gebhart/patrepeval huggingface dataset:
The therapeutic effects of Rho-ROCK inhibitors on CNS disorders (2008)

Rho-kinase (ROCK) is a serine/threonine kinase and one of the major downstream effectors of the small GTPase Rho. The Rho-ROCK pathway is involved in many aspects of neuronal functions including neurite outgrowth and retraction. The Rho-ROCK pathway becomes an attractive target for the development of drugs for treating central nervous system (CNS) disorders, since it has been recently revealed that this pathway is closely related to the pathogenesis of several CNS disorders such as spinal cord injuries, stroke, and Alzheimer's disease (AD). In the adult CNS, injured axons regenerate poorly due to the presence of myelin-associated axonal growth inhibitors such as myelin-associated glycoprotein (MAG), Nogo, oligodendrocyte-myelin glycoprotein (OMgp), and the recently identified repulsive guidance molecule (RGM). The effects of these inhibitors are reversed by blockade of the Rho-ROCK pathway in vitro, and the inhibition of this pathway promotes axonal regeneration and functional recovery in the injured CNS in vivo. In addition, the therapeutic effects of the Rho-ROCK inhibitors have been demonstrated in animal models of stroke. In this review, we summarize the involvement of the Rho-ROCK pathway in CNS disorders such as spinal cord injuries, stroke, and AD and also discuss the potential of Rho-ROCK inhibitors in the treatment of human CNS disorders.
A Transcriptome Database for Astrocytes, Neurons, and Oligodendrocytes: A New Resource for Understanding Brain Development and Function (2008)

Understanding the cell-cell interactions that control CNS development and function has long been limited by the lack of methods to cleanly separate neural cell types. Here we describe methods for the prospective isolation and purification of astrocytes, neurons, and oligodendrocytes from developing and mature mouse forebrain. We used FACS (fluorescent-activated cell sorting) to isolate astrocytes from transgenic mice that express enhanced green fluorescent protein (EGFP) under the control of an S100beta promoter. Using Affymetrix GeneChip Arrays, we then created a transcriptome database of the expression levels of >20,000 genes by gene profiling these three main CNS neural cell types at various postnatal ages between postnatal day 1 (P1) and P30. This database provides a detailed global characterization and comparison of the genes expressed by acutely isolated astrocytes, neurons, and oligodendrocytes. We found that Aldh1L1 is a highly specific antigenic marker for astrocytes with a substantially broader pattern of astrocyte expression than the traditional astrocyte marker GFAP. Astrocytes were enriched in specific metabolic and lipid synthetic pathways, as well as the draper/Megf10 and Mertk/integrin alpha(v)beta5 phagocytic pathways suggesting that astrocytes are professional phagocytes. Our findings call into question the concept of a "glial" cell class as the gene profiles of astrocytes and oligodendrocytes are as dissimilar to each other as they are to neurons. This transcriptome database of acutely isolated purified astrocytes, neurons, and oligodendrocytes provides a resource to the neuroscience community by providing improved cell-type-specific markers and for better understanding of neural development, function, and disease.
Tissue-Specific Expression of Kallikrein Family Transgenes in Mice and Rats (1992)

To define the regulatory strategy for the transcriptional control of the kallikrein multigene family, we analyzed the expression of several kallikrein/SV40 T-antigen (TAg) fusion genes in transgenic mice and rats. Kallikrein family members are normally expressed at a high level in the submandibular gland and are expressed in a wide range of tissues that vary among individual family members. A total of 1.7 kb of proximal 5'-flanking DNA from the tissue kallikrein gene (rKlk1) was sufficient to confer much of the correct tissue-specific pattern on a TAg reporter gene. TAg mRNA was detectable in tissues that normally express rKlk1 and TAg-induced tumors arose in brain and pancreas. However, absolute levels of transgene mRNA were very low relative to the expression of the normal endogenous tissue kallikrein gene. In particular, expression in the salivary glands, normally very high for endogenous rKlk1, was either low or absent. An intact rKlk1 transgene with extensive flanking DNA (4.5 kb 5' and 4.7 kb 3') and complete intragenic (4 kb) sequences was expressed similarly to the fusion transgene, demonstrating that regulatory elements necessary for comprehensively correct expression are not contained within these additional gene regions. Two additional kallikrein/SV40 fusion transgenes were derived from other family members, one from the rKlk2 gene, which encodes tonin, and another from the rKlk8 gene, which encodes a prostate kallikrein. Whereas the endogenous rKlk2 and rKlk8 genes normally are expressed at high levels in rat salivary glands, they were not expressed in the salivary glands as transgenes. The results for these transgenes of three different family members indicate that control elements that direct the particular nonsalivary gland expression pattern characteristic of each family member may be present within the proximal 5'-flanking region of each gene, whereas regulatory sequences necessary for normal levels of expression in these tissues and for maximal salivary gland expression are not. We propose that the gene-associated regulatory sequences are complemented by a dominant control region that imposes salivary gland expression on the extended kallikrein family locus.
Versatility of Microbial Transglutaminase (2014)

Although microbial transglutaminases (mTGs) were initially discovered to offset the cost of producing mammalian transglutaminases for food applications, they have quickly become important tools in research and biotechnology. Today, mTGs are utilized for a large number of applications to conjugate proteins and peptides to small molecules, polymers, surfaces, and DNA, as well as to other proteins. It is important to know how to maximize the advantages of the enzymatic approach and avoid undesired cross-linking. This review focuses on the versatility of transglutaminases in the field of bioconjugation and covers recent developments in utilizing mTG for generating antibody drug conjugates (ADCs) for therapeutic applications.
Endotoxin Recognition Molecules MD-2 and Toll-like Receptor 4 as Potential Targets for Therapeutic Intervention of Endotoxin Shock (2004)

Gram-negative sepsis is the major cause of deaths in intensive care units of hospitals and continues to increase worldwide due to the increased frequency of invasive procedures and therapy leading to immunosuppression. This syndrome is characterized by endothelial damage, coagulopathy, loss of vascular tone, tissue hypoperfusion, and multiple-organ failure. They are caused by uncontrolled, overwhelming inflammatory responses, which are triggered by microbial products. Amongst these products, endotoxin also called LPS (lipopolysaccharide), a constituent of the outer membrane of Gram-negative bacteria, is known to play a central role by eliciting immune responses leading to production of proinflammatory cytokines. Our understanding of LPS recognition has increased dramatically over the last several years by identification of Toll-like receptor 4 (TLR4) and MD-2 as LPS recognition molecules. TLR4 is a mammalian homologue of drosophila Toll. The extracellular domain of TLR4 is associated with a molecule called MD-2. Mice lacking either TLR4 or MD-2 do not respond to LPS and are resistant to endotoxin shock. Here, the potential for TLR4-MD-2 as target molecules for therapeutic intervention is discussed.
3-D Interfaces to Improve the Performance of Visual Known-Item Search (2014)

Most interfaces in the field of image and video search use a two-dimensional grid interface, which presents image thumbnails in a left-to-right arrangement that can be browsed from top to bottom. This grid interface, however, has several drawbacks that become particularly apparent when performing interactive search tasks for target items in large collections of images or videos. Therefore, we propose to use 3-D interfaces as an alternative to the grid interface for interactive known-item search in visual data as they can partially overcome these drawbacks. In this paper, we first summarize our ideas and discuss design aspects of a 3-D ring and a 3-D globe interface. Next, we present results from four different user studies, where we evaluated the performance of these interfaces for known-item search tasks in image collections. Our results from these studies show that the proposed 3-D interfaces allow for significantly faster visual target search on desktop computers with mouse interaction as well as on tablet devices. The interfaces also achieve better subjective ratings. However, our evaluation also shows that on smartphones with 3.5-in screens an improvement over the grid interface in terms of visual search time is only possible in collections with more than 200 images.
Role of human factor I and C3b receptor in the cleavage of surface‐bound C3bi molecules (1983)

Control of functions mediated by the third component of complement (C3) depends on the rate of generation and degradation of biologically active C3 fragments. To evaluate the mechanisms of degradation of active C3 fragments, the role of the control protein C3b/C4b inactivator (factor I) was investigated under conditions approximating those found in vivo, i.e. in the presence of plasma. The breakdown of human erythrocyte-bound C3bi molecules in serum or plasma was mediated only by factor I, since factor I-deficient or -depleted plasma was inactive until reconstituted with highly purified factor I. The rate of cleavage of C3bi bound to human erythrocytes by purified factor I was not affected by the presence or absence of beta 1H (factor H). The released breakdown product of C3bi has been shown to be C3c antigenically and on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Two different monospecific antibodies to the human C3b receptor totally abrogated factor I-mediated cleavage of cell-bound C3bi, suggesting that the C3b receptor (but not factor H) is required as an obligate cofactor. The rate of this C3b receptor-dependent, factor I-mediated cleavage of bound C3bi is strongly regulated by the surface to which C3bi is bound. Whereas C3bi bound to particulate nonactivators of the alternative complement pathway such as human erythrocytes is rapidly degraded by this mechanism, the rate of cleavage of C3bi bound to activators is significantly slower. These data suggest a physiologic role of C3b receptors in the degradation of biologically active C3 fragments deposited on host tissues. They also suggest that C3bi molecules on restricted surfaces are relatively stable and can thereby interact with complement C3 receptors in vivo.
Shotgun Lipidomics Identifies Cardiolipin Depletion in Diabetic Myocardium Linking Altered Substrate Utilization with Mitochondrial Dysfunction (2005)

Diabetic cardiomyopathy is characterized by excessive utilization of fatty acid substrate, diminished glucose transport, and mitochondrial dysfunction. However, the chemical mechanisms linking altered substrate utilization to mitochondrial dysfunction are unknown. Herein, we use shotgun lipidomics and multidimensional mass spectrometry to identify dramatic decreases in the critical mitochondrial inner membrane lipid, cardiolipin, in diabetic murine myocardium (from 7.2 +/- 0.3 nmol/mg of protein in control hearts to 3.1 +/- 0.1 nmol/mg of protein in diabetic myocardium; p < 0.001, n = 7). Moreover, the direct metabolic precursor of cardiolipin, phosphatidylglycerol, was also substantially depleted (2.5 +/- 0.2 nmol/mg of protein in control hearts vs 1.3 +/- 0.1 nmol/mg of protein in diabetic myocardium; p < 0.001, n = 7). Similarly, glycerol 3-phosphate, necessary for the penultimate step in phosphatidylglycerol production, decreased by 58% in diabetic myocardium (from 4.9 +/- 0.9 to 2.2 +/- 0.3 nmol/mg of protein; n = 4). Since Barth's syndrome (a disorder of cardiolipin metabolism) induces mitochondrial dysfunction and cardiomyopathy, and since decreases in cardiolipin content precipitate mitochondrial dysfunction, these results provide a unifying hypothesis linking altered substrate utilization and metabolic flux in diabetic myocardium with altered lipid metabolism, cardiolipin depletion, mitochondrial dysfunction, and resultant hemodynamic compromise.
Turkmenistan - A profile of living standards in Turkmenistan (2001)

The study reviews the living standards in Turkmenistan, shaped by the Soviet legacy - whose income levels in 1989 were below the socially acceptable minimum -; by the economic decline throughout the 1990s, until recent economic resumption; and, by current approaches, and government policies. In an attempt to ensure good living standards, the country maintained one of the highest levels of subsidization of basic goods: water, gas, fuel, and social services, are mostly free. To some extent, the poor do benefit from these subsidies, but troubling issues reveal that: the costs of these non-targeted subsidies are not transparent, because they are paid by the providing agency, which in turn receives subsidized inputs. Nonetheless, real costs make it impossible to operate on a commercial basis, and, the non-payment system as it relates to maintenance and operation, has led to poor quality of services. But poverty alleviation implies much more than just subsidies, for measured in access to opportunity, it is seriously limited: few mechanisms exist for enabling the poor to benefit from most of the country's energy export earnings. Based on evidence that funding for social services represent transparent expenditures, and that subsidized commodities are disproportionately benefiting the wealthy, the potential for commercialization is undermined, unless services move to market pricing standards.
Hepcidin agonists as therapeutic tools (2018)

Hepcidin agonists are a new class of compounds that regulate blood iron levels, limit iron absorption, and could improve the treatment of hemochromatosis, β-thalassemia, polycythemia vera, and other disorders in which disrupted iron homeostasis causes or contributes to disease. Hepcidin agonists also have the potential to prevent severe complications of siderophilic infections in patients with iron overload or chronic liver disease. This review highlights the preclinical studies that support the development of hepcidin agonists for the treatment of these disorders.
AXL kinase as a novel target for cancer therapy (2014)

The AXL receptor tyrosine kinase and its major ligand, GAS6 have been demonstrated to be overexpressed and activated in many human cancers (such as lung, breast, and pancreatic cancer) and have been correlated with poor prognosis, promotion of increased invasiveness/metastasis, the EMT phenotype and drug resistance. Targeting AXL in different model systems with specific small molecule kinase inhibitors or antibodies alone or in combination with other drugs can lead to inactivation of AXL-mediated signaling pathways and can lead to regained drug sensitivity and improved therapeutic efficacy, defining AXL as a promising novel target for cancer therapeutics. This review highlights the data supporting AXL as a novel treatment candidate in a variety of cancers as well as the current status of drug development targeting the AXL/GAS6 axis and future perspectives in this emerging field.
[Separation and determination of metsulfuron, bensulfuron, acetochlor by high performance liquid chromatography]. (1997)

In this paper a high performance liquid chromatographic method for the separation and determination of metsulfuron, bensulfuron and acetochlor in the composite herbicide "Nongjiayi" is described. The concentration of methanol in the mobile phase and the temperature of the column affected the k' factor and the separation of the three active ingredients. Impurities in the "Nongjiayi" did not interfere with the determination. Chromatographic conditions were Shim-Pack CLC-C8 (150 mm x 6 mm i.d., 5 microm), mobile phase of methanol-water (60:40, V/V) and UV detector at 240 nm. Quantification was carried out with the three external standards. The average recovery was 98.81% with RSD=0.80% for metsulfuron, 99.10% with RSD=0.78% for bensulfuron and 99.72% with RSD=0.69% for acetochlor. The linear range of this method was 0.10-0.40 microg (r=0.9994) for metsulfuron, 0.40-1.60 microg (r=0.9995) for bensulfuron and 10-40 microg (r=0.9987) for acetochlor. The method is accurate, rapid and reproducible and can be applied to quality control for the "Nongjiayi".
Synthesis of 2-(2,6-Dinitrophenyl)malonates, -acetates and acetonitrile by Copper-Mediated Vicarious Nucleophilic Substitution (1994)

A regioselective, vicarious nucleophilic substitution of 1,3-dinitrobenzene with α-bromo- and iodocarbanions proceeds in the presence of copper(I) tert-butoxide and pyridine giving 2,6-dinitrophenylmalonates, 2,6-dinitrophenylacetates or 2,6-dinitrophenylacetonitrile as the only isomers from bromomalonate esters, bromoacetate esters, iodoacetate esters or iodoacetonitrile, respectively. Without copper(I) tert-butoxide, the 4-substituted isomer is the only product. We believe that the reaction proceeds via a σ-adduct of 1,3-dinitrobenzene and halocarbanion from which hydrogen and halogen are eliminated. This elimination is dependent upon the concentration of copper(I) tert-butoxide.
Schizophrenia and smoking: Evidence for a common neurobiological basis? (2000)

Several previous investigations have suggested that the gene for the α7-nicotinic receptor may play a role in the pathogenesis of schizophrenia and may be responsible for the heavy smoking among schizophrenic patients. In a study of 129 healthy controls and 127 schizophrenic, schizoaffective, and bipolar patients we have aimed 1) to confirm the potential association between schizophrenia and the α7-nicotinic receptor, 2) to test the diagnostic specificity of α7-receptor subunits with respect to psychiatric diagnoses, and 3) to investigate potential receptor differences between smokers and nonsmokers in the general population. Our analysis included the two dinucleotide polymorphisms D15S1360 and L76630 that are localized in a genomic fragment containing the α7-nicotinic receptor gene CHRNA7. Highly significant differences (P < 0.0001) between the allele distributions of patients and controls were detected for these two markers with all three diagnostic subgroups contributing to the discrimination. An independently ascertained replication sample of 24 patients confirmed this finding. Our results suggested an unspecific vulnerability that depended on the severity of overall psychopathology in terms of the co-occurrence of psychopathology with no clear-cut boundary between the diagnostic entities. In comparison with healthy controls, this vulnerability was lowest among schizophrenics, intermediate among bipolars, and highest among schizoaffectives. As to the question of α7-receptor differences between smokers and nonsmokers among the healthy control subjects, our analysis revealed no significant differences, thus indicating that the differences between patients and controls are more than just a smoker/nonsmoker distinction. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:173–177, 2000. © 2000 Wiley-Liss, Inc.
Coded 64-CAP ADSL in an impulse-noise environment-simulation results (2002)

This paper describes performance results of E1-ADSL (2.048 Mb/s asymmetrical digital subscriber line) transmission based on carrierless amplitude/phase modulation (CAP) in an impulse-noise environment. Various coding schemes for error protection are investigated. Code options are Reed Solomon code with interleaving, array code and trellis coding, or interleaved trellis coding. The simulation results are based on real measured impulses from an impulse-noise measurement campaign carried out by German Telekom. The inter-arrival times between impulses were either assumed to be constant (worst-case scenario) or were delivered from a distinctive stochastic generator with an inter-arrival time density according to a model also derived in the German campaign. It was found that the RS codes, even with a quite small error-correcting capability, achieved acceptable error performance. Array codes can also be a low-complexity alternative. Trellis coding alone, as expected, was not very effective against the impulse noise.
Mechanism of the Stimulation of RNA Synthesis in Rat Liver Nuclei by Silybin (1977)

The influence of the flavonolignane derivatives silybin, silybinhemisuccinate and silybindihemisuccinate on the RNA synthesis in isolated nuclei from rat livers was studied. A stimulatory effect of silybin on the incorporation of [3H]UTP into nuclear RNA was found and the dose dependence could be demonstrated. The results support former findings that silybin stimulates RNA synthesis in rat livers in vivo and in hepatocytes. Experiments with purified nucleoli indicated that mainly the rate of rRNA synthesis is increased. The mechanism of this stimulation was elucidated by experiments with isolated RNA polymerases. It could be demonstrated that polymerase B is not affected by the flavonolignane, but the activity of polymerase A is increased, due to higher V at constant Km values. Thus silybin is shown to be an enzyme-stimulating effector.
Pleiotropy and Redundancy of STAT Proteins in Early Pregnancy (2007)

Signal transducers and activators of transcription (STATs) are a group of proteins involved in signal transduction from numerous bioactive substances. Hormones and cytokines such as leukaemia inhibitory factor, interferon-tau and prolactin, which play key roles during early pregnancy, activate the Janus kinase (JAK)/STAT signalling pathway. The STATs are thus involved in the regulation of implantation, establishing uterine receptivity and regulation of the maternal immune response. It seems that STATs can orchestrate signals from hormones and cytokines in different cell types and may therefore generate numerous biological effects, despite the relatively small number of receptors activating the JAK/STAT pathway. This review summarizes the participation of STATs in the main processes of early pregnancy, especially regarding their pleiotropy and redundancy.