gebhart/patrepeval huggingface dataset:
Alanine Scanning Mutagenesis of HIV-1 gp41 Heptad Repeat 1: Insight into the gp120−gp41 Interaction (2010)

On the basis of mutagenesis, biochemical, and structural studies, heptad repeat 1 of HIV gp41 (HR1) has been shown to play numerous critical roles in HIV entry, including interacting with gp120 in prefusion states and interacting with gp41 heptad repeat 2 (HR2) in the fusion state. Moreover, HR1 is the site of therapeutic intervention by enfuviritide, a peptide analogue of HR2. In this study, the functional importance of each amino acid residue in gp41 HR1 has been systematically examined by alanine scanning mutagenesis, with subsequent characterization of the mutagenic effects on folding (as measured by incorporation into virions), association with gp120, and membrane fusion. The mutational effects on entry can be grouped into three classes: (1) wild type (defined as >40% of wild-type entry), (2) impaired (defined as 5-40% of wild-type entry), and (3) nonfunctional (defined as <5% of wild-type entry). Interestingly, the majority of HR1 mutations (77%) exhibit impaired or nonfunctional entry. Surprisingly, effects of mutations on folding, association, or fusion are not correlated to heptad position; however, folding defects are most often found in the N-terminal region of HR1. Moreover, disruption of the gp41-gp120 interaction is correlated to the C-terminal region of HR1, suggesting that this region interacts most closely with gp120. In summary, the sensitivity of gp41 HR1 to alanine substitutions suggests that even subtle changes in the local environment may severely affect envelope function, thereby strengthening the notion that HR1 is an attractive site for therapeutic intervention.
Crystal Structure of an Antagonist Mutant of Human Growth Hormone, G120R, in Complex with Its Receptor at 2.9 Å Resolution (1996)

Human growth hormone binds two receptor molecules and thereby induces signal transduction through receptor dimerization. At high concentrations, growth hormone acts as an antagonist because of a large difference in affinities at the respective binding sites. This antagonist action can be enhanced further by reducing binding in the low affinity binding site. A growth hormone antagonist mutant Gly-120 --> Arg, has been crystallized with its receptor as a 1:1 complex and the crystal structure determined at 2.9 A resolution. The 1:1 complex is remarkably similar to the native growth hormone-receptor 1:2 complex. A comparison between the two structures reveals only minimal differences in the conformations of the hormone or its receptor in the two complexes, including the angle between the two immunoglobulin-like domains of the receptor. Further, two symmetry-related 1:1 complexes in the crystal form a 2:2 complex with a large solvent inaccessible area between two receptor molecules. In addition, we present here a native human growth hormone-human growth hormone-binding protein 1:2 complex structure at 2.5 A resolution. One important difference between our structure and the previously published crystal structure at 2.8 A is revealed. Trp-104 in the receptor, a key residue in the hormone-receptor interaction, has an altered conformation in the low affinity site enabling a favorable hydrogen bond to be formed with Asp-116 of the hormone.
Nephritic Factor of the Classical Pathway of Complement (1980)

A factor, functionally characterized by its capacity to stabilize the normally labile classical pathway C3-converting complex of the classical pathway of complement, has been isolated from the serum of one patient with a case of acute glomerulonephritis, subsequent to a cutaneous infection. The factor confers long-lived stabilization of classical pathway C3 convertase complexes formed both in the solid (sensitized sheep erythrocytes bearing activated C1 and the classical pathway C3 convertase) and fluid phase. The half-life of such stabilized C3-cleaving enzymes extended beyond several hours at 37 degrees C. The stabilizing activity was associated with a protein fraction immunochemically identified as immunoglobulin (Ig)G, a sizeable population of which exhibited a gamma chain of 60,000 daltons. The IgG-associated stabilizing activity was found to bind to the classical pathway C3 convertase enzyme via a fragment bearing the antigen-binding site of the molecule [F(ab)(2) and F(ab)]. Such binding was demonstrable for classical pathway and not for alternative pathway C3 convertase. Thus, the stabilizing factor behaves like an autoantibody to the C3-converting complex of the classical pathway of complement. The binding of the antibody to the enzyme affords protection of the latter against decay-degradation. By analogy with the nephritic factor of the alternative pathway situation where IgG autoantibodies specifically bind to alternative pathway C3 convertase enzymes and protect them from degradation, the functionally unusual IgG in our patient was designated as the nephritic factor of the classical pathway. Indirect evidence suggests that nephritic factor of the classical pathway-IgG might be of the IgG3 subclass.
Role of extracellular Na and K in lymphocyte activation (1982)

The transmembrane electrical potential has been measured across human peripheral blood lymphocytes under culture conditions using equilibrium distributions of the lipophilic cation 3H-tetraphenylphosphonium (TPP). The TPP equilibrates to a steady-state level that gives calculated voltages of -80 mV for unstimulated lymphocytes. This value of the potential is constant during the first few hours of succinyl concanavalin A stimulation. When the transmembrane electrical potential is lowered by isotonic replacement of Na with K, this neither by itself stimulates proliferation nor does it inhibit mitogen-stimulated proliferation. Lymphocytes with similar membrane potentials, such as those incubated in normal-Na MEM and low-Na-mannitol MEM, exhibit drastically different proliferative responses to mitogen stimulation (Deutsch et al., 1981). These results show that isotonic replacement of K for Na prevents low Na inhibition of DNA synthesis and that at least during the first 2.5 hours of lymphocyte activation transmembrane electrical potential per se does not play a significant role in the activation process.
Learning Motion Patterns in Videos (2017)

The problem of determining whether an object is in motion, irrespective of camera motion, is far from being solved. We address this challenging task by learning motion patterns in videos. The core of our approach is a fully convolutional network, which is learned entirely from synthetic video sequences, and their ground-truth optical flow and motion segmentation. This encoder-decoder style architecture first learns a coarse representation of the optical flow field features, and then refines it iteratively to produce motion labels at the original high-resolution. We further improve this labeling with an objectness map and a conditional random field, to account for errors in optical flow, and also to focus on moving things rather than stuff. The output label of each pixel denotes whether it has undergone independent motion, i.e., irrespective of camera motion. We demonstrate the benefits of this learning framework on the moving object segmentation task, where the goal is to segment all objects in motion. Our approach outperforms the top method on the recently released DAVIS benchmark dataset, comprising real-world sequences, by 5.6%. We also evaluate on the Berkeley motion segmentation database, achieving state-of-the-art results.
Observation of the Two-Dimensional Plasmon in Silicon Inversion Layers (1977)

The two-dimensional plasmon of an $n$ inversion layer of (100) $p$-type Si is observed at a fixed wave vector as a function of electron density. The position, width, and strength of the resonance agree with existing theory at electron densities \ensuremath{\gtrsim}${10}^{12}$/${\mathrm{cm}}^{2}$. At lower densities, the resonance position is below the predicted value, implying a substantial increase in the electron mass.
Myeloma-Specific Multiple Peptides Able to Generate Cytotoxic T Lymphocytes: A Potential Therapeutic Application in Multiple Myeloma and Other Plasma Cell Disorders (2012)

These results highlight the potential therapeutic application of vaccination with a cocktail of HLA-A2-specific peptides to induce CTLs with a broad spectrum of immune responses against multiple myeloma antigens.
A Murine Leukemia Virus (MuLV) Long Terminal Repeat Derived from Rhesus Macaques in the Context of a Lentivirus Vector and MuLV gag Sequence Results in High-Level Gene Expression in Human T Lymphocytes (2000)

We constructed human immunodeficiency virus type 1 (HIV-1) vectors that will allow higher levels of gene expression in T cells. Gene expression under the control of an internal cytomegalovirus (CMV) immediate-early promoter in a self-inactivating lentiviral vector (CSCG) is 4- to 15-fold lower in T-cell lines (SUPT1 and CEMX174) than in non-lymphoid-cell lines (HeLa and 293T). This is in contrast to a Moloney murine leukemia virus (MoMLV)-based retrovirus vector (SRalphaLEGFP). We therefore replaced the internal CMV promoter of CSCG with three different murine oncoretroviral long terminal repeat (LTR) promoters-murine sarcoma virus (MSV), MoMLV (MLV), and the LTR (termed Rh-MLV) that is derived from the ampho-mink cell focus-forming (AMP/MCF) retrovirus in the serum of one rhesus macaque monkey that developed T-cell lymphoma following autologous transplantation of enriched bone marrow stem cells transduced with a retrovirus vector preparation containing replication-competent viruses (E. F. Vanin, M. Kaloss, C. Broscius, and A. W. Nienhuis, J. Virol. 68:4241-4250, 1994). We found that the combination of Rh-MLV LTR and a partial gag sequence of MoMLV (Deltagag(871-1612)) in CS-Rh-MLV-E gave the highest level of enhanced green fluorescent protein (EGFP) gene expression compared with MLV, MSV LTR, phosphoglycerate kinase, and CMV promoters in T-cell lines, as well as activated primary T cells. Interestingly, there was a further two- to threefold increase in EGFP expression (thus, 10-fold-higher expression than with CMV) when the Rh-MLV promoter and Deltagag(871-1612) were used in a self-inactivating-vector setting that has a further deletion in the U3 region of the HIV-1 LTR. These hybrid vectors should prove useful in gene therapy applications for T cells.
Neuropeptides and their peptidases (1987)

Part I_Molecular Biology of Neuropeptides Overview: Peptides in the Nervous System Neuropeptide Gene Families Vasopressinergic and Oxytocinergic Cells: Models in Neuropeptide Gene Expression Processing of Neuropeptide Precursors Part II_Selected Neuropeptides Mammalian Tachykinins: Neurochemistry and Pharmacology Gastrin, Cholecystokinin and Gastrin Releasing Peptide: Physiological Roles in the Alimentary Tract and the Brain Atrial Natriuretic Factor: Physiology and Biochemistry Neuropeptides and Their Peptidases in Neurological Illness Part III_Peptidases and Neuropeptide Metabolism Angiotensin I Converting Enzyme and its Role in Neuropeptide Metabolism Endopeptidase_24.11 Calpains and Neuropeptide Metabolism Inhibition of Zinc Peptidases that Hydrolyse Neuropeptides Index.
Relative effectiveness of various anions on the solubility of acidicHypoderma lineatumcollagenase at pH 7.2 (1995)

The effects of various anions on decreasing the solubility of acidic Hypoderma lineatum collagenase at pH 7.2 and 18 degrees C were qualitatively defined by replacing the crystallizing agent of known crystallization conditions by various ammonium salts. The solubility curves measured in the presence of the sulfate, phosphate, citrate, and chloride ammonium salts gave the following ranking of anions: HPO4(2-)/H2PO4- > SO4(2-) > citrate 3-/citrate2- >> Cl-. This order is in agreement with the Hofmeister series. In a previous study on the solubility at pH 4.5 of lysozyme, a basic protein, the effectiveness of anions in decreasing the solubility was found to be in the reverse order. This suggests that the effectiveness of anions in the crystallization of proteins is dependent on the net charge of the protein, i.e., depending on whether a basic protein is crystallized at acidic pH or an acidic protein at basic pH.
A Circular RNA Binds To and Activates AKT Phosphorylation and Nuclear Localization Reducing Apoptosis and Enhancing Cardiac Repair (2017)

As central nodes in cardiomyocyte signaling, nuclear AKT appears to play a cardio-protective role in cardiovascular disease. Here we describe a circular RNA, circ-Amotl1 that is highly expressed in neonatal human cardiac tissue, and potentiates AKT-enhanced cardiomyocyte survival. We hypothesize that circ-Amotl1 binds to PDK1 and AKT1, leading to AKT1 phosphorylation and nuclear translocation. In primary cardiomyocytes, epithelial cells, and endothelial cells, we found that forced circ-Amotl1 expression increased the nuclear fraction of pAKT. We further detected increased nuclear pAKT in circ-Amotl1-treated hearts. In vivo, circ-Amotl1 expression was also found to be protective against Doxorubicin (Dox)-induced cardiomyopathy. Putative PDK1- and AKT1-binding sites were then identified <i>in silico</i>. Blocking oligonucleotides could reverse the effects of exogenous circ-Amotl1. We conclude that circ-Amotl1 physically binds to both PDK1 and AKT1, facilitating the cardio-protective nuclear translocation of pAKT.
Vaccine-Induced Antibodies Inhibit CETP Activity In Vivo and Reduce Aortic Lesions in a Rabbit Model of Atherosclerosis (2000)

Using a vaccine approach, we immunized New Zealand White rabbits with a peptide containing a region of cholesteryl ester transfer protein (CETP) known to be required for neutral lipid transfer function. These rabbits had significantly reduced plasma CETP activity and an altered lipoprotein profile. In a cholesterol-fed rabbit model of atherosclerosis, the fraction of plasma cholesterol in HDL was 42% higher and the fraction of plasma cholesterol in LDL was 24% lower in the CETP-vaccinated group than in the control-vaccinated group. Moreover, the percentage of the aorta surface exhibiting atherosclerotic lesion was 39.6% smaller in the CETP-vaccinated rabbits than in controls. The data reported here demonstrate that CETP activity can be reduced in vivo by vaccination with a peptide derived from CETP and support the concept that inhibition of CETP activity in vivo can be antiatherogenic. In addition, these studies suggest that vaccination against a self-antigen is a viable therapeutic strategy for disease management.
Surfactant Protein A and Saturated Phosphatidylcholine in Respiratory Distress Syndrome (1994)

We measured surfactant protein A (SP-A) by ELISA using a rabbit antihuman SP-A polyclonal antibody and saturated phosphatidylcholine (SPC) by thin-layer chromatography in sequential tracheal fluid samples obtained from 16 preterm neonates without lung disease and 37 with respiratory distress syndrome (RDS). SP-A and SPC were lower in neonates with RDS than in control infants (1.0 +/- 0.1 versus 8.9 +/- 2.2 ng SP-A/microgram protein [p < 0.0001] and 0.20 +/- 0.05 versus 0.70 +/- 0.19 mumol SPC/mg protein [p < 0.01], respectively). Initial SP-A concentrations correlated inversely with severity of RDS (r = 0.45, p < 0.01) but did not correlate with initial SPC levels. Significant increases in SP-A were detectable within 12 to 24 h after birth in neonates with RDS. Further increases occurred subsequently and were similar for neonates treated with either a synthetic (Exosurf) or a modified natural (Survanta) surfactant. Using two-dimensional gel electrophoresis, SP-A in tracheal fluid obtained during the early and recovery phases of RDS exhibited lesser degrees of posttranslational modification than SP-A forms from control neonates. Administration of Exosurf or Survanta resulted in comparable increases in SPC in tracheal fluid. Preterm neonates with RDS seem to have an immature SP-A metabolism that persists for several days after birth. The type of surfactant used does not modify the recovery of SP-A or SPC in tracheal fluid from infants with RDS.
Neuromodulation: present and emerging methods (2014)

Neuromodulation has wide ranging potential applications in replacing impaired neural function (prosthetics), as a novel form of medical treatment (therapy), and as a tool for investigating neurons and neural function (research). Voltage and current controlled electrical neural stimulation (ENS) are methods that have already been widely applied in both neuroscience and clinical practice for neuroprosthetics. However, there are numerous alternative methods of stimulating or inhibiting neurons. This paper reviews the state-of-the-art in ENS as well as alternative neuromodulation techniques-presenting the operational concepts, technical implementation and limitations-in order to inform system design choices.
Design and implementation of an MPEG-2 transport stream multiplexer for HDTV satellite broadcasting (1998)

This paper describes the design and implementation of an HDTV program multiplexer which is based on MPEG-2 systems specifications for satellite broadcasting. We have developed an MPEG-2 TS compliant multiplexer with special considerations for timing and synchronization. In particular, we introduce a scheduling algorithm, which use the monitoring information of the buffers of T-STD as one of scheduling factors. We have also implemented a software simulator and used it for efficient verification of MPEG-2 compliance from an early design stage.
Fitch: : Most Asian governments to support failing banks. (2014)

Fitch Ratings analysts have predicted that nearly all Asian jurisdictions will support their failing financial institutions
Combination Therapy with Glucagon-Like Peptide-1 and Gastrin Induces β-Cell Neogenesis from Pancreatic Duct Cells in Human Islets Transplanted in Immunodeficient Diabetic Mice (2008)

Pancreatic islet transplantation as a treatment for type 1 diabetes is limited by human donor tissue availability. We investigated whether the beta-cell mass in human isolated islets could be expanded by treatments with glucagon-like peptide-1 (GLP-1) and gastrin, peptides reported to stimulate beta-cell growth in mice and rats with deficits in beta-cell mass. Human islets with low endocrine cell purity (7% beta-cells, 4% alpha-cells) and abundant exocrine cells (29% duct cells and 25% acinar cells) were implanted under the renal capsule of nonobese diabetic-severe combined immune deficiency (NOD-scid) mice made diabetic with streptozotocin. The mice were treated with GLP-1 and gastrin, separately and together, daily for 5 weeks. Blood glucose was significantly reduced only in mice implanted with human pancreatic cells and treated with GLP-1 plus gastrin. Correction of hyperglycemia was accompanied by increased insulin content in the human pancreatic cell grafts as well as by increased plasma levels of human C-peptide in the mice. Immunocytochemical examination revealed a fourfold increase in insulin-positive cells in the human pancreatic cell grafts in GLP-1 plus gastrin-treated mice, and most of this increase was accounted for by the appearance of cytokeratin 19-positive pancreatic duct cells expressing insulin. We conclude that combination therapy with GLP-1 and gastrin expands the beta-cell mass in human islets implanted in immunodeficient diabetic mice, largely from pancreatic duct cells associated with the islets, and this is sufficient to ameliorate hyperglycemia in the mice.
Systemic administration of recombinant methionyl human interleukin-2 (Ala 125) to cancer patients: clinical results. (1989)

Nineteen evaluable patients with advanced malignancy were treated with recombinant methionyl human interleukin-2 (Ala 125), 5 days per week by intravenous bolus. Patients were entered in five groups at starting doses ranging from 0.05 to 2.56 x 10(6) U/m2. Doses were escalated weekly as tolerated toward a potential maximal dose of 11.6 x 10(6) U/m2. Maximal tolerated dose was 3.84 x 10(6) U/m2. Dose-limiting toxicity included fatigue, rigors, nausea/vomiting, fever, and diarrhea. Other toxicities included hyperesthesias, arthralgias/myalgias, rash, fluid retention, balanitis, and mild confusion. Leukocytosis, including granulocytosis, eosinophilia, and mild lymphocytosis, was observed, as was rare mild thrombocytopenia. No partial or complete response occurred. T1/2 alpha averaged 13.4 min, with interleukin-2 detectable 2 h after doses of greater than or equal to 2.56 x 10(6) U/m2. Three patients developed anti-IL-2 antibodies without demonstrable clinical significance.
Formulation and Release Characteristics of Hydroxypropyl Methylcellulose Matrix Tablet Containing Melatonin (1999)

A hydroxypropyl methylcellulose (HPMC) matrix tablet containing melatonin (MT) was formulated as a function of HPMC viscosity, drug loading, type and amount of disintegrant, lubricant and glidant, and aqueous polymeric coating level and was compared with two commercial products. The release characteristics of the HPMC matrix tablet were investigated in the gastric fluid for 2 hr followed by study in intestinal fluid. The surface morphology of an uncoated HPMC matrix tablet using scanning electron microscopy (SEM) was crude, showing aggregated particles and rough crystals or pores, but it became smoother as the coating levels increased. As the HPMC polymer viscosity increased, the release rate had a tendency to decrease. As the drug loadings increased, the release rate slightly decreased. When Polyplasdone XL, Primojel, and Ac-Di-Sol, except Avicel, were incorporated in the HPMC matrix tablet, the release rate was markedly increased. There was no significant difference in release profiles when a mixture of lubricants and glidants (magnesium stearate, talc, and Cab-O-Sil), except for magnesium stearate alone, was incorporated into low and high viscosity grade HPMC matrix tablets. As the coating level increased, the release rate gradually decreased, giving an increased lag time. The sustained-release HPMC matrix tablet with optimizing formulations may provide an alternative for oral controlled delivery of MT and be helpful in the future treatment of circadian rhythmic disorders.
Professionalism and Patient Safety (2006)

Over the past year, a representative faculty group at Jefferson Medical College began revisiting its "Code of Professional Conduct" and its views on "Medical Professionalism." 1,2The code and Jefferson's core values go beyond simply targeting faculty and clinicians, extending their reach to include medical students and housestaff.Through the reassessment of the code and professional principles, leaders at Jefferson have become keenly aware that these professional behaviors and ethics are distinctly linked to patient safety.In this editorial, we wish to draw upon some of the key principles of The Charter on Medical Professionalism, and discuss how these principles are essential to creating a culture of professionalism and safety. 3Finally, we will share highlights from Jefferson Medical College events and activities dedicated to promoting professionalism and patient safety among medical students and housestaff.