gebhart/patrepeval huggingface dataset:
NAD binding site of diphtheria toxin: identification of a residue within the nicotinamide subsite by photochemical modification with NAD. (1984)

We showed earlier that exposing mixtures of NAD and diphtheria toxin fragment A to ultraviolet radiation (253.7 nm) induced the formation of covalently linked protein-ligand photoproducts. Here we report that when [carbonyl-14C]NAD was employed in such procedures, the efficiency of labeling of the protein approached 1 mol/mol, and at least 94% of the incorporated label was associated with a single residue, glutamic acid at position 148. Fragment A photolabeled in this manner was enzymically inactive. The efficiency of photolabeling was much lower (less than 0.2 mol/mol) when NAD radiolabeled in either the adenine moiety or the adenylate phosphate was used, and the label was attached to different site(s) within fragment A. Efficient photochemical transfer of label from [carbonyl-14C]NAD occurred under identical conditions with the nucleotide-free form of whole diphtheria toxin, CRM-45, or activated exotoxin A from Pseudomonas aeruginosa, but not with nucleotide-bound diphtheria toxin, CRM-197, native exotoxin A, or any of several NAD-linked dehydrogenases. On the basis of these and other results we suggest that part or all of the nicotinamide moiety of NAD is efficiently transferred to glutamate-148 of fragment A under the influence of ultraviolet irradiation and that this residue is located within the nicotinamide subsite. This location implies that glutamate-148 is at or near the catalytic center of the toxin. Our data provide direct evidence for the location of the NAD site in an ADP-ribosylating toxin and demonstrate highly efficient and specific photolabeling by [carbonyl-14C]NAD.
Contraction and Relaxation Induced by Some Prostanoids in Isolated Human Penile Erectile Tissue and Cavernous Artery (1985)

Contractant and relaxant effects of prostaglandins (PG) F2 alpha, E1 and E2, prostacyclin (PGI2), the thromboxane A2 agonist U46619 and the prostaglandin endoperoxide analogue U44069 were investigated in isolated preparations of the human corpus cavernosum, corpus spongiosum and cavernous artery. In corpus cavernosum and corpus spongiosum preparations, PGF2 alpha produced concentration-dependent contractions showing rhythmic variations in tension. The contractions were effectively relaxed by carbachol and vasoactive intestinal polypeptide. U46619, U44069 and PGI2 also contracted corpus cavernosum and corpus spongiosum strips at resting tension, U46619 being the most potent drug. PGE1 and PGE2, but not PGI2 relaxed corpus cavernosum and corpus spongiosum preparations contracted by noradrenaline (NA) and PGF2 alpha. PGE1 was the more effective agent; high concentrations of PGE2 produced contraction. In cavernous artery segments, PGF2 alpha produced concentration-dependent contractions. No oscillations in tension were observed; carbachol had no relaxant action, but VIP effectively relaxed the vessels. U46619 and U44069, but not PGI2 had contractant effects on cavernous artery segments at resting tension. PGE1 and PGI2, but not PGE2 relaxed NA contracted vessel preparations; all agents (PGE2 less effectively) relaxed PGF2 alpha contracted vessel segments. It is concluded that cavernous artery and erectile tissue proper (corpus cavernosum and corpus spongiosum) differ importantly in their reaction to various prostanoids. It cannot be excluded that products of the arachidonate cascade can be involved in the control of penile tumescence and erection.
Effect of doping level on the gain constant and modulation bandwidth of InGaAsP semiconductor lasers (1984)

Using the threshold carrier density measurement technique, the differential gain dg/dn at lasing threshold was measured. It was found that the differential gain dg/dn of 1.3-μm InGaAsP lasers is a strong function of the active layer doping level P0. At a doping level of 2.5×1018 cm−3, the differential gain is several times larger than at 4×1017 cm−3. A factor of 2 increase in the modulation bandwidth is demonstrated using the dg/dn dependency on P0.
A C–H Borylation Approach to Suzuki–Miyaura Coupling of Typically Unstable 2–Heteroaryl and Polyfluorophenyl Boronates (2012)

A method for the synthesis of biaryls and heterobiaryls from arenes and haloarenes without the intermediacy of unstable boronic acids is described. Pinacol boronate esters that are analogous to unstable boronic acids are formed in high yield by iridium-catalyzed C-H borylation of heteroarenes and fluoroarenes. These boronates are stable in the solid state or in solution and can be generated and used in situ. They couple with aryl halides in the presence of simple palladium catalysts, providing a convenient route to biaryl and heteroaryl products that have been challenging to prepare via boronic acids.
Universal Microfluidic Gradient Generator (2006)

The study of cellular responses to chemical gradients in vitro would greatly benefit from experimental systems that can generate precise and stable gradients comparable to chemical nonhomogeneities occurring in vivo. Recently, microfluidic devices have been demonstrated for linear gradient generation for biological applications with unmatched accuracy and stability. However, no systematic approach exists at this time for generating other gradients of target spatial configuration. Here we demonstrate experimentally and provide mathematical proof for a systematic approach to generating stable gradients of any profile by the controlled mixing of two starting solutions.
Molecular Characterization of a Putative K-Cl Cotransporter in Rat Brain (1996)

Using a combination of data base searching, polymerase chain reaction, and library screening, we have identified a putative K-Cl cotransporter isoform (KCC2) in rat brain that is specifically localized in neurons. A cDNA of 5566 bases was obtained from overlapping clones and encoded a protein of 1116 amino acids with a deduced molecular mass of 123.6 kDa. Over its full length, the amino acid sequence of KCC2 is 67% identical to the widely distributed K-Cl cotransporter isoform (KCC1) identified in rat brain and rabbit kidney (Gillen, C., Brill, S., Payne, J.A., and Forbush, B., III(1996) J. Biol. Chem. 271, 16237-16244) but only approximately25% identical to other members of the cation-chloride cotransporter gene family, including "loop" diuretic-sensitive Na-K-Cl cotransport and thiazide-sensitive Na-Cl cotransport. Based on analysis of the primary structure as well as homology with other cation-chloride cotransporters, we predict 12 transmembrane segments bounded by N- and C-terminal cytoplasmic regions. Four sites for N-linked glycosylation are predicted on an extracellular intermembrane loop between putative transmembrane segments 5 and 6. Northern blot analysis using a KCC2-specific cDNA probe revealed a very highly expressed approximately5.6-kilobase transcript only in brain. Reverse transcriptase-polymerase chain reaction revealed that KCC1 was present in rat primary astrocytes and rat C6 glioma cells but that KCC2 was completely absent from these cells, suggesting KCC2 was not of glial cell origin. In situ hybridization studies demonstrated that the KCC2 transcript was expressed at high levels in neurons throughout the central nervous system, including CA1-CA4 pyramidal neurons of the hippocampus, granular cells and Purkinje neurons of the cerebellum, and many groups of neurons throughout the brainstem.
Thrombospondin functions as a cytoadhesion molecule for human hematopoietic progenitor cells (1990)

We explored the role that thrombospondin (TSP), a multifunctional extracellular matrix protein, plays in hematopoietic cell-cell and cell-matrix interactions. Thrombospondin synthesis is differentially regulated in human long-term bone marrow cultures. Consistent with this, human hematopoietic progenitor cells of all three lineages (erythrocyte, megakaryocyte, and granulocyte) use TSP as an attachment protein. However, terminally differentiated cells (erythrocytes and neutrophils) show absent or reduced attachment to TSP. The region within the TSP molecule that mediates cell attachment (cell binding domain) was delineated by examining both attachment to proteolytic fragments of TSP and by inhibition of cytoadhesion using monoclonal antibodies directed against TSP domains. The cell binding domain resides toward the C-terminus of a 140 Kd chymotryptic fragment of TSP. We conclude that thrombospondin functions as a hematopoietic cytoadhesion molecule, capable of binding primary hematopoietic progenitor cells, and may, therefore, be important in blood cell development.
Absolute Quantification of Monoclonal Antibodies in Biofluids by Liquid Chromatography−Tandem Mass Spectrometry (2008)

The development of a quantification method for monoclonal antibodies in serum has been accomplished by high-performance liquid chromatography multiple reactions monitoring mass spectrometry. A human monoclonal antibody (HmAb) was used as the model protein for method development and validation. A peptide from the CDR3-region of its heavy chain was selected and used for quantifying the entire mAb. This signature peptide served as a template for the internal standard. Prior to mass spectrometric analysis approximately 50% of the total serum protein content was removed by albumin depletion. The accuracy of the method ranged between 99 and 112% in cynomolgus monkey serum. The intra-assay coefficient of variation (CV) was lower than 4% at 4 microg/mL and 200 microg/mL HmAb (n = 3). The CV at 400 microg/mL corresponded to 9% (n = 3). In addition, the interassay variation was investigated in a male cynomolgus serum pool and in a female cynomolgus serum pool. The CV for the male cynomolgus pool at 4 microg/mL HmAb was 7% (n = 3). The CV obtained from the female pool was 8% (n = 3), at 4 microg/mL. The dynamic range of the method was 3 orders of magnitude. After albumin depletion of 25 microL of serum, a lowest limit of quantification of 2 microg/mL HmAb was reached in both human and cynomolgus monkey samples.
The Respiratory Role of the Upper Airways: A Selective Clinical and Pathophysiological Review (1992)

A review of upper airway physiology and its applications to otolaryngology, including coverage of current topics such as breathing disorders in sleep and the effects of pollution on the respiratory system. All chapters contain opening outlines. Chapters also contain clinical comments, which consist of a brief summary of the information. The focus of this book is on respiratory function. Current topics that are widely scattered through several biomedical fields and as yet incompletely incorporated in general ENT texts have been chosen for their importance and physiological interest. The modification of air in the respiratory passages is described and a critical discussion of symptomatology, assessment and methods of objective measurement of nasal, oral and pharyngeal respiratory function is presented in the concluding chapter. This selective review will assist in decision-making by otolaryngologists, who, in addition to treating traditional ENT diseases, are increasingly involved in the management of such diverse disorders as those concerned with breathing in sleep, orthodontics and allergy.
Complications in patients after intravitreal injection of bevacizumab (2007)

Intravitreal injection of bevacizumab may cause systemic or ocular complications. Caution is advised when considering intravitreal injection of this drug.
Impact of pretransplant conditioning and donor T cells on chimerism, graft-versus-host disease, graft-versus-leukemia reactivity, and tolerance after bone marrow transplantation (1991)

Graft rejection, mixed chimerism, graft-versus-host disease (GVHD), leukemia relapse, and tolerance are interrelated manifestations of immunologic reactivity between donor and host cells that significantly affect survival after allogeneic bone marrow transplantation (BMT). In this report, a mouse model of BMT, in which the donor and host were compatible at the major histocompatibility complex (MHC), was used (1) to examine the interrelationship of pretransplant conditioning and T-cell content of donor BM with regard to lymphoid chimerism and GVHD and (2) to determine how these factors affected graft-versus-leukemia (GVL) reactivity and donor-host-tolerance. AKR (H-2k) host mice were administered optimal or suboptimal total body irradiation (TBI) as pretransplant conditioning followed by administration of BM cells from B10.BR (H-2k) donor mice with or without added spleen cells as a source of T lymphocytes. Transplanted mice were injected with a supralethal dose of AKR leukemia cells 20 and 45 days post-BMT to assess GVL reactivity in vivo. The pretransplant conditioning of the host and T-cell content of the donor marrow affected the extent of donor T-cell chimerism and the severity of GVH disease. GVL reactivity was dependent on transplantation of mature donor T cells and occurred only in complete chimeras. Transplantation of T-cell-deficient BM resulted in the persistence of host T cells, ie, incomplete donor T-cell chimerism, even when lethal TBI was used. Mixed chimerism was associated with a lack of GVL reactivity, despite the fact that similar numbers of donor T cells were present in the spleens of mixed and complete chimeras. In this model, moderate numbers of donor T cells facilitated complete donor T-cell engraftment, caused only mild GVHD, and provided a significant GVL effect without preventing the subsequent development of tolerance after conditioning with suboptimal TBI. In contrast, severe, often lethal, GVHD developed when the dose of TBI was increased, whereas tolerance and no GVH/GVL reactivity developed when the T-cell content of the marrow was decreased.
THE NUCLEAR HORMONE RECEPTOR GENE SUPERFAMILY (1995)

The nuclear hormone receptor gene superfamily encodes structurally related proteins that regulate transcription of target genes. These macromolecules include receptors for steroid and thyroid hormones, vitamins, and other proteins for which no ligands have been found. These receptors have modular domains. The DNA-binding domain directs the receptors to bind specific DNA sequences as monomers, homodimers, or heterodimers. The ligand-binding domain responds to binding of the cognate hormone; this domain and the amino terminal domain interact with other transcription factors. Nuclear receptor-specific actions are derived from a combination of diverse elements, including availability of ligand, receptors, and nonreceptor factors; target-site structure; interactions with other proteins, such as the general transcription factors; and influences of other signaling pathways. These interactions result in ligand-regulated and ligand-independent effects on initiation of transcription of the target genes. Understanding the mechanisms of nuclear receptor action will enhance our knowledge of transcription and hormone influences on disease and facilitate the design of drugs with greater therapeutic value.
Use of Administrative Claims Data for Identifying Patients with Cirrhosis (2012)

Administrative data can identify patients with cirrhosis with high accuracy, although ascites has a significantly lower positive predictive value than other ICD-9 codes.
Clozapine Plus Lamotrigine in Treatment-Resistant Schizophrenia (1999)

C lozapine is the only antipsychotic agent with proven efficacy in treatment-resistant schizophrenia; however, a substantial minority of patients fail to respond or have only a partial response to clozapine, leading clinicians to search for potential augmentation strategies to improve outcomes. To date, these augmentation strategies with clozapine have generally been disappointing. Glutamate is an excitatory neurotransmitter, and clozapine acts as a glutamate antagonist. Lamotrigine, an anticonvulsant and mood stabilizer, inhibits excessive release of glutamate. Both drugs block the psychotomimetic effects of phencyclidine (PCP). These schizophrenia-like symptoms are attributed to PCP’s activity at the NMDA (glutamate) receptor. The biochemical significance of these glutamate interactions in schizophrenia remains unclear and is hotly debated. There is evidence to suggest that there is abnormal glutamatergic binding in the areas of the brain associated with psychotic symptoms in patients with schizophrenia. We are reporting on a small, open-label, nonrandomized case series of 6 outpatients who had a partial response to clozapine. All patients were taking the maximum tolerated dose of clozapine, with lamotrigine added as an augmentation strategy. Clozapine dosages were stable at the time lamotrigine therapy was initiated and remained the same throughout the 24-week period monitored by the Brief Psychiatric Rating Scale. No patient dropped out of the study. All patients had therapeutic plasma clozapine levels and had been taking clozapine for a minimum of 16 months. Lamotrigine therapy was initiated at 12.5 mg/d and titrated by patient response. When baseline Brief Psychiatric Rating Scale scores were compared with scores in each subsequent week using a pairwise approach for the sample, all were found to be significantly different (P#.05) by Wilcoxon signed rank test (Table). Reported side effects included headache, sedation, dizziness, and mild hand tremor. No dermatological side effects were observed, and none of the side effects were considered disturbing by the patients. Despite the significant limitations of a small sample size and open-label, nonrandomized design, the preliminary data suggest that clozapine plus lamotrigine may be a useful augmentation for treatment-resistant schizophrenia. Clozapine is metabolized primarily through the liver CYP450 system (isoenzyme 1A2), while lamotrigine is metabolized in the liver by glucuronidation. Therefore, any synergism between the 2 is very likely pharmacodynamic (perhaps involving glutamate and/or nitric oxide) rather than the result of a pharmacokinetic interaction. We believe this finding warrants further study.
Understanding TCP incast throughput collapse in datacenter networks (2009)

TCP Throughput Collapse, also known as Incast, is a pathological behavior of TCP that results in gross under-utilization of link capacity in certain many-to-one communication patterns. This phenomenon has been observed by others in distributed storage, MapReduce and web-search workloads. In this paper we focus on understanding the dynamics of Incast. We use empirical data to reason about the dynamic system of simultaneously communicating TCP entities. We propose an analytical model to account for the observed Incast symptoms, identify contributory factors, and explore the efficacy of solutions proposed by us and by others.
Posterior capsule opacificationPart 1: Experimental investigations (1999)

Posterior capsule opacification (PCO) is the most frequent complication associated with decreased vision after cataract surgery. Previous methods of preventing PCO have not proven to be practical, effective, and safe for routine clinical procedure, but some novel concepts and methods have recently been developed. This 2-part review looks at clinical and experimental investigations of PCO, focusing on developments since 1992. Clinical aspects will be presented in a later issue. This paper addresses (1) in vitro models for PCO research; (2) pathophysiology and molecular biology of lens epithelial cells (LECs); (3) prevention of PCO. Of special interest are methods of culturing human LECs obtained by capsulotomy during cataract surgery, including those obtained with an intact capsular bag, to provide an in vitro model for investigating the pathophysiology of LECs; the effect of a sharp bend in the lens capsule that induces contact inhibition of migrating LECs; more specific inhibition of migrating LECs using an immunotoxin, b-FGF-saporin, or EDTA and RGD-peptides.
Art of MBoC4 : the complete set of figures from Molecular biology of the cell fourth edition (2002)

The Art of Molecular Biology of the Cell, fourth edition, CD-ROM contains the complete set of figures from Molecular Biology of the Cell, fourth edition for lecture presentation purposes.
Coagulation abnormalities in critically ill patients. (2006)

Many critically ill patients develop hemostatic abnormalities, ranging from isolated thrombocytopenia or prolonged global clotting tests to complex defects, such as disseminated intravascular coagulation. There are many causes for a deranged coagulation in critically ill patients and each of these underlying disorders may require specific therapeutic or supportive management. In recent years, new insights into the pathogenesis and clinical management of many coagulation defects in critically ill patients have been accumulated and this knowledge is helpful in determining the optimal diagnostic and therapeutic strategy.
Engineering and use of 32P‐labeled human recombinant interleukin‐11 for receptor binding studies (2002)

Human interleukin-11 (hIL-11) is a pleiotropic cytokine that is involved in numerous biological activities such as hematopoiesis, osteoclastogenesis, neurogenesis and female fertility. IL-11 is obviously a key reagent to study the IL-11 receptors. However, conventional radio-iodination techniques lead to a loss of IL-11 bioactivity. Here, we report the construction and the production of a new recombinant human IL-11 (FP Delta IL-11). In this molecule, a specific phosphorylation site (RRASVA) has been introduced at the N-terminus of rhIL-11. It can be specifically phosphorylated by bovine heart protein kinase and accordingly, easily radiolabeled with (32)P. A high radiological specific activity (250,000 c.p.m x ng(-1) of protein) was obtained with the retention of full biological activity of the protein. The binding of (32)P-labeled FP Delta IL-11 to Ba/F3 cells stably transfected with plasmids encoding human IL-11 receptors alpha and beta chains (IL-11R alpha and gp130) was specific and saturable with a high affinity as determined from Scatchard plot analysis. Availability of this new ligand should prompt further studies on IL-11R structure, expression and regulation.
Mapping Protein Modifications (2002)

An emerging truism of proteomics is that most proteins are present in living systems in multiply modified forms. In reviewing the “life cycle” of a protein in Chapter 2, we considered the formation of polypeptides on ribosomes, their posttranslational cleavage, their modification by endogenous and exogenous agents, the accumulation of oxidative damage, and their eventual degradation. All of these events involve distinct modifications to protein structures. The occurrence of modifications at multiple sites on some proteins adds to the complexity of the situation. Many of the techniques of protein biochemistry used over the past 50 years have allowed us to determine whether a protein is modified. In most cases, the determination tells us that the protein is modified, but does not tell us where it is modified. Knowing this is important, because the same modification at different sites may have different consequences.
WOUND CONTRACTION, THE EFFECTS OF SCAB FORMATION AND THE NATURE OF THE WOUND BED (1982)

The effects of scab formation and the nature of the wound bed on the contraction of wounds have been investigated. Rabbit paraffin gauze dressed flank wounds with the panniculus carnosus intact and rat paraffin gauze dressed full skin thickness back wounds had constant linear rates of movement of the wound margins throughout the time of contraction. Rabbit undressed wounds with the panniculus carnosus retained or excised and rat undressed wounds showed phases of rapid movement, no movement and normal movement of the wound margins during the course of contraction. These were effects of scab formation, they were transient and had little or no effect on the overall rate of wound contraction. The behaviour of rabbit undressed wounds with the panniculus excised was similar to that of comparable wounds with the panniculus intact, except that healing was delayed by approximately 3 days. Very variable behaviour was observed with rabbit paraffin gauze dressed wounds with the panniculus excised.