gebhart/patrepeval huggingface dataset:
Mutation detection in cholestatic patients using microarray resequencing of ATP8B1 and ABCB11 (2013)

Background : Neonatal cholestasis is a common presentation of childhood liver diseases and can be a feature of various conditions including disorders of bile acid biogenesis and transport, various inborn errors of metabolism and perinatal infections. Some inherited metabolic diseases can be easily screened using biochemical assays, however many can only be accurately diagnosed by DNA sequencing. Fluorescent capillary Sanger sequencing (FS) is the gold standard method used by clinical laboratories for genetic diagnosis of many inherited conditions; however, it does have limitations. Recently microarray resequencing (MR) has been introduced into research and clinical practice as an alternative method for genetic diagnosis of heterogeneous conditions. In this report we compared the accuracy of mutation detection for MR with FS in a group of patients with 'low-normal' gamma glutamyl transpeptidase (gGT) cholestasis without known molecular diagnoses. Methods : 29 patient DNA samples were tested for mutations in the ATP8B1 and ABCB11 genes using both FS and MR. Other known causes of "low gGT cholestasis" such as ARC syndrome and bile acid biosynthesis disorders were excluded. Results : Mutations were identified in 13/29 samples. In 3/29 samples FS and MR gave discordant results: MR had a false positive rate of 3.4% and a false negative rate of 7%. Conclusions : The major advantage of MR over FS is that multiple genes can be screened in one experiment, allowing rapid and cost-effective diagnoses. However, we have demonstrated that MR technology is limited in sensitivity. We therefore recommend that MR be used as an initial evaluation, with FS deployed when genetic and clinical or histopathological findings are discordant.
Sutureless aortic valve replacement: catheter-based transapical versus direct transaortic implantation. (2012)

Aortic valve replacement can be performed safely using either sutureless device. The transaortic approach has the additional advantage of allowing for the resection of native leaflets and for the performance of concomitant procedures. Laboratory investigations demonstrated an elevated creatine kinase MB fraction in the transapical group and comparable inflammatory parameters between groups, despite the use of CPB in the transaortic group.
An organic radical in the lysine 2,3-aminomutase reaction (1992)

Lysine 2,3-aminomutase from Clostridium SB4 has been studied by electron paramagnetic resonance (EPR) spectroscopy at 77 K. Although the reaction catalyzed by this enzyme is similar to rearrangements catalyzed by enzymes requiring adenosylcobalamin, lysine 2,3-aminomutase does not utilize this cofactor. The enzyme instead contains iron-sulfur clusters, cobalt, and pyridoxal phosphate and is activated by S-adenosylmethionine. Subsequent to a reductive incubation procedure that is required to activate the enzyme, EPR studies reveal the appearance of an organic radical signal (g = 2.001) upon addition of both L-lysine and S-adenosylmethionine. The radical signal is complex, having multiple hyperfine transitions. The total radical concentration is proportional to enzyme activity and decreases in parallel with the approach to chemical equilibrium between alpha-lysine and beta-lysine. The signal changes over the time course of the reaction in a way that suggests the presence of more than one radical species, with different relative proportions of species in the steady state and equilibrium state. Isotopic substitution experiments show that unpaired spin density resides on the molecular framework of lysine and that solvent-exchangeable protons do not participate in strong hyperfine coupling to the radical. The results indicate that lysine radicals participate in the rearrangement mechanism.
11C-acetate PET imaging of prostate cancer. (2002)

(11)C-Acetate shows marked uptake in prostate cancer and is more sensitive in detection of prostate cancer than is (18)F-FDG PET. (11)C-Acetate represents a new tracer for detection of prostate cancer with PET, measuring radiopharmaceutical uptake pathways that are different from those measured by (18)F-FDG.
Organization, nucleotide sequence, and transcription of the chicken HSP70 gene. (1986)

We have isolated a gene encoding a 70,000-Da heat shock protein (HSP70) from a chicken genomic library. The recombinant clone C411 was isolated by hybridization to a radioactively labeled plasmid containing Drosophila HSP70 gene sequences. The identity was established by hybrid selected translation using a subcloned restriction fragment, pC1.8, and total cytoplasmic RNA from chicken cells. The selected mRNA translated in vitro a product which co-migrates with in vivo synthesized chicken HSP70 by SDS-polyacrylamide gel electrophoresis. By Northern blot analysis of poly(A)+ mRNA from heat-shocked cells, we detected a 2.6-kilobase pair mRNA homologous to pC1.8. The nucleotide sequences within pC1.8 and a flanking 2.0-kilobase pair HindIII fragment contain a single contiguous open reading frame of 1905 nucleotides that corresponds to a protein of predicted size 70,000 daltons. Upstream of the initiator methionine codon, ATG, lie sequences homologous to the canonical transcription elements TATA, CCAAT, and SP1 binding site, and two overlapping heat shock elements. The order and spacing of these sequences share many features in common with the promoter for the human HSP70 gene.
The Activity of Collagenase-1 Is Required for Keratinocyte Migration on a Type I Collagen Matrix (1997)

We have shown in a variety of human wounds that collagenase-1 (MMP-1), a matrix metalloproteinase that cleaves fibrillar type I collagen, is invariably expressed by basal keratinocytes migrating across the dermal matrix. Furthermore, we have demonstrated that MMP-1 expression is induced in primary keratinocytes by contact with native type I collagen and not by basement membrane proteins or by other components of the dermal or provisional (wound) matrix. Based on these observations, we hypothesized that the catalytic activity of MMP-1 is necessary for keratinocyte migration on type I collagen. To test this idea, we assessed keratinocyte motility on type I collagen using colony dispersion and colloidal gold migration assays. In both assays, primary human keratinocytes migrated efficiently on collagen. The specificity of MMP-1 in promoting cell movement was demonstrated in four distinct experiments. One, keratinocyte migration was completely blocked by peptide hydroxymates, which are potent inhibitors of the catalytic activity of MMPs. Two, HaCaTs, a line of human keratinocytes that do not express MMP-1 in response to collagen, did not migrate on a type I collagen matrix but moved efficiently on denatured type I collagen (gelatin). EGF, which induces MMP-I production by HaCaT cells, resulted in the ability of these cells to migrate across a type I collagen matrix. Three, keratinocytes did not migrate on mutant type I collagen lacking the collagenase cleavage site, even though this substrate induced MMP-1 expression. Four, cell migration on collagen was completely blocked by recombinant tissue inhibitor of metalloproteinase-1 (TIMP-1) and by affinity-purified anti-MMP-1 antiserum. In addition, the collagen-mediated induction of collagenase-1 and migration of primary keratinocytes on collagen was blocked by antibodies against the alpha2 integrin subunit but not by antibodies against the alpha1 or alpha3 subunits. We propose that interaction of the alpha2beta1 integrin with dermal collagen mediates induction of collagenase-1 in keratinocytes at the onset of healing and that the activity of collagenase-1 is needed to initiate cell movement. Furthermore, we propose that cleavage of dermal collagen provides keratinocytes with a mechanism to maintain their directionality during reepithelialization.
The dissemination of Salmonella typhi, S. paratyphi A and S. paratyphi B through the organs of the white mouse by oral infection (1960)

A dose of 5 × 10 9 S. typhi (strain Ty 2 ) and S. paratyphi B (strain HB 3 ) administered to white mice orally, caused an infection of various organs of the mouse, namely: spleen, liver, kidneys, lungs, gall-bladder, mesenteric lymph nodes, jejunum and of the blood stream. The percentage of infected spleens was higher than that of other organs. With the above-mentioned dose of Ty 2 , the infection of the liver was found to be five times higher than that of the gall-bladder. The infection of the latter lasted for about 8–9 days, whereas that of the liver for 18–19 days. The bacteria appeared in the various organs: liver, spleen, kidneys, and lungs in about 2 min. after oral infection, and in the blood stream after about 20 sec. The speed and intensity of the invasion of micro-organisms from the gastrointestinal tract to the blood stream depends neither upon the volume of the dose (0·5 ml. or 0·1 ml.), nor upon the content of the mouse's stomach. The M.I.D. for the blood stream of the mouse by oral infection is about 5 × 10 5 bacteria for Ty 2 , HB 3 and AH 6 . In blood samples collected by cardiac puncture 2–3 min. after oral infection, an average of 5 × 10 2 micro-organisms/ml. blood was found. The count of bacteria increased and reached its peak after 20 min. (about 3 × 10 3 bacteria). After that period, the number decreased: 1·6 × 10 3 after 1 hr., 8 × 10 2 after 2 hr. and 1·7 × 10 2 after 3 hr. In spite of this considerable decrease, the blood did not became sterile until after several days. In the infected spleen (by oral infection) an inverse process was observed: at the beginning only a small number of micro-organisms was found (about 5 × 10/100 mg. spleen), but afterwards the number of bacteria increased (1·2 × 10 2 after 24 hr. and 5 × 10 2 after 4 days). In mice infected by the subcutaneous route with a dose of 5 × 10 9 bacteria, the number of micro-organisms in the blood stream did not differ significantly from that found after oral infection, whereas infection by intraperitoneal route caused a severe infection. When 5 × 10 7 micro-organisms (LD 50 ) were administered by intraperitoneal route, 10 7 bacteria appeared in the blood stream of the moribund mice while in the spleen about 4·1 × 10 7 were found. The author wishes to express his appreciation to Prof. I. Gurewitch and to Dr R. Rozansky from the Department of Clinical Microbiology, the Hebrew University-Hadassah Medical School, Jerusalem, for their advice and criticism.
Foxo3a drives proliferation in anaplastic thyroid carcinoma via transcriptional regulation of cyclin A1: A paradigm shift that impacts current therapeutic strategies (2012)

The Forkhead transcription factor, FoxO3a, is a known suppressor of primary tumor growth through transcriptional regulation of key genes regulating cell cycle arrest and apoptosis. In many types of cancer, in response to growth factor signaling, FoxO3a is phosphorylated by Akt, resulting in its exclusion from the nucleus. Here we show that FoxO3a remains nuclear in anaplastic thyroid carcinoma (ATC). This correlates with lack of Akt phosphorylation at serine473 in ATC cell lines and tissues of ATC patients, providing a potential explanation for nuclear FoxO3a. Mechanistically, nuclear FoxO3a promotes cell cycle progression by transcriptional upregulation of cyclin A1, promoting proliferation of human ATC cells. Silencing FoxO3a with a reverse genetics approach leads to downregulation of CCNA1 mRNA and protein. These combined data suggest an entirely novel function for FoxO3a in ATC promotion by enhancing cell cycle progression and tumor growth through transcriptional upregulation of cyclin A1. This is clinically relevant since we detected highly elevated CCNA1 mRNA and protein levels in tumor tissues of ATC patients. Our data indicate therapeutic inactivation of FoxO3a may lead to attenuation of tumor expansion in ATC. This new paradigm also suggests caution in relation to current dogma focused upon reactivation of FoxO3a as a therapeutic strategy against cancers harboring active PI3-K and Akt signaling pathways.
Influence of host-related risk indicators on dental caries in permanent dentition. (2006)

The aim of this study was to assess the individual and grouped influence of host-related factors on dental caries experience in permanent dentition of 7-9 year-old children. One hundred and twenty one children were recruited applying a stratified cluster sampling without replacement. Clinical examinations, Colorimetric Test and non-stimulated and stimulated saliva collection were performed; the samples obtained were later incubated using Snyder culture medium. Simple and multiple binary logistic regression analyses were performed to assess the individual and grouped influence of the host-related factors and establish a modelfor predicting dental caries in permanent dentition. 78.5% of the evaluated children presented dental caries in permanent dentition. Binary logistic regression analyses revealMd that only dental caries in deciduous dentition and stimulated salivary flow were significantly associated to dental caries in permanent dentition. The final multivariate model showed that the adjusted OR was 1.76 for an increase of 1 tooth in dmft and 2.29 for a decrease of 1 ml in stimulated salivary flow. Dental caries in deciduous dentition is a risk indicator for dental caries in permanent dentition, and stimulated salivary flow is a protective factor Variables like enamel resistance to acid dissolution and buffer capacity are not related to dental caries in permanent dentition, making them inappropriate for risk studies.
An antibody diagnostic for hymenopteran parasitism is specific for a homologue of elongation factor-1α (1998)

An enzyme-linked immunosorbent assay (ELISA) useful for identifying noctuid pests parasitized by hymenopteran endoparasitoids was recently described. The ELISA employed a monoclonal antibody (MAb 9A5) that appeared highly polyspecific for parasitoid antigens, yielding banding patterns more typical of a polyclonal antiserum than of a monoclonal antibody in immunoblots of parasitoid homogenates subjected to SDS-PAGE. Although MAb 9A5 appeared capable of binding to dozens of parasitoid antigens, no cross-reactivity for noctuid antigens was evident by either immunoblotting or ELISA. In the study described here, immunoprecipitation, SDS-PAGE, and N-terminus amino acid sequencing were used to identify the protein recognized by MAb 9A5 as a homologue of elongation factor-1 alpha (EF-1 alpha). The propensity for EF-1 alpha to bind to cytoskeletal components, the additional subunits of EF-1, and other proteins may account for the apparent polyspecificity of MAb 9A5 in immunoblots of whole-body parasitoid homogenates. The presence of a unique hymenopteran epitope suggests that EF-1 alpha molecules from other insect groups could similarly express novel determinants. These determinants may prove useful not only for insect detection, but also as targets for selective insecticides that act by inhibiting protein synthesis.
Optimum Detection Times for Bacteria and Yeast Species with the BACTEC 9120 Aerobic Blood Culture System: Evaluation for a 5-Year Period in a Turkish University Hospital (2003)

We tracked and documented the time of positivity of blood cultures by using the BACTEC 9120 (Becton Dickinson Diagnostic Instrument Systems) blood culture system over a 5-year study period. A 7-day protocol of the incubation period was selected, and a total of 11156 blood cultures were evaluated. The clinically significant microorganisms (32.95%) were isolated in 3676 specimens. Gram-positive and -negative bacterial isolation rates were found to be 41.07 and 44.88%, respectively. Yeasts were found in 14.03% of all pathogens. Both the false-positivity and -negativity rates were very low (0.1 and 0.3%, respectively). The mean detection times for all of the pathogens were determined to be 19.45 h. Yeasts, nonfermentative gram-negative bacteria, and Brucella melitensis strains were isolated within 5 days. By taking these data into account, we decided to establish a 5-day-incubation protocol in our laboratory instead of the 7 days that are commonly used.
Isolation, identification and growth determination of lactic acid-utilizing yeasts from the ruminal fluid of dairy cattle (2013)

This study demonstrates that yeasts isolated from the ruminal fluid of dairy cattle can utilize lactic acid as a carbon and energy source for growth. The isolated yeasts can be used as probiotic supplements for dairy cattle that are fed highly concentrated diets to reduce ruminal lactic acid production.
Chromosome changes in Alzheimer's presenile dementia. (1983)

Lymphocyte chromosomes were examined in 36 patients with Alzheimer's presenile dementia, 36 healthy, age and sex matched controls, and 36 sex matched, non-demented, elderly controls, approximately 20 years older than the Alzheimer patients. Increased chromosome aneuploidy was found in females with Alzheimer's disease but not in male subjects. Chromosome abnormalities observed in female patients were similar to those observed in elderly controls, though in this latter group there was an increase in the frequency of cells that had lost an X chromosome. In the female Alzheimer patients and the elderly controls, there was an increase in the frequency of autosomal aneuploid cells but no single chromosome was preferentially affected. Because the chromosome abnormalities found in Alzheimer's disease are similar in nature but not as extensive as those observed in senescence in the absence of dementia, it is argued that chromosome aneuploidy is more likely to be related to processes concerned with ageing rather than being specifically linked to the dementia of Alzheimer's disease.
AKT/PKB Phosphorylation of p21Cip/WAF1 Enhances Protein Stability of p21Cip/WAF1 and Promotes Cell Survival (2002)

p21(Cip1/WAF1) (p21), a p53-inducible protein, is a critical regulator of cell cycle and cell survival. p21 binds to and inhibits both the DNA synthesis regulator proliferating cell nuclear antigen and cyclin A/E-CDK2 complexes. Recently, p21 has also been shown to be a positive regulator of cell cycle progression as p21 is necessary for the assembly and activation of cyclin D1-CDK4/6 complexes. Furthermore, elevated p21 protein levels have been observed in various aggressive tumors as well as linked to chemoresistance. Here we demonstrate that p21 is directly phosphorylated by AKT/PKB, a survival kinase that is hyperactivated in many late stage tumors. Two sites (Thr(145) and Ser(146)) in the carboxyl terminus of p21 are phosphorylated by AKT/PKB in vitro and in vivo. Phosphorylation of Thr(145) inhibits PCNA binding, whereas phosphorylation of Ser(146) significantly increases p21 protein stability. Glioblastoma cell lines with activated AKT/PKB show enhanced p21 stability, and they are more resistant to taxol-mediated toxicity. Finally, AKT/PKB controls the assembly of cyclin D1-CDK4 complexes through modulation of p21 and cyclin D1 levels. These data imply that enhanced levels of p21 in tumors are due, in part, to phosphorylation by activated AKT/PKB. Furthermore, they suggest that one mechanism of AKT/PKB regulation of tumor cell survival and/or proliferation is to stabilize p21 protein.
Studies on the constituents of Clematis species. V. On the saponins of the root of Clematis chinensis Osbeck. (5). (1982)

Three triterpenoid prosapogenins tentatively named CP0 (I), CP2a (VI) and CP3a (VIII) have been isolated from the alkaline hydrolysate of the crude saponin obtained from the root of Clematis chinensis OSBECK. On the basis of chemical and physicochemical evidence, they were characterized as follows : I, hederagenin 23-O-α-L-arabinopyranoside ; VI, hederagenin 23-O-β-D-glucopyranoside ; VIII, olean-12-ene-28-oic acid-3β, 24-diol (4-epihederagenin) 3-O-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranoside. I and VI are the first examples of 23-O-glycosides of oleanane-type triterpenes to be isolated from nature. Six less polar genuine saponins were isolated and they appeared to be identical with prosapogenins CP4, CP6, CP7, CP8, CP9 and CP10, 1, 4) on the basis of the results of high performance thin-layer chromatography (HPTLC).
Detection of Late Intermediates in Virus Capsid Assembly by Charge Detection Mass Spectrometry (2014)

The assembly of hundreds of identical proteins into an icosahedral virus capsid is a remarkable feat of molecular engineering. How this occurs is poorly understood. Key intermediates have been anticipated at the end of the assembly reaction, but it has not been possible to detect them. In this work we have used charge detection mass spectrometry to identify trapped intermediates from late in the assembly of the hepatitis B virus T = 4 capsid, a complex of 120 protein dimers. Prominent intermediates are found with 104/105, 110/111, and 117/118 dimers. Cryo-EM observations indicate the intermediates are incomplete capsids and, hence, on the assembly pathway. On the basis of their stability and kinetic accessibility we have proposed plausible structures. The prominent trapped intermediate with 104 dimers is attributed to an icosahedron missing two neighboring facets, the 111-dimer species is assigned to an icosahedron missing a single facet, and the intermediate with 117 dimers is assigned to a capsid missing a ring of three dimers in the center of a facet.
Synthesis of neutral red covalently functionalized graphene nanocomposite and the electrocatalytic properties toward uric acid (2011)

The preparation of neutral red covalently-functionalized graphene nanosheets (NR-FGN) is presented via replacement of the carboxyl acid groups at the edges of graphene nanosheets using NR. The obtained NR-FGN was characterized by UV-vis, Fourier transform infrared (FT-IR), Raman spectroscopy, X-ray diffraction (XRD) and transmission electron microscopy (TEM). It was found that the introduction of NR at the edges of graphene nanosheets (GN) improved the solubility and stability of the graphene. The electrochemical impedance result further confirmed that NR-FGN could effectively accelerate the electron transfer. Due to the synergic effect between GN and NR, the nanocomposite exhibited excellent electrocatalytic activity toward the oxidation of uric acid.
Creating highly-interactive and graphical user interfaces by demonstration (1986)

It is very time-consuming and expensive to create the graphical, highly-interactive styles of user interfaces that are increasingly common. User Interface Management Systems (UIMSs) attempt to make the creation of user interfaces easier, but most existing UIMSs cannot create the low-level interaction techniques (pop-up pull-down and fixed menus, on-screen "light buttons", scroll-bars, elaborate feedback mechanisms and animations, etc.) that are frequently used. This paper describes Peridot, a system that automatically creates the code for these user interfaces while the designer demonstrates to the system how the interface should look and work. Peridot uses rule-based inferencing so no programming by the designer is required, and Direct Manipulation techniques are used to create Direct Manipulation interfaces, which can make full use of a mouse and other input devices. This allows extremely rapid prototyping of user interfaces.
Asymmetric Catalysis of Carbon-Carbon Bond-Forming Reactions Using Metal(salen) Complexes (2005)

The use of metal(salen) complexes in the asymmetric syntheses of cyanohydrins and amino acids have been developed as important and reliable methods of obtaining these highly versatile chiral intermediates. Thus, we have developed a number of titanium and vanadium(salen) complexes, with ligands derived from (R,R)-cyclohexane-1,2-diamine, which catalyze the synthesis of enantiomerically enriched O-protected cyanohydrins from various carbonyl compounds and cyanide sources. Nickel, copper and cobalt(salen) complexes have also been developed, as catalysts for the preparation of non-racemic amino acids under phase-transfer conditions.