gebhart/patrepeval huggingface dataset:
The Closed Headpiece of Integrin alphaIIB beta3 and its Complex with an alpahIIB beta3 -Specific Antagonist That Does Not Induce Opening (2010)

The platelet integrin {alpha}{sub IIb}{beta}{sub 3} is essential for hemostasis and thrombosis through its binding of adhesive plasma proteins. We have determined crystal structures of the {alpha}{sub IIb}{beta}{sub 3} headpiece in the absence of ligand and after soaking in RUC-1, a novel small molecule antagonist. In the absence of ligand, the {alpha}{sub IIb}{beta}{sub 3} headpiece is in a closed conformation, distinct from the open conformation visualized in presence of Arg-Gly-Asp (RGD) antagonists. In contrast to RGD antagonists, RUC-1 binds only to the {alpha}{sub IIb} subunit. Molecular dynamics revealed nearly identical binding. Two species-specific residues, {alpha}{sub IIb} Y190 and {alpha}{sub aIIb} D232, in the RUC-1 binding site were confirmed as important by mutagenesis. In sharp contrast to RGD-based antagonists, RUC-1 did not induce {alpha}{sub IIb}{beta}{sub 3} to adopt an open conformation, as determined by gel filtration and dynamic light scattering. These studies provide insights into the factors that regulate integrin headpiece opening, and demonstrate the molecular basis for a novel mechanism of integrin antagonism.
Inhibition of HIV-1 by lentiviral vector-transduced siRNAs in T lymphocytes differentiated in SCID-hu mice and CD34+ progenitor cell-derived macrophages (2003)

The phenomenon of RNA interference mediated by small interfering RNAs (siRNAs) is a potent gene-silencing mechanism. A number of recent studies demonstrated inhibition of HIV-1 replication in cultured cells using this approach. To make further progress and harness this technology for HIV-1 gene therapy in a stem cell setting, in vivo studies using primary hematopoietic cells are needed. Using an HIV-based lentiviral vector we introduced an anti-Rev siRNA construct into CD34(+) hematopoietic progenitor cells. The siRNA-transduced progenitor cells were allowed to mature into macrophages in vitro and T cells in vivo in SCID-hu mouse thy/liv grafts. Phenotypically normal T cells and macrophages displaying characteristic surface markers were obtained. In vitro HIV-1 challenge of the siRNA-expressing macrophages and T cells with macrophage-tropic and T-cell-tropic HIV-1, respectively, showed marked viral resistance. These experiments demonstrate the utility of siRNAs delivered into hematopoietic stem cells via lentiviral vectors for future in vivo applications.
Prognostic Significance of a Novel Hypoxia-Regulated Marker, Carbonic Anhydrase IX, in Invasive Breast Carcinoma (2001)

CA IX expression was associated with worse relapse-free survival and overall survival in an unselected cohort of patients with invasive breast carcinoma. The potential role of CA IX as a marker of hypoxia within breast carcinomas was also indicated by a significant association with necrosis. Further work assessing its prognostic significance in breast cancer is warranted, particularly interactions with radiotherapy and chemotherapy resistance.
Reduced NPY Induced Feeding in Diabetic but not Steroid‐Treated Rats: Lack of Evidence for Changes in Receptor Number or Affinity (1996)

Concentrations of the potent hypothalamic appetite stimulating peptide neuropeptide Y (NPY), and its mRNA, are increased in rats with experimental diabetes, suggesting a role in the hyperphagia of this disorder. The 2-h feeding responses to intracerebroventricular (i.c.v.) injection of neuropeptide Y (NPY) (5, 10, and 15 mu g doses) were measured in male Wistar rats treated with streptozotocin (55 mg/kg) to induce diabetes. Streptozotocin-diabetic rats given i.c.v. NPY exhibited reduced feeding responses compared to controls (P < 0.05). Dexamethasone treated rats exhibit similar changes in NPY content and mRNA in the hypothalamus to those seen in diabetes, but are not hyperphagic. Feeding responses were also measured in this model, to assess whether high levels of endogenous NPY might account for the reduced response in diabetes. In contrast, the feeding response to NPY in comparison to controls was unaltered in dexamethasone treated rats. To investigate whether altered NPY receptor number or affinity, was the underlying mechanism for these divergent responses, receptor binding experiments were performed using (125)I-PYY and membranes prepared from rat hypothalamus. No significant difference was found in receptor number or affinity between the 2 groups (B(max): 114.7 +/- 18.9 vs 127.4 +/- 27.1 fmol/mg protein, K(d): 99.6 +/- 28.2 vs 135.1 +/- 32.4 pM). Similarly no difference was found between hypothalamic membranes prepared from dexamethasone-treated and control animals. NPY receptor subtypes in the hypothalamus were compared with that of cortex (predominantly Y1) and hippocampus (predominantly Y2) using the Y1-specific ligand [Leu(31)Pro(34)] NPY. These studies showed that the binding profile in the hypothalamus most closely matched that in the hippocampus, suggesting that the majority of hypothalamic receptors were of the Y2 subtype. Receptor autoradiography revealed low binding in the hypothalamus, and particularly in the paraventricular nucleus of the hypothalamus. Competition with [Leu(31)Pro(34)] NPY confirmed that only a low density of binding to Y1 like receptors was present in the hypothalamus. No difference was observed between control and streptozotocin treated animals. The feeding response to exogenous NPY is reduced in experimental diabetes, but not in dexamethasone treated rats. These differing responses do not appear to be due to altered NPY receptor number or affinity in the hypothalamus.
Role of the Amygdala in Antidepressant Effects on Hippocampal Cell Proliferation and Survival and on Depression-like Behavior in the Rat (2010)

The stimulation of adult hippocampal neurogenesis by antidepressants has been associated with multiple molecular pathways, but the potential influence exerted by other brain areas has received much less attention. The basolateral complex of the amygdala (BLA), a region involved in anxiety and a site of action of antidepressants, has been implicated in both basal and stress-induced changes in neural plasticity in the dentate gyrus. We investigated here whether the BLA modulates the effects of the SSRI antidepressant fluoxetine on hippocampal cell proliferation and survival in relation to a behavioral index of depression-like behavior (forced swim test). We used a lesion approach targeting the BLA along with a chronic treatment with fluoxetine, and monitored basal anxiety levels given the important role of this behavioral trait in the progress of depression. Chronic fluoxetine treatment had a positive effect on hippocampal cell survival only when the BLA was lesioned. Anxiety was related to hippocampal cell survival in opposite ways in sham- and BLA-lesioned animals (i.e., negatively in sham- and positively in BLA-lesioned animals). Both BLA lesions and low anxiety were critical factors to enable a negative relationship between cell proliferation and depression-like behavior. Therefore, our study highlights a role for the amygdala on fluoxetine-stimulated cell survival and on the establishment of a link between cell proliferation and depression-like behavior. It also reveals an important modulatory role for anxiety on cell proliferation involving both BLA-dependent and -independent mechanisms. Our findings underscore the amygdala as a potential target to modulate antidepressants' action in hippocampal neurogenesis and in their link to depression-like behaviors.
Low-dose danazol for mastalgia. (1989)

A low-dose danazol maintenance therapy (mean total dose 800 mg per month) was given during the luteal phase to 34 women with severe relapsing cyclical mastalgia. On conventional danazol dosage, all subjects had previously obtained a useful clinical response, but side effects occurred in 29 (85 per cent). Using this low-dose regimen, complete relief of symptoms was achieved in 15 women (44 per cent); the remainder obtained a substantial clinical improvement. Side effects were reduced to 12 per cent of women and were considered mild and tolerated by all patients. A low-dose regimen may be suitable for women with severe persistent cyclical mastalgia and minimises side effects that develop on conventional dosage.
The Human Uncoupling Protein-3 Gene (1997)

Uncoupling protein-3 (UCP3) is a recently identified candidate mediator of adaptive thermogenesis in humans. Unlike UCP1 and UCP2, UCP3 is expressed preferentially and at high levels in human skeletal muscle and exists as short and long form transcripts, UCP3S and UCP3L. UCP3S is predicted to encode a protein which lacks the last 37 C-terminal residues of UCP3L. In the present study, we have defined the intron-exon structure for the human UCP3 gene and determined that UCP3S is generated when a cleavage and polyadenylation signal (AATAAA) located in the last intron prematurely terminates message elongation. In addition we have mapped UCP3 to the distal segment of human chromosome 11q13 (between framework markers D11S916 and D11S911), adjacent to UCP2. Of note, UCP2 and UCP3 in both mice and humans colocalize in P1 and BAC genomic clones indicating that these two UCPs are located within 75-150 kilobases of each other and most likely resulted from a gene duplication event. Previous studies have noted that mouse UCP2 maps to a region of chromosome 7 which is coincident with three independently mapped quantitative trait loci for obesity. Our study shows that UCP3 is also coincident with these quantitative trait loci raising the possibility that abnormalities in UCP3 are responsible for obesity in these models.
Technical writing and word processing using T_EX (1991)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text A. E. Siegman, "Technical writing and word processing using TEX," Optics & Photonics News 2(4), 12-16 (1991) Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Electrodeposition of Titanium-Aluminum Alloys in the Lewis Acidic Aluminum Chloride-1-Ethyl-3-Methylimidazolium Chloride Molten Salt (2002)

The chemical and electrochemical behavior of titanium was examined in the Lewis acidic aluminum chloride-1-ethyl-3-methylimidazolium chloride (AlCl3-EtMeImCl) molten salt at 353.2 K. Dissolved Ti(II), as TiCl2, is stable in the 66.7–33.3 m/o composition of this melt, but shows a slight tendency to disproportionate in the 60.0–40.0 m/o melt. At low current densities, the anodic oxidation of Ti(0) does not lead to dissolved Ti(II), but to an insoluble passivating film of TiCl3. At high current densities or very positive potentials, Ti(0) is oxidized to Ti(IV); however, the electrogenerated Ti(IV) vaporizes from the melt as TiCl4(g). The electrodeposition of Ti-Al alloys was investigated at Cu rotating wire electrodes. Ti-Al alloys containing up to ~ 19 a/o titanium could be electrodeposited from saturated solutions of Ti(II) in the 66.7–33.3 m/o melt at low current densities, but the titanium content of these alloys decreased as the reduction current density was increased. The pitting potentials of these electrodeposited Ti-Al alloys exhibited a positive shift with increasing titanium content comparable to that observed for alloys prepared by sputter deposition.
Delta-like 4/Notch Signaling and Its Therapeutic Implications (2007)

Intense research efforts have been focused toward the identification of regulators of angiogenesis and the development of antiangiogenesis-based cancer therapies. The approval of anti-vascular endothelial growth factor (VEGF) monoclonal antibody (bevacizumab) for use in colorectal and lung cancer provides clinical validation for targeting angiogenesis for the treatment of cancer. Delta-like 4 (Dll4)-mediated Notch signaling represents another key pathway essential for vascular development. Recent studies yield substantial insights into the role of Dll4 in angiogenesis. Dll4 is downstream of VEGF signaling and its activation triggers a negative feedback that restrains the effects of VEGF. Attenuation of Dll4/Notch signaling results in chaotic vascular network with excessive branching and sprouting. In preclinical studies, blocking of Dll4/Notch signaling is associated with a paradoxical increase in tumor vessel density, yet causes marked growth inhibition due to functionally defective vasculature. Dll4 blockade holds promise as an additional strategy for angiogenesis-based cancer therapy, especially when resistance to and/or escape from existing therapies evolve.
Polarization of recombination radiation from nonequilibrium plasmas (1982)

Formulas have been obtained for the degree of linear polarization of recombination radiation from a homogeneous plasma having an anisotropic electron velocity distribution $f(\stackrel{\ensuremath{\rightarrow}}{\mathrm{v}})$ characterized by an axis of symmetry. Polarization measurements are described which utilize these formulas to determine aspects of the anisotropy such as the symmetry axis direction and the lowest-order even angular moments of $f(\stackrel{\ensuremath{\rightarrow}}{\mathrm{v}})$. As a special case, if the plasma conforms to a distribution such as a "bi-Maxwellian with drift," we determine the quantities $\frac{{u}_{D}}{{T}_{\ensuremath{\parallel}}}$ and ($\frac{1}{{T}_{\ensuremath{\parallel}}}\ensuremath{-}\frac{1}{{T}_{\ensuremath{\perp}}}$) which involve the electron drift speed, and the "perpendicular" and "parallel" electron temperatures.
The angiogenic regulator CD13/APN is a transcriptional target of Ras signaling pathways in endothelial morphogenesis (2003)

Angiogenesis, the formation of new blood vessels, is a critical step for tumor growth and metastasis and an integral component of the pathologic inflammatory response in arthritis and the proliferative retinopathies. The CD13/aminopeptidase N (CD13/APN) metalloprotease is an important regulator of angiogenesis where its expression on activated blood vessels is induced by angiogenic signals. Here, we show that cytokine induction of CD13/APN in endothelial cells is regulated by distinct Ras effector pathways involving Ras/mitogen-activated protein kinase (MAPK) or PI-3K. Signals transduced by activated Ras, Raf, and mitogen-induced extracellular kinase (MEK) stimulate transcription from the CD13/APN proximal promoter. Inhibition of these pathways and extracellular signal-regulated serine/threonine kinase (ERK-2) and PI-3K by expression of dominant-negative proteins or chemical inhibitors prevented induction of CD13/APN transcription in response to basic fibroblast growth factor (bFGF). We show that Ras-induced signal transduction is required for growth factor-induced angiogenesis, because inhibition of downstream mediators of Ras signaling (MEK or PI-3K) abrogated endothelial cell migration, invasion, and morphogenesis in vitro. Reintroduction of CD13/APN, a shared downstream target of these pathways, overrode the suppressive effect of these inhibitors and restored the function of endothelial cells in migration/invasion and capillary morphogenesis assays. Similarly, inhibition of MEK abrogated cell invasion and the formation of endothelial-lined capillaries in vivo, which was effectively rescued by addition of exogenous CD13/APN protein. These studies provide strong evidence that CD13/APN is an important target of Ras signaling in angiogenesis and is a limiting factor in angiogenic progression.
SAR imaging technique for reduction of sidelobes and noise (2009)

Multiplicative noise poses a big challenge for SAR imaging system, in which energy from the sidelobes of large RCS man-made and natural clutter objects spread throughout the resulting SAR imagery. Detection of small RCS targets is very difficult since their signatures might be obscured or even embedded in this multiplicative noise floor that is proportional to the RCS of surrounding clutter objects. ARL has developed a Recursive Sidelobe Minimization (RSM) technique that is combined with the standard backprojection image formation algorithm to suppress the multiplicative noise floor in the resulting SAR imagery. In this paper, we present the Recursive Sidelobe Minimization (RSM) technique. Although the technique is originally developed and tested using data from the Army Research Lab (ARL) UWB Synchronous Impulse Reconstruction (SIRE) forward-looking radar, it is also applicable for other SAR data sets with different configurations.
Schizophrenia is a TH2 Dominant Autoimmune Disease Possibly Against Acetylcholine Receptors of CNS (2012)

Schizophrenia is a very common psychiatric disorder. However, its etiology and pathogenesis is still unknown. Current theory saying that neurotransmitter imbalance such as serotonin or dopamine only provides limited effectiveness in schizophrenia treatment by drugs changing serotonin and dopamine concentration. Despite of such treatment, majority of schizophrenia patients still have very poor prognosis. Thus, the neurotransmitter imbalance theory is not correct. Here, I propose that schizophrenia is actually a TH2 dominant autoimmune disorder. The candidate of autoantigen could be acetylcholine receptors of CNS. My theory can explain the positive as well as negative symptoms of schizophrenia. By microarray analysis of PBMCS, one-tenth of the total 519 significantly expressed genes are immune-related genes. Among them, TH2 related genes are significantly up-regulated including IL-4, histidine decarboxylase, aldehyde dehydrogenase, CCR9, IgE Fc receptor, GATA2, serotonin receptor, phospholipase A2, and prostaglandin D2 synthase. Besides, TH1 and TH17 related genes are down-regulated including CXCL5, cathepsin C, and neutrophil related S100 binding proteins. The new theory sheds a light to better control this detrimental illness. Anti-inflammatory agents could be used to manage schizophrenia in the near future.
Classification of Kinase Inhibitors Using BCUT Descriptors (2000)

BCUTs are an interesting class of molecular descriptor which have been proposed for a number of design and QSAR type tasks. It is important to understand what kind of information any particular descriptor encodes and to be able to relate this to the biological properties of the molecules. In this paper we present studies with BCUTs for the classification of ATP site directed kinase inhibitors active against five different protein kinases: three from the serine/threonine family and two from the tyrosine kinase family. In combination with a chemometric method, PLS discriminant analysis, the BCUTs are able to correctly classify the ligands according to their target. A novel class of kinase inhibitors is correctly predicted as inhibitors of the EGFR tyrosine kinase. Comparison with other descriptor types such as two-dimensional fingerprints and three-dimensional pharmacophore-based descriptors allows us to gain an insight into the level of information contained within the BCUTs.
High-Performance Liquid Chromatography Analyses of Pyoverdin Siderophores Differentiate among Phytopathogenic Fluorescent Pseudomonas Species (2003)

The relationship of pyoverdins produced by 41 pathovars of Pseudomonas syringae and by phytopathogenic Pseudomonas species was investigated. A high-performance liquid chromatography method for analyzing the culture medium proved to be superior to isoelectric focusing for detecting pyoverdin production, for differentiating slightly different pyoverdins, and for differentiating atypical from typical Fe(III)-chelated pyoverdins. Nonfluorescent strains were found in Pseudomonas amygdali, Pseudomonas meliae, Pseudomonas fuscovaginae, and P. syringae. Pseudomonas agarici and Pseudomonas marginalis produced typical pyoverdins. Among the arginine dihydrolase-negative fluorescent Pseudomonas species, spectral, amino acid, and mass spectrometry analyses underscored for the first time the clear similarities among the pyoverdins produced by related species. Within this group, the oxidase-negative species Pseudomonas viridiflava and Pseudomonas ficuserectae and the pathovars of P. syringae produced the same atypical pyoverdin, whereas the oxidase-positive species Pseudomonas cichorii produced a similar atypical pyoverdin that contained a glycine instead of a serine. The more distantly related species Pseudomonas asplenii and Pseudomonas fuscovaginae both produced a less similar atypical pyoverdin. The spectral characteristics of Fe(III)-chelated atypical pyoverdins at pH 7.0 were related to the presence of two beta-hydroxyaspartic acids as iron ligands, whereas in typical pyoverdins one of the ligands is always ornithine based. The peptide chain influenced the chelation of iron more in atypical pyoverdins. Our results demonstrated that there is relative pyoverdin conservation in the amino acids involved in iron chelation and that there is faster evolution of the other amino acids, highlighting the usefulness of pyoverdins in systematics and in identification.
The use of controlled subatmospheric pressure to promote wound healing in preparation for split-thickness skin grafting in a fourth degree burn. (1999)

Subatmospheric pressure application to acute and chronic wounds has been shown to increase local wound blood flow, increase the rate of formation of granulation tissue, and enhance bacterial clearance. The mechanical forces applied to the wound enhance the rate of granulation tissue formation by the increase intracellular messengers regulating protein production and turnover. This method of wound care is particularly useful for larger wounds that could not be readily closed by local methods, but may also be useful for chronic wounds in debilitated patients who may not be ideal surgical candidates. Further basic scientific research is needed to discern the exact mechanisms of action of subatmospheric pressure, and more clinical experience is needed to establish guidelines for its application. Further clinical studies with larger subject populations in a randomized prospective study would lend support to the utility of this wound management protocol.
A family of fatty acid transporters conserved from mycobacterium to man (1998)

Long chain fatty acids (LCFAs) are an important source of energy for most organisms. They also function as blood hormones, regulating key metabolic functions such as hepatic glucose production. Although LCFAs can diffuse through the hydrophobic core of the plasma membrane into cells, this nonspecific transport cannot account for the high affinity and specific transport of LCFAs exhibited by cells such as cardiac muscle, hepatocytes, and adipocytes. Transport of LCFAs across the plasma membrane is facilitated by fatty acid transport protein (FATP), a plasma membrane protein that increases LCFA uptake when expressed in cultured mammalian cells [Schaffer, J. E. & Lodish, H. F. (1994) Cell 79, 427-436]. Here, we report the identification of four novel murine FATPs, one of which is expressed exclusively in liver and another only in liver and kidney. Both genes increase fatty acid uptake when expressed in mammalian cells. All five murine FATPs have homologues in humans in addition to a sixth FATP gene. FATPs are found in such diverse organisms as Fugu rubripes, Caenorhabditis elegans, Drosophila melanogaster, Saccharomyces cerevisiae, and Mycobacterium tuberculosis. The function of the FATP gene family is conserved throughout evolution as the C. elegans and mycobacterial FATPs facilitate LCFA uptake when overexpressed in COS cells or Escherichia coli, respectively. The identification of this evolutionary conserved fatty acid transporter family will allow us to gain a better understanding of the mechanisms whereby LCFAs traverse the lipid bilayer as well as yield insight into the control of energy homeostasis and its dysregulation in diseases such as diabetes and obesity.