gebhart/patrepeval huggingface dataset:
Processing of human acid sphingomyelinase in normal and I-cell fibroblasts. (1994)

The biosynthesis of acid sphingomyelinase in normal and I-cell disease fibroblasts was investigated by metabolic labeling with [35S]methionine and immunoprecipitation followed by polyacrylamide gel electrophoresis and fluorography. Two major polypeptides with apparent molecular masses of 75 and 72 kDa (peptide chains of 64 and 61 kDa, respectively) and a minor one with molecular mass of 57 kDa (peptide chain of 47 kDa) were found intracellularly soon after pulse labeling. The 75-kDa form is assumed to be the propropolypeptide of sphingomyelinase which is converted into the precursor form of 72 kDa. The precursor is subjected to two distinct processing events. A minor part is already cleaved in the endoplasmic reticulum-Golgi complex yielding the beta-endo-N-acetylglucosaminidase H-resistant form of 57 kDa; whereas, the major part of the precursor is processed within 4 h to a 70-kDa mature beta-endo-N-acetylglucosaminidase H-sensitive form of sphingomyelinase, which is subsequently converted into a polypeptide with molecular mass of 52 kDa within a chase of about 20 h. Both the precursor (72 kDa) as well as its early cleavage product of 57 kDa are secreted into the culture medium to a minor extent. Intracellular transport of sphingomyelinase into lysosomes depends on the phosphomannosyl specific receptor by following criteria: (i) about 80% of newly synthesized precursor was secreted in NH4Cl-treated fibroblasts as well as in I-cells, (ii) the maturation of sphingomyelinase was inhibited in normal fibroblasts exposed to NH4Cl as well as in I-cell fibroblasts, and (iii) the [32P]phosphate associated with oligosaccharides was cleavable by beta-endo-N-acetylglucosaminidase H. However, endocytosis of radiolabeled extracellular precursor by fibroblasts was not prevented by the addition of mannose 6-phosphate, whereas uptake of arylsulfatase A and beta-hexosaminidase was almost completely blocked under these conditions. This indicates that endocytosis of acid sphingomyelinase by cultured fibroblasts might be mediated by an alternative pathway.
Enzyme Replacement Therapy of Exocrine Pancreatic Insufficiency in Man (1977)

I assayed 16 commercially available pancreatic extracts (representing capsules, tablets and enteric-coated tablets) for enzyme activities and the relation between the in vitro activities and in vivo potency evaluated in man. Lipase activity ranged from 10 to 3600 units per unit, with 11 preparations containing less than 600 units per unit. The preparations with the highest lipase activities were llozyme, 3600, Kuzyme HP, 2330, Festal, 2073, Cotazym, 2014, and Viokase, 1636 units. Lipase activity in vitro correlated with potency in vivo for tablets and capsules, with tablets and capsules being effective in reducing steatorrhea by 56.1±9 per cent and 48.6±10 per cent (mean ±S.E.M.) respectively, P<0.001. Enteric-coated tablets were less effective (20±13 per cent reduction, P>0.02). The longer the gastric pH remained ≥4 (r = 0.915, P<0.01) and the higher the average duodenal pH (r = 0.966, P<0.01), the more marked the reduction in steatorrhea. (N Engl J Med 296:1314–1317, 1977)
Automated modelling of the transmembrane region of G-protein coupled receptor by Swiss-model. (1996)

Molecular modelling of the transmembrane helices of G-protein coupled receptors is an increasingly used method to identify the possible three-dimensional environment of key residues. Thereby site-directed mutagenesis experiments, aimed at the understanding of the receptor-ligand interactions, can be designed in a rational way. The modelling methods are however not generally available to experimentalists, and often require expensive software and hardware. To overcome these limitations, we have constructed a World Wide Web server for the automated protein modelling of user-defined transmembrane helices. The service is freely available at this address: http:/(/)expasy.hcuge.ch/swissmod/SWISS-MODEL.++ +html.
Iron Status in the Female Blood Donor (1998)

Iron deficiency has important clinical significance in the American population. Many women are at risk for iron deficiency anemia and those who are blood donors are more susceptible for iron deficiency anemia due to the increased blood loss. The traditional measure of hemoglobin fails to detect the first two stages of iron deficiency. Because female blood donors are at higher risk for iron deficiency it is necessary to improve detection of the earlier stages of iron deficiency before anemia and other clinical symptoms are manifested. Female blood donors exhibit a protective mechanism and have been found to increase rates of iron absorption due to a hypothesized increase in their setpoint for iron storage. The increased demand for iron as a result of blood donation is due to increased activity of erythropoiesis. Iron supplementation may be an important factor in preventing iron deficiency anemia in repeat female blood donors.
Protease-Activated Receptor-1 and Platelet-Derived Growth Factor in Spinal Cord Neurons Are Implicated in Neuropathic Pain after Nerve Injury (2005)

Recently, it has been reported that both thrombin-sensitive protease-activated receptor 1 (PAR-1) and platelet-derived growth factor (PDGF) are present not only in platelets, but also in the CNS, which indicates that they have various physiological functions. In this study, we evaluated whether PAR-1/PDGF in the spinal cord could contribute to the development of a neuropathic pain-like state in mice. Thermal hyperalgesia and tactile allodynia induced by sciatic nerve ligation were significantly suppressed by repeated intrathecal injection of hirudin, which is characterized as a specific and potent thrombin inhibitor. Furthermore, a single intrathecal injection of thrombin produced long-lasting hyperalgesia and allodynia, and these effects were also inhibited by hirudin in normal mice. In nerveligated mice, the increase in the binding of [35S]GTPgammaS to membranes of the spinal cord induced by thrombin and PAR-1-like immunoreactivity (IR) in the spinal cord were each greater than those in sham-operated mice. Thermal hyperalgesia and tactile allodynia induced by sciatic nerve ligation were also suppressed by repeated intrathecal injection of either the PDGF alpha receptor (PDGFRalpha)/Fc chimera protein or the PDGFR-dependent tyrosine kinase inhibitor AG17 [(3,5-di-tert-butyl-4-hydroxybenzylidene)-malononitrile]. Moreover, thermal hyperalgesia and tactile allodynia induced by thrombin in normal mice were virtually eliminated by intrathecal pretreatment with PDGFRalpha/Fc. In immunohistochemical studies, PAR-1-like IR-positive cells in the spinal dorsal horn were mostly colocated on PDGF-like IR-positive neuronal cells. These data provide novel evidence that PAR-1 and PDGF-A-mediated signaling pathway within spinal cord neurons may be directly implicated in neuropathic pain after nerve injury in mice.
Temporal processing deficits in high‐functioning children with autism (2004)

It is well known that complex functions (e.g. perception, attention, memory, emotions, social interactions and language) are usually disturbed in autism. As these functions are characterized by specific temporal patterns, the present study examined whether children with autism show typical temporal processing in the time domain of a few seconds. Using a temporal-reproduction paradigm, we found that they were unable to link their responses to stimulus duration. Independently of stimulus duration, they reproduced auditory or visual stimuli with the same response duration of, on average, 3 s. These results demonstrate important deficits in duration judgment in individuals with autism. As other experiments provide evidence for a temporal processing platform of approximately 2-3 s in normal individuals, this platform may be preserved in a residual form in autism.
A patient with de novo 0.45 Mb deletion of 2p16.1: The role of BCL11A, PAPOLG, REL, and FLJ16341 in the 2p15‐p16.1 microdeletion syndrome (2013)

The 2p15-p16.1 microdeletion syndrome is a novel, rare disorder characterized by developmental delay, intellectual disability, microcephaly, growth retardation, facial abnormalities, and other medical problems. We report here on an 11-year-old female showing clinical features consistent with the syndrome and carrying a de novo 0.45 Mb long deletion of the paternally derived 2p16.1 allele. The deleted region contains only three protein-coding RefSeq genes, BCL11A, PAPOLG, and REL, and one long non-coding RNA gene FLJ16341. Based on close phenotypic similarities with six reported patients showing typical clinical features of the syndrome, we propose that the critical region can be narrowed down further, and that these brain expressed genes can be considered candidates for the features seen in this microdeletion syndrome.
Treatment Guidelines for HIV-Associated Wasting (2004)

(2004). Treatment Guidelines for HIV-Associated Wasting. HIV Clinical Trials: Vol. 5, No. 1, pp. 50-61.
Review of Two Years of Experiences with SPECT Among Psychiatric Patients in a Rural Hospital Setting (2008)

We summarize single proton emission computed tomography (SPECT) findings from 63 psychiatric patients in a small rural hospital in western Minnesota. SPECT scans were ordered only for patients in whom documentation of hypoperfusion and functional deficits might be helpful in clarifying diagnoses and treatment planning. The patients referred for SPECT scans had histories of traumatic brain injuries, atypical psychiatric symptom presentations, or conditions that were refractory to standard treatments. In the context of strict referral guidelines and close psychiatrist-radiologist collaboration, a much higher yield of significant findings was obtained compared with those noted in other reports in the literature.
The Cardiovascular Pharmacology of COX-2 Inhibition (2005)

Selective inhibitors of cyclooxygenase (COX)-2, the coxibs, were developed to inhibit inflammatory prostaglandins derived from COX-2, while sparing gastroprotective prostaglandins primarily formed by COX-1. However, COX-2-derived prostaglandins mediate not only pain and inflammation but also affect vascular function, the regulation of hemostasis/ thrombosis, and blood pressure control. All coxibs depress COX-2-dependent prostacyclin (PGI(2)) biosynthesis without effective suppression of platelet COX-1-derived thromboxane (Tx) A(2), unlike aspirin or traditional nonsteroidal anti-inflammatory drugs, which inhibit both COX-1 and COX-2. The actions of PGI(2) oppose mediators, which stimulate platelets, elevate blood pressure, and accelerate atherogenesis, including TxA(2). Indeed, structurally distinct inhibitors of COX-2 have increased the likelihood of hypertension, myocardial infarction and stroke in controlled clinical trials. The detection of these events in patients is related to the duration of exposure and to their baseline risk of cardiovascular disease. Thus, coxibs should be withheld from patients with preexisting cardiovascular risk factors, and exposed patients at low cardiovascular baseline risk should be monitored for changes in their risk factor profile, such as increases in arterial blood pressure.
Construction of plasmid cloning vectors for lactic streptococci which also replicate in Bacillus subtilis and Escherichia coli (1984)

The cryptic Streptococcus cremoris Wg2 plasmid pWV01 (1.5 megadaltons) was genetically marked with the chloramphenicol resistance (Cmr) gene from pC194. The recombinant plasmid (pGK1, 2.4 megadaltons) replicated and expressed Cmr in Bacillus subtilis. From this plasmid an insertion-inactivation vector was constructed by inserting the erythromycin resistance (Emr) gene from pE194 cop-6. This plasmid (pGK12, 2.9 megadaltons) contained a unique BclI site in the Emr gene and unique ClaI and HpaII sites outside both resistance genes. It was stably maintained in B. subtilis at a copy number of approximately 5. pGK12 also transformed Escherichia coli competent cells to Cmr and Emr. The copy number in E. coli was about 60. Moreover, pGK12 transformed protoplasts of Streptococcus lactis. In this host both resistance genes are expressed. pGK12 is stably maintained in S. lactis at a copy number of 3.
TGF‐βS and TGF‐β type II receptor in human epidermis: Differential expression in acute and chronic skin wounds (1993)

Exogenously applied transforming growth factor-beta (TGF-beta) isoforms enhance wound healing processes in animal models; however, little is known about the expression of endogenous TGF-beta s and TGF-beta receptors in intact human skin or during wound healing. The present study has revealed several unexpected findings by means of in situ hybridization and immunohistology techniques. In humans, TGF-beta 3 is constitutively expressed in the epidermis of intact skin and in that of acute and chronic wounds--a pattern of expression closely mirrored by the TGF-beta type II receptor. Although not detected in intact skin, TGF-beta 1 mRNA expression was observed in the regenerating epidermis of acute (thermal) wounds but was not found in chronic decubital (pressure) wounds. TGF-beta 2 mRNA expression was not detected in the epidermis of any human skin or wound biopsies. From these findings we suggest that constitutive expression of TGF-beta 3 is important for maintenance of epidermal differentiation and that an induction of TGF-beta 1 expression is essential for re-epithelialization of human skin wounds. Lack of TGF-beta 1 expression in chronic pressure wounds may be associated with their protracted healing tendencies.
FRACAS: A system for computer-aided image-guided long bone fracture surgery (1998)

This article describes FRACAS, a computer-integrated orthopedic system for assisting surgeons in performing closed medullary nailing of long bone fractures. FRACAS's goal is to reduce the surgeon's cumulative exposure to radiation and surgical complications associated with alignment and positioning errors of bone fragments, nail insertion, and distal screw locking. It replaces uncorrelated, static fluoroscopic images with a virtual reality display of three-dimensional bone models created from preoperative computed tomography and tracked intraoperatively in real time. Fluoroscopic images are used to register the bone models to the intraoperative situation and to verify that the registration is maintained. This article describes the system concept, software prototypes of preoperative modules (modeling, nail selection, and visualization), intraoperative modules (fluoroscopic image processing and tracking), and preliminary in vitro experimental results to date. Our experiments suggest that the modeling, nail selection, and visualization modules yield adequate results and that fluoroscopic image processing with submillimetric accuracy is practically feasible on clinical images.
Retinoic acid treatment alters the distribution of retinoic acid receptor-β transcripts in the embryonic chick face (1991)

Retinoic acid is a metabolite of vitamin A that can act as a signalling molecule in a number of developmental systems. Retinoic acid is also known to be teratogenic in mammals, causing a range of defects including abnormalities in craniofacial development. Exposure of the developing chick face to retinoic acid released slowly from a bead implanted in the wing bud results in a specific facial defect, in which outgrowth of the frontonasal mass is inhibited. This results in clefting of the primary palate and absence of the upper beak. To investigate the role of nuclear retinoic acid receptors in normal and abnormal chick face morphogenesis, we isolated chick retinoic acid receptor-beta (RAR-beta) cDNA clones and probed northern blots of RNA isolated from chick embryos at stages 22, 24 and 25 and from adults. RAR-beta transcripts of 2.8 and 3.5 kb were present in several regions of the embryo, including the facial primordia, and were also present at much lower levels in adult tissues. In situ hybridisation showed that RAR-beta transcripts were present in all of the facial primordia at embryonic stages 20, 24 and 28, but that their distribution was not uniform. Transcripts were abundant in the lateral nasal processes, at the edges and corners of the frontonasal mass and in the anterior part of the maxillary primordia. Lower levels were present elsewhere. Treatment of stage 20 embryos with retinoic acid altered the distribution of RAR-beta transcripts in the maxillary primordia, such that high levels of transcripts were present throughout, rather than being confined to the anterior part. This change was detectable at stage 24, before any alterations in the morphology of the facial primordia were apparent. By stage 28, when the morphology of the facial primordia was clearly abnormal, there were more widespread changes in the distribution of RAR-beta transcripts. These results show that RAR-beta transcripts are particularly concentrated in regions of the primordia that give rise to the upper beak, the development of which is specifically affected by retinoic acid. In addition, they demonstrate that retinoic acid can induce changes in the pattern of expression of RAR-beta transcripts in vivo.
GPR109A Is a G-protein–Coupled Receptor for the Bacterial Fermentation Product Butyrate and Functions as a Tumor Suppressor in Colon (2009)

Short-chain fatty acids, generated in colon by bacterial fermentation of dietary fiber, protect against colorectal cancer and inflammatory bowel disease. Among these bacterial metabolites, butyrate is biologically most relevant. GPR109A is a G-protein-coupled receptor for nicotinate but recognizes butyrate with low affinity. Millimolar concentrations of butyrate are needed to activate the receptor. Although concentrations of butyrate in colonic lumen are sufficient to activate the receptor maximally, there have been no reports on the expression/function of GPR109A in this tissue. Here we show that GPR109A is expressed in the lumen-facing apical membrane of colonic and intestinal epithelial cells and that the receptor recognizes butyrate as a ligand. The expression of GPR109A is silenced in colon cancer in humans, in a mouse model of intestinal/colon cancer, and in colon cancer cell lines. The tumor-associated silencing of GPR109A involves DNA methylation directly or indirectly. Reexpression of GPR109A in colon cancer cells induces apoptosis, but only in the presence of its ligands butyrate and nicotinate. Butyrate is an inhibitor of histone deacetylases, but apoptosis induced by activation of GPR109A with its ligands in colon cancer cells does not involve inhibition of histone deacetylation. The primary changes in this apoptotic process include down-regulation of Bcl-2, Bcl-xL, and cyclin D1 and up-regulation of death receptor pathway. In addition, GPR109A/butyrate suppresses nuclear factor-kappaB activation in normal and cancer colon cell lines as well as in normal mouse colon. These studies show that GPR109A mediates the tumor-suppressive effects of the bacterial fermentation product butyrate in colon.
A surrounding gate transistor (SGT) cell for 64/256 Mbit DRAMs (2003)

A novel three-dimensional memory cell called the surrounding gate transistor (SGT) cell has been developed for 64/256-Mb DRAMs (dynamic RAMs). In the SGT cell structure, a transfer gate and a capacitor electrode surround a pillar silicon island. Contact of the bit line is made on top of the silicon pillar. All devices for a memory cell are located in one silicon pillar. Each silicon pillar is isolated by matrixlike trenches. Therefore, there is no intercell leakage current even in small cell-to-cell spacing. The SGT cell can achieve an extremely small cell size of 1.2 mu m/sup 2/ and a large capacitance of 30 fF using a relaxed design rule of 0.5 mu m. The cell has been fabricated and its functionality confirmed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Transactors (2005)

We introduce transactors , a fault-tolerant programming model for composing loosely-coupled distributed components running in an unreliable environment such as the internet into systems that reliably maintain globally consistent distributed state. The transactor model incorporates certain elements of traditional transaction processing, but allows these elements to be composed in different ways without the need for central coordination, thus facilitating the study of distributed fault-tolerance from a semantic point of view. We formalize our approach via the τ-calculus, an extended lambda-calculus based on the actor model, and illustrate its usage through a number of examples. The τ-calculus incorporates constructs which distributed processes can use to create globally-consistent checkpoints . We provide an operational semantics for the τ-calculus, and formalize the following safety and liveness properties: first, we show that globally-consistent checkpoints have equivalent execution traces without any node failures or application-level failures, and second, we show that it is possible to reach globally-consistent checkpoints provided that there is some bounded failure-free interval during which checkpointing can occur.
Synthesis of Cadmium Sulfide Q Particles in Water-in-CO2 Microemulsions (1999)

Semiconductor nanoparticles of cadmium sulfide were synthesized in ammonium perfluoropolyether (PFPE-NH4) stabilized water-in-CO2 microemulsions. The particle size was tuned by varying the water-to-surfactant molar ratio (w0): w0 ratios of 5 and 10 yielded nanocrystals with exciton energies of 3.86 and 3.09 eV, corresponding to mean particle radii of 0.9 and 1.8 nm, respectively. These exciton energies are significantly higher than the bulk band gap energy for CdS (2.45 eV) due to quantum confinement effects. Effectively, w0 controls the size of the compartmentalized water droplets in which the particles grow.
Differences in Virus-Induced Cell Morphology and in Virus Maturation between MVA and Other Strains (WR, Ankara, and NYCBH) of Vaccinia Virus in Infected Human Cells (2003)

Live recombinants based on attenuated modified vaccinia virus Ankara (MVA) are potential vaccine candidates against a broad spectrum of diseases and tumors. To better understand the efficacy of MVA as a human vaccine, we analyzed by confocal and electron microscopy approaches MVA-induced morphological changes and morphogenetic stages during infection of human HeLa cells in comparison to other strains of vaccinia virus (VV): the wild-type Western Reserve (WR), Ankara, and the New York City Board of Health (NYCBH) strains. Confocal microscopy studies revealed that MVA infection alters the cytoskeleton producing elongated cells (bipolar), which do not form the characteristic actin tails. Few virions are detected in the projections connecting neighboring cells. In contrast, cells infected with the WR, Ankara, and NYCBH strains exhibit a stellated (multipolar) or rounded morphology with actin tails. A detailed transmission electron microscopy analysis of HeLa cells infected with MVA showed important differences in fine ultrastructure and amounts of the viral intermediates compared to cells infected with the other VV strains. In HeLa cells infected with MVA, the most abundant viral forms are intracellular immature virus, with few intermediates reaching the intracellular mature virus (IMV) form, at various stages of maturation, which exhibit a more rounded shape than IMVs from cells infected with the other VV strains. The "IMVs" from MVA-infected cells have an abnormal internal structure ("atypical" viruses) with potential alterations in the core-envelope interactions and are unable to significantly acquire the additional double envelope to render intracellular envelope virus. The presence of potential cell-associated envelope virus is very scarce. Our findings revealed that MVA in human cells promotes characteristic morphological changes to the cells and is able to reach the IMV stage, but these virions were not structurally normal and the subsequent steps in the morphogenetic pathway are blocked.