gebhart/patrepeval huggingface dataset:
Prognostic biomarkers in uveal melanoma: evidence for a stem cell-like phenotype associated with metastasis (2008)

Uveal melanomas frequently metastasize and cause patient death. Many clinical, histopathologic, molecular, and genetic factors have been linked to metastasis. We hypothesized that understanding the relationships between, and relative prognostic significance of these factors would provide new insights into the pathogenesis of metastasis. To this end, we collected clinical, pathologic, and molecular data for 65 uveal melanomas, including patient age, sex, tumor size, location, cell type, vasculogenic mimicry looping matrix patterns, gene expression profiles, and immunohistochemistry for cytokeratin-18, vascular endothelial cadherin, E-cadherin, beta-catenin, and hypoxia-inducible factor 1alpha. In addition, we used Gene Set Enrichment Analysis to identify statistically significant overlap in genes that were differentially expressed in metastasizing tumors and those expressed in other well-characterized biological systems. Our results show that the class 2 gene expression signature was the most accurate predictor of metastasis (P=0.0001) and that the biomarkers most strongly associated with the class 2 signature included epithelioid cell type, beta-catenin, E-cadherin, and hypoxia-inducible factor 1alpha (P< or =0.001 for each). Thus, the class 2 gene expression signature continues to be the most accurate predictor of uveal melanoma metastasis and can, therefore, serve as a benchmark for evaluating other biomarkers. Importantly, Gene Set Enrichment Analysis showed a significant association between genes expressed in class 2 tumors and those expressed in primitive ectodermal and neural stem cells. Taken together with the constellation of biomarkers associated with the class 2 signature, this suggests the presence of cancer cells with a primitive neural/ectodermal stem cell-like phenotype that may be responsible for metastasis in these highly aggressive tumors.
Rapid HPLC Method for Measurement of Vitamin D3 and 25(OH)D3 in Blood Plasma (2003)

The present work describes a novel, simplified high-performance liquid chromatography (HPLC) method for evaluation of vitamin D3 and its 25-hydroxy metabolite in blood plasma. The retrieval of the analytes from the blood plasma matrix is based on a single-step extraction using acetonitrile. The method is specific, sensitive, and ensures good reproducibility. The recovery of the analytes, precision, and reproducibility obtained using the present approach gave results comparable to or better than more complex, laborious, and time-consuming procedures. This method is suitable for evaluation of the host's vitamin D physiological status, as well as for rapid analysis of blood plasma samples in suspected cholecalciferol toxicity. With a significantly shortened time of analysis (10 minutes), the present method allows the possibility for processing of a large number of samples rapidly, efficiently, and at a low cost.
Extending recombinant factor IX Fc fusion protein dosing interval to 14 or more days in patients with hemophilia B (2018)

Most patients on rFIXFc prophylaxis, with a dosing interval of ≥14 days, remained well controlled; ABRs were consistent with those reported in the overall study population. A ≥14-day dosing interval can be utilized in some well controlled individuals and reduces the burden imposed by frequent prophylactic injections while maintaining adequate bleed suppression.
Achieving accurate estimates of fetal gestational age and personalised predictions of fetal growth based on data from an international prospective cohort study: a population-based machine learning study (2020)

Bill & Melinda Gates Foundation, Office of Science (US Department of Energy), US National Science Foundation, and National Institute for Health Research Oxford Biomedical Research Centre.
Induction of cyclophosphamide-resistance by aldehyde-dehydrogenase gene transfer (1996)

The identification of genes inducing resistance to anticancer chemotherapeutic agents and their introduction into hematopoietic cells represents a promising approach to overcome bone marrow toxicity, the limiting factor for most high-dose chemotherapy regimens. Because resistance to cyclophosphamide has been correlated with increased levels of expression of the aldehyde-dehydrogenase (ALDH1) gene in tumor cell lines in vitro, we tested whether ALDH1 overexpression could directly induce cyclophosphamide resistance. We have cloned a full-length human ALDH1 cDNA and used retroviral vectors to transduce it into human (U937) and murine (L1210) hematopoietic cell lines that were then tested for resistance to maphosphamide, an active analogue of cyclophosphamide. Overexpression of the ALDH1 gene resulted in a significant increases in cyclophosphamide resistance in transduced L1210 and U937 cells (50% inhibition concentration [IC50], approximately 13 mumol/L). The resistant phenotype was specifically caused by ALDH1 overexpression as shown by its reversion by disulfiram, a specific ALDH1 inhibitor. ALDH1 transduction into peripheral blood human hematopoietic progenitor cells also led to significant increases (4- to 10-fold; IC50, approximately 3 to 4 mumol/L) in cyclophosphamide resistance in an in vitro colony-forming assay. These findings indicate that ALDH1 overexpression is sufficient to induce cyclophosphamide resistance in vitro and provide a basis for testing the efficacy of ALDH1 gene transduction to protect bone marrow cells from high-dose cyclophosphamide in vivo.
Effects of prenatal androgenization and lactation on adipose tissue metabolism in finishing single-calf heifers. (1997)

Twelve control (C) and 12 prenatally androgenized (PA) lactating (L) first-calf heifers and five (two C and three PA) similar, nonlactating (NL) heifers were used to assess the effects of PA and L on the metabolic activity of s.c. adipose tissue (AT). Heifers were fed an 85% concentrate diet, and their calves were weaned at 112 +/- 1 d of age. Adipose tissue was biopsied at approximately 77 d (period 1, during lactation for L heifers) and 126 d (period 2, after L heifers had calves weaned) postpartum. The NL heifers gained .22 kg/d faster (P = .20) and had greater fat deposition than L heifers during period 1. The PA heifers were fatter and gained 14.6% faster than C heifers during lactation. Epinephrine (E) and norepinephrine (NE) increased in vitro fatty acid (FA) release 25 (P < .01) and 15% (P < .06), respectively, above basal rates. Near-maximal release of FA, as estimated by stimulation with E plus theophylline plus adenosine deaminase (ETAD), was 73% (4,110 vs 2,379 +/- 161 nEq/[2 h.100 mg of tissue]; P < .01) above basal rates. Basal FA release was unaffected, but ETAD-stimulated rates were decreased (P < .04; 4,430 +/- 246 vs 3,789 +/- 209 nEq/[2 h.100 mg of tissue]) by PA. Stimulation of FA release by E (P = .22) or NE (P = .31) did not differ between C and PA. For NL heifers, PA decreased (P < .02) FA release, which corresponded with their greater fat deposition, but PA did not affect L heifers (PA x L interaction, P = .14). The content of NEFA in s.c. AT (pool size) was 34% greater (P < .01) during period 2 than during period 1. Pool size was not affected (P = .72) by NE but was increased by E (1,628 vs 1,777 +/- 92 nEq/100 mg of tissue; P < .05) and ETAD (1,628 vs 2,176 +/- 93 nEq/100 mg of tissue; P < .01). For L heifers, PA tended (P < .07) to increase incorporation of acetate into FA during period 1. Thus, PA resulted in subtle increases in lipogenesis and decreases in lipolysis during the first lactation-weaning cycle that were consistent with greater rates of gain and fat deposition.
Proteases as activators for cytotoxic prodrugs in antitumor therapy. (2014)

Proteases are often overexpressed in tumor cells and/or the stromal compartment and can thus be exploited in tumor therapy to activate cytotoxic prodrugs as, for example, in cytolytic fusion proteins, and for tumor imaging. Specifically, we discuss cathepsin B-activated prodrug conjugates, antibody-directed prodrug therapy, protease-activated peptide-thapsigargin conjugates, protease-activated cytotoxic receptor ligands and other cytotoxic proteins, protease-mediated activation of anthrax toxin, granzyme B as a therapeutic principle in cytolytic fusion proteins, and tumor-imaging based on deregulated proteases.
<title>Lip synchronization in talking head video utilizing speech information</title> (1995)

We utilize speech information to improve the quality of audio-visual communications such as video telephony and videoconferencing. We show that the marriage of speech analysis and image processing can solve problems related to lip synchronization. We present a technique called speech-assisted frame-rate conversion, and demonstrate speech-assisted coding of talking head video. Demonstration sequences are presented. Extensions and other applications are outlined.
Recognition of Double-Stranded RNA by TLR3 Induces Severe Small Intestinal Injury in Mice (2007)

The role of TLRs on intestinal epithelial cells (IECs) is controversial, and the mechanisms by which TLRs influence mucosal homeostasis are obscure. In this study, we report that genomic dsRNA from rotavirus, and its synthetic analog polyinosinic-polycytidylic acid (poly(I:C)), induce severe mucosal injury in the small intestine. Upon engaging TLR3 on IECs, dsRNA triggers IECs to secrete IL-15, which functions to increase the percentage of CD3+NK1.1+ intestinal intraepithelial lymphocytes (IELs) and enhances the cytotoxicity of IELs. Moreover, The CD3+NK1.1+ IELs are proved as CD8alphaalpha+ IELs. These results provide direct evidence that abnormal TLR3 signaling contributes to breaking down mucosal homeostasis and the first evidence of pathogenic effects mediated by CD8alphaalpha+ IELs. The data also suggest that genomic dsRNA may be involved in the pathogenesis of acute rotavirus gastroenteritis.
Stability and Dissolution Rates of Corticosteroids in Polyethylene Glycol Solid Dispersions (1984)

A study has been made to examine the stability and dissolution rates of prednisolone, prednisone and hydrocortisone formulated as solid dispersions in polyethylene glycols. Of the five PEG samples used, three enhanced the chemical instability of the steroids; the effect being dependent on the PEG sample and storage conditions of the solid dispersions. Dissolution rates of the steroids were relatively fast from the solid dispersions and showed no significant changes upon storage. Using two methods of analysis (direct UV spectrophotometry and the USP blue tetrazolium method), it is concluded that the chemical instability of the steroids in some PEG samples was due to alterations in the dihydroxy acetone side chain. One of the decomposition products found appeared to be an acidic compound resulting from oxidation of the C17 side chain. The oxidation is presumably accelerated by a peroxide impurity in PEG samples.
The Expression of p53 and PCNA in Patients with Locally RecurrentLaryngeal Cancer after Radiotherapy (2004)

Background and Objectives : The biologic changes in recurrent laryngeal cancer following radiotherapy are not fully understood. The authors investigated the expression of p53 and proliferating cell nuclear antigen (PCNA) in patients with locallyrecurrent laryngeal cancer after radiotherapy. Materials and Method : The authors investigated the expression of p53 andPCNA by immunohistochemical stain in 15 patients with recurrent laryngeal cancer after radiotherapy. Results : The expressionof p53 protein was significantly different between laryngeal cancer before radiotherapy (4/15, 26.7%) and recurrent laryngealcancer after radiotherapy (8/15, 53.3%) (P
[Pharmacological study of the anti-inflammatory agent glyderinine]. (1989)

In experiments on various animals glyderinine, a derivative of glycyrrhizic acid isolated from Glycyrrhiza glabra, was found to exert a pronounced anti-inflammatory effect exceeding that of hydrocortisone and amidopyrine. The mechanism of the anti-inflammatory effect was to a certain degree related to the adrenal cortex, suppression of vascular permeability and antagonism to inflammation as well. Similarly to other anti-inflammatory agents, glyderinine possesses analgesic and antipyretic properties, but unlike them it fails to suppress hemopoiesis and to cause ulceration of the gastrointestinal mucosa. The drug is of low toxicity and exerts the antiallergic effect. Glyderinine was successfully tried and recommended for a wide use as an ointment for treating skin diseases.
Hamstring tendon fixation using interference screws: a biomechanical study in calf tibial bone (1998)

It has recently been shown that graft fixation close to the ACL insertion site is optimal in order to increase anterior knee stability. Hamstring tendon fixation using interference screws offers this possibility and a round threaded titanium interference screw has been previously developed. The use of a round threaded biodegradable interference screw may be equivalent. In addition, to increase initial fixation strength, graft harvest with a distally attached bone plug may be advantageous, but biomechanical data do not exist. This study compares the initial pullout force, stiffness of fixation, and failure modes of three strand semitendinosus grafts in 36 proximal calf tibiae using either biodegradable poly-(D,L-lactide) (Sysorb; Sulzer Orthopaedics Ltd, Münsingen, Switzerland) or round threaded titanium (RCI; Smith & Nephew DonJoy, Carlsbad, CA) interference screws, harvested either without (biodegradable: group I, titanium III) or with (biodegradable: group II, titanium: group IV) attached tibial bone plugs. Maximum pullout force in group I (507 +/- 93 N) was significantly higher than in group III (419 +/- 77 N). Pullout force of bone plug fixation was significantly higher than that of direct tendon fixation (717 +/- 90 N in group II and 602 +/- 117 N in group IV). Pullout force of biodegradable fixation was significantly higher in both settings. These results indicate that initial pullout force of hamstring-tendon graft interference screw fixation can be increased by using a biodegradable interference screw. In addition, initial pullout force of hamstring-tendon graft fixation with an interference screw can be greatly increased by harvesting the graft with its distally attached tibial bone plug.
Molecular cloning of a second phospholipase B gene, caPLB2 from Candida albicans 1 (1999)

Accumulating evidence suggests that phospholipase B, secreted by pathogenic fungi such as Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus, functions as one of the virulence factors. In the present study, we have attempted to clone phospholipase B gene from C. albicans. By RT-PCR analysis with degenerate primers based on conserved regions of phospholipase B from Saccharomyces cerevisiae, Penicillium notatum and Torulaspora delbrueckii two similar but different cDNA fragments were obtained. One corresponded to the partial sequence of caPLB1, recently cloned phospholipase B gene from C. albicans by a different approach (Leidich et al.: J Biol Chem 1998; 273: 26078-86). The other fragments contained sequences similar to the corresponding sequences of phospholipase B from other fungi. The presence of two related genes was confirmed by Southern and Northern blot analyses. The full length of the second C. albicans phospholipase B gene (caPLB2) encoded a putative protein with 608 amino acids and contained a potential signal peptide sequence and a putative catalytic region, which are found in phospholipase B from other fungi. Consistent with the findings of caPLB1, caPLB2 also lacks a cluster of hydrophobic amino acids at the COOH-terminal, which may function as a signal of glycosylphosphatidylinositol anchor.
Structure and Expression of the Gene Encoding Secretor‐Type Galactoside 2‐α‐l‐fucosyltransferase (FUT2) (1997)

The expression and secretion of ABO antigens in epithelial cells of glands are controlled by secretor-type alpha (1,2)fucosyltransferase activity. We have examined the expression of the secretor-type alpha(1,2)fucosyltransferase gene (FUT2) and a pseudogene of FUT2 (Sec1) in several tumor cell lines by northern blot and/or reverse-transcription-PCR (RT-PCR) analyses. Transcripts of FUT2 were found in total RNA from ovarian, gastric and colonic cancer cell lines but not from six leukemic cell lines, including erythroleukemic HEL cells, by RT-PCR. On the other hand, RT-PCR indicated that Sec1 was expressed in all these tumor cells, including all hematopoietic cells studied. Northern blot analysis indicated that FUT2 transcripts with a similar size (3.3 kb) were expressed in cancer cell lines. Rapid amplification of cDNA ends suggested that the entire FUT2 cDNA is 3.1-kb long and has two Alu repetitive elements in its 3' untranslated region, including an inverted repeat. The mRNA, therefore, may form a large stem-and-loop structure (1.2 kb). Each stem contains about 300 bases, the loop contains 640 bases, and the percentage of complementary nucleotide sequences in the stem region is 85%. The presence of a large stem-and-loop structure in the 3' untranslated region may regulate the level of the FUT2 transcript by affecting the stability of the mRNA.
KBMA Listeria monocytogenes is an effective vector for DC-mediated induction of antitumor immunity (2008)

Vaccine strategies that utilize human DCs to enhance antitumor immunity have yet to realize their full potential. Approaches that optimally target a spectrum of antigens to DCs are urgently needed. Here we report the development of a platform for loading DCs with antigen. It is based on killed but metabolically active (KBMA) recombinant Listeria monocytogenes and facilitates both antigen delivery and maturation of human DCs. Highly attenuated KBMA L. monocytogenes were engineered to express an epitope of the melanoma-associated antigen MelanA/Mart-1 that is recognized by human CD8+ T cells when presented by the MHC class I molecule HLA-A*0201. The engineered KBMA L. monocytogenes induced human DC upregulation of costimulatory molecules and secretion of pro-Th1 cytokines and type I interferons, leading to effective priming of Mart-1-specific human CD8+ T cells and lysis of patient-derived melanoma cells. KBMA L. monocytogenes expressing full-length NY-ESO-1 protein, another melanoma-associated antigen, delivered the antigen for presentation by MHC class I and class II molecules independent of the MHC haplotype of the DC donor. A mouse therapeutic tumor model was used to show that KBMA L. monocytogenes efficiently targeted APCs in vivo to induce protective antitumor responses. Together, our data demonstrate that KBMA L. monocytogenes may be a powerful platform that can both deliver recombinant antigen to DCs for presentation and provide a potent DC-maturation stimulus, making it a potential cancer vaccine candidate.
Potential Therapeutic Applications of Magainins and other Antimicrobial Agents of Animal Origin (2007)

Magainins are a family of linear, amphipathic, cationic antimicrobial peptides, 21 to 27 residues in length, found in the skin of Xenopus laevis. They kill microbial targets through disruption of membrane permeability. They exhibit selectivity, on the basis of their affinity for membranes which contain accessible acidic phospholipids, a property characterizing the cytoplasmic membranes of many species of bacteria. Magainins are broad-spectrum antimicrobial agents exhibiting cidal activity against Gram-negative and Gram-positive bacteria, fungi and protozoa. In addition these peptides lyse many types of murine and human cancer cells at concentrations 5-10-fold lower than normal human cells. Because of their selectivity, broad spectrum, low degree of bacterial resistance and ease of chemical synthesis, magainins are being developed as human therapeutic agents. The most advanced candidate is MSI-78, a 22-residue magainin analogue. This peptide is currently in human Phase IIb/III clinical trials in studies intended to evaluate its efficacy as a topical agent for the treatment of impetigo. Preclinical studies have demonstrated that analogues of magainin exhibit activity in vivo against malignant melanoma and ovarian cancer cells in mouse models. Intravenous administration of several magainin analogues has been shown to treat effectively systemic Escherichia coli infections in the mouse.
Formation of Closed-Cage Nanostructures by Self-Assembly of Aromatic Dipeptides (2004)

We recently demonstrated that the diphenylalanine recognition motif of the Alzheimer's β-amyloid polypeptide self-assembles into ordered and discrete nanotubes. Here, we reveal that diphenylglycine, a highly similar analogue and the simplest aromatic peptide, forms spherical nanometric assemblies. As the nanotubes, the nanospheres assemble efficiently and have remarkable stability. The introduction of a thiol group into the diphenylalanine peptide alters its assembly from tubular to spherical particles similar to those formed by diphenylglycine. The formation of either nanotubes or closed-cages by fundamentally similar peptides is consistent with a two-dimensional layer closure, as described both for carbon and inorganic nanotubes and their corresponding buckminsterfullerene and fullerene-like structures.
The Metabolism and Biological Activity of a 9-Substituted Cytokinin (1971)

In order to test the metabolic stability of 9-substituted cytokinins, 6-benzylamino-9-methyl purine has been synthesized and labeled with (14)C in the 9-methyl carbon or doubly labeled with (14)C in the 9-methyl carbon and (3)H in the methylene moiety of the side chain. Although the 6-benzylamino-9-methylpurine is chemically stable, cytokinin-requiring tissues begin removing the 9-substituent in as little as 10 minutes. Among the various metabolic products is free benzylaminopurine. Thus, the biological activity of 9-substituted cytokinins could be accounted for by their conversion to the free base.
Animating reactive motion using momentum-based inverse kinematics: Motion Capture and Retrieval (2005)

Interactive generation of reactive motions for virtual humans as they are hit, pushed and pulled are very important to many applications, such as computer games. In this paper, we propose a new method to simulate reactive motions during arbitrary bipedal activities, such as standing, walking or running. It is based on momentum based inverse kinematics and motion blending. When generating the animation, the user first imports the primary motion to which the perturbation is to be applied to. According to the condition of the impact, the system selects a reactive motion from the database of pre-captured stepping and reactive motions. It then blends the selected motion into the primary motion using momentum-based inverse kinematics. Since the reactive motions can be edited in real-time, the criteria for motion search can be much relaxed than previous methods, and therefore, the computational cost for motion search can be reduced. Using our method, it is possible to generate reactive motions by applying external perturbations to the characters at arbitrary moment while they are performing some actions. Copyright © 2005 John Wiley & Sons, Ltd.
DNA Sequence Analysis of the Type-Common Glycoprotein-D Genes of Herpes Simplex Virus Types 1 and 2 (1984)

The DNA sequences for the coding and flanking regions of the type-common glycoprotein-D (gD) genes of herpes simplex virus (HSV) types 1 and 2 have been determined. The resultant protein sequences are approximately 80% homologous. Both gD proteins are 393 amino acids long and both have maintained three identical potential glycosylation sites. Amino acid changes are found throughout the proteins, with the majority of changes located in the amino and carboxyl/termini. Most of the amino acid differences were found to be conservative. Hydropathy analysis, which determines hydrophobic and hydrophilic regions, reveals a remarkable structural similarity between the proteins. Examination of 5' flanking sequences demonstrates extensive DNA sequence homology adjacent to the start of gD gene transcription. In addition, another homologous noncoding region was found 3' to the gD gene. This second homologous sequence is 5' to a 1.6-kb transcription unit.