gebhart/patrepeval huggingface dataset:
Role of the Gla and First Epidermal Growth Factor-like Domains of Factor X in the Prothrombinase and Tissue Factor-Factor VIIa Complexes (2003)

Factor X (FX) has high structure homology with other proteins of blood coagulation such as factor IX (FIX) and factor VII (FVII). These proteins present at their amino-terminal extremity a gamma-carboxyglutamic acid containing domain (Gla domain), followed by two epidermal growth factor-like (EGF1 and EGF2) domains, an activation peptide, and a serine protease domain. After vascular damage, the tissue factor-FVIIa (TF-FVIIa) complex activates both FX and FIX. FXa interacts stoichiometrically with tissue pathway inhibitor (TFPI), regulating TF-FVIIa activity by forming the TF-FVIIa-TFPI-FXa quaternary complex. Conversely, FXa boosts coagulation by its association with its cofactor, factor Va (FVa). To investigate the contribution of the Gla and EGF1 domains of FX in these complexes, FX chimeras were produced in which FIX Gla and EGF1 domains substituted the corresponding domains of FX. The affinity of the two chimeras, FX/FIX(Gla) and FX/FIX(EGF1), for the TF-FVIIa complex was markedly reduced compared with that of wild-type-FX (wt-FX) independently of the presence of phospholipids. Furthermore, the association rate constants of preformed FX/FIX(Gla)-TFPI and FX/FIX(EGF1)-TFPI complexes with TF-FVIIa were, respectively, 10- and 5-fold slower than that of wt-FXa-TFPI complex. Finally, the apparent affinity of FVa was 2-fold higher for the chimeras than for wt-FX in the presence of phospholipids and equal in their absence. These data demonstrate that FX Gla and EGF1 domains contain residues, which interact with TF-FVIIa exosites contributing to the formation of the TF-FVIIa-FX and TF-FVIIa-TFPI-FXa complexes. On the opposite, FXa Gla and EGF1 domains are not directly involved in FVa binding.
Movement and dissolution of the nucleus (germinal vesicle) during Rana oocyte meiosis: Effect of demecolcine (Colcemid) and centrifugation (1986)

Abstract Demecolcine (Colcemid; DE), a colchicine derivative, augmented meiosis reinitiation by progesterone in the follicle‐enclosed oocyte of the frog, Rana pipiens . Whereas DE treatment alone had a minor stimulatory effect on germinal vesicle dissolution (GVD), this treatment elicited significant germinal vesicle movement (GVM) as evidenced by translocation of the GV to the oocyte surface. The effects of DE on GVM and progesterone‐induced GVD were also elicited in oocytes lacking follicle cells or other follicle wall components (type IV follicles), indicating that DE has a direct action on the oocyte itself. DE alone did not alter oocyte membrane voltage (V m ), resistance (R m ), or current (I m ) and did not interfere with the changes in these parameters usually elicited by progesterone. After 5 hr incubation of follicle‐enclosed oocytes with either DE or progesterone, or combinations of both, the GV could be moved to the animal pole surface with less centrifugal force compared to control follicles. This result suggests that a decrease in ooplasmic viscoelasticity is induced by progesterone, which is mimicked by DE before GVM or GVD normally begins. The results presented here support the idea that DE‐sensitive oocyte components such as microtubules are involved in the process of steroid‐induced meiosis. These findings provide a physiological basis for future studies of cytoskeletal involvement in the events of meiosis.
Distinct Hypermethylation Profile of Primary Breast Cancer Is Associated with Sentinel Lymph Node Metastasis (2005)

Hypermethylation profiling of primary breast tumors is significantly associated with known pathologic prognostic factors and may have additional clinical and pathologic utility for assessing patient prognosis and predicting early regional metastasis.
Cyclic Guanosine Monophosphate: Elevation in Degenerating Photoreceptor Cells of the C3H Mouse Retina (1974)

As a result of an early deficiency in cyclic nucleotide phosphodiesterase activity, guanosine 3',5'-monophosphate accumulates in retinal photoreceptor cells before they begin to degenerate. It is suggested that degeneration of the photoreceptor cells is related to an imbalance in their metabolism or function which is caused by the elevated levels of cyclic guanosine monophosphate.
Implementation of holonomic quantum computation through engineering and manipulating the environment (2007)

We consider an atom-field coupled system in which two pairs of four-level atoms are respectively driven by laser fields and trapped in two distant cavities that are connected by an optical fiber. First, we show that an effective squeezing reservoir can be engineered under appropriate conditions. Then, we show that a two-qubit geometric controlled-PHASE (CPHASE) gate between the atoms in the two cavities can be implemented through adiabatically manipulating the engineered reservoir along a closed loop. This scheme that combines an engineering environment with decoherence-free space and geometric phase quantum computation together has the following remarkable feature: a CPHASE gate with arbitrary phase shift is implemented by simply changing the strength and relative phase of the driving fields.
Clinical and immunologic effects of long‐term sublingual immunotherapy in asthmatic children sensitized to mites:a double‐blind, placebo‐controlled study (2000)

Our results suggest that treatment for 2 years with SLIT is clinically safe and effective in significantly decreasing respiratory symptoms in children with mild to moderate asthma sensitized to HDM. On the other hand, the lack of changes of the immunologic parameters calls for further investigations with special reference to kinetics and mechanism(s) of action of this mode of treatment.
An internal antisense RNA regulates expression of the photosynthesis gene isiA (2006)

Small regulatory noncoding RNAs exist in both eukaryotic and prokaryotic organisms. Most of these RNA transcripts are trans-encoded RNAs with short and only partial antisense complementarity to their target RNAs, which regulate gene expression by modifying mRNA stability and translation. In contrast, reports on the function of cis-encoded, perfectly complementary antisense RNAs in eubacteria are rare. Cyanobacteria respond to iron deficiency by expressing IsiA (iron stress-induced protein A), which forms a giant ring structure around photosystem I. Here, we show that this process is controlled by IsrR (iron stress-repressed RNA), a cis-encoded antisense RNA transcribed from the isiA noncoding strand. Artificial overexpression of IsrR under iron stress causes a strongly diminished number of IsiA-photosystem I supercomplexes, whereas IsrR depletion results in premature expression of IsiA. The coupled degradation of IsrR/isiA mRNA duplexes appears to be a reversible switch that can respond to environmental changes. IsrR is the only RNA known so far to regulate a photosynthesis component.
Emergence of immunoreactivities for phosphorylated tau and amyloid-β protein in chronic stage of fluid percussion injury in rat brain (1998)

Head injury is one of the potential environmental factors in Alzheimer's disease (AD). To study the chronic stage of concussive brain injury, histological analyses were performed 2-6 months after right lateral fluid percussion (FP) brain injury (3.6-4.8 atm) in rats. Six months after injury, numerous normal-looking neurons in the telencephalon and brain stem were immunoreactive with either antibody to phosphorylated tau or with four antibodies to beta-amyloid protein. Neuronal counts in the cortices were gradually decreased after injury, up to 42% loss at 6 months after injury. These neuropathological changes suggest that this animal model could serve as a good animal model of neurodegenerative diseases such as AD.
Comparison of heuristic dynamic programming and dual heuristic programming adaptive critics for neurocontrol of a turbogenerator (2002)

This paper presents the design of an optimal neurocontroller that replaces the conventional automatic voltage regulator (AVR) and the turbine governor for a turbogenerator connected to the power grid. The neurocontroller design uses a novel technique based on the adaptive critic designs (ACDs), specifically on heuristic dynamic programming (HDP) and dual heuristic programming (DHP). Results show that both neurocontrollers are robust, but that DHP outperforms HDP or conventional controllers, especially when the system conditions and configuration change. This paper also shows how to design optimal neurocontrollers for nonlinear systems, such as turbogenerators, without having to do continually online training of the neural networks, thus avoiding risks of instability.
CYTOKINE mRNA EXPRESSION IN THE LABIAL SALIVARY GLAND TISSUES FROM PATIENTS WITH PRIMARY SJöGREN'S SYNDROME (1995)

The pattern of cytokine mRNA expression in frozen minor salivary gland tissues from patients with primary Sjögren's syndrome (pSS) (n = 12) and controls (n = 8) using an in situ hybridization technique and oligonucleotide probes of interleukin-1 beta (IL-1 beta), tumour necrosis factor alpha and beta (TNF-alpha and TNF-beta), interleukin-6 (IL-6), interleukin-2 (IL-2) and its receptor (IL-2R), interleukin-4 (IL-4), interleukin-10 (IL-10), interferon-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta) was examined. In addition to in situ hybridization, immunohistochemistry was used to identify the subset of cells expressing IL-2 and IL-4 mRNA. Mononuclear cells involved in the minor salivary gland lesions of pSS patients were found to express mRNA for pro-inflammatory cytokines such as TNF-alpha and IL-1 beta, and cytokines involved in the regulation of B- and T-cell function (IL-2 and IL-6). In contrast, only three biopsies from patients with pSS express mRNA of inhibitory cytokines such as IFN-gamma and TGF-beta. Furthermore mRNA for IL-6 and IL-1 beta was also detected in the glandular epithelial cells suggesting that these cells may play a role in the pathogenesis of autoimmune lesion in Sjögren's syndrome. IL-10 mRNA was not detected while IL-4 mRNA was primarily detected in naïve T-lymphocytes of patients with a mild and early lesion. These results suggest that local production of cytokines by both mononuclear and epithelial cells may be involved in the immune-mediated destruction of exocrine glands in patients with pSS.
Direct appearance models (2005)

Active appearance model (AAM), which makes ingenious use of both shape and texture constraints, is a powerful tool for face modeling, alignment and facial feature extraction under shape deformations and texture variations. However, as we show through our analysis and experiments, there exist admissible appearances that are not modeled by AAM and hence cannot be reached by AAM search; also the mapping from the texture subspace to the shape subspace is many-to-one and therefore a shape should be determined entirely by the texture in it. We propose a new appearance model, called direct appearance model (DAM), without combining from shape and texture as in AAM. The DAM model uses texture information directly in the prediction of the shape and in the estimation of position and appearance (hence the name DAM). In addition, DAM predicts the new face position and appearance based on principal components of texture difference vectors, instead of the raw vectors themselves as in AAM. These lead to the following advantages over AAM: (1) DAM subspaces include admissible appearances previously unseen in AAM, (2) convergence and accuracy are improved, and (3) memory requirement is cut down to a large extent. The advantages are substantiated by comparative experimental results.
Synthesis of Leukotriene B4 Antagonists Labeled with In-111 or Tc-99m to Image Infectious and Inflammatory Foci (2005)

In previous studies we demonstrated that lipophilic (99m)Tc-labeled LTB4 antagonist 1 (RP517) accumulated in infectious foci in rabbits, but hepatobiliary clearance hampered imaging of abdominal lesions. We now report the use of cysteic acid as a pharmacokinetic modifier to improve the water solubility and renal clearance of three hydrophilic analogues of 1. Divalent LTB4 antagonist 17 (DPC11870-11) is a DTPA conjugate for radiolabeling with In-111. Monovalent LTB4 antagonists 15 (BMS57868-88) and divalent LTB4 antagonist 18 (BMS57868-81) are conjugated to bifunctional chelator HYNIC for radiolabeling with (99m)Tc. The three compounds labeled efficiently with 111In or (99m)Tc with high radiochemical purity and specific activities. Scintigraphic images obtained in New Zealand White rabbits having acute intramuscular E. coli infection demonstrated that all agents were able to clearly visualize the abscess, and clearance was exclusively renal. The biodistribution of the (99m)Tc-labeled LTB4 antagonists was affected by the coligands used with the HYNIC chelator and by the monovalent or divalent nature of the receptor binding moiety. The best scintigraphic images were obtained with monovalent HYNIC conjugate 15 using tricine and isonicotinic acid as coligands with HYNIC for coordination with (99m)Tc.
Enhanced Detection of Low Abundance Human Plasma Proteins Using a Tandem IgY12-SuperMix Immunoaffinity Separation Strategy (2008)

The enormous dynamic range of human bodily fluid proteomes poses a significant challenge for current MS-based proteomics technologies as it makes it especially difficult to detect low abundance proteins in human biofluids such as blood plasma, which is an essential aspect for successful biomarker discovery efforts. Here we present a novel tandem IgY12-SuperMix immunoaffinity separation system for enhanced detection of low abundance proteins in human plasma. The tandem IgY12-SuperMix system separates approximately 60 abundant proteins from the low abundance proteins in plasma, allowing for significant enrichment of low abundance plasma proteins in the SuperMix flow-through fraction. High reproducibility of the tandem separations was observed in terms of both sample processing recovery and LC-MS/MS identification results based on spectral count data. The ability to quantitatively measure differential protein abundances following application of the tandem separations was demonstrated by spiking six non-human standard proteins at three different levels into plasma. A side-by-side comparison between the SuperMix flow-through and IgY12 flow-through samples analyzed by both one- and two-dimensional LC-MS/MS revealed a 60-80% increase in proteome coverage as a result of the SuperMix separations, suggesting significantly enhanced detection of low abundance proteins. A total of 695 plasma proteins were confidently identified in a single analysis (with a minimum of two peptides per protein) by coupling the tandem separation strategy with two-dimensional LC-MS/MS, including 42 proteins with reported normal concentrations of approximately 100 pg/ml to 100 ng/ml. The concentrations of two selected proteins, macrophage colony-stimulating factor 1 and matrix metalloproteinase-8, were independently validated by ELISA as 202 pg/ml and 12.4 ng/ml, respectively. Evaluation of binding efficiency revealed that 45 medium abundance proteins were efficiently captured by the SuperMix column with >90% retention. Taken together, these results illustrate the potential broad utilities of this tandem IgY12-SuperMix strategy for proteomics applications involving human biofluids where effectively addressing the dynamic range challenge of the specimen is imperative.
Enhanced Osteoclastogenesis Causes Osteopenia in Twisted Gastrulation-Deficient Mice Through Increased BMP Signaling (2009)

The uncoupling of osteoblastic and osteoclastic activity is central to disorders such as osteoporosis, osteolytic malignancies, and periodontitis. Numerous studies have shown explicit functions for bone morphogenetic proteins (BMPs) in skeletogenesis. Their signaling activity has been shown in various contexts to be regulated by extracellular proteins, including Twisted gastrulation (TWSG1). However, experimental paradigms determining the effects of BMP regulators on bone remodeling are limited. In this study, we assessed the role of TWSG1 in postnatal bone homeostasis. Twsg1-deficient (Twsg1(-/-)) mice developed osteopenia that could not be explained by defective osteoblast function, because mineral apposition rate and differentiation markers were not significantly different compared with wildtype (WT) mice. Instead, we discovered a striking enhancement of osteoclastogenesis in Twsg1(-/-) mice, leading to increased bone resorption with resultant osteopenia. Enhanced osteoclastogenesis in Twsg1(-/-) mice was caused by increased cell fusion, differentiation, and function of osteoclasts. Furthermore, RANKL-mediated osteoclastogenesis and phosphorylated Smad1/5/8 levels were enhanced when WT osteoclasts were treated with recombinant BMP2, suggesting direct regulation of osteoclast differentiation by BMPs. Increase in detectable levels of phosphorylated Smad 1/5/8 was noted in osteoclasts from Twsg1(-/-) mice compared with WT mice. Furthermore, the enhanced osteoclastogenesis in Twsg1(-/-) mice was reversed in vitro in a dose-dependent manner with exposure to Noggin, a BMP antagonist, strongly suggesting that the enhanced osteoclastogenesis in Twsg1 mutants is attributable to increased BMP signaling. Thus, we present a novel and previously uncharacterized role for TWSG1 in inhibiting osteoclastogenesis through regulation of BMP activity.
Echinomycin Binding Sites on DNA (1984)

The preferred binding sites of echinomycin on DNA can be determined by a method called "footprinting." A 32P end-labeled restriction fragment from pBR322 DNA is protected by binding to echinomycin, and cleaved by a synthetic DNA cleaving reagent, methidiumpropyl--EDTA . Fe(II); the DNA cleavage products are then subjected to high-resolution gel analyses. This method reveals that echinomycin has a binding site size of four base pairs. The strong binding sites for echinomycin contain the central two-base-pair sequence 5'-CG-3'. From an analysis of 15 echinomycin sites on 210 base pairs of DNA, key recognition elements for echinomycin are contained in the sequences (5'-3') ACGT and TCGT (A, adenine; C, cytosine; G, guanine; T, thymine).
Activation of the Protein Kinase ERK5/BMK1 by Receptor Tyrosine Kinases (1999)

ERK5 (also known as BMK1), a member of the mitogen-activated protein kinase (MAPK) superfamily, was known to be activated strongly by oxidant and osmotic stresses. Here we have found that ERK5 is strongly activated by epidermal growth factor and nerve growth factor, whose receptors are tyrosine kinases. The activation of ERK5 was inhibited by expression of dominant-negative Ras and induced by expression of active Ras in PC12 cells, indicating a requirement for Ras in ERK5 activation. The epidermal growth factor-induced activation of ERK5 was found to be inhibited by PD98059 and U0126 inhibitors, which were previously thought to act specifically on classical MAPK kinase (also known as MEK1) and readily reversed by CL100 and MKP-3 dual-specificity phosphatases for which classical MAPKs were previously shown to serve as preferred substrates. The reporter assays demonstrated that the serum-induced enhancement of transcription from serum response element was significantly inhibited by expression of a dominant-negative form of MEK5, which was a direct and specific activator for ERK5 and that transcription from serum response element mediated by the Ets-domain transcription factor Sap1a, but not by Elk1, was stimulated by coexpression of ERK5 and active MEK5. In addition, Sap1a was shown to be phosphorylated by ERK5 in vitro and by the activation of the ERK5 pathway in cells. Moreover, the serum-induced c-Fos expression was markedly inhibited by expression of dominant-negative MEK5. These results reveal a novel signaling pathway to the nucleus mediated by ERK5 that functions downstream of receptor tyrosine kinases to induce immediate early genes, in parallel with the classical MAPK cascade.
Processes for the Production of Xylitol—A Review (2012)

Xylitol is a sugar alcohol that is used as a sweetener for diabetics and also for other purposes (e.g., in chewing gum). Industrially, xylitol is manufactured through a chemical process that has some disadvantages, including a high energy requirement, extensive purification steps, and a high cost of product. The microbial production of xylitol has been examined as an alternative to the chemical process, which on an industrial scale is time-consuming mainly due to sterilization and inoculum development. The enzymatic production of xylitol from lignocellulosics is an attractive and promising alternative to the chemical process, potentially eliminating the major disadvantages of conventional processes. This article reviews the literature on xylitol production processes and identifies ways to further improve xylitol synthesis to compete with the current chemical process.
Sugar profiling proves that human serum erythropoietin differs from recombinant human erythropoietin (2001)

Erythropoietin (EPO) from sera obtained from anemic patients was successfully isolated using magnetic beads coated with a human EPO (hEPO)-specific antibody. Human serum EPO emerged as a broad band after sodium dodecyl sulfate-polyacrylamide gel electrophoresis, with an apparent molecular weight slightly smaller than that of recombinant hEPO (rhEPO). The bandwidth corresponded with microheterogeneity because of extensive glycosylation. Two-dimensional gel electrophoresis revealing several different glycoforms confirmed the heterogeneity of circulating hEPO. The immobilized anti-hEPO antibody was capable of binding a representative selection of rhEPO glycoforms. This was shown by comparing normal-phase high-performance liquid chromatography profiles of oligosaccharides released from rhEPO with oligosaccharides released from rhEPO after isolation with hEPO-specific magnetic beads. Charge analysis demonstrated that human serum EPO contained only mono-, di-, and tri-acidic oligosaccharides and lacked the tetra-acidic structures present in the glycans from rhEPO. Determination of charge state after treatment of human serum EPO with Arthrobacter ureafaciens sialidase showed that the acidity of the oligosaccharide structures was caused by sialic acids. The sugar profiles of human serum EPO, describing both neutral and charged sugar, appeared significantly different from the profiles of rhEPO. The detection of glycan structural discrepancies between human serum EPO and rhEPO by sugar profiling may be significant for diagnosing pathologic conditions, maintaining pharmaceutical quality control, and establishing a direct method to detect the misuse of rhEPO in sports.
Peroxisomal Degradation of Branched-Chain 2-Oxo Acids (1989)

Branched-chain 2-oxo acids which are formed by transamination of leucine, isoleucine, and valine are metabolized by the peroxisomes from mung bean (Vigna radiata L.) hypocotyls. Acylcoenzyme A (CoA) thio ester intermediates of the pathways were separated by reversed-phase high performance liquid chromatography. Retention time and cochromatography of individual acyl-CoA reference standards were used for identification of the acyl-CoA esters separated from the assay mixtures. Based on the results of identification and those of kinetic experiments, pathways of the peroxisomal degradation of 2-oxoisocaproate, 2-oxoisovalerate, and 2-oxo-3-methylvalerate are suggested.
Transient expression of SorCS in developing telencephalic and mesencephalic structures of the mouse (2001)

Here we describe the expression of a third member of the VPS10 domain containing receptor family, SorCS, during mouse embryonal and early postnatal nervous system development. SorCS is expressed in a unique transient and dynamic pattern in regions where cells proliferate, as well as in areas where already differentiated cells reside, including the cerebral cortex, the ventral tegmental area, and the globus pallidus. Transcripts were absent from fiber tracts hinting at a neuronal expression. The only exception was hybridization signals on the developing optic nerve correlating with the appearance of astrocytes migrating into the retina.