gebhart/patrepeval huggingface dataset:
Circadian variations in mouse bone marrow. (1983)

Circadian variations in mouse hemopoiesis were investigated in the early spring and summer using spleen colony assay, agar colony technique and differential counting. The multipotent stem cells and committed stem cells as well as the numbers of myelopoietic cells/femur underwent strong circadian variations with similar type of rhythmicity. In both types of stem cells (CFUS, CFUC) the rhythm was correlated to the variations in the numbers of myeloid cells/femur. Highest value (acrophase) was found at 1300 (MET). The amplitudes for CFUS and CFUC were between 50 and 80% of the 24 h mean values (mesor), whereas the variations in the other compartments of the bone marrow were less pronounced. For the CFUC the circadian rhythms were reproducible both at two different times of the year and over 48 h. Changes were found in erythroid cells as well, but the rhythm was not so pronounced.
Inflammation and Oxidative Stress in Gastroesophageal Reflux Disease (2007)

The etiology of esophageal mucosal injury is complex, since it may involve the reflux of gastric acid, bile acid, and pancreatic juice, external factors such as drugs and alcohol, or functional factors such as esophagogastric motility. The mechanism of esophageal mucosal injury has gradually been understood at the molecular biological level. It is particularly important that pro-inflammatory factors, such as inflammatory cytokines (interleukin-6 and -8), leukocytes and oxidative stress, have been demonstrated to be involved in the development of gastroesophageal reflux disease (GERD) including nonerosive reflux disease (NERD). In addition, nociceptors such as acid-sensitive vanilloid receptors, protease-activated receptors and substance P have also been implicated in the pathogenesis of neurogenic inflammation in NERD patients with esophageal hypersensitivity. The development of new therapy with anti-inflammatory and anti-oxidant effects is expected to assist in the treatment of intractable NERD/GERD and the prevention of carcinogenesis.
Intracellular antibody against erbB-2 mediates targeted tumor cell eradication by apoptosis. (1996)

Methods were developed to achieve targeted eradication of the erbB-2 oncoprotein using gene constructs encoding anti-erbB-2 intracellular single-chain antibodies. This method of genetic intervention caused a marked cytocidal effect in erbB-2-overexpressing human ovarian tumor cells. Evaluation of the mechanistic basis of this phenomenon demonstrated that programmed cell death had been induced. Significantly, no cytocidal effect was observed in non-erbB-2-overexpressing tumors. The induction of apoptosis could be shown to be secondary to the intracellular antibody-mediated ectopic localization of the erbB-2 oncoprotein. Thus, the strategy of selective oncogene "knock-out" using intracellular antibodies represents a novel anticancer gene therapy strategy that offers the potential to achieve highly specific, targeted eradication of human tumor cells.
Essential amino acid and carbohydrate ingestion before resistance exercise does not enhance postexercise muscle protein synthesis (2008)

Ingestion of an essential amino acid-carbohydrate (EAA + CHO) solution following resistance exercise enhances muscle protein synthesis during postexercise recovery. It is unclear whether EAA + CHO ingestion before resistance exercise can improve direct measures of postexercise muscle protein synthesis (fractional synthetic rate; FSR). We hypothesized that EAA + CHO ingestion before a bout of resistance exercise would prevent the exercise-induced decrease in muscle FSR and would result in an enhanced rate of muscle FSR during postexercise recovery. We studied 22 young healthy subjects before, during, and for 2 h following a bout of high-intensity leg resistance exercise. The fasting control group (n = 11) did not ingest nutrients, and the EAA + CHO group (n = 11) ingested a solution of EAA + CHO 1 h before beginning the exercise bout. Stable isotopic methods were used in combination with muscle biopsies to determine FSR. Immunoblotting procedures were utilized to assess cell signaling proteins associated with the regulation of FSR. We found that muscle FSR increased in the EAA + CHO group immediately following EAA + CHO ingestion (P < 0.05), returned to basal values during exercise, and remained unchanged at 1 h postexercise. Muscle FSR decreased in the fasting group during exercise and increased at 1 h postexercise (P < 0.05). However, the 2 h postexercise FSR increased by approximately 50% in both groups with no differences between groups (P > 0.05). Eukaryotic elongation factor 2 phosphorylation was reduced in both groups at 2 h postexercise (EAA + CHO: 39 +/- 7%; fasting: 47 +/- 9%; P < 0.05). We conclude that EAA + CHO ingestion before resistance exercise does not enhance postexercise FSR compared with exercise without nutrients.
CT-guided Celiac Plexus Neurolysis: A Review of Anatomy, Indications, Technique, and Tips for Successful Treatment (2011)

The celiac plexus is the largest visceral plexus and is located deep in the retroperitoneum, over the anterolateral surface of the aorta and around the origin of the celiac trunk. It serves as a relay center for nociceptive impulses that originate from the upper abdominal viscera, from the stomach to the proximal transverse colon. Celiac plexus neurolysis, with agents such as ethanol, is an effective means of diminishing pain that arises from these structures. Percutaneous imaging-guided celiac plexus neurolysis has been established as an invaluable therapeutic option in the management of intractable abdominal pain in patients with upper abdominal malignancy. The use of multidetector computed tomography (CT) for imaging guidance has superseded other modalities and allows direct visualization of the spread of the neurolytic agent in the antecrural space. Accurate depiction of the retroperitoneal anatomy and the position of the needle tip helps avoid crucial anatomic structures such as the pancreas, aorta, celiac artery, and superior mesenteric artery. Proper patient education, meticulous preprocedure planning, use of optimal multidetector CT techniques, adjunctive CT maneuvers, and postprocedure care are integral to successful celiac plexus neurolysis. Celiac plexus neurolysis does not completely abolish pain; rather, it diminishes pain, helping to reduce opioid requirements and their related side effects and improving survival in patients with upper abdominal malignancy.
Distribution and fate of free and liposome-encapsulated [3H]nor-muramyl dipeptide and [3H]muramyl tripeptide phosphatidylethanolamine in mice. (1985)

The pharmacokinetics and metabolism of i.v. administered free (unencapsulated) or liposome-encapsulated hydrophilic [3H]-labeled nor-muramyl dipeptide (nor-MDP) and lipophilic [3H]-labeled muramyl tripeptide phosphatidylethanolamine (MTP-PE) were evaluated. In addition we also examined the distribution and fate of these immunomodulators subsequent to intranasal (i.n.) administration. Unique patterns of circulatory clearance, organ distribution, metabolism, and excretion were observed for each of the four preparations. Nor-MDP in saline was rapidly cleared from the circulation and excreted in the urine as intact molecules. MTP-PE dissolved in saline was cleared from the circulation at a slow rate and found within various organs as intact MTP-PE, lyso-MTP-PE, and MDP. Following the i.v. administration of nor-MDP or MTP-PE in liposomes, patterns of clearance and organ distribution corresponded to that of liposome distribution, i.e., the reticuloendothelial system. Extensive dissociation of hydrophilic nor-MDP from the carrier liposomes occurred, and the immunomodulator was recovered in the urine. In contrast, MTP-PE entrapped in liposomes was retained in target organs for the duration of the study. The i.n. instillation of radiolabeled nor-MDP or MTP-PE was associated with the accumulation of these immunomodulators in the brain. Our results demonstrate the feasibility of targeting hydrophilic and lipophilic immunomodulators to cells of the macrophage-histiocyte series.
Coding Television Signals at 320 and 64 kbit/s (1986)

This paper explains a coding technique for transmitting television scenes at rates ranging from 64 to 320 kbit/s. The algorithms to be described are applied to TV input signals with reduced spatial and temporal resolution. Use is made of a hybrid coding algorithm, with predictive coding in the time domain and transform coding in the spatial domain. To improve coding efficiency an object matching technique is used for movement compensation. The residual prediction errors are coded by adaptive block quantization with a 16*16 discrete cosine transform (DCT). On the receiver side skipped fields are reconstructed by motion adaptive interpolation (MAI).
Nucleotide Sequence of a cDNA Clone Encoding γ-Coixin from Coix lacryma-jobi Seeds (1991)

Coixins are the major seed storage proteins of Coix (2). They account for more than 60% of the total endosperm protein and share extensive homology to zeins, the prolamins ofmaize (1). Like zeins, coixins are synthesized by membrane- bound polyribosomes and assembled into protein bodies (
Signaling-inactive epidermal growth factor receptor/ligand complexes in intact carcinoma cells by quinazoline tyrosine kinase inhibitors. (2001)

Several inhibitors of EGF receptor (EGFR) tyrosine kinase activity have been developed that compete with ATP at its binding site such as the quinazolines PD 153035 and ZD 1839 or the 4,5-dianilino-phthalimides DAPH1 and DAPH2. When tested on human A431 cells, the quinazolines completely blocked EGF-induced receptor phosphorylation at 100 nM, whereas it was inhibited by DAPH1 and DAPH2 by only 20% at 3 microM. Quinazoline-treated A431 as well as tumor cells expressing less EGFR (A549, MDA MB 231, and T47D) bound 3- to 6-fold more (125)I-labeled EGF than untreated intact control cells. Scatchard analysis revealed the disappearance of low- and high-affinity EGFR on A431 cells upon PD 153035 treatment. A single receptor class of intermediate ligand binding affinity emerged and its number corresponded to the sum of the two classes. DAPH1 and DAPH2 did not change ligand binding properties of EGFR. PD 153035 exerted the most potent effects on EGF binding to A431 or on inhibiting EGF-stimulated growth of rat MTLn3 cells at low ligand concentrations. Cross-linking of EGFR on PD 153035-treated A431 cells indicated the formation of inactive dimers that further increased upon addition of EGF. Chemical cross-linking of (125)I-labeled EGF to PD 153035-treated A431 cells revealed increased binding to monomeric and dimeric EGFR. Thus, the quinazolines sequestered EGFR plus the ligand into inactive receptor/ligand complexes. This novel mode of action of quinazoline tyrosine kinase inhibitors may be the basis for their extraordinary potency especially in conditions when the ligand is present in limiting amounts.
Structure–Activity Relationship Studies toward the Discovery of Selective Apelin Receptor Agonists (2014)

Apelin is the endogenous ligand for the previously orphaned G protein-coupled receptor APJ. Apelin and its receptor are widely distributed in the brain, heart, and vasculature, and are emerging as an important regulator of body fluid homeostasis and cardiovascular functions. To further progress in the pharmacology and the physiological role of the apelin receptor, the development of small, bioavailable agonists and antagonists of the apelin receptor, is crucial. In this context, E339-3D6 (1) was described as the first nonpeptidic apelin receptor agonist. We show here that 1 is actually a mixture of polymethylated species, and we describe an alternative and versatile solid-phase approach that allows access to highly pure 27, the major component of 1. This approach was also applied to prepare a series of derivatives in order to identify the crucial structural determinants required for the ligand to maintain its affinity for the apelin receptor as well as its capacity to promote apelin receptor signaling and internalization. The study of the structure-activity relationships led to the identification of ligands 19, 21, and 38, which display an increased affinity compared to that of 27. The latter and 19 behave as full agonists with regard to cAMP production and apelin receptor internalization, whereas 21 is a biased agonist toward cAMP production. Interestingly, the three ligands display a much higher stability in mouse plasma (T1/2 > 10 h) than the endogenous apelin-17 peptide 2 (T1/2 < 4 min).
MOLECULAR-CLONING OF THE HUMAN CYCG1 GENE ENCODING A G-TYPE CYCLIN - OVEREXPRESSION IN HUMAN OSTEOSARCOMA CELLS (1994)

Cyclins constitute a growing family of regulatory proteins that complex with, and activate, protein kinases involved in cell cycle control. Dysregulation of cyclin expression and/or cyclin-dependent kinase (cdk) activities may play a pivotal role in oncogenesis. In this report, we characterize a novel human cyclin gene by molecular cloning. This gene, designated CYCG1, encodes a human homologue of the rat G-type cyclin, exhibiting structural features and conserved sequence motifs of identified G(1) cyclins. The CYCG1 gene is expressed constitutively in synchronized human WI-38 fibroblasts and MG-63 osteosarcoma cells, which is reminiscent of CLN3 in Saccharomyces cerevisiae. Marked overexpression of CYCG1 is observed in a subset of human osteosarcoma cells, providing a potential link to cancer.
Denileukin diftitox: a concise clinical review (2005)

Denileukin diftitox (DAB389IL-2; Ontak) is a novel recombinant fusion protein approved by the US Food and Drug Administration for the treatment of relapsed or refractory cutaneous T-cell lymphoma. It consists of fragments of diphtheria toxin linked to human interleukin-2 and works by targeting the high-affinity interleukin-2 receptor expressed on malignant cells. This article will review the clinical trials leading to the approval of denileukin diftitox for cutaneous T-cell lymphoma, and discuss the potential future role of this novel drug in patients with both malignant and nonmalignant diseases, including non-Hodgkin's lymphoma, chronic lymphocytic leukemia, solid tumors, psoriasis and graft-versus-host disease.
DeepLab: Semantic Image Segmentation with Deep Convolutional Nets, Atrous Convolution, and Fully Connected CRFs (2017)

In this work we address the task of semantic image segmentation with Deep Learning and make three main contributions that are experimentally shown to have substantial practical merit. First, we highlight convolution with upsampled filters, or 'atrous convolution', as a powerful tool in dense prediction tasks. Atrous convolution allows us to explicitly control the resolution at which feature responses are computed within Deep Convolutional Neural Networks. It also allows us to effectively enlarge the field of view of filters to incorporate larger context without increasing the number of parameters or the amount of computation. Second, we propose atrous spatial pyramid pooling (ASPP) to robustly segment objects at multiple scales. ASPP probes an incoming convolutional feature layer with filters at multiple sampling rates and effective fields-of-views, thus capturing objects as well as image context at multiple scales. Third, we improve the localization of object boundaries by combining methods from DCNNs and probabilistic graphical models. The commonly deployed combination of max-pooling and downsampling in DCNNs achieves invariance but has a toll on localization accuracy. We overcome this by combining the responses at the final DCNN layer with a fully connected Conditional Random Field (CRF), which is shown both qualitatively and quantitatively to improve localization performance. Our proposed "DeepLab" system sets the new state-of-art at the PASCAL VOC-2012 semantic image segmentation task, reaching 79.7 percent mIOU in the test set, and advances the results on three other datasets: PASCAL-Context, PASCAL-Person-Part, and Cityscapes. All of our code is made publicly available online.
Generation of recombinant fragments of CD11b expressing the functional beta-glucan-binding lectin site of CR3 (CD11b/CD18). (1999)

CR3 (Mac-1; alphaMbeta2 integrin) functions as both a receptor for the opsonic iC3b fragment of C3 triggering phagocytosis or cytotoxicity and an adhesion molecule mediating leukocyte diapedesis. Recent reports have suggested that a CR3 lectin site may be required for both cytotoxic responses and adhesion. Cytotoxic responses require dual recognition of iC3b via the I domain of CD11b and specific microbial surface polysaccharides (e.g., beta-glucan) via a separate lectin site. Likewise, adhesion requires a lectin-dependent membrane complex between CR3 and CD87. To characterize the lectin site further, a recombinant baculovirus (rBv) system was developed that allowed high level expression of rCD11b on membranes and in the cytoplasm of Sf21 insect cells. Six rBv were generated that contained truncated cDNA encoding various CD11b domains. Immunoblotting of rBv-infected Sf21 cells showed that some native epitopes were expressed by five of six rCD11b fragments. Lectin activity of rCD11b proteins was evaluated by both flow cytometry with beta-glucan-FITC and radioactive binding assays with [125I]beta-glucan. Sf21 cells expressing rCD11b that included the C-terminal region, with or without the I-domain, exhibited lectin activity that was inhibited by unlabeled beta-glucan or anti-CR3 mAbs. The smallest rCD11b fragment exhibiting lectin activity included the C-terminus and part of the divalent cation binding region. The beta-glucan binding affinities of the three C-terminal region-containing rCD11bs expressed on Sf21 cell membranes were not significantly different from each other and were similar to that of neutrophil CR3. These data suggest that the lectin site may be located entirely within CD11b, although lectin site-dependent signaling through CD18 probably occurs with the heterodimer.
Consequence of neo-antigenicity of the 'altered self' (2008)

Post-translational modifications play a central role in determining the function of proteins. Such protein modifications come in a great variety of guises, and include phosphorylation, proteolysis, glycosylation, citrullination and oxidative modifications. In relation to inflammatory autoimmune diseases, some post-translational modifications appear to result in the generation of new antigens, and hence autoantibodies. Examples include: the induction of peptide immunogenicity by the spontaneous conversion of aspartic acid residues to isoaspartic acid; granzyme B-mediated cleavage of SLE autoantigens; the oxidative modification--on the surface of apoptotic cells--of lipids and proteins, rendering them immunogenic; and the presence of antibodies to oxidatively modified type II collagen and C1q in RA and SLE patients, respectively. The measurement of autoantibodies to citrullinated proteins has been verified as a very useful diagnostic tool in RA. Proteomics techniques, in principle, allow the detection of all types of in vivo protein modifications, and the increasing application of such technologies to the study of rheumatological diseases will further our understanding of autoantigenicity.
G-protein ligands inhibit in vitro reactions of vacuole inheritance. (1994)

During budding in Saccharomyces cerevisiae, maternal vacuole material is delivered into the growing daughter cell via tubular or vesicular structures. One of the late steps in vacuole inheritance is the fusion in the bud of vesicles derived from the maternal vacuole. This process has been reconstituted in vitro and requires isolated vacuoles, a physiological temperature, cytosolic factors, and ATP (Conradt, B., J. Shaw, T. Vida, S. Emr, and W. Wickner. 1992. J. Cell Biol. 119:1469-1479). We now report a simple and reliable assay to quantify vacuole-to-vacuole fusion in vitro. This assay is based on the maturation and activation of vacuole membrane-bound pro-alkaline phosphatase by vacuolar proteinase A after vacuole-to-vacuole fusion. In vitro fusion allowed maturation of 30 to 60% of pro-alkaline phosphatase. Vacuoles prepared from a mutant defective in vacuole inheritance in vivo (vac2-1) were inactive in this assay. Vacuole fusion in vitro required a vacuole membrane potential. Inhibition by nonhydrolyzable guanosine derivatives, mastoparans, and benzalkonium chloride suggest that GTP-hydrolyzing G proteins may play a key role in the in vitro fusion events.
Red New York (2002)

On the panorama of the twentieth century, occasionally a red glow emanated from a city electrified by the culture of the left: red Vienna of the 1920s and 1930s; Moscow, after the Revolution; Weimar Berlin; Paris '68. Midcentury New York, with its Broadway musicals, liberal Democratic leaders, and commercialized mass culture, seems a world apart. "Cultural Capital of the World," some dubbed it, not for its radicalism, but for its embrace of depoliticized modernism—abstract painting, modern dance, jazz, International-style architecture. Yet in its own way, New York in the 1940s and early 1950s had a tangle of left culture as dense as any in the history of the United States.This article can also be found at the Monthly Review website, where most recent articles are published in full.Click here to purchase a PDF version of this article at the Monthly Review website.
Erythropoietic therapy for the treatment of anemia in patients with cancer: a valuable clinical and economic option (2007)

Significant costs are incurred when anemia in cancer is not treated. Erythropoietic protein therapy is more cost effective than blood transfusion for the treatment of cancer-related anemia. Transfusion should be reserved for patients with poor responses to erythropoietic protein or for the emergency setting, when rapid improvement in Hb is required.
Raman spectroscopic study of the avidin—biotin complex (1995)

Abstract Raman spectra of avidin, biotin and the avidin‐biotin complex were recorded. The percentages of secondary structure of avidin and the avidin‐biotin complex were obtained from the Raman spectra. The vibrational results indicate that, as a consequence of the interaction of avidin with biotin, the β‐sheet conformation percentage decreases and the α‐helical conformation percentage increases. Moreover, the interaction of avidin with biotin is also able to change slightly the tertiary structure of the protein. In fact, as a consequence of the binding of biotin, the hydrophobicity of the environment of Trp increases slightly according to the intensity increase of the 1360 cm −1 component. The intesity of all bands attributable to Trp residues increases with biotin binding, indicating that Trp is directly involved in the interaction. These results are in agreement with the results of UV measurements which indicate a red shift of the avidin Trp absorption bands as a consequence of the binding to biotin.