gebhart/patrepeval huggingface dataset:
Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy (2017)

Immunotherapies based on immune checkpoint blockade are highly effective in a subset of patients. An ongoing challenge is the identification of biomarkers that predict which patients will benefit from these therapies. Aneuploidy, also known as somatic copy number alterations (SCNAs), is widespread in cancer and is posited to drive tumorigenesis. Analyzing 12 human cancer types, we find that, for most, highly aneuploid tumors show reduced expression of markers of cytotoxic infiltrating immune cells, especially CD8<sup>+</sup> T cells, and increased expression of cell proliferation markers. Different types of SCNAs predict the proliferation and immune signatures, implying distinct underlying mechanisms. Using published data from two clinical trials of immune checkpoint blockade therapy for metastatic melanoma, we found that tumor aneuploidy inversely correlates with patient survival. Together with other tumor characteristics such as tumor mutational load, aneuploidy may thus help identify patients most likely to respond to immunotherapy.
Uroguanylin inhibits proliferation of pancreatic cancer cells (2008)

Our data suggest therapeutic properties of uroguanylin in pancreatic cancer via GC-C-dependent mechanisms. In addition, determination of GC-C expression might be a useful marker for differentiation between pancreatic cancer and chronic pancreatitis.
Frequent subgraph discovery (2002)

As data mining techniques are being increasingly applied to non-traditional domains, existing approaches for finding frequent itemsets cannot be used as they cannot model the requirement of these domains. An alternate way of modeling the objects in these data sets is to use graphs. Within that model, the problem of finding frequent patterns becomes that of discovering subgraphs that occur frequently over the entire set of graphs.The authors present a computationally efficient algorithm for finding all frequent subgraphs in large graph databases. We evaluated the performance of the algorithm by experiments with synthetic datasets as well as a chemical compound dataset. The empirical results show that our algorithm scales linearly with the number of input transactions and it is able to discover frequent subgraphs from a set of graph transactions reasonably fast, even though we have to deal with computationally hard problems such as canonical labeling of graphs and subgraph isomorphism which are not necessary for traditional frequent itemset discovery.
A novel gene (HIP) activated in human primary liver cancer. (1992)

Differential screening of a human hepatocellular carcinoma complementary DNA library using subtracted probes allowed us to identify a novel gene named HIP whose expression at the transcriptional level was elevated in liver tumors. The protein potentially encoded by the complementary DNA showed 68.5% identity with the bovine pancreatic thread protein and 49% identity with the human reg protein, which has been proposed as a pancreatic islet cell regenerating factor and is identical to the pancreatic stone or pancreatic thread protein. Sequence analysis suggests that the bovine pancreatic thread protein encoding gene is, in fact, the bovine homologue of the HIP gene. Furthermore, data base searches revealed a significant similarity of the HIP and pancreatic stone protein/pancreatic thread protein/reg sequences with the C-type lectin superfamily. The HIP sequence, like pancreatic stone protein/pancreatic thread protein/reg protein, consists of a single carbohydrate recognition domain linked to a signal peptide which would be involved in secretion of the protein. HIP mRNA was expressed at a high level in the tumors of seven of 29 hepatocellular carcinomas. In contrast, HIP mRNA was not detected in nontumorous adjacent areas or in normal adult and fetal liver, suggesting that HIP could be involved in liver cell proliferation or differentiation. HIP mRNA expression is tissue specific, since it is present in the normal small intestine and pancreas, while it could not be evidenced in colon, brain, kidney, or lung. In summary, our results show the existence of a novel family within the superfamily of C-type lectin which may be involved in liver, pancreatic, and intestinal cell proliferation or differentiation.
Targeting antibodies to the cytoplasm (2011)

A growing number of research consortia are now focused on generating antibodies and recombinant antibody fragments that target the human proteome. A particularly valuable application for these binding molecules would be their use inside a living cell, e.g., for imaging or functional intervention. Animal-derived antibodies must be brought into the cell through the membrane, whereas the availability of the antibody genes from phage display systems allows intracellular expression. Here, the various technologies to target intracellular proteins with antibodies are reviewed.
Studies on Antiulcer Agents. II. Antiulcer Properties of N-(1H-Tetrazol-5-yl)-2-anilino-5-pyrimidinecarboxamides Inhibiting Release of Histamine from Passively Sensitized Rat Peritoneal Mast Cells. (1995)

With the aim of applying mast cell-stabilizing agents as antiulcer agents, N-(1H-tetrazol-5-yl)-2-anilino-5-pyrimidinecarboxamides were synthesized, and initially evaluated pharmacologically for activity in the rat passive cutaneous anaphylaxis test by oral administration. The most active compound 6 was proved to inhibit potently the release of histamine from passively sensitized rat peritoneal mast cells in vitro. When compared with other mast cell-stabilizing agents and an antiulcer agent, compound 6 was found to show excellent gastric mucosal protection and gastric antisecretion activities. Furthermore, compound 6 revealed good activity against acidified aspirin ulcer in rats and water-immersion stress ulcer in rats.
Fluorescent Cyclodextrins for Detecting Organic Compounds with Molecular Recognition (1993)

Cyclodextrin derivatives with one or two chromophores were used as fluorescent sensors for detecting organic compounds in aqueous solution. They undergo induced-fit type of conformational changes associated with guest binding, changing the location of the chromophores mostly from inside to outside of the cavities. The guest binding abilities of the hosts are usually reflected in the sensitivities of the sensors, and various compounds including steroids were detected with remarkable molecular recognition.
A Simple Mathematical Model of Adaptation to High Osmolarity in Yeast (2006)

We present a simple ordinary differential equation (ODE) model of the adaptive response to an osmotic shock in the yeast Saccharomyces cerevisiae. The model consists of two main components. First, a biophysical model describing how the cell volume and the turgor pressure are affected by varying extra-cellular osmolarity. The second component describes how the cell controls the biophysical system in order to keep turgor pressure, or equivalently volume, constant. This is done by adjusting the glycerol production and the glycerol outflow from the cell. The complete model consists of 4 ODEs, 3 algebraic equations and 10 parameters. The parameters are constrained from various literature sources and estimated from new and previously published absolute time series data on intra-cellular and total glycerol. The qualitative behaviour of the model has been successfully tested on data from other genetically modified strains as well as data for different input signals. Compared to a previous detailed model of osmoregulation, the main strength of our model is its lower complexity, contributing to a better understanding of osmoregulation by focusing on relationships which are obscured in the more detailed model. Besides, the low complexity makes it possible to obtain more reliable parameter estimates.
Transmission Electron Microscope Observation of Pt Deposited on Nb-Doped Titania (2009)

Pt nanoparticles supported on niobium (Nb)-doped titania were prepared using the alcohol reduction method. The Nb-doped was subjected to various heat-treatments. Depending on the heat-treatment either anatase or rutile was produced. The change in Pt morphology when deposited on supports that were treated under hydrogen at different temperatures was investigated by high-resolution transmission electron microscopy. Platinum particles deposited on rutile and anatase have distinctly different morphologies. Those deposited on anatase are similar to and are essentially spherical. Platinum particles on rutile , however, appear flattened, indicating a strong metal-support interaction.
Clinical Characteristics of Perinatal Lethal Hypophosphatasia: A Report of 6 Cases (2010)

Hypophosphatasia is a rare inherited disorder caused by deficient tissue-nonspecific alkaline phosphatase activity. It is classified into 6 subtypes, and the perinatal lethal form of hypophosphatasia is the most severe. Patients with this form suffer from various symptoms, including respiratory failure, premature craniosynostosis, rachitic changes in the metaphyses, convulsions and hypercalcemia. This report presents 6 cases of the perinatal lethal form of hypophosphatasia. All of the patients showed shortening of the long bones in utero in ultrasonographic examinations. Two of the six patients died at birth because they could not establish spontaneous breathing. Three of the remaining four patients also died before 1 yr of age. The major cause of death was respiratory failure due to hypoplastic lung. All of the patients, except for the two who died at birth, experienced convulsions in their clinical courses. Vitamin B6 therapy effectively reduced the frequency and severity of convulsions. However, it could not always make the patients convulsion free. Three patients underwent a genetic analysis. The 1559delT mutation, which abolishes Alkaline Phosphatase (ALP) activity, was a hot spot. A homozygous 1559delT mutation was observed in two patients. However, they differed in severity of symptoms. Although a good genotype-phenotype correlation has been reported in hypophosphatasia, the genotype alone does not always predict the life span of the patients. These cases therefore suggested the importance of genetic counseling.
Etretin Therapy for Severe Psoriasis (1987)

We have investigated the clinical responses of 21 patients with severe psoriasis to therapy with etretin, a metabolite of etretinate. In a preliminary double-blind dose-finding study, the optimum dose of etretin was determined to be 50 mg/d (mean, 0.66 mg/kg/d). In an open study, patients receiving etretin therapy were followed up for a minimum of six months. An excellent or good response (greater than 50% clearance) was obtained in 18 of 21 patients. The incidence of mucocutaneous side effects from etretin therapy was similar to that previously reported with etretinate therapy. As a group, patients who received etretin therapy for six or more months showed no significant aberrations from normal levels of serum lipids or serum liver enzymes. However, five patients had mild elevation of liver enzymes or blood lipids, which were corrected by dose reduction. Etretin showed equivalent efficacy to that previously reported with etretinate in severe recalcitrant plaque psoriasis vulgaris. Taken with the reportedly more rapid clearance of etretin from the body, there may be clinical advantages of the use of etretin over the use of etretinate.
Amelioration of collagen II-induced arthritis in rats by the type IV phosphodiesterase inhibitor Rolipram (1997)

The effect of Rolipram, a selective inhibitor of the cyclic AMP specific phosphodiesterase (PDE IV) was evaluated in the rat collagen type II (RCII)-induced arthritis model in the DA rat. Rolipram was given either shortly before expected onset of disease (days 10-14) or shortly after the onset of clinically evident arthritis (days 15-19 after immunization). Administration at days 10-14 delayed the onset of arthritis for approximately 5 days, but the severity of arthritis was thereafter comparable to that seen in a non-treated control group. Rolipram treatment of animals with manifest arthritis inhibited further arthritis development and also tended to diminish its severity at a phase of disease where non-treated control animals showed a rapidly progressing disease development. Serum levels of antibodies to RCII were in all experiments similar between Rolipram-treated and control animals. An in situ hybridization method for determining cytokine mRNA synthesis in regional lymph nodes, after administration of Rolipram (at days 2-7), demonstrated a strong inhibitory effect on tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) mRNA expression, whereas no effects were seen on IL-2 mRNA synthesis after in vivo challenge with native RCII emulsified in Freund's incomplete adjuvant. The results thus demonstrate strong preventive as well as therapeutic effects of Rolipram in a model for arthritis that is very similar to human rheumatoid arthritis with respect to cytokine regulation, and suggest that Rolipram has its major effects in the effector stage of the arthritogenic immune response.
Synthesis and Biological Studies of Inducible DNA Cross‐Linking Agents (2007)

Checking the traps: When a phenyl selenide compound such as 1 was oxidized with sodium periodate or irradiated, an ortho-quinone methide intermediate formed and reacted with a DNA duplex by cross-linking. In the crystal structure of a derivative of 1 the biphenyl unit is twisted, and this might explain how 1 can interact effectively with the DNA backbone. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2007/z700844_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Synergic Role of Nucleophosmin Three-helix Bundle and a Flanking Unstructured Tail in the Interaction with G-quadruplex DNA (2014)

Nucleophosmin (NPM1) is a nucleocytoplasmic shuttling protein, mainly localized at nucleoli, that plays a number of functions in ribosome biogenesis and export, cell cycle control, and response to stress stimuli. NPM1 is the most frequently mutated gene in acute myeloid leukemia; mutations map to the C-terminal domain of the protein and cause its denaturation and aberrant cytoplasmic translocation. NPM1 C-terminal domain binds G-quadruplex regions at ribosomal DNA and at gene promoters, including the well characterized sequence from the nuclease-hypersensitive element III region of the c-MYC promoter. These activities are lost by the leukemic variant. Here we analyze the NPM1/G-quadruplex interaction, focusing on residues belonging to both the NPM1 terminal three-helix bundle and a lysine-rich unstructured tail, which has been shown to be necessary for high affinity recognition. We performed extended site-directed mutagenesis and measured binding rate constants through surface plasmon resonance analysis. These data, supported by molecular dynamics simulations, suggest that the unstructured tail plays a double role in the reaction mechanism. On the one hand, it facilitates the formation of an encounter complex through long range electrostatic interactions; on the other hand, it directly contacts the G-quadruplex scaffold through multiple and transient electrostatic interactions, significantly enlarging the contact surface.
Tantalum-based diffusion barriers in Si/Cu VLSI metallizations (1991)

We have studied sputter-deposited Ta, Ta36Si14, and Ta36Si14N50 thin films as diffusion barriers between Cu overlayers and Si substrates. Electrical measurements on Si n+p shallow junction diodes demonstrate that a 180-nm-thick Ta film is not an effective diffusion barrier. For the standard test of 30-min annealing in vacuum applied in the present study, the Ta barrier fails after annealing at 500 °C. An amorphous Ta74Si26 thin film improves the performance by raising the failure temperature of a 〈Si〉/Ta74Si26(100 nm)/Cu(500 nm) metallization to 650 °C. Unparalled results are obtained with an amorphous ternary Ta36Si14N50 thin film in the Si/Ta36Si14N50(120 nm)/Cu(500 nm) and in the Si/TiSi2(30 nm)/Ta36SiN50(80 nm)/Cu(500 nm) metallization that break down only after annealing at 900 °C. The failure is induced by a premature crystallization of the Ta36Si14N50 alloy (whose crystallization temperature exceeds 1000 °C) when in contact with copper.
Typing of the uropathogenic E. coli strains using O-serotyping and detection of pap adhesion-encoding operon by polymerase chain reaction. (2009)

Background: Urinary tract infection (UTI) is a frequently diagnosed renal and urologic disease. Escherichia coli is by far the most common etiologic agent of this disease. This study was aimed to type the E.coli strains isolated from the patients with urinary tract infection using sero-grouping. Detection of pap adhesion-encoding operon was also targeted. Patients and methods: A total of 130 E. coli strains isolated from patients with UTI were investigated for O-serotyping. The presence of pap adhesion-encoding operon was detected using polymerase chain reaction (PCR). Results: In serogrouping with 13 antisera, 86 strains (66.14%) were O-serogroupable and belonging to O1, O6, O15, O18 & O20 serogroups, while 44 strains (33.86%) were O-non typeable. Predominant serogroups were O6 and O18. The PCR results showed that 61% of strains exhibited the pap genotype. Serogroups O1, O6, O15 and O18 possessed pap operon. There was an obvious correlation between the pap operon and the O-serogroups of the strains. Conclusion: Our results showed that obtained protein patterns of the isolated strains were more reliable than serotyping results for typing purposes. Our findings indicated that pap adhesion-encoding operon has an important role in the development and severity of UTI. Many cases of serious urogenital diseases are caused by a limited number of uropathogenic E.coli strains that generally possess special virulence factors such as pap operon.
Isolation and characterization of chromosomal promoters of Streptococcus salivarius subsp. thermophilus (1991)

A promoter probe vector, pTG244, was constructed with the aim of isolating transcription initiation signals from Streptococcus thermophilus (Streptococcus salivarius subsp. thermophilus). pTG244 is based on the Escherichia coli-streptococcus shuttle vector pTG222, into which the promoterless chloramphenicol acetyltransferase gene of Bacillus pumilus (cat-86) was cloned. Random Sau3A fragments from the S. thermophilus A054 chromosomal DNA were cloned upstream of the cat-86 gene by using E. coli as the host. The pool of recombinant plasmids were introduced into S. thermophilus and Lactococcus lactis subsp. lactis in order to search for promoter activity in these hosts. For S. thermophilus, it was necessary to first select erythromycin-resistant transformants and then to screen for chloramphenicol resistance among these. Direct selection of chloramphenicol-resistant clones was, however, possible in L. lactis subsp. lactis. Six fragments exhibiting promoter activity were characterized in S. thermophilus by measuring the levels of cat-86 transcription and/or chloramphenicol acetyltransferase specific activity. Three of the promoter-carrying fragments were sequenced. The 5' ends of their corresponding mRNAs were determined by S1 mapping and shown to correspond to a purine residue in all cases. Upstream from these potential transcription start points, sequences homologous to the E. coli sigma 70 and the Bacillus subtilis vegetative sigma 43 (or sigma A) consensus promoters were identified.
Cancer prevention with dehydroepiandrosterone and non-androgenic structural analogs (1995)

There is increasing evidence that the adrenocortical steroid, dehydroepiandrosterone (DHEA), is an important mammalian hormone. Administration of DHEA to laboratory mice and rats inhibits development of experimental tumors of the breast, lung, colon, liver, skin and lymphatic tissue. In the two-stage skin tumorigenesis model in mice, DHEA treatment inhibits tumor initiation, as well as tumor promoter-induced epidermal hyperplasia and promotion of papillomas. There is much evidence that DHEA produces its antiproliferative and tumor preventive effects by inhibiting glucose-6-phosphate dehydrogenase and the pentose phosphate pathway. This pathway is an important source of NADPH, a critical reductant for many biochemical reactions that generate oxygen free radicals, which may act as second messengers in stimulating hyperplasia. The therapeutic use of DHEA in humans may be limited by its sex hormonal side effects. DHEA is metabolized in vivo to both testosterone and estrone, producing both androgenic and estrogenic effects in laboratory animals. We have developed a synthetic steroid, 16 alpha-fluoro-5-androsten-17-one, which does not demonstrate the androgenic or estrogenic activity of DHEA, yet retains the antiproliferative and cancer preventive activity of the native steroid.
ChemInform Abstract: An Improved One‐Pot Procedure for the Synthesis of Alkynes from Aldehydes. (1996)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Automatic verification of hybrid systems: an audio control protocol (2002)

The work is concerned with formal approaches to specification and verification for a better development in systems design. Automatic verification is a solution for validating highly critical systems, like controlling robots or supervising electronical devices. Important efforts have been realized in industry and education for supporting its development. Nevertheless, technical problems keep arising due to the size of specifications, in some cases requiring too much effort to obtain some results. We present the specification of the EEL communication protocol, used by Phillips in its audio components. This protocol verifies the correct communication between an audio system and its remote control, and is a typical case for studying hybrid systems. Hybrid systems are specified by finite automata enriched with a set of real variables. Properties to prove are usually written in some temporal logic. Automatic verification tools solve the "model checking" problem: does property /spl pi/ hold in system S?. To solve difficulties associated to the size of systems, different tools have implemented techniques such as symbolic model checking, "on the fly" analysis, modularization and clock reduction. We believe that there are still ways to improve these tools: diminish redundancy in modelling, optimization for data management and storage, randomization of algorithms.