gebhart/patrepeval huggingface dataset:
Protective immunity elicited by recombinant bacille Calmette-Guerin (BCG) expressing outer surface protein A (OspA) lipoprotein: a candidate Lyme disease vaccine. (1993)

The current vaccine against tuberculosis, Mycobacterium bovis strain bacille Calmette-Guerin (BCG), offers potential advantages as a live, innately immunogenic vaccine vehicle for the expression and delivery of protective recombinant antigens (Stover, C.K., V.F. de la Cruz, T.R. Fuerst, J.E. Burlein, L.A. Benson, L.T. Bennett, G.P. Bansal, J.F. Young, M.H. Lee, G.F. Hatfull et al. 1991. Nature [Lond]. 351:456; Jacobs, W.R., Jr., S.B. Snapper, L. Lugosi and B.R. Bloom. 1990. Curr. Top. Microbiol. Immunol. 155:153; Jacobs, W.R., M. Tuckman, and B.R. Bloom. 1987. Nature [Lond.]. 327:532); but as an attenuated intracellular bacterium residing in macrophages, BCG would seem to be best suited for eliciting cellular responses and not humoral responses. Since bacterial lipoproteins are often among the most immunogenic of bacterial antigens, we tested whether BCG expression of a target antigen as a membrane-associated lipoprotein could enhance the potential for a recombinant BCG vaccine to elicit high-titered protective antibody responses to target antigens. Immunization of mice with recombinant BCG vaccines expressing the outer surface protein A (OspA) antigen of Borrelia burgdorferi as a membrane-associated lipoprotein resulted in protective antibody responses that were 100-1,000-fold higher than responses elicited by immunization with recombinant BCG expressing OspA cytoplasmically or as a secreted fusion protein. Furthermore, these improved antibody responses were observed in heterogeneous mouse strains that vary in their immune responsiveness to OspA and sensitivity to BCG growth. Thus, expression of protective antigens as chimeric membrane-associated lipoproteins on recombinant BCG may result in the generation of new candidate vaccines against Lyme borreliosis and other human or veterinary diseases where humoral immunity is the protective response.
Expression of Ixodes scapularis Antifreeze Glycoprotein Enhances Cold Tolerance in Drosophila melanogaster (2012)

Drosophila melanogaster experience cold shock injury and die when exposed to low non-freezing temperatures. In this study, we generated transgenic D. melanogaster that express putative Ixodes scapularis antifreeze glycoprotein (IAFGP) and show that the presence of IAFGP increases the ability of flies to survive in the cold. Male and female adult iafgp-expressing D. melanogaster exhibited higher survival rates compared with controls when placed at non-freezing temperatures. Increased hatching rates were evident in embryos expressing IAFGP when exposed to the cold. The TUNEL assay showed that flight muscles from iafgp-expressing female adult flies exhibited less apoptotic damage upon exposure to non-freezing temperatures in comparison to control flies. Collectively, these data suggest that expression of iafgp increases cold tolerance in flies by preventing apoptosis. This study defines a molecular basis for the role of an antifreeze protein in cryoprotection of flies.
Locoregional cancer treatment with magnetic drug targeting. (2000)

The specific delivery of chemotherapeutic agents to their desired targets with a minimum of systemic side effects is an important, ongoing challenge of chemotherapy. One approach, developed in the past to address this problem, is the i.v. injection of magnetic particles [ferrofluids (FFs)] bound to anticancer agents that are then concentrated in the desired area (e.g., the tumor) by an external magnetic field. In the present study, we treated squamous cell carcinoma in rabbits with FFs bound to mitoxantrone (FF-MTX) that was concentrated with a magnetic field. Experimental VX-2 squamous cell carcinoma was implanted in the median portion of the hind limb of New Zealand White rabbits (n = 26). When the tumor had reached a volume of approximately 3500 mm3, FF-MTX was injected intraarterially (i.a.; femoral artery) or i.v. (ear vein), whereas an external magnetic field was focused on the tumor. FF-MTX i.a. application with the external magnetic field resulted in a significant (P < 0.05), complete, and permanent remission of the squamous cell carcinoma compared with the control group (no treatment) and the i.v. FF-MTX group, with no signs of toxicity. The intratumoral accumulation of FFs was visualized both histologically and by magnetic resonance imaging. Thus, our data show that i.a. application of FF-MTX is successful in treating experimental squamous cell carcinoma. This "magnetic drug targeting" offers a unique opportunity to treat malignant tumors locoregionally without systemic toxicity. Furthermore, it may be possible to use these magnetic particles as a "carrier system" for a variety of anticancer agents, e.g., radionuclides, cancer-specific antibodies, and genes.
Predicting fault incidence using software change history (2000)

This paper is an attempt to understand the processes by which software ages. We define code to be aged or decayed if its structure makes it unnecessarily difficult to understand or change and we measure the extent of decay by counting the number of faults in code in a period of time. Using change management data from a very large, long-lived software system, we explore the extent to which measurements from the change history are successful in predicting the distribution over modules of these incidences of faults. In general, process measures based on the change history are more useful in predicting fault rates than product metrics of the code: For instance, the number of times code has been changed is a better indication of how many faults it will contain than is its length. We also compare the fault rates of code of various ages, finding that if a module is, on the average, a year older than an otherwise similar module, the older module will have roughly a third fewer faults. Our most successful model measures the fault potential of a module as the sum of contributions from all of the times the module has been changed, with large, recent changes receiving the most weight.
Testosterone Therapy in Women with Gynecological and Sexual Disorders: A Triumph of Clinical Endocrinology from 1938 to 2008 (2008)

Health-care professionals engaged in the management of women's health issues have observed the benefits of androgen therapy throughout much of the 20th century. Despite this clinical use of testosterone in women for more than seven decades, contemporary testosterone therapy in women is hotly debated, misunderstood, and often misrepresented in the medical community.
Avena and the World Court's Death Penalty Jurisdiction in Texas: Addressing the Odd Notion of Texas's Independence from the World (2005)

On March 31, 2004, the International Court of Justice ("ICJ" or "World Court") issued its ruling in Avena and Other Mexican Nationals (Mex. v. US.). The World Court held that various states within the United States had violated the rights of fifty-one Mexican nationals. The states had failed to notify the Mexican citizens of their rights, under the Vienna Convention on Consular Relations, to contact Mexican consulates. By unanimous vote, the World Court then required that the United States "shall provide, by means of its own choosing, review and reconsideration of the conviction[s] and sentence[s]" at issue. Mexico, in turn, indicated that it expected the United States to abide by the World Court decision.
Anti-prostate cancer activity of a nanoformulation of the spleen tyrosine kinase (SYK) inhibitor C61 (2020)

Patients with advanced or metastatic castration-resistant prostate cancer have a dismal prognosis and are therefore in urgent need for therapeutic innovations. Spleen tyrosine kinase has emerged as a new molecular target for castration-resistant prostate cancer. This study was done to test the cytotoxicity of the lead nanoformulation of a potent spleen tyrosine kinase inhibitor, C61-LNP, against the human prostatic carcinoma cell line, PC-3. PC-3 cells were treated with various concentrations of C61-LNP either alone or in combination with cisplatin (CDDP) for 24, 48 and 72 hours. The cell viability was evaluated by MTS assay. Cellular expression levels of various regulatory proteins in treated PC-3 cells were evaluated by Western blot analyses. C61-LNP exhibited dose-dependent cytotoxicity against PC-3 cells. C61-LNP, as well as C61-LNP + CDDP treatments, caused pro-apoptotic proteomic changes including an increase in cleaved fragments of caspases-3 and -9 consistent with caspase activation as well as an improvement in the anti-apoptotic Bcl2 and Bax levels. The combination of C61-LNP and CDDP changed in alterations of the cell cycle regulatory proteins p53, p21, p27, cyclin D1 and cyclin E levels. C61-LNP exhibited cytotoxicity against the castration-resistant prostate cancer cell line PC3. It also caused alterations in expression levels of regulatory proteins involved in apoptosis and cell cycle regulation and these effects were not abrogated by the standard chemotherapy drug CDDP. We are planning to further develop C61-LNP as a selective spleen tyrosine kinase inhibitor as part of a multi-modality treatment strategy for advanced/metastatic castration-resistant prostate cancer.
Cloning gibberellin dioxygenase genes from pumpkin endosperm by heterologous expression of enzyme activities in Escherichia coli (1997)

Gibberellin (GA) plant hormones are biosynthesized via complex pathways, the final steps of which are catalyzed by 2-oxoglutarate-dependent dioxygenases. Here, the cloning of two such enzymes, the GA 7-oxidase and the GA 20-oxidase, is reported using a novel approach, namely, by screening for GA dioxygenase activities expressed as T7 gene 10 fusion proteins in recombinant Escherichia coli. In vitro translation products of mRNA from endosperm of immature pumpkin seeds contained three GA dioxygenase activities, including 7-oxidase, 20-oxidase, and 3beta-hydroxylase. A cDNA expression library was prepared from the endosperm mRNA in lambdaMOSElox. An aliquot of the amplified library was converted to plasmids in vivo and used for transformation of E. coli BL21(DE3), which thereafter expressed recombinant fusion proteins containing 7-oxidase, 20-oxidase, and 3beta-hydroxylase activities. By screening for specific GA dioxygenase expression, clones harboring 7-oxidase and 20-oxidase cDNA were isolated. The ORF of the 7-oxidase cDNA is 945 bp long, encoding for 314 amino acid residues with a calculated Mr of 35,712 and pI of 5.7. Recombinant GA 7-oxidase oxidizes GA12-aldehyde to GA12 and GA14-aldehyde to GA14. Evidence was obtained for further metabolism of GA12 by the 7-oxidase to four products, two of which are monohydroxylated GA12. The ORF of the 20-oxidase is-apart from seven changes, resulting in four amino acid substitutions-identical to the 20-oxidase cDNA previously cloned from pumpkin cotyledon mRNA; both 20-oxidases have the same catalytic properties.
Quasi-Static Transduction Characterization of Galfenol (2003)

The objective of the work presented is characterization of the magnetoelastic transduction properties of single crystal and textured polycrystalline Fe-Ga alloys (Galfenol) under controlled mechanical, magnetic and thermal conditions. Polycrystalline samples of interest include a directionally solidified specimen, which possesses a favorable saturation magnetostriction output, and an extruded specimen, whose magnetostriction properties were significantly reduced by annealing. A brief discussion of the thermally controlled transducer used for the magnetic testing is presented first. Thereafter, the single crystal response to major-loop cyclic magnetic fields under different temperature and stress conditions, as well as its response to minor-loop cyclic magnetic fields and major-loop cyclic stress is examined. Next, the magnetic and magnetostrictive responses to major-loop cyclic magnetic field conditions are compared for the directionally solidified, extruded and single crystal specimens. The paper concludes with a magnetic characterization summary of the different Fe-Ga alloys examined.
Instantaneous Phase Measuring Interferometry (1984)

Conventional phase measuring interferometry normally requires one-half to sixty seconds acquisition time, limiting measurement to stationary phenomena such as optical element wavefronts. We have developed an instantaneous phase measuring interferometer (PMI) that measures displacements at one point to a resolution of 0.003 um. We describe this instrument and an interferometer measuring phase to X/2000 with a measurement time aperture of less than 1 As. Also described is an attached system for analyzing and displaying wavefronts at up to 10 Hz.
Vasopressin in catecholamine‐resistant septic and cardiogenic shock in very‐low‐birthweight infants (2006)

Although vasopressin appears to be a suitable rescue therapy in catecholamine-resistant septic shock in VLBW infants, further evaluation in controlled clinical trials is warranted.
Alternative scenarios for data applications via Internet-mobile and DECT-ATM interworking (2002)

The standardization of DECT in ETSI has been very productive, as a matter of fact the DECT standard was one of the first to be completed with different profiles. DECT Data profile gives the possibility to interconnect a wireless access to any possible data network. This paper deals with an interworking solution to access the Internet through the DECT air interface, using ATM as transport network. The mobility management will be done using the IF-Mobile (IMHP) protocol.
Tenascin C Promotes Hematoendothelial Development and T Lymphoid Commitment from Human Pluripotent Stem Cells in Chemically Defined Conditions (2014)

The recent identification of hemogenic endothelium (HE) in human pluripotent stem cell (hPSC) cultures presents opportunities to investigate signaling pathways that are essential for blood development from endothelium and provides an exploratory platform for de novo generation of hematopoietic stem cells (HSCs). However, the use of poorly defined human or animal components limits the utility of the current differentiation systems for studying specific growth factors required for HE induction and manufacturing clinical-grade therapeutic blood cells. Here, we identified chemically defined conditions required to produce HE from hPSCs growing in Essential 8 (E8) medium and showed that Tenascin C (TenC), an extracellular matrix protein associated with HSC niches, strongly promotes HE and definitive hematopoiesis in this system. hPSCs differentiated in chemically defined conditions undergo stages of development similar to those previously described in hPSCs cocultured on OP9 feeders, including the formation of VE-Cadherin(+)CD73(-)CD235a/CD43(-) HE and hematopoietic progenitors with myeloid and T lymphoid potential.
Long-term cultures to evaluate engraftment potential of CD34+ cells from peripheral blood after mobilization by chemotherapy with and without GM-CSF. (1995)

In this study we used a long-term culture system to evaluate engraftment potential of human peripheral blood (PB) cells mobilized by chemotherapy (CT) associated or not with granulocyte-macrophage colony-stimulating factor (GM-CSF). In six patients who underwent blood cell transplantation, PB CD34+ cells were cultured after mobilization and were compared to CD34+ cells in steady state from PB and bone marrow (BM). Qualitative differences were shown between PBC samples obtained after CT with and without GM-CSF. Despite similar CFU-GM counts at culture initiation, GM-CSF-mobilized CD34+ cells might contain a lower proportion of primitive stem cells, as suggested by the significant decrease in CFU-GM numbers produced beyond week 5 compared to CT-mobilized CD34+ cells (p = 0.033). Likewise, the percentage of CFU-GM produced beyond week 5 in relation to initial input was significantly lower than steady-state PB (p = 0.039) and than CT-mobilized CD34+ cells (p = 0.033). However, this CFU-GM production with GM-CSF-mobilized PB CD34+ cells was not different from cultures with BMC CD34+ cells. These results suggest that GM-CSF can mobilize CFU-GM in the blood mainly by differentiation at the expense of the primitive stem cell compartment. It appears valuable to define clearly for each mobilizing procedure a particular threshold of CFU-GM which reflects sufficient numbers of primitive stem cells to ensure long-term engraftment.
Technical Report Improved Production and Purification of Minicircle DNA Vector Free of Plasmid Bacterial Sequences and Capable of Persistent Transgene Expression In Vivo (2005)

We have shown previously that minicircle DNA vectors free of plasmid bacterial DNA sequences are capable of persistent high level of transgene expression in vivo. The minicircle is generated in bacteria from a parental plasmid containing an inducible phageC31 integrase gene and a therapeutic expression cassette flanked with attB and attP sites. TheC31-mediated intramolecular recombination between attB and attP results in the formation of two circular DNA molecules, one containing the eukaryotic expression cassette (minicircle), and the other the plasmid bacterial DNA backbone (BB). Previously, the minicircle was purified away from the plasmid BB by a restriction enzyme digestion step and ultracentrifugation in cesium chloride. We have now included the endonuclease I-SceI gene together with its recognition site in the minicircle-producing plas- mid to allow the linearization and degradation of the plasmid BB in bacteria. The minicircle can then be iso- lated by routine plasmid purification procedures such as a one-step affinity column. With additional modifi- cations to our previous strategy, we can prepare a minicircle encoding a 4-kb human factor IX expression cassette, up to 1.8 mg of minicircle with 97% purity was prepared from a 1 liter bacterial culture. The high yield, simple purification, and robust and persistent transgene expression make these vectors viable for gene therapy applications.
Chemical and Biochemical Studies with Dithioate DNA (1991)

Abstract Dithioate DNA was synthesized and used for various biochemical studies. Results from these studies indicate that dithioate DNA is a potent inhibitor of HIV Reverse Transcriptase, activates endogenous RNase H in Hela cell nuclear extracts, and is a useful probe for studying protein-DNA interactions.
ANATOMICAL VARIATIONS OF THE COMMON CAROTID ARTERY BIFURCATION (2006)

The presence of a high CCA bifurcation should caution surgeons that the hypoglossal nerve lies in closer proximity and is more vulnerable. Preoperatively documenting the level of the CCA bifurcation may be helpful in identifying those patients at increased risk of iatrogenic injury.
Development and validation of an antibody-dependent cell-mediated cytotoxicity-reporter gene assay (2012)

Humanized monoclonal antibodies (mAbs) are the fastest growing class of biological therapeutics that are being developed for various medical indications, and more than 30 mAbs are already approved and in the market place. Antibody-dependent cell-mediated cytotoxicity (ADCC) is an important biological function attributed to the mechanism of action of several therapeutic antibodies, particularly oncology targeting mAbs. The ADCC assay is a complicated and highly variable assay. Thus, the use of an ADCC assay as a lot release test or a stability test for clinical trial batches of mAbs has been a substantial challenge to install in quality control laboratories. We describe here the development and validation of an alternate approach, an ADCC-reporter gene assay that is based on the key attributes of the PBMC-based ADCC assay. We tested the biological relevance of this assay using an anti-CD20 based model and demonstrated that this ADCC-reporter assay correlated well with standard ADCC assays when induced with the drugable human isotypes [IgG1, IgG2, IgG4, IgG4S > P (S228P) and IgG4PAA (S228P, F234A, L235A)] and with IgG1 isotype variants with varying amounts of fucosylation. This data demonstrates that the ADCC-reporter gene assay has performance characteristics (accuracy, precision and robustness) to be used not only as a potency assay for lot release and stability testing for antibody therapeutics, but also as a key assay for the characterization and process development of therapeutic molecules.
An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer (2008)

Individualization of cancer management requires prognostic markers and therapy-predictive markers. Prognostic markers assess risk of disease progression independent of therapy, whereas therapy-predictive markers identify patients whose disease is sensitive or resistant to treatment. We show that an experimentally derived IFN-related DNA damage resistance signature (IRDS) is associated with resistance to chemotherapy and/or radiation across different cancer cell lines. The IRDS genes STAT1, ISG15, and IFIT1 all mediate experimental resistance. Clinical analyses reveal that IRDS(+) and IRDS(-) states exist among common human cancers. In breast cancer, a seven-gene-pair classifier predicts for efficacy of adjuvant chemotherapy and for local-regional control after radiation. By providing information on treatment sensitivity or resistance, the IRDS improves outcome prediction when combined with standard markers, risk groups, or other genomic classifiers.
TAN-1057 A-D, new antibiotics with potent antibacterial activity against methicillin-resistant Staphylococcus aureus. Taxonomy, fermentation and biological activity. (1993)

Two Gram-negative bacteria were found to produce the new antibacterial antibiotics TAN-1057 A, B, C and D. The producing bacteria were characterized and designated as Flexibacter sp. PK-74 and PK-176. These antibiotics were active against Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. TAN-1057 A inhibited protein biosynthesis in Escherichia coli and S. aureus. It showed excellent protective effects against an experimental methicillin-resistant S. aureus infection in mice.
Formation in Vitro of Sperm Pronuclei and Mitotic Chromosomes Induced by Amphibian Ooplasmic Components (1983)

A cell-free preparation of the cytoplasm from activated eggs of Rana pipiens induces, in demembranated sperm nuclei of Xenopus laevis, formation of a nuclear envelope, chromatin decondensation, initiation of DNA synthesis, and chromosome condensation. Both soluble and particulate cytoplasmic constituents are required to initiate these processes in vitro. The observed changes resemble processes occurring during fertilization and the mitotic cycle in early amphibian embryos. Therefore, this cell-free system may be useful in biochemical analysis of the interactions of nucleus and cytoplasm that control nuclear behavior.
Antagonism of microRNA-126 suppresses the effector function of T H 2 cells and the development of allergic airways disease (2009)

Allergic asthma is an inflammatory disease of the lung characterized by abnormal T helper-2 (T(H)2) lymphocyte responses to inhaled antigens. The molecular mechanisms leading to the generation of T(H)2 responses remain unclear, although toll-like receptors (TLRs) present on innate immune cells play a pivotal role in sensing molecular patterns and in programming adaptive T cell responses. Here we show that in vivo activation of TLR4 by house dust mite antigens leads to the induction of allergic disease, a process that is associated with expression of a unique subset of small, noncoding microRNAs. Selective blockade of microRNA (miR)-126 suppressed the asthmatic phenotype, resulting in diminished T(H)2 responses, inflammation, airways hyperresponsiveness, eosinophil recruitment, and mucus hypersecretion. miR-126 blockade resulted in augmented expression of POU domain class 2 associating factor 1, which activates the transcription factor PU.1 that alters T(H)2 cell function via negative regulation of GATA3 expression. In summary, this study presents a functional connection between miRNA expression and asthma pathogenesis, and our data suggest that targeting miRNA in the airways may lead to anti-inflammatory treatments for allergic asthma.