gebhart/patrepeval huggingface dataset:
Abnormal neurotransmission in mice lacking synaptic vesicle protein 2A (SV2A) (1999)

Synaptic vesicle protein 2 (SV2) is a membrane glycoprotein common to all synaptic and endocrine vesicles. Unlike many proteins involved in synaptic exocytosis, SV2 has no homolog in yeast, indicating that it performs a function unique to secretion in higher eukaryotes. Although the structure and protein interactions of SV2 suggest multiple possible functions, its role in synaptic events remains unknown. To explore the function of SV2 in an in vivo context, we generated mice that do not express the primary SV2 isoform, SV2A, by using targeted gene disruption. Animals homozygous for the SV2A gene disruption appear normal at birth. However, they fail to grow, experience severe seizures, and die within 3 weeks, suggesting multiple neural and endocrine deficits. Electrophysiological studies of spontaneous inhibitory neurotransmission in the CA3 region of the hippocampus revealed that loss of SV2A leads to a reduction in action potential-dependent gamma-aminobutyric acid (GABA)ergic neurotransmission. In contrast, action potential-independent neurotransmission was normal. Analyses of synapse ultrastructure suggest that altered neurotransmission is not caused by changes in synapse density or morphology. These findings demonstrate that SV2A is an essential protein and implicate it in the control of exocytosis.
Different preparation methods to obtain platelet components as a source of growth factors for local application (2001)

Various methods enable the preparation of platelet components and of highly concentrated components for local use according to standard blood banking criteria. The obtained components differ, particularly in their WBC content and in vitro platelet activation. These findings are relevant for planning and evaluating further studies of locally usable autologous platelet components.
Tumour‐infiltrating T‐cell subsets, molecular changes in colorectal cancer, and prognosis: cohort study and literature review (2010)

The abundance of tumour-infiltrating T-cells has been associated with microsatellite instability (MSI) and a favourable prognosis in colorectal cancer. However, numerous molecular alterations have been associated with clinical outcome, and potentially confounding the biological and prognostic significance of tumour-infiltrating T-cells. We utilized a database of clinically and molecularly-annotated colon and rectal carcinoma cases (N = 768; stage I-IV) in two prospective cohort studies (the Nurses' Health Study and the Health Professionals Follow-up Study) and quantified the densities of CD3(+), CD8(+), CD45RO(+) (PTPRC), and FOXP3(+) cells within neoplastic epithelial areas using an Ariol image analysis system and tissue microarray. We used Cox proportional hazard models to compute the mortality hazard ratio, adjusting for clinical and molecular features including KRAS, BRAF, and PIK3CA mutations, MSI, CIMP, and LINE-1 hypomethylation. The densities of CD8(+), CD45RO(+), and FOXP3(+) cells were significantly associated with patient survival in univariate analyses (P(trend) < 0.007). In the multivariate model, tumour-infiltrating CD45RO(+)-cell density, but not CD3(+), CD8(+) or FOXP3(+)-cell density, was significantly associated with survival (p = 0.0032). In multivariate linear regression analysis, MSI-high (p < 0.0001) and high-level tumour LINE-1 methylation (p = 0.0013) were independently associated with higher CD45RO(+)-cell density. The survival benefit associated with CD45RO(+) cells was independent of MSI and LINE-1 status. In conclusion, tumour-infiltrating CD45RO(+)-cell density is a prognostic biomarker associated with longer survival of colorectal cancer patients, independent of clinical, pathological, and molecular features. In addition, MSI-high and tumour LINE-1 methylation level are independent predictors of CD45RO(+)-cell density. Our data offer a possible mechanism by which MSI confers an improved clinical outcome and support efforts to augment the host immune response in the tumour microenvironment as a strategy of targeted immunotherapy.
Color Atlas of Pharmacology (2017)

This pocket atlas covers general aspects of pharmacology, such as formulation, absorption, distribution, and molecular mechanisms of action. It also looks at specific groups of agents, emphasizing fucntional and therapeutic aspects.
Stepwise Solvation of the Intramolecular-Charge-Transfer Molecule p-(Dimethylamino)benzonitrile (1987)

This paper presents a systematic study of gas-phase p-(N,N-dimethy1amino)benzonitrile (DMABN) both in a supersonic&#13;\njet expansion and in a thermalized vapor. From the jet studies, the excited- and ground-state vibrational spectra of the isolated molecule are resolved, and the spectroscopy of the stoichiometric complex with water, methanol, ammonia, and acetonitrile in the beam is reported. It is concluded that 1:l complexes are not sufficient for the local perturbation to cause charge separation. At higher temperatures in the jet, we observe emission that we attribute to DMABN self-complexes. Under high pressure&#13;\nand temperature vapor conditions (&gt;30 mTorr, 60 °C), red-shifted fluorescence from DMABN is observed. This is attributed to the charge-transfer state of DMABN in self-complexes.
Scanning Joule expansion microscopy at nanometer scales (1998)

We report a new technique called scanning Joule expansion microscopy that can simultaneously image surface topography and material expansion due to Joule heating with vertical resolution in the 1 pm range and lateral resolution similar to that of an atomic force microscope. By coating the sample with a polymer film, we demonstrate that sample temperature distribution can be directly measured without the need of fabricating temperature-sensing scanning probes.
Proteins Phosphorylated during Stress-induced Apoptosis Are Common Targets for Autoantibody Production in Patients with Systemic Lupus Erythematosus (1997)

Proteins cleaved by interleukin-1 beta converting enzyme family proteases during apoptosis are common targets for autoantibody production in patients with systemic lupus erythematosus (SLE). We have tested the possibility that proteins phosphorylated in cells undergoing apoptosis are also targets for autoantibody production in patients with autoimmune disease. Sera from 9/12 patients containing antinuclear antibodies (10/12 meeting diagnostic criteria for SLE or a lupus overlap syndrome), precipitated new phosphoproteins from lysates derived from Jurkat T cells treated with apoptotic stimuli (i.e., Fas-ligation, gamma irradiation, ultraviolet irradiation), but not with an activation (i.e., CD3-ligation) stimulus. Sera derived from individual patients precipitated different combinations of seven distinct serine-phosphorylated proteins. None of these phosphoproteins were included in precipitates prepared using sera from patients with diseases that are not associated with autoantibody production or using serum from rheumatoid arthritis patients. Protein phosphorylation precedes, or is coincident with, the induction of DNA fragmentation, and is not observed when apoptosis is inhibited by overexpression of bcl-2. Serum from four patients precipitated a serine/threonine kinase from apoptotic cell lysates that phosphorylates proteins of 23-, 34-, and 46-kD in in vitro kinase assays. Our results suggest that proteins phosphorylated during apoptosis may be preferred targets for autoantibody production in patients with SLE.
Transfection of a rat cell line with the v-Ki-ras oncogene is associated with enhanced susceptibility to natural killer cell lysis. (1985)

Transfection of the v-Ki-ras oncogene into rat-1 fibroblasts resulted in the establishment of cell lines that were transformed, tumorigenic, and sensitive to lysis by natural killer (NK) cells. Characterization of effectors indicated that the killing was not related to Lyt-1+ or Lyt-2+ cells (T cells) but was associated with cells bearing NK markers (asialo GM1, NK-1.2+, and NK-2.1+). Transfected targets were also killed by cloned NK lines. The transformation determinants on rat-1 transfectants cross-competed with YAC 1.2 lymphoma cells, suggesting a common target structure on these two diverse cell types. The results indicate that the NK surveillance system can recognize and kill cells newly transformed by a member of the ras oncogene family.
The clinical efficacy of a 5-HT1A agonist, SM-3997, in the treatment of bulimia. (1990)

Psychotherapeutic and pharmacological treatment of bulimia and vomiting require long duration and frequently entail considerable obstacles in patience compliance, making such regimens difficult to pursue. The regulating mechanism of the appetite center is recognized to be complex and recently an important role of serotonin (5-HT), a neurotransmitter, has been shown in rats. In the present study a newly developed 5-HT1A agonist, SM-3997, was administered to 12 patients with bulimia and its clinical efficacy was evaluated. The patients were treated on an open basis with SM-3997, 30-40 mg/day, for 6-15 weeks. Bulimic behavior stopped completely in 4 patients, was improved in 4 others and was unchanged in the remaining 4. These results suggest that the administration of a 5-HT1A agonist, SM-3997, may be effective in the treatment of bulimia and vomiting and that further investigation is warranted.
Identification of Complex Carbon Nanotube Structures (1998)

A variety of complex carbon nanotube (CNT) structures have been observed experimentally. These include sharp bends, branches, tori, and helices. They are believed to be formed by using topological defects such as pentagons and heptagons to connect different CNT. The effects of type, number, and arrangement (separation and orientation) of defects on atomic structures and energetics of complex CNT are investigated using topology, quantum mechanics and molecular mechanics calculations. Energetically stable models are derived for identification of observed complex CNT structures.
New class of potent catalysts of O2˙−dismutation. Mn(iii) ortho-methoxyethylpyridyl- and di-ortho-methoxyethylimidazolylporphyrins (2004)

Three new Mn(III) porphyrin catalysts of O2.-dismutation (superoxide dismutase mimics), bearing ether oxygen atoms within their side chains, were synthesized and characterized: Mn(III) 5,10,15,20-tetrakis[N-(2-methoxyethyl)pyridinium-2-yl]porphyrin (MnTMOE-2-PyP(5+)), Mn(III)5,10,15,20-tetrakis[N-methyl-N'-(2-methoxyethyl)imidazolium-2-yl]porphyrin (MnTM,MOE-2-ImP(5+)) and Mn(III) 5,10,15,20-tetrakis[N,N'-di(2-methoxyethyl)imidazolium-2-yl]porphyrin (MnTDMOE-2-ImP(5+)). Their catalytic rate constants for O2.-dismutation (disproportionation) and the related metal-centered redox potentials vs. NHE are: log k(cat)= 8.04 (E(1/2)=+251 mV) for MnTMOE-2-PyP(5+), log k(cat)= 7.98 (E(1/2)=+356 mV) for MnTM,MOE-2-ImP(5+) and log k(cat)= 7.59 (E(1/2)=+365 mV) for MnTDMOE-2-ImP(5+). The new porphyrins were compared to the previously described SOD mimics Mn(III) 5,10,15,20-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP(5+)), Mn(III) 5,10,15,20-tetrakis(N-n-butylpyridinium-2-yl)porphyrin (MnTnBu-2-PyP(5+)) and Mn(III) 5,10,15,20-tetrakis(N,N'-diethylimidazolium-2-yl)porphyrin (MnTDE-2-ImP(5+)). MnTMOE-2-PyP(5+) has side chains of the same length and the same E(1/2), as MnTnBu-2-PyP(5+)(k(cat)= 7.25, E(1/2)=+ 254 mV), yet it is 6-fold more potent a catalyst of O2.-dismutation , presumably due to the presence of the ether oxygen. The log k(cat)vs. E(1/2) relationship for all Mn porphyrin-based SOD mimics thus far studied is discussed. None of the new compounds were toxic to Escherichia coli in the concentration range studied (up to 30 microM), and protected SOD-deficient E. coli in a concentration-dependent manner. At 3 microM levels, the MnTDMOE-2-ImP(5+), bearing an oxygen atom within each of the eight side chains, was the most effective and offered much higher protection than MnTE-2-PyP(5+), while MnTDE-2-ImP(5+) was of very low efficacy.
Selective Removal of an N-BOC Protecting Group in the Presence of a tert-Butyl Ester and Other Acid-Sensitive Groups (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSelective Removal of an N-BOC Protecting Group in the Presence of a tert-Butyl Ester and Other Acid-Sensitive GroupsFrank S. Gibson, Stephen C. Bergmeier, and Henry RapoportCite this: J. Org. Chem. 1994, 59, 11, 3216–3218Publication Date (Print):June 1, 1994Publication History Published online1 May 2002Published inissue 1 June 1994https://pubs.acs.org/doi/10.1021/jo00090a045https://doi.org/10.1021/jo00090a045research-articleACS PublicationsRequest reuse permissionsArticle Views16173Altmetric-Citations109LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Expression of mdm-2 oncoprotein in the primary and metastatic sites of mammary tumor (GI-101) implanted athymic nude mice. (1999)

The expression of mdm-2 oncoprotein (p90) was determined in a human breast tumor xenograft line (GI-101) that was derived from a 57 year old female cancer patient with recurrent, infiltrating ductal adenocarcinoma (Stage IIIa, T3N2MX). Immunoprecipitation coupled western blot analysis of the primary tumors that have been obtained from xenograft implanted athymic nude mice, using mdm-2 (Ab-1) mouse monoclonal antibody, primarily revealed high level expression of a 90 kD full length mdm-2 protein. In the GI-101 tumor the level of full length mdm-2 (p90) protein expression increased with the increase in the size of the tumor (100 to 2,000 mm(3)) and a maximum expression was detected in 2,000 mm(3) size tumors. In addition to the expression in the primary site, a significantly high level expression of mdm-2 protein (p90) was detected in the lung and liver tissues also, which are the known metastatic sites for GI-101 xenograft tumors. However, the level of mdm-2 protein expression was undetectable in the lung and liver tissues obtained from control mice. A cell line (GI-101A) derived from the GI-101 xenograft tumor also showed a high level expression of mdm-2 protein after several generations of cell passage. When the GI-101A cells were treated with DES (Diethylstilbestrol) the mdm-2 protein expression increased after 10 min treatment and reached a peak level at 40 min. Interestingly, DES (10 and 20 microM) treatment increased the total cell number also after 96 hr treatment compared to the non-treated cells. It appears that mdm-2 (p90) may have a significant role in supporting the tumor cell growth as well as the metastatic process of the GI-101A cells.
Morphine Exaggerates Retinopathy in Transgenic Sickle Mice. (2005)

Abstract Proliferative retinopathy is a complication of sickle cell disease (SCD). Promotion of angiogenesis by opioids (Cancer Res62: 4491, 2002) suggests that opioid analgesics used to treat pain may exaggerate retinopathy in patients with SCD. To examine the hypothesis that morphine augments retinopathy, we used sickle mice with transgenes for human α and βS globin (NY1DD model) and their wild type (WT) C57/BL6 controls. Simulating the analgesic doses used in humans, we injected morphine subcutaneously (50 mg / day / 70 Kg with 10 mg increments every 2 weeks and / or equimolar amount of naloxone) for 6 to 15 months into 9 – 11 months old mice. Retinal vasculature was visualized with darkfield illumination using adenosine diphosphatese reaction. Morphine induced neovascularization, corkscrew formation resembling microangiopathy in human, arterio-venous anastomoses and several vascular tufts in the inner 1/3 and whole retina after 10 and 15 months of treatment, respectively in all NY1DD but not in WT mice. Only 1/5 or 2/7 PBS-treated NY1DD mice showed early neovascular changes at 20 (treated for 10 mo) or 26 (treated for 15 mo) months of age, respectively. Retinopathy scores by ICROP system used in neonatal intensive care units for abnormal vessels, blood vessel tortuosity and tufts in NY1DD mice were: 10 mo treatment, PBS, 1.5±0.5; morphine, 10±0.7 (p&lt;0.0001 vs PBS); morphine + naloxone, 4±1; naloxone, 3.8±1.2 and 15 mo treatment, PBS, 5.9±2 and morphine, 13±0.5 (p&lt;0.003 vs PBS). Naloxone significantly inhibited (p&lt;0.005, morphine vs morphine +naloxone) morphine-induced retinopathy, suggesting an opioid receptor-mediated mechanism. To elucidate the mechanism of morphine-induced retinopathy we isolated retinal endothelial cells (REC) by panning with anti-CD31 from WT and NY1DD mice. Similar to VEGF induced proliferation and survival, morphine stimulated 5–6 fold proliferation and increased survival by about 75% in both WT and NY1DD REC, in a dose dependent manner. Both VEGF164 and morphine stimulated time-dependent MAPK/ERK and STAT3 phosphorylation in WT REC. VEGF and morphine stimulate nitric oxide synthase pathway and stimulate angiogenesis. This raised the possibility of a cross-talk between VEGF receptor(s) and opioid receptor(s). We found that morphine stimulates the phosphorylation of VEGFR2/Flk1 in WT REC which co-immunoprecipitated with mu opioid receptor (MOR) using anti-MOR antibodies. Both, morphine- or VEGF-induced phospho STAT3 also co-immunoprecipitated with MOR, suggesting that activation of either MOR or Flk1 transactivates the other. Thus, addition of morphine to the VEGF replete microenvironment in SCD can have an exaggerating effect on the progression of retinopathy. Since patients with SCD receive opioids for long periods of time, we speculate that retinopathy in these patients may in part be due to opioid use.
Targeting heat shock protein 90 with non-quinone inhibitors: A novel chemotherapeutic approach in human hepatocellular carcinoma # (2009)

Hsp90 constitutes a promising therapeutic target in HCC. Non-quinone Hsp90 inhibitors exhibit tumor-specific accumulation and exert potent antineoplastic activity without causing significant hepatotoxicity.
K-edge imaging in x-ray computed tomography using multi-bin photon counting detectors (2007)

After passage through matter, the energy spectrum of a polychromatic beam of x-rays contains valuable information about the elemental composition of the absorber. Conventional x-ray systems or x-ray computed tomography (CT) systems, equipped with scintillator detectors operated in the integrating mode, are largely insensitive to this type of spectral information, since the detector output is proportional to the energy fluence integrated over the whole spectrum. The main purpose of this paper is to investigate to which extent energy-sensitive photon counting devices, operated in the pulse-mode, are capable of revealing quantitative information about the elemental composition of the absorber. We focus on the detection of element-specific, K-edge discontinuities of the photo-electric cross-section. To be specific, we address the question of measuring and imaging the local density of a gadolinium-based contrast agent, in the framework of a generalized dual-energy pre-processing. Our results are very promising and seem to open up new possibilities for the imaging of the distribution of elements with a high atomic number Z in the human body using x-ray attenuation measurements. To demonstrate the usefulness of the detection and the appropriate processing of the spectral information, we present simulated images of an artherosclerotic coronary vessel filled with gadolinium-based contrast agent. While conventional systems, equipped with integrating detectors, often fail to differentiate between contrast filled lumen and artherosclerotic plaque, the use of an energy-selective detection system based on the counting of individual photons reveals a strong contrast between plaque and contrast agent.
Internalization pathway of C3b receptors in human neutrophils and its transmodulation by chemoattractant receptors stimulation. (1991)

On the surface of phagocytes, C3b receptors (CR1) bind C3b-coated particles and promote their ingestion after activation by appropriate stimuli such as lymphokines or the chemoattractant formyl methionyl leucyl phenylalanine (fMLP) and fibronectin. The aims of the present study were 1) to define at the electron microscopic level the nature of the process responsible for CR1 internalization and 2) to dissect the mechanism by which a physiological activator (fMLP) stimulates this process. CR1 was visualized either by the immunogold technique or by quantitative electron microscopic autoradiography using a monoclonal anti-CR1 antibody. Both techniques revealed that after anti-CR1 binding, CR1 cluster on the neutrophil surface in a time-, temperature-, and antibody-dependent fashion, but do not concentrate in coated pits. CR1 internalization requires receptor cross-linking (does not occur in the presence of Fab fragments of anti-CR1) and intact microfilaments. It results in the association of the internalized material with large flattened vacuoles, organized in stacks. Together with the surface localization of CR1 close to cytoplasmic projections (ruffles), these observations suggest that uptake of CR1 occurs through a macropinocytotic process. Eventually, CR1 concentrate in lysosomal structures. fMLP markedly stimulates this pattern of CR1 internalization without affecting their clustering or their lack of association with coated pits. Stimulation by fMLP is inhibited by pertussis toxin, unaffected by preventing receptor-triggered cytosolic free calcium [Ca2+]i elevations, and mimicked by phorbol myristate acetate. Taken together our data demonstrate 1) that, in neutrophils, CR1 is internalized via a coated pit independent macropinocytotic process, dependent on intact microfilaments and receptor cross-linking; 2) that, in the same cells, fMLP is internalized via the classical coated pits pathway; and 3) that fMLP amplifies CR1 uptake possibly via protein kinase C stimulation.