gebhart/patrepeval huggingface dataset:
Pentoxifylline inhibits hypoxia-induced upregulation of tumor cell tissue factor and vascular endothelial growth factor. (1998)

Tissue factor (TF), the membrane glycoprotein that initiates blood coagulation, is constitutively expressed by many tumor cells and is implicated in peri-tumor fibrin deposition and hypercoagulability in cancer. Upregulation of tumor TF correlates with enhanced metastatic potential. Furthermore, TF has been colocalized with VEGF in breast cancer, specially at sites of early angiogenesis. There are no data on the effect of hypoxia on tumor cell TF expression. Since hypoxia is known to stimulate VEGF production, we studied whether this also induces tumor cell TF expression. Confluent monolayers of A375 melanoma, MCF-7 breast carcinoma and A549 lung carcinoma were cultured in either 95% air, 5% CO2 (normoxic) or 95% N2, 5% CO2 (hypoxic; 25-30 mmHg) for 24 h. Procoagulant activity (PCA) was measured by amidolytic and clotting assays, surface TF antigen by flow cytometry, early apoptosis by annexin V binding and VEGF levels in culture supernatants by ELISA. Hypoxia significantly increased tumor cell PCA in all three cell lines tested and TF antigen on A375 cells was increased four-fold (P <0.05). Pentoxifylline (PTX), a methylxanthine derivative, significantly inhibited the hypoxia-induced increase in PCA as well as VEGF release in all three cell lines tested. In A375 cells, PTX significantly inhibited TF antigen expression by both normoxic and hypoxic cells. Hypoxia induced a slight (5%) but not significant, increase in early apoptosis. Intravenous injection of hypoxic A375 cells into nude rats produced more pronounced thrombocytopenia (n = 5, P <0.01) and more lung metastases (n = 3, P <0.05) compared to normoxic cells. We conclude that hypoxia increases TF expression by malignant cells which enhances tumor cell-platelet binding and hematogenous metastasis. Hypoxia-induced upregulation of TF appears to parallel that of VEGF, although the mechanism remains unclear.
Photosensitive polynorbornene as a dielectric material for packaging applications (2002)

The rapid development of the microelectronics industry creates high demand for low dielectric constant (low-k) materials. Polynorbornene (Avatrel/sup TM/) is a new photodefinable dielectric material developed by the BF Goodrich Company. A type of cationic photoinitiator, onium salts, is used to initiate the crosslinking reaction of epoxide groups. The reaction mechanism of poly(decylnorbornene-co-epoxidenorbornene) was studied. The structure/properties relationships of the polymer film were investigated. Copolymer composition and process conditions affect the properties of the polymer film. A lower epoxidenorbornene content results in lower dielectric constant, lower residual stress, better adhesion, and good photodefinition, but poor multilayer capability. Lower exposure dose, lower post bake temperature and shorter post bake time improve photodefinition.
Effect of different cell culture conditions on the polypeptide integrity and N‐glycosylation of a recombinant model glycoprotein (1995)

The effect of different short-term controlled cell culture conditions on the product quality of a genetically engineered human interleukin-2 N-glycosylation variant protein expressed from a baby hamster kidney cell line (BHK-21) has been investigated. A perfused 2-L stirred tank reactor was used. Products purified from the culture supernatant of cells grown under experimentally initiated nutrient limitations (glucose, amino acids, pO(2)) were characterized by their HPLC-elution profile, SDS-PAGE and western blotting, amino acid sequencing as well as for their N-linked carbohydrates, using "HPAEC-PAD fingerprinting" and methylation analysis. The glycoprotein products secreted from cells under the different culture conditions (kept for 24 h, after an adaption time period of 48 h) showed an almost identical oligosaccharide pattern. By contrast, short-term changes of the culture condition led to considerable differences in the ratio of glycosylated to unglycosylated protein forms. Significant amounts of NH(2)-terminally truncated polypeptide forms were observed. They lacked proponderantly the first two amino acids; however, under certain culture conditions forms lacking up to eight NH(2)-terminal amino acids were detected. (
Structure−Activity Relationship Studies of Novel Benzophenones Leading to the Discovery of a Potent, Next Generation HIV Nonnucleoside Reverse Transcriptase Inhibitor (2005)

Despite the progress of the past two decades, there is still considerable need for safe, efficacious drugs that target human immunodeficiency virus (HIV). This is particularly true for the growing number of patients infected with virus resistant to currently approved HIV drugs. Our high throughput screening effort identified a benzophenone template as a potential nonnucleoside reverse transcriptase inhibitor (NNRTI). This manuscript describes our extensive exploration of the benzophenone structure-activity relationships, which culminated in the identification of several compounds with very potent inhibition of both wild type and clinically relevant NNRTI-resistant mutant strains of HIV. These potent inhibitors include 70h (GW678248), which has in vitro antiviral assay IC(50) values of 0.5 nM against wild-type HIV, 1 nM against the K103N mutant associated with clinical resistance to efavirenz, and 0.7 nM against the Y181C mutant associated with clinical resistance to nevirapine. Compound 70h has also demonstrated relatively low clearance in intravenous pharmacokinetic studies in three species, and it is the active component of a drug candidate which has progressed to phase 2 clinical studies.
Enhanced Antitumor Immunity in Mice Deficient in CD69 (2003)

We investigated the in vivo role of CD69 by analyzing the susceptibility of CD69-/- mice to tumors. CD69-/- mice challenged with MHC class I- tumors (RMA-S and RM-1) showed greatly reduced tumor growth and prolonged survival compared with wild-type (WT) mice. The enhanced anti-tumor response was NK cell and T lymphocyte-mediated, and was due, at least in part, to an increase in local lymphocytes. Resistance of CD69-/- mice to MHC class I- tumor growth was also associated with increased production of the chemokine MCP-1, diminished TGF-beta production, and decreased lymphocyte apoptosis. Moreover, the in vivo blockade of TGF-beta in WT mice resulted in enhanced anti-tumor response. In addition, CD69 engagement induced NK and T cell production of TGF-beta, directly linking CD69 signaling to TGF-beta regulation. Furthermore, anti-CD69 antibody treatment in WT mice induced a specific down-regulation in CD69 expression that resulted in augmented anti-tumor response. These data unmask a novel role for CD69 as a negative regulator of anti-tumor responses and show the possibility of a novel approach for the therapy of tumors.
Prognostic value of tumour associated antigen immunoreactivity and apoptosis in cerebral glioblastomas: an analysis of 168 cases. (1999)

EGFR immunoreactivity and apoptotic index were found to be useful for assessing prognosis of individual glioblastomas but it seems unlikely that p53 and bcl-2 immunohistochemistry will be of value in determining survival in such patients.
Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease (2020)

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the etiological agent responsible for the global COVID-19 (coronavirus disease 2019) outbreak. The main protease of SARS-CoV-2, M<sup>pro</sup>, is a key enzyme that plays a pivotal role in mediating viral replication and transcription. We designed and synthesized two lead compounds (<b>11a</b> and <b>11b</b>) targeting M<sup>pro</sup> Both exhibited excellent inhibitory activity and potent anti-SARS-CoV-2 infection activity. The x-ray crystal structures of SARS-CoV-2 M<sup>pro</sup> in complex with <b>11a</b> or <b>11b</b>, both determined at a resolution of 1.5 angstroms, showed that the aldehyde groups of <b>11a</b> and <b>11b</b> are covalently bound to cysteine 145 of M<sup>pro</sup> Both compounds showed good pharmacokinetic properties in vivo, and <b>11a</b> also exhibited low toxicity, which suggests that these compounds are promising drug candidates.
Study of the Diels–Alder and retro-Diels–Alder reaction between furan derivatives and maleimide for the creation of new materials (2015)

This study showed a way to increase the<italic>endo</italic>/<italic>exo</italic>ratio in favor of the<italic>endo</italic>adduct in furan derivatives/maleimide systems.
Maternal Autoimmune Diseases, Asthma and Allergies, and Childhood Autism Spectrum Disorders (2005)

These findings suggest that maternal autoimmune disorders present in women around the time of pregnancy are unlikely to contribute significantly to autism risk. Further etiologic investigations are needed to confirm these results and should include objective documentation of diagnoses and consider a larger set of maternal immune-related conditions, including asthma and allergies.
ZEB1 drives prometastatic actin cytoskeletal remodeling by downregulating miR-34a expression (2012)

Metastatic cancer is extremely difficult to treat, and the presence of metastases greatly reduces a cancer patient's likelihood of long-term survival. The ZEB1 transcriptional repressor promotes metastasis through downregulation of microRNAs (miRs) that are strong inducers of epithelial differentiation and inhibitors of stem cell factors. Given that each miR can target multiple genes with diverse functions, we posited that the prometastatic network controlled by ZEB1 extends beyond these processes. We tested this hypothesis using a mouse model of human lung adenocarcinoma metastasis driven by ZEB1, human lung carcinoma cells, and human breast carcinoma cells. Transcriptional profiling studies revealed that ZEB1 controls the expression of numerous oncogenic and tumor-suppressive miRs, including miR-34a. Ectopic expression of miR-34a decreased tumor cell invasion and metastasis, inhibited the formation of promigratory cytoskeletal structures, suppressed activation of the RHO GTPase family, and regulated a gene expression signature enriched in cytoskeletal functions and predictive of outcome in human lung adenocarcinomas. We identified several miR-34a target genes, including Arhgap1, which encodes a RHO GTPase activating protein that was required for tumor cell invasion. These findings demonstrate that ZEB1 drives prometastatic actin cytoskeletal remodeling by downregulating miR-34a expression and provide a compelling rationale to develop miR-34a as a therapeutic agent in lung cancer patients.
Concise Review: Mesenchymal Stem Cells: Their Phenotype, Differentiation Capacity, Immunological Features, and Potential for Homing (2007)

MSCs are nonhematopoietic stromal cells that are capable of differentiating into, and contribute to the regeneration of, mesenchymal tissues such as bone, cartilage, muscle, ligament, tendon, and adipose. MSCs are rare in bone marrow, representing approximately 1 in 10,000 nucleated cells. Although not immortal, they have the ability to expand manyfold in culture while retaining their growth and multilineage potential. MSCs are identified by the expression of many molecules including CD105 (SH2) and CD73 (SH3/4) and are negative for the hematopoietic markers CD34, CD45, and CD14. The properties of MSCs make these cells potentially ideal candidates for tissue engineering. It has been shown that MSCs, when transplanted systemically, are able to migrate to sites of injury in animals, suggesting that MSCs possess migratory capacity. However, the mechanisms underlying the migration of these cells remain unclear. Chemokine receptors and their ligands and adhesion molecules play an important role in tissue-specific homing of leukocytes and have also been implicated in trafficking of hematopoietic precursors into and through tissue. Several studies have reported the functional expression of various chemokine receptors and adhesion molecules on human MSCs. Harnessing the migratory potential of MSCs by modulating their chemokine-chemokine receptor interactions may be a powerful way to increase their ability to correct inherited disorders of mesenchymal tissues or facilitate tissue repair in vivo. The current review describes what is known about MSCs and their capacity to home to tissues together with the associated molecular mechanisms involving chemokine receptors and adhesion molecules.
Repairing faulty genes by aminoglycosides: Identification of new pharmacophore with enhanced suppression of disease-causing nonsense mutations (2011)

New pseudo-trisaccharide derivatives of aminoglycosides containing a chiral methyl group at the side-chain of the ribosamine ring (ring III) were designed, synthesized and their ability to readthrough nonsense mutations was examined in both in vitro and ex vivo systems, along with toxicity tests. Novel lead structures, exhibiting significantly reduced cell toxicity, enhanced specificity to eukaryotic cytoplasmic ribosome, and superior readthrough efficiency compared with those of gentamicin, were discovered. The comparative benefit of new leads was demonstrated in six different nonsense DNA-constructs underling the genetic diseases cystic fibrosis, Duchenne muscular dystrophy, Usher syndrome and Hurler syndrome.
Improving the virtual source method by wavefield separation (2007)

Abstract The virtual source method has recently been proposed to image and monitor below complex and time-varying overburden. The method requires surface shooting recorded at downhole receivers placed below the distorting or changing part of the overburden. Redatuming with the measured Green's function allows the reconstruction of a complete downhole survey as if the sources were also buried at the receiver locations. There are still some challenges that need to be addressed in the virtual source method, such as limited acquisition aperture and energy coming from the overburden. We demonstrate that up-down wavefield separation can substantially improve the quality of virtual source data. First, it allows us to eliminate artifacts associated with the limited acquisition aperture typically used in practice. Second, it allows us to reconstruct a new optimized response in the absence of downgoing reflections and multiples from the overburden. These improvements are illustrated on a synthetic data set of a complex layered model modeled after the Fahud field in Oman, and on ocean-bottom seismic data acquired in the Mars field in the deepwater Gulf of Mexico.
DIVSEL and COMPLIB - Strategies for the Design and Comparison of Combinatorial Libraries using Pharmacophoric Descriptors (1998)

Screening synthetic combinatorial libraries may facilitate rapid drug lead discovery by substantially increasing the number of molecules tested. Drug discovery efficiency and productivity can be further improved by designing libraries to maximize their molecular diversity or by comparing them to existing collections of compounds and/or libraries to select those that complement the properties already well represented. In this paper we describe two strategies to aid in the design and comparison of combinatorial libraries. The methods employ multi-pharmacophore three-dimensional (3D) descriptors in combination with two recent proposals for dissimilarity-based compound selection and library comparison. This method allows the design to be performed in product space and library comparison to consider all pair-wise intermolecular contributions to the diversity.
Copper conductors by reduction of copper (I) complex in a host polymer (1985)

A technique for generating fine copper conductors using a laser is described. The laser radiation is focused onto a Cu(CH3CN)4BF4-doped poly (N-vinylpyrrolidone) polymer thin film, and scanned across the polymer surface to produce a highly conductive copper run. The measured resistance is ony a factor of 5 above the calculated value for a copper conductor of comparable dimensions.
Crystal Structures of Unbound and Aminooxyacetate-Bound Escherichia coli γ-Aminobutyrate Aminotransferase (2004)

The X-ray crystal structures of Escherichia coli gamma-aminobutyrate aminotransferase unbound and bound to the inhibitor aminooxyacetate are reported. The enzyme crystallizes from ammonium sulfate solutions in the P3(2)21 space group with a tetramer in the asymmetric unit. Diffraction data were collected to 2.4 A resolution for the unliganded enzyme and 1.9 A resolution for the aminooxyacetate complex. The overall structure of the enzyme is similar to those of other aminotransferase subgroup II enzymes. The ability of gamma-aminobutyrate aminotransferase to act on primary amine substrates (gamma-aminobutyrate) in the first half-reaction and alpha-amino acids in the second is proposed to be enabled by the presence of Glu211, whose side chain carboxylate alternates between interactions with Arg398 in the primary amine half-reaction and an alternative binding site in the alpha-amino acid half-reaction, in which Arg398 binds the substrate alpha-carboxylate. The specificity for a carboxylate group on the substrate side chain is due primarily to the presence of Arg141, but also requires substantial local main chain rearrangements relative to the structurally homologous enzyme dialkylglycine decarboxylase, which is specific for small alkyl side chains. No iron-sulfur cluster is found in the bacterial enzyme as was found in the pig enzyme [Storici, P., De Biase, D., Bossa, F., Bruno, S., Mozzarelli, A., Peneff, C., Silverman, R. B., and Schirmer, T. (2004) J. Biol. Chem. 279, 363-73.]. The binding of aminooxyacetate causes remarkably small changes in the active site structure, and no large domain movements are observed. Active site structure comparisons with pig gamma-aminobutyrate aminotransferase and dialkylglycine decarboxylase are discussed.
Worst-Case and Average-Case Floating Codes for Flash Memory (2009)

Flash memory is used in portable electronic devices like cell phones, mp3 players, digital cameras, and PDAs. The question of how to code information in flash memory is a difficult one whose answer can have effects on the speed and lifespan of a chip of flash memory. The main factor to be taken into account when designing codes for flash memory is the difference in cost between decreasing and increasing the state of a cell; decreasing the state of a cell requires first the resetting of an entire section of cells. Codes that focus on maximizing the number of updates between these reset operations are called floating codes. Worst-case floating codes focus on maximizing the lower bound on the number of updates between resets, and average-case floating codes focus on maximizing the average number of updates between resets. In this thesis, we review the work done on both worst-case and average-case floating codes. We also introduce a new code which performs as well as the previous best worst-case floating code but is significantly simpler, and a second code which performs asymptotically better.
Cloning of ASH, a ubiquitous protein composed of one Src homology region (SH) 2 and two SH3 domains, from human and rat cDNA libraries. (1992)

The protein ASH (for abundant Src homology), composed of one Src homology region (SH) 2 and two SH3 domains, was cloned by screening human and rat cDNA libraries with an oligonucleotide probe directed to a consensus sequence of the SH2 domains. The rat-derived ASH peptide was comprised of 217 amino acids with a molecular mass of 25-28 kDa and was found to be ubiquitous in rat tissues. A human cDNA clone was also found to code for part of the same protein, suggesting that ASH is common to human and rat. The amino acid sequence of ASH was strikingly similar to Sem-5, the product of a nematode cell-signaling gene, and ASH is most probably a mammalian homologue of Sem-5. ASH bound in vitro to phosphotyrosine-containing proteins, including activated epidermal growth factor receptor, the ASH SH2 domain being responsible for the binding. Induced expression of an antisense ASH cDNA led to a reduction in cell growth. Considering these observations and the structural homology to Sem-5, ASH is likely to function as a ubiquitous signal transducer, possibly resembling Sem-5, which communicates between a receptor protein tyrosine kinase and a Ras protein.
Next-Generation Dengue Vaccines: Novel Strategies Currently Under Development (2011)

Dengue has become the most important arboviral infection worldwide with more than 30 million cases of dengue fever estimated to occur each year. The need for a dengue vaccine is great and several live attenuated dengue candidate vaccines are proceeding through clinical evaluation. The need to induce a balanced immune response against all four DENV serotypes with a single vaccine has been a challenge for dengue vaccine developers. A live attenuated DENV chimeric vaccine produced by Sanofi Pasteur has recently entered Phase III evaluation in numerous dengue-endemic regions of the world. Viral interference between serotypes contained in live vaccines has required up to three doses of the vaccine be given over a 12-month period of time. For this reason, novel DENV candidate vaccines are being developed with the goal of achieving a protective immune response with an immunization schedule that can be given over the course of a few months. These next-generation candidates include DNA vaccines, recombinant adenovirus vectored vaccines, alphavirus replicons, and sub-unit protein vaccines. Several of these novel candidates will be discussed.
Thrombin cleavage analysis of a novel antihaemophilic factor variant, factor VIII Δ II (1991)

Factor VIII delta II is a genetically engineered deletion variant of factor VIII expressed by recombinant Chinese hamster ovary cells, in which a major portion of the central (B) domain and a part of the light chain (Pro771-Asp1666) are missing. After immunoaffinity purification, the kinetics of thrombin cleavage of the novel molecule was analysed by SDS/PAGE, Western blotting and N-terminal amino acid sequencing. Thrombin first cleaves factor VIII delta II at Arg740-Ser741 to generate the 90-kDa heavy chain and an 80-kDa fusion polypeptide consisting of the remaining portion of the B domain and the 73-kDa light chain. The 90-kDa fragment is further cleaved, giving rise to 50-kDa and 40-kDa fragments while the 80-kDa fragment generates a 71/73-kDa doublet. The 71/73-kDa doublet, 50-kDa and 40-kDa fragments were further analysed by N-terminal amino acid sequencing and found to correspond to the predicted amino acid sequences. Our study shows that, in spite of the 900 amino acid deletion present in factor VIII delta II, the essential structural elements required for thrombin activation are conserved.
Assessment of post-laparotomy pain in laboratory mice by telemetric recording of heart rate and heart rate variability (2007)

In conclusion, real-time telemetric recordings of heart rate and heart rate variability were indicative of mild-to-moderate post-laparotomy pain and could define its duration in our mouse model. This level of pain cannot easily be detected by direct observation.
Analog VLSI synaptic matrices as building blocks for neural networks (1989)

An associative memory circuit that may let designers expand neural networks around a matrix of analog synapses is described. The architecture of the chip and its basic cell are discussed, and some SPICE simulation results are presented and compared with measures provided by the first prototype. In particular, the linearity and dynamic response of the complete chip, which includes an array of 25 synapses and two address decoders used for programming the weights, are examined.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>