gebhart/patrepeval huggingface dataset:
Tob, a novel protein that interacts with p185erbB2, is associated with anti-proliferative activity. (1996)

We have molecularly cloned a cDNA for a novel protein termed Tob (Transducer of ErbB-2) that interacts with the c-erbB-2 gene product p185erbB2. Nucleotide sequencing reveals that the Tob protein is a 45 kDa protein that does not contain either SH2 (Src Homology 2) or SH3 domain but is homologous to the previously characterized anti-proliferative gene product BTG-1 at its amino-terminal half. The carboxyl-terminal half of Tob is characterized by the presence of a sequence rich in proline and glutamine and shows no homology to known proteins. Like BTG-1, exogenously expressed Tob is able to suppress growth of NIH3T3 cells, but the growth suppression is hampered by the presence of kinase-active p185erbB2. By using the GST-Tob protein that contains either full length or amino-terminal half of Tob, we show that the carboxyl-terminal half of Tob is relevant to its interaction with p185erbB2. Furthermore, we could co-immunoprecipitate the Tob protein with anti-ErbB-2 antibody, and reciprocally the p185erbB2 with anti-Tob antibodies. These data suggest that p185erbB2 negatively regulates the Tob-mediated anti-proliferative pathway through its interaction with Tob, resulting possibly in growth stimulation by p185erbB2. Finally, expression of the Tob mRNA is observed in various cell types and is not correlated with expression of c-erbB-2, suggesting that other receptor-type protein-tyrosine kinases are also involved in the Tob-mediated regulation of cell growth.
EXTRACELLULAR GLYCOLIPIDS OF RHODOTORULA SPECIES: THE ISOLATION AND SYNTHESIS OF 3-D-HYDROXYPALMITIC AND 3-D-HYDROXYSTEARIC ACIDS (1964)

Several species of the red yeast Rhodotorula produce extracellular glycolipids which consist of a mixture of mannitol and pentitol esters of 3-D-hydroxypalmitic and 3-D-hydroxystearic acids. One molecule of the long chain acid is attached to each polyol molecule and most of the remaining hydroxyl groups including the one on the fatty acid are acetylated.
A clinical and neurophysiological trial on nootropic drugs in patients with mental decline. (1991)

The different expressions of mental decline in elderly people, from simple senile benign forgetfulness to SDAT, can be evaluated by psychometric and neurophysiological tests. In the present study, the effects of oxiracetam, piracetam and placebo were compared in a group of elderly subjects. The results of the trial, structured as single blind, clearly showed that nootropics positively effect both clinical and neurophysiological performances and that oxiracetam produces a more pronounced effect when compared to piracetam. In fact, oxiracetam was found more effective in improving psychometric scales such as GDS (clinical performances) as well as the amplitude and the latency of the P300 (neurophysiological performances), which reflect a functional recovery of the cerebral pathways related to attention and memory.
Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Glaucoma Using Optical Coherence Tomography–Based Microangiography (2016)

Peripapillary RNFL vascular microcirculation measured as blood flux index by OMAG showed significant differences among OAG, glaucoma suspect, and normal controls and was significantly correlated with functional and structural defects. Retinal nerve fiber layer microcirculation measurement using OMAG may help physicians monitor glaucoma.
Inhibition of Respiratory Syncytial Virus In Vitro and In Vivo by the Immunosuppressive Agent Leflunomide (2010)

These findings suggest promise for leflunomide as a convenient, orally administered addition to the growing arsenal of antiviral therapeutics. While specific antiviral mechanisms remain to be elucidated, leflunomide shows unique bifunctional potential to both reduce viral load and, by virtue of its well-documented anti-inflammatory activity, attenuate the destructive inflammation associated with RSV disease.
Technology challenges for integration near and below 0.1 μm (1997)

Technology challenges for silicon integrated circuits with a design rule of 0.1 /spl mu/m and below are addressed. We begin by reviewing the state-of-the-art CMOS technology at 0.25 /spl mu/m currently in development, covering a logic-oriented processes and dynamic random access memory (DRAM) processes. CMOS transistor structures are compared by introducing a figure of merit. We then examine scaling guidelines for 0.1 /spl mu/m which has started to deviate for optimized performance from the classical theory of constant-field scaling. This highlights the problem of nontrivial subthreshold current associated with the scaled-down CMOS with low threshold voltages. Interconnect issues are then considered to assess the performance of microprocessors in 0.1 /spl mu/m technology. 0.1 /spl mu/m technology will enable a microprocessor which runs at 1000 MHz with 500 million transistors. Challenges below 0.1 /spl mu/m are then addressed. New transistor and circuit possibilities such as silicon on insulator (SOI), dynamic-threshold (DT) MOSFET, and back-gate input MOS (BMOS) are discussed. Two problems below 0.1 /spl mu/m are highlighted. They are threshold voltage control and pattern printing. It is pointed out that the threshold voltage variations due to doping fluctuations is a limiting factor for scaling CMOS transistors for high performance. The problem with lithography below 0.1 /spl mu/m is the low throughput for a single probe. The use of massively parallel scanning probe assemblies working over the entire wafer is suggested to overcome the problem of low throughput.
Striking Increase of Survival of Mice Bearing M 109 Madison Carcinoma Treated With a Novel Protein From With a Novel Protein From Amphibian Embryos (1990)

Journal Article Striking Increase of Survival of Mice Bearing M 109 Madison Carcinoma Treated With a Novel Protein From With a Novel Protein From Amphibian Embryos Get access STANISLAW M. MIKULSKI, STANISLAW M. MIKULSKI Alfacell Corporation 225 Belleville Ave. Bloomfield, NJ 07003PA Search for other works by this author on: Oxford Academic PubMed Google Scholar WOJCIECH ARDELT, WOJCIECH ARDELT Alfacell Corporation 225 Belleville Ave. Bloomfield, NJ 07003PA Search for other works by this author on: Oxford Academic PubMed Google Scholar KUSLIMA SHOGEN, KUSLIMA SHOGEN Alfacell Corporation 225 Belleville Ave. Bloomfield, NJ 07003PA Search for other works by this author on: Oxford Academic PubMed Google Scholar EUGENE H. BERNSTEIN, EUGENE H. BERNSTEIN University Laboratories, Inc. Hoghland Park, NJPA Search for other works by this author on: Oxford Academic PubMed Google Scholar HYMAN MENDUKE HYMAN MENDUKE Department of Pharmacology Jefferson Medical College PhiladelphiaPA 1 We thank Joyce H. Smoyak of University Laboratories, Inc., for her devotion and commitment in conducting the animal studies. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 2, 17 January 1990, Pages 151–153, https://doi.org/10.1093/jnci/82.2.151-a Published: 17 January 1990
Size-Dependent Immunogenicity: Therapeutic and Protective Properties of Nano-Vaccines against Tumors (2004)

Infection can protect against subsequent disease by induction of both humoral and cellular immunity, but inert protein-based vaccines are not as effective. In this study, we present a new vaccine design, with Ag covalently conjugated to solid core nano-beads of narrowly defined size (0.04-0.05 microm) that localize to dendritic cells (DEC205(+) CD40(+), CD86(+)) in draining lymph nodes, inducing high levels of IFN-gamma production (CD8 T cells: precursor frequencies 1/5000 to 1/1000) and high Ab titers in mice. Conjugation of Ag to these nano-beads induced responses that were significantly higher (2- to 10-fold) than those elicited by other bead sizes, and higher than a range of currently used adjuvants (alum, QuilA, monophosphoryl lipid A). Responses were comparable to CFA/IFA immunization for Abs and ex vivo peptide-pulsed dendritic cell immunization for CD8 T cells. A single dose of Ag-conjugated beads protected mice from tumors in two different model challenges and caused rapid clearance of established tumors in mice. Thus, a range of Ags conjugated to nano-beads was effective as immunogens in both therapeutic and prophylactic scenarios.
Cell penetration by exogenous superoxide dismutase. (1980)

The fixation and penetration of liposomal encapsulated dismutase (SOD) with human erythrocytes and other eucaryote cells is described. Such preparations not only facilitate fixation and penetration of the enzyme as a function of liposome composition, but also confer an increased physiological life time as well as a marked organ specificity. Such packed SOD could be useful for a pharmacological application of the enzyme.
Valproic acid reduces brain damage induced by transient focal cerebral ischemia in rats: potential roles of histone deacetylase inhibition and heat shock protein induction (2004)

Growing evidence from in vitro studies supports that valproic acid (VPA), an anti-convulsant and mood-stabilizing drug, has neuroprotective effects. The present study investigated whether VPA reduces brain damage and improves functional outcome in a transient focal cerebral ischemia model of rats. Subcutaneous injection of VPA (300 mg/kg) immediately after ischemia followed by repeated injections every 12 h, was found to markedly decrease infarct size and reduce ischemia-induced neurological deficit scores measured at 24 and 48 h after ischemic onset. VPA treatment also suppressed ischemia-induced neuronal caspase-3 activation in the cerebral cortex. VPA treatments resulted in a time-dependent increase in acetylated histone H3 levels in the cortex and striatum of both ipsilateral and contralateral brain hemispheres of middle cerebral artery occlusion (MCAO) rats, as well as in these brain areas of normal, non-surgical rats, supporting the in vitro finding that VPA is a histone deacetylase (HDAC) inhibitor. Similarly, heat shock protein 70 (HSP70) levels were time-dependently up-regulated by VPA in the cortex and striatum of both ipsilateral and contralateral sides of MCAO rats and in these brain areas of normal rats. Altogether, our results demonstrate that VPA is neuroprotective in the cerebral ischemia model and suggest that the protection mechanisms may involve HDAC inhibition and HSP induction.
[Comparison of coronary artery bypass graft imaging between 64-slice and 16-slice spiral CT]. (2006)

64-slice spiral CT is superior to 16-slice spiral CT in CABG imaging. It can be used as a non-invasive tool for the post-operative follow-up of CABG.
Aminophosphine Palladium Pincer-Catalyzed Carbonylative Sonogashira and Suzuki–Miyaura Cross-Coupling with High Catalytic Turnovers (2019)

This work documents the first palladium pincer complex-catalyzed carbonylative Sonogashira (CS) and carbonylative Suzuki-Miyaura (CSM) cross-coupling. Compared to previous protocols, which employ hazardous and toxic solvents, the aminophosphine pincer complex {[C<sub>6</sub>H<sub>3</sub>-2,6-(NHP{piperidinyl}<sub>2</sub>)<sub>2</sub>]Pd(Cl)} (<b>III</b>) catalyzes both the cross-coupling reactions in propylene carbonate, an eco-friendly and sustainable polar aprotic solvent. Advantageously, employing <b>III</b> allows the CS cross-coupling to be carried out at a palladium loading of 10<sup>-4</sup> mol % and the CSM cross-coupling to be carried out at 10<sup>-6</sup> mol %, thus resulting in catalytic turnovers of 10<sup>5</sup> and 10<sup>7</sup>, respectively. Relative comparison of the pincer complex with conventional palladium precursors Pd(OAc)<sub>2</sub> and PdCl<sub>2</sub>(PPh<sub>3</sub>)<sub>2</sub> shows the efficiency and robustness of the pincer complex in effecting higher catalytic activity at low palladium loadings.
Phase 1 Safety and Immunogenicity Evaluation of a Multiclade HIV‐1 DNA Candidate Vaccine (2006)

DNA vaccination induced antibody to and T cell responses against 3 major HIV-1 subtypes and will be further evaluated as a potential component of a preventive AIDS vaccine regimen.
Quantitative Profiling of Protein Tyrosine Kinases in Human Cancer Cell Lines by Multiplexed Parallel Reaction Monitoring Assays (2015)

Protein tyrosine kinases (PTKs) play key roles in cellular signal transduction, cell cycle regulation, cell division, and cell differentiation. Dysregulation of PTK-activated pathways, often by receptor overexpression, gene amplification, or genetic mutation, is a causal factor underlying numerous cancers. In this study, we have developed a parallel reaction monitoring-based assay for quantitative profiling of 83 PTKs. The assay detects 308 proteotypic peptides from 54 receptor tyrosine kinases and 29 nonreceptor tyrosine kinases in a single run. Quantitative comparisons were based on the labeled reference peptide method. We implemented the assay in four cell models: 1) a comparison of proliferating versus epidermal growth factor-stimulated A431 cells, 2) a comparison of SW480Null (mutant APC) and SW480APC (APC restored) colon tumor cell lines, and 3) a comparison of 10 colorectal cancer cell lines with different genomic abnormalities, and 4) lung cancer cell lines with either susceptibility (11-18) or acquired resistance (11-18R) to the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib. We observed distinct PTK expression changes that were induced by stimuli, genomic features or drug resistance, which were consistent with previous reports. However, most of the measured expression differences were novel observations. For example, acquired resistance to erlotinib in the 11-18 cell model was associated not only with previously reported up-regulation of MET, but also with up-regulation of FLK2 and down-regulation of LYN and PTK7. Immunoblot analyses and shotgun proteomics data were highly consistent with parallel reaction monitoring data. Multiplexed parallel reaction monitoring assays provide a targeted, systems-level profiling approach to evaluate cancer-related proteotypes and adaptations. Data are available through Proteome eXchange Accession PXD002706.
Molecular cloning and expression in photosynthetic bacteria of a soybean cDNA coding for phytoene desaturase, an enzyme of the carotenoid biosynthesis pathway. (1991)

Carotenoids are orange, yellow, or red photo-protective pigments present in all plastids. The first carotenoid of the pathway is phytoene, a colorless compound that is converted into colored carotenoids through a series of desaturation reactions. Genes coding for carotenoid desaturases have been cloned from microbes but not from plants. We report the cloning of a cDNA for pds1, a soybean (Glycine max) gene that, based on a complementation assay using the photosynthetic bacterium Rhodobacter capsulatus, codes for an enzyme that catalyzes the two desaturation reactions that convert phytoene into zeta-carotene, a yellow carotenoid. The 2281-base-pair cDNA clone analyzed contains an open reading frame with the capacity to code for a 572-residue protein of predicted Mr 63,851. Alignment of the deduced Pds1 peptide sequence with the sequences of fungal and bacterial carotenoid desaturases revealed conservation of several amino acid residues, including a dinucleotide-binding motif that could mediate binding to FAD. The Pds1 protein is synthesized in vitro as a precursor that, upon import into isolated chloroplasts, is processed to a smaller mature form. Hybridization of the pds1 cDNA to genomic blots indicated that this gene is a member of a low-copy-number gene family. One of these loci was genetically mapped using restriction fragment length polymorphisms between Glycine max and Glycine soja. We conclude that pds1 is a nuclear gene encoding a phytoene desaturase enzyme that, as its microbial counterparts, contains sequence motifs characteristic of flavoproteins.
Restricted immunoglobulin VH usage and VDJ combinations in the human response to Haemophilus influenzae type b capsular polysaccharide. Nucleotide sequences of monospecific anti-Haemophilus antibodies and polyspecific antibodies cross-reacting with self antigens. (1993)

To examine the human antibody repertoire generated against a biologically significant antigen we have obtained sequences of heavy chain variable region genes (IgVH) from 15 monoclonal antibodies specific for the capsular polysaccharide of Haemophilus influenzae type b (Hib PS). All VH segments are members of the VH3 family and 9 of 15 are members of the smaller VH3b subfamily. Restriction is evident by the shared use of certain VDJ joints in independent hybridomas from different subjects. Two hybridomas generated from the same subject demonstrate identical heavy chain variable region gene sequences but differ in isotype and rearrange alternative light chain variable region genes (IgVL), suggesting that in a normal immune response, a single pre-B cell clone may use different light chain rearrangements and give rise to progeny capable of reacting with antigen. Using a polymerase chain reaction assay optimized to detect base pair differences among VH genes we demonstrate that at least a portion of expressed anti-Hib PS VH genes have undergone somatic mutation. Anti-Hib PS heavy chain genes are homologous to VH segments encoding autoantibodies and two hybridomas secrete anti-Hib PS antibody that cross-reacts with self antigens (double-stranded DNA and single-stranded DNA). Comparison of VH regions of self-reactive and monospecific anti-Hib PS Ab demonstrates no consistent structural feature correlating with fine antigen specificity. These data demonstrate significant restriction in VH usage and VDJ recombination in the anti-Hib PS response and confirm that autoantibodies may be elicited during normal immune responses.
Regulation of ROCK Activity in Cancer (2012)

Cancer-associated changes in cellular behavior, such as modified cell-cell contact, increased migratory potential, and generation of cellular force, all require alteration of the cytoskeleton. Two homologous mammalian serine/threonine kinases, Rho-associated protein kinases (ROCK I and II), are key regulators of the actin cytoskeleton acting downstream of the small GTPase Rho. ROCK is associated with cancer progression, and ROCK protein expression is elevated in several types of cancer. ROCKs exist in a closed, inactive conformation under quiescent conditions, which is changed to an open, active conformation by the direct binding of guanosine triphosphate (GTP)-loaded Rho. In recent years, a number of ROCK isoform-specific binding partners have been found to modulate the kinase activity through direct interactions with the catalytic domain or via altered cellular localization of the kinases. Thus, these findings demonstrate additional modes to regulate ROCK activity. This review describes the molecular mechanisms of ROCK activity regulation in cancer, with emphasis on ROCK isoform-specific regulation and interaction partners, and discusses the potential of ROCKs as therapeutic targets in cancer.
Distinct patterns of Cas9 mismatch tolerancein vitroandin vivo (2016)

Cas9, a CRISPR-associated RNA-guided nuclease, has been rapidly adopted as a tool for biochemical and genetic manipulation of DNA. Although complexes between Cas9 and guide RNAs (gRNAs) offer remarkable specificity and versatility for genome manipulation, mis-targeted events occur. To extend the understanding of gRNA::target homology requirements, we compared mutational tolerance for a set of Cas9::gRNA complexes in vitro and in vivo (in Saccharomyces cerevisiae). A variety of gRNAs were tested with variant libraries based on four different targets (with varying GC content and sequence features). In each case, we challenged a mixture of matched and mismatched targets, evaluating cleavage activity on a wide variety of potential target sequences in parallel through high-throughput sequencing of the products retained after cleavage. These experiments evidenced notable and consistent differences between in vitro and S. cerevisiae (in vivo) Cas9 cleavage specificity profiles including (i) a greater tolerance for mismatches in vitro and (ii) a greater specificity increase in vivo with truncation of the gRNA homology regions.
Ascorbic acid enhances arsenic trioxide–induced cytotoxicity in multiple myeloma cells (2001)

Multiple myeloma (MM) is a clonal B-cell malignancy characterized by slow-growing plasma cells in the bone marrow (BM). Patients with MM typically respond to initial chemotherapies; however, essentially all progress to a chemoresistant state. Factors that contribute to the chemorefractory phenotype include modulation of free radical scavenging, increased expression of drug efflux pumps, and changes in gene expression that allow escape from apoptotic signaling. Recent data indicate that arsenic trioxide (As(2)O(3)) induces remission of refractory acute promyelocytic leukemia and apoptosis of cell lines overexpressing Bcl-2 family members; therefore, it was hypothesized that chemorefractory MM cells would be sensitive to As(2)O(3). As(2)O(3) induced apoptosis in 4 human MM cell lines: 8226/S, 8226/Dox40, U266, and U266/Bcl-x(L). The addition of interleukin-6 had no effect on cell death. Glutathione (GSH) has been implicated as an inhibitor of As(2)O(3)-induced cell death either through conjugating As(2)O(3) or by sequestering reactive oxygen induced by As(2)O(3). Consistent with this possibility, increasing GSH levels with N-acetylcysteine attenuated As(2)O(3) cytotoxicity. Decreases in GSH have been associated with ascorbic acid (AA) metabolism. Clinically relevant doses of AA decreased GSH levels and potentiated As(2)O(3)-mediated cell death of all 4 MM cell lines. Similar results were obtained in freshly isolated human MM cells. In contrast, normal BM cells displayed little sensitivity to As(2)O(3) alone or in combination with AA. Together, these data suggest that As(2)O(3) and AA may be effective antineoplastic agents in refractory MM and that AA might be a useful adjuvant in GSH-sensitive therapies. (Blood. 2001;98:805-813)
Tumor stem cell assay for detecting metastases of human lung cancer. (1983)

We applied a tumor stem cell assay using an enriched double-layered soft agar system for the detection of metastatic sites of lung cancer. Lung cancer colonies grew from 7 of 10 effusions cytologically positive for tumor cells and 7 of 10 bone marrow aspirates cytologically and histologically positive for tumor cells. Twenty-six of 29 bone marrow aspirates cytologically and histologically negative for tumor cells showed no colony growth. However, the remaining three bone marrow aspirates, which were obtained from patients with small cell lung cancer, formed colonies in soft agar. These results indicate that the tumor stem cell assay is useful for detecting metastatic sites of lung cancer.