gebhart/patrepeval huggingface dataset:
Dynamics of Glomerular Ultrafiltration in the Rat. IV. DETERMINATION OF THE ULTRAFILTRATION COEFFICIENT (1973)

Pressures and flow rates were measured in accessible surface glomeruli of mutant Wistar rats under conditions deliberately designed to prevent achievement of filtration pressure equilibrium, that is, the equalization of transcapillary hydrostatic and oncotic pressures by the efferent end of the glomerulus as typically observed in the normal hydropenic rat. Disequilibrium was obtained at elevated levels of glomerular plasma flow (GPF) brought about by acute expansion of plasma volume with a volume of rat plasma equal to 5% of body weight. Glomerular hydrostatic and oncotic pressures measured at high GPF were used to calculate the ultrafiltration coefficient, K(f), the product of effective hydraulic permeability and surface area. GPF was then either lowered (by aortic constriction) or raised (by carotid occlusion) in order to examine the dependence of K(f) on GPF. The value of K(f) per glomerulus, 0.08 nl/(s.mm Hg), was found not to vary over an approximately twofold range of GPF. This finding, taken together with data from previous studies from this laboratory, leads us to conclude that plasma-flow dependence of glomerular filtration rate (GFR) results primarily from flow-induced changes in mean ultrafiltration pressure, rather than large changes in K(f).
Molecular physiology of SLC4 anion exchangers (2005)

Plasmalemmal Cl- -HCO3- exchangers regulate intracellular pH and [Cl-] and cell volume. In polarized epithelial cells, they contribute also to transepithelial secretion and reabsorption of acid-base equivalents and of Cl-. Members of both the SLC4 and SLC26 mammalian gene families encode Na+-independent Cl- -HCO3- exchangers. Human SLC4A1/AE1 mutations cause either the erythroid disorders spherocytic haemolytic anaemia or ovalocytosis, or distal renal tubular acidosis. SLC4A2/AE2 knockout mice die at weaning. Human SLC4A3/AE3 polymorphisms have been associated with seizure disorder. Although mammalian SLC4/AE polypeptides mediate only electroneutral Cl- -anion exchange, trout erythroid AE1 also promotes osmolyte transport and increased anion conductance. Mouse AE1 is required for DIDS-sensitive erythroid Cl- conductance, but definitive evidence for mediation of Cl- conductance is lacking. However, a single missense mutation allows AE1 to mediate both electrogenic SO4(2-) -Cl- exchange or electroneutral, H+-independent SO4(2)- -SO4(2-) exchange. In the Xenopus oocyte, the AE1 C-terminal cytoplasmic tail residues reported to bind carbonic anhydrase II are dispensable for Cl- -Cl- exchange, but required for Cl- -HCO3- exchange. AE2 is acutely and independently inhibited by intracellular and extracellular H+, and this regulation requires integrity of the most highly conserved sequence of the AE2 N-terminal cytoplasmic domain. Individual missense mutations within this and adjacent regions identify additional residues which acid-shift pHo sensitivity. These regions together are modelled to form contiguous surface patches on the AE2 cytoplasmic domain. In contrast, the N-terminal variant AE2c polypeptide exhibits an alkaline-shifted pHo sensitivity, as do certain transmembrane domain His mutants. AE2-mediated anion exchange is also stimulated by ammonium and by hypertonicity by a mechanism sensitive to inhibition by chelation of intracellular Ca2+ and by calmidazolium. This growing body of structure-function data, together with increased structural information, will advance mechanistic understanding of SLC4 anion exchangers.
Design of HIV-1 Protease Inhibitors with Pyrrolidinones and Oxazolidinones as Novel P1′-Ligands To Enhance Backbone-Binding Interactions with Protease: Synthesis, Biological Evaluation, and Protein−Ligand X-ray Studies (2009)

Structure-based design, synthesis, and biological evaluation of a series of novel HIV-1 protease inhibitors are described. In an effort to enhance interactions with protease backbone atoms, we have incorporated stereochemically defined methyl-2-pyrrolidinone and methyl oxazolidinone as the P1'-ligands. These ligands are designed to interact with Gly-27' carbonyl and Arg-8 side chain in the S1'-subsite of the HIV protease. We have investigated the potential of these ligands in combination with our previously developed bis-tetrahydrofuran (bis-THF) and cyclopentanyltetrahydrofuran (Cp-THF) as the P2-ligands. Inhibitor 19b with a (R)-aminomethyl-2-pyrrolidinone and a Cp-THF was shown to be the most potent compound. This inhibitor maintained near full potency against multi-PI-resistant clinical HIV-1 variants. A high resolution protein-ligand X-ray crystal structure of 19b-bound HIV-1 protease revealed that the P1'-pyrrolidinone heterocycle and the P2-Cp-ligand are involved in several critical interactions with the backbone atoms in the S1' and S2 subsites of HIV-1 protease.
Interleukin 1 regulates hematopoietic activity, a role previously ascribed to hemopoietin 1. (1987)

A murine in vitro assay was developed to measure potentiation of a proliferative response to suboptimal concentrations of the hematopoietic regulatory molecule granulocyte/macrophage colony-stimulating factor by an immature bone marrow population. The assay, designated the 5-fluorouracil bone marrow proliferation assay, was used to characterize potentiating activity in serum-free culture supernatants of the human tumor cell line HBT 5637. Molecular and biochemical analyses indicated that the HBT 5637-derived potentiating activity could be attributed to interleukin 1 alpha. Serologic analysis using a monoclonal antibody against purified recombinant interleukin 1 alpha proved conclusively that the potentiating activity in HBT 5637 serum-free supernatants is due to interleukin 1 alpha. From these data, the activity of interleukin 1 alpha seems to be the same synergistic activity formerly ascribed to hemopoietin 1.
Nausea and Vomiting Side Effects with Opioid Analgesics during Treatment of Chronic Pain: Mechanisms, Implications, and Management Options (2009)

Nausea and vomiting side effects limit the analgesic efficiency of current opioid therapies. There is a clear need for the development of improved opioid-based analgesics that mitigate these intolerable effects.
Synthesis of Secondary Arylamines through Copper-Mediated Intermolecular Aryl Amination (2003)

A mild intermolecular copper-mediated amination of aryl iodides has been developed. The reaction takes place at room temperature or heating at 90 degrees C and tolerates halogens attached to the aromatic ring. Its synthetic applications include a synthetic protocol for unsymmetrical N,N'-dialkylated phenylenediamines and both a stepwise and a general synthetic method for N-aryl secondary amines via Ns-anilides (readily obtained by reaction of the Ns-amide). [reaction: see text]
Analysis ofThalassiosira pseudonanaSilicon Transporters Indicates Distinct Regulatory Levels and Transport Activity through the Cell Cycle (2006)

An analysis of the expression and activity of silicon transporters (SITs) was done on synchronously growing cultures of the diatom Thalassiosira pseudonana to provide insight into the role these proteins play in cellular silicon metabolism during the cell cycle. The first SIT-specific polyclonal peptide antibody was generated and used in the immunoblot analysis of whole-cell protein lysates to monitor SIT protein levels during synchronized progression through the cell cycle. Peaks in SIT protein levels correlated with active periods of silica incorporation into cell wall substructures. Quantitative real-time PCR on each of the three distinct SIT genes (TpSIT1, TpSIT2, and TpSIT3) showed that mRNA levels for the most highly expressed SIT genes peaked during the S phase of the cell cycle, a period prior to maximal silicon uptake and during which cell wall silicification does not occur. Variations in protein and mRNA levels did not correlate, suggesting that a significant regulatory step of SITs is at the translational or posttranslational level. Surge uptake rates also did not correlate with SIT protein levels, suggesting that SIT activity is internally controlled by the rate of silica incorporation. This is the first study to characterize SIT mRNA and protein expression and cellular uptake kinetics during the course of the cell cycle and cell wall synthesis, and it provides novel insight into SIT regulation.
Superconducting Qubits: A Short Review (2004)

Superconducting qubits are solid state electrical circuits fabricated using techniques borrowed from conventional integrated circuits. They are based on the Josephson tunnel junction, the only non-dissipative, strongly non-linear circuit element available at low temperature. In contrast to microscopic entities such as spins or atoms, they tend to be well coupled to other circuits, which make them appealling from the point of view of readout and gate implementation. Very recently, new designs of superconducting qubits based on multi-junction circuits have solved the problem of isolation from unwanted extrinsic electromagnetic perturbations. We discuss in this review how qubit decoherence is affected by the intrinsic noise of the junction and what can be done to improve it.
Adenomatous Polyposis Coli Control of C-terminal Binding Protein-1 Stability Regulates Expression of Intestinal Retinol Dehydrogenases (2006)

Mutations in the human adenomatous polyposis coli (APC) gene are thought to initiate colorectal tumorigenesis. The tumor suppressor function of APC is attributed primarily to its ability to regulate the WNT pathway by targeting the destruction of beta-catenin. We report here a novel role for APC in regulating degradation of the transcriptional co-repressor C-terminal-binding protein-1 (CtBP1) through a proteasome-dependent process. Further, CtBP1 suppresses the expression of intestinal retinol dehydrogenases, which are required for retinoic acid production and intestinal differentiation. In support of a role for CtBP1 in initiation of colorectal cancer, adenomas taken from individuals with familial adenomatous polyposis contain high levels of CtBP1 protein in comparison with matched, uninvolved tissue. The relationship between APC and CtBP1 is conserved between humans and zebrafish and provides a mechanistic model explaining APC control of intestinal retinoic acid biosynthesis.
Local politicians and Officials perspective on Health Promotion activities in four municipalities in Sweden. (2007)

Introduction: In the Swedish National Public Health Policy (SNPHP) from year 2003 the overall aim is to create social conditions which ensure good health for the entire population. The policy inc ...
Prevention of transmission of Babesia canis by Dermacentor reticulatus ticks to dogs after topical administration of fluralaner spot-on solution (2016)

A single topical administration of fluralaner spot-on solution effectively prevented the transmission of B. canis by infected D. reticulatus ticks over a 12-week period.
Non‐iterative Second‐order Approximation of Signed Distance Functions for Any Isosurface Representation (2010)

Abstract Signed distance functions (SDF) to explicit or implicit surface representations are intensively used in various computer graphics and visualization algorithms. Among others, they are applied to optimize collision detection, are used to reconstruct data fields or surfaces, and, in particular, are an obligatory ingredient for most level set methods. Level set methods are common in scientific visualization to extract surfaces from scalar or vector fields. Usual approaches for the construction of an SDF to a surface are either based on iterative solutions of a special partial differential equation or on marching algorithms involving a polygonization of the surface. We propose a novel method for a non‐iterative approximation of an SDF and its derivatives in a vicinity of a manifold. We use a second‐order algebraic fitting scheme to ensure high accuracy of the approximation. The manifold is defined (explicitly or implicitly) as an isosurface of a given volumetric scalar field. The field may be given at a set of irregular and unstructured samples. Stability and reliability of the SDF generation is achieved by a proper scaling of weights for the Moving Least Squares approximation, accurate choice of neighbors, and appropriate handling of degenerate cases. We obtain the solution in an explicit form, such that no iterative solving is necessary, which makes our approach fast.
Fragment E1 labeled with I-123 in the detection of venous thrombosis. (1985)

Fragment E1, which has been shown to have specific binding affinity for thrombi in an animal model, was investigated in humans for its safety and ability to bind to venous thrombi. Human Fragment E1 was labeled with I-123 and administered intravenously to patients with proved or suspected deep vein thrombosis. The vascular distribution of radioactivity was documented by obtaining gamma camera images of the patients' legs for 30 minutes following administration of I-123-Fragment E1. All patients (n = 5) with documented venous thrombi had rapid localization of labeled Fragment E1 in the area of thrombus. Patients without evidence of thrombi (n = 5) showed no focal localization, although two of these patients showed diffuse uptake along the length of the veins, due to superficial phlebitis. Analysis of blood samples in four patients indicated that disappearance of Fragment E1 from the circulation was more rapid in individuals with thrombosis (t 1/2 = 20 min) than in individuals without thrombosis (t 1/2 = 90 min), and a radiolabeled species of high molecular weight was found in patients with thrombosis but was absent from patients without thrombosis. These early results suggest that radiolabeled Fragment E1 is a safe and potentially valuable agent for the rapid detection of venous thrombosis.
Natural variation of tyrosyl-tRNA synthetase and comparison with engineered mutants (1986)

We report the cloning and sequence analysis of the gene for the tyrosyl-tRNA synthetase from Bacillus caldotenax and properties of the gene product. The amino acid sequence of the tyrosyl-tRNA synthetase was found to be 99% homologous with the corresponding enzyme from B. stearothermophilus, with only four amino acid differences. Two of these natural variations were found to involve active site residues of the enzyme and correspond to mutations that have been engineered previously in vitro. One, Thr-51----Ala-51, produced a more active enzyme, possessing a higher value of kcat/KM for ATP. Position 51 is a "hot spot" in the tyrosyl-tRNA synthetase, differing in enzymes derived from Escherichia coli, B. stearothermophilus, and B. caldotenax. The other, His-48----Asn-48, is found to be a neutral mutation but is in one of the rare regions that are conserved with other aminoacyl-tRNA synthetases. The equivalence of histidine and asparagine at position 48 extends the homology in this region to more enzymes. These residues, His-Ile-Gly-His, and now His-Ile-Gly-Asn, form part of the binding site for ATP in the transition state of the reaction. Although B. caldotenax is an obligate thermophile with an optimal growth temperature of 80 degrees C, as much as 20 degrees C above the growth optima of strains of Bacillus stearothermophilus, its tyrosyl-tRNA synthetase has an identical thermal stability in vitro to that from B. stearothermophilus.
Cultured marrow stromal cells express common acute lymphoblastic leukaemia antigen (CALLA): implications for marrow transplantation (1983)

This study demonstrates the presence of an antigenic determinant associated with the common acute lymphoblastic leukaemia antigen (CALLA), and presumably CALLA itself, on stromal cells in normal human long-term marrow cultures by using two monoclonal anti-CALLA antibodies, J-5 and 24.1. Treatment of cultured stromal cells with antibody and complement resulted in the loss of most flat angulated cells and many of the fat-containing cells. However, long-term cultures were generated with cytotoxic antibody-treated marrow buffy coat cells, and the stromal cells in these cultures were also CALLA-positive. We conclude that CALLA-bearing stromal cells arise from CALLA-negative progenitors. CALLA therefore could be either a differentiation antigen acquired on mature marrow stromal cells or may arise as a proliferation-dependent antigen. These studies suggest that the generation of long-term cultures from cytotoxic antibody-treated marrow may be an appropriate in vitro model for the functional assessment of such marrow prior to its use in autologous transplantation.
TCP Congestion Control (1999)

This document defines TCP's four intertwined congestion control algorithms: slow start, congestion avoidance, fast retransmit, and fast recovery. In addition, the document specifies how TCP should begin transmission after a relatively long idle period, as well as discussing various acknowledgment generation methods. This document obsoletes RFC 2581.
Hedgehog pathway inhibitors – current status and future prospects (2012)

The Hedgehog (Hh) proteins comprise a group of secreted proteins that regulate cell growth, differentiation and survival. Inappropriate activation of the Hh signaling pathway has been implicated in the development of a variety of cancers. Hedgehog pathway inhibitors are a relatively new class of therapeutic agents that act by targeting the proteins involved in the regulation of Hh pathway (PTCH, SMO and Gli). Together, they serve as exciting new prospects, with a bright future, both alone or as an adjuvant to the more traditional anti-cancer drugs.
Polymers for siRNA Delivery: Inspired by Viruses to be Targeted, Dynamic, and Precise (2011)

Synthetic small interfering RNA (siRNA) presents an exciting novel medical opportunity. Although researchers agree that siRNA could have a great therapeutic impact, the required extracellular and intracellular delivery of these molecules into the disease-associated target cells presents the primary roadblock for the broader translation of these molecules into medicines. Thus, the design of adequate delivery technologies has utmost importance. Viruses are natural masterpieces of nucleic acid delivery and present chemists and drug delivery experts with a template for the design of artificial carriers for synthetic nucleic acids such as siRNA. They have been developed into gene vectors and have provided convincing successes in gene therapy. Optimized by biological evolution, viruses are programmed to be dynamic and bioresponsive as they enter living cells, and they carry out their functions in a precisely defined sequence. However, because they are synthesized within living cells and with naturally available nucleotides and amino acids, the chemistry of viruses is limited. With the use of diverse synthetic molecules and macromolecules, chemists can provide delivery solutions beyond the scope of the natural evolution of viruses. This Account describes the design and synthesis of "synthetic siRNA viruses." These structures contain elements that mimic the delivery functions of viral particles and surface domains that shield against undesired biological interactions and enable specific host cell receptor binding through the presentation of multiple targeting ligands. For example, cationic polymers can reversibly package one or more siRNA molecules into nanoparticle cores to protect them against a degradative bioenvironment. After internalization by receptor-mediated endocytosis into the acidifying endosomes of cells, synthetic siRNA can escape from these vesicles through the activation of membrane-disruption domains as viruses do and reach the cytoplasm, the location of RNA interference. This multistep task presents an attractive challenge for chemists. Similar to the design of prodrugs, the functional domains of these systems have to be activated in a dynamic mode, triggered by conformational changes or bond cleavages in the relevant microenvironment such as the acidic endosome or disulfide-reducing cytoplasm. These chemical analogues of viral domains are often synthetically simpler and more easily accessible molecules than viral proteins. Their precise assembly into multifunctional macromolecular and supramolecular structures is facilitated by improved analytical techniques, precise orthogonal conjugation chemistries, and sequence-defined polymer syntheses. The chemical evolution of microdomains using chemical libraries and macromolecular and supramolecular evolution could provide key strategies for optimizing siRNA carriers to selected medical indications.
Krüppel-like transcription factors and control of pluripotency (2010)

Recent papers have demonstrated a role for Krüppel-like transcription factors 2, 4 and 5 in the control of mouse embryonic stem cell pluripotency. However, it is not clear whether each factor has a unique role or whether they are functionally redundant. A paper by Parisi and colleagues in BMC Biology now sheds light on the mechanism by which Klf5 regulates pluripotency. See research article http://www.biomedcentral.com/1741-7007/8/128.
Vascular Smooth Muscle Cell Proliferation: Basic Investigations and New Therapeutic Approaches (1993)

Our investigations are based upon the hypothesis that synthesis and release of numerous mitogens allow interaction with a correspondingly large set of specific receptors to initiate a variety of secondary messages which eventually lead to SMC proliferation and migration. Unfortunately, the experimental tools available for studying these critical biologic systems under in vivo conditions are quite limited. Previous investigators have partially elucidated the growth factors responsible for intimal accumulation by infusing specific antibodies against individual mitogens such as PDGF or bFGF. However, no general approach was available to identify critical intracellular intermediates of the above pathway. We thought that antisense oligonucleotides might be useful in pinpointing these key components by specifically inhibiting their expression and then determining the effects of the suppression on SMC response in vivo. Data summarized above strongly imply that c-myb is a critical intermediate of a common mitogenic pathway required by all growth factors involved in SMC migration and growth. Given the previously documented in vitro effect of antisense oligonucleotide, we believe that the proto-oncogene is involved in proliferation. The drug heparin and blood vessel wall heparan sulfates probably also inhibit SMC growth via suppression of c-myb. Thus, endothelial cell and SMC heparan sulfates appear to constitute a natural blood vessel wall antiproliferative pathway. To the best of our knowledge, these studies constitute the first reported use of antisense oligonucleotide to inhibit synthesis of a normal gene product under in vivo conditions with a subsequent effect upon a cellular process.(ABSTRACT TRUNCATED AT 250 WORDS)
Solid-Phase Sequencing of Biotinylated PCR Products with Streptavidin-Coated Magnetic Beads (2003)

A novel approach to generating high-quality single-stranded DNA involves solid-phase sequencing. A biotin group is incorporated at the 5'-end of one of the amplification primers and as a result becomes incorporated into PCR product during the amplification reaction. The DNA can then be immobilized onto streptavidin-coated paramagnetic beads, simultaneously removing buffers, dNTPs, and unincorporated PCR primers. By alkali denaturation, the immobilized double-stranded DNA is converted into a single-stranded template, which can then be purified away from its complementary strand, avoiding any competition in the subsequent sequencing reaction. Although the protocol detailed in this chapter is designed to purify and sequence PCR products, the method is broadly applicable to the solid-phase sequencing of many other templates, e.g., plasmid DNA.