectively. Interferon gamma production in response to Shigella antigens was observed in 1 of 4 (25%) and 4 of 7 (57%) subjects, following inoculation with 10(8) and 10(9) CFU. We conclude that CVD 1208S retains a favorable safety and immunogenicity profile after reconstruction on animal-free media, comparable to that seen with CVD 1208, which was constructed on media containing animal products, and shows promise as a live, oral Shigella vaccine.
ChemInform Abstract: Indian Medicinal Plants. Part 91. Structure and Synthesis of Alamaridine, a Novel 5‐Methylbenzopyridoquinolizine Alkaloid from Alangium lamarckii. (1988)

Abstract The relative stereochemistry of the title compound (VI) is confirmed by its total synthesis starting from the amine (Ia) and 3‐acetylpyridine (II).
Nefazodone versus sertraline in outpatients with major depression: focus on efficacy, tolerability, and effects on sexual function and satisfaction. (1996)

Nefazodone and sertraline are well tolerated, and there was no statistically significant difference in their antidepressant activity. Sertraline treatment has negative effects on sexual function and performance in both sexes, while nefazodone has none. These findings may have clinical implications when choosing antidepressant therapy.
Comparative metabolism and retention of iodine-125, yttrium-90, and indium-111 radioimmunoconjugates by cancer cells. (1996)

Radiolabeled antibodies have produced encouraging remissions in patients with chemotherapy-resistant hematological malignancies; however, the selection of therapeutic radionuclides for clinical trials remains controversial. In this study, we compared the internalization, lysosomal targeting, metabolism, and cellular retention of radiolabeled murine and humanized monoclonal antibodies targeting the CD33 antigen (monoclonal antibodies mP67 and hP67, respectively) on myeloid leukemia cell lines (HEL and HL-60) and of anti-carcinoma antibodies (monoclonal antibodies hCTM01 and hA33) targeting breast cancer and colorectal carcinoma cell lines (MCF7 and Colo 205, respectively). Each antibody was labeled with 125I (by the IodoGen method) and with 111In and 90Y using macrocyclic chelation technology. Targeted tumor cells were analyzed for retention and metabolism of radioimmunoconjugates using cellular-radioimmunoassays, Percoll gradient fractionation of cell organelles, SDS-PAGE, and TLC of cell lysates and culture supernatants. Our results suggest that antibodies are routed to lysosomes after endocytosis, where they are proteolytically degraded. [125I]monoiodotyrosine is rapidly excreted from cells after lysosomal catabolism of antibodies radioiodinated by conventional methods, whereas small molecular weight 111In and 90Y catabolites remain trapped in lysosomes. As a consequence of the differential disposition of small molecular weight catabolites, 111In and 90Y conjugates displayed superior retention of radioactivity compared with 125I conjugates when tumor cells were targeted using rapidly internalizing antibody-antigen systems (e.g., hP67 with HEL cells and hCTM01 with MCF7 cells). When tumor cells were targeted using antibody-antigen systems exhibiting slow rates of endocytosis (e.g., hP67 on HL-60 cells and hA33 on Colo 205 cells), little differences in cellular retention of radioactivity was observed, regardless of whether 125I, 111In, or 90Y was used.
Silicon-germanium base heterojunction bipolar transistors by molecular beam epitaxy (1988)

The devices were fabricated using molecular-beam epitaxy (MBE), low-temperature processing, and germanium concentrations of 0, 6%, and 12%. The transistors demonstrate current gain, and show the expected increase in collector current as a result of reduced bandgap due to Ge incorporation in the base. For a 1000-AA base device containing 12% Ge, a six-times increase in collector current was measured at room temperature, while a 1000-times increase was observed to 90 K. The temperature dependence of the collector current of the Si/sub 0.88/Ge/sub 0.12/ base transistor is consistent with a bandgap shrinkage in the base of 50 meV. For the homojunction transistors, base widths as thin as 800 AA were grown, corresponding to a neutral base width of no more than 400 AA.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Gene Expression of GLUT4 in Skeletal Muscle From Insulin-Resistant Patients With Obesity, IGT, GDM, and NIDDM (1992)

In obesity, impaired glucose tolerance (IGT), non-insulin-dependent diabetes mellitus (NIDDM), and gestational diabetes mellitus (GDM), defects in glucose transport system activity, contribute to insulin resistance in target tissues. In adipocytes from obese and NIDDM patients, we found that pretranslational suppression of the insulin-responsive GLUT4 glucose transporter isoform is a major cause of cellular insulin resistance; however, whether this process is operative in skeletal muscle is not clear. To address this issue, we performed percutaneous biopsies of the vastus lateralis in lean and obese control subjects and in obese patients with IGT and NIDDM and open biopsies of the rectus abdominis at cesarian section in lean and obese gravidas and gravidas with GDM. GLUT4 was measured in total postnuclear membrane fractions from both muscles by immunoblot analyses. The maximally insulin-stimulated rate of in vivo glucose disposal, assessed with euglycemic glucose clamps, decreased 26% in obesity and 74% in NIDDM, reflecting diminished glucose uptake by muscle. However, in vastus lateralis, relative amounts of GLUT4 per milligram membrane protein were similar (NS) among lean (1.0 +/- 0.2) and obese (1.5 +/- 0.3) subjects and patients with IGT (1.4 +/- 0.2) and NIDDM (1.2 +/- 0.2). GLUT4 content was also unchanged when levels were normalized per wet weight, per total protein, and per DNA as an index of cell number. Levels of GLUT4 mRNA were similarly not affected by obesity, IGT, or NIDDM whether normalized per RNA or for the amount of an unrelated constitutive mRNA species. Because muscle fibers (types I and II) exhibit different capacities for insulin-mediated glucose uptake, we tested whether a change in fiber composition could cause insulin resistance without altering overall levels of GLUT4. However, we found that quantities of fiber-specific isoenzymes (phopholamban and types I and II Ca(2+)-ATPase) were similar in all subject groups. In rectus abdominis, GLUT4 content was similar in the lean, obese, and GDM gravidas whether normalized per milligram membrane protein (relative levels were 1.0 +/- 0.2, 1.3 +/- 0.1, and 1.0 +/- 0.2, respectively) or per wet weight, total protein, and DNA. We conclude that in human disease states characterized by insulin resistance, i.e., obesity, IGT, NIDDM, and GDM, GLUT4 gene expression is normal in vastus lateralis or rectus abdominis. To the extent that these muscles are representative of total muscle mass, insulin resistance in skeletal muscle may involve impaired GLUT4 function or translocation and not transporter depletion as observed in adipose tissue.
Selectively increasing inducible heat shock protein 70 via TAT‐protein transduction protects neurons from nitrosative stress and excitotoxicity (2005)

Induction of heat shock protein 70 (Hsp70) via sublethal stress protects neurons from subsequent lethal injuries. Here we show that specific and efficient intracellular transduction of Hsp70 can be achieved utilizing an 11 amino acid leading sequence from human immunodeficiency virus (TAT-Hsp70) in primary neuronal cultures. Western blot and immunohistochemistry demonstrated intracellular accumulation of Hsp70 in insoluble protein fractions and mitochondrial compartments. We then examined the effects of Hsp70 overexpression using TAT-Hsp70 in models of nitrosative and excitotoxic neuronal death in vitro. Neurons were pre-incubated with 300 nM TAT-Hsp 70 overnight, then exposed to either peroxynitrite (ONOO-) or glutamate. TAT-Hsp70 maintained cellular respiration, inhibited extracellular lactate dehydrogenase release, and/or reduced cell death assessed by flow cytometry vs. vehicle, wild-type Hsp70, and TAT-beta-galactosidase controls. Hsp70 transduction using a TAT fusion protein is an effective method to selectively increase Hsp70 in neurons and is sufficient to provide neuroprotection from nitrosative stress and excitotoxicity. Further study is needed to confirm whether TAT-Hsp70 is protective in in vivo models of brain injury.
Glove: Global Vectors for Word Representation (2014)

Recent methods for learning vector space representations of words have succeeded in capturing fine-grained semantic and syntactic regularities using vector arithmetic, but the origin of these regularities has remained opaque. We analyze and make explicit the model properties needed for such regularities to emerge in word vectors. The result is a new global logbilinear regression model that combines the advantages of the two major model families in the literature: global matrix factorization and local context window methods. Our model efficiently leverages statistical information by training only on the nonzero elements in a word-word cooccurrence matrix, rather than on the entire sparse matrix or on individual context windows in a large corpus. The model produces a vector space with meaningful substructure, as evidenced by its performance of 75% on a recent word analogy task. It also outperforms related models on similarity tasks and named entity recognition.
Long-range prediction of fading signals (2000)

It was previously proposed to adapt several transmission methods, including modulation, power control, channel coding, and antenna diversity to rapidly time variant fading channel conditions. Prediction of the channel coefficients several tens-to-hundreds of symbols ahead is essential to realize these methods in practice. We describe a novel adaptive long-range fading channel prediction algorithm (LRP) and its utilization with adaptive transmission methods. The LRP is validated for standard stationary fading models and tested with measured data and with data produced by our novel realistic physical channel model. Both numerical and simulation results show that long-range prediction makes adaptive transmission techniques feasible for mobile radio channels.