gebhart/patrepeval huggingface dataset:
Multiple Integration Events into Several Putative Oncogenes Was Required To Cause Leukemogenesis in Two Primate Recipients of RCR Contaminated Stem-Cells. (2004)

Abstract Integrating vectors are essential for stem-cell and T cell gene-therapy approaches to enable passage of the transgene to subsequent progeny, and retroviral vectors have been the commonly utilized for clinical applications. However, insertional events can potentially cause malignant transformation of transduced cells. In 1991, adult rhesus macaques received CD34+ cells transduced with a NEO expressing retroviral vector which was inadvertently contaminated with ampho-pseudotyped replication competent retrovirus(RCR). Three primates (88053, 15445 and 88049) developed a rapidly progressive lymphoid neoplasm 6–7 months after transplantation characterized by diffuse lymphadenompathy, hepatosplenomegaly and a large thymic mass. Immunohistochemistry of the neoplasm revealed a CD8+ CD2+ alphabeta TCR+ phenotype strongly positive for RCR. The neoplasm was preceeded by increasing amphotropic envelope detectable in peripheral blood by PCR which was ultimately detectable in 100% of peripheral blood leukocytes. Tissue is available for study from primates 15445 and 88049. Genomic Southern blotting revealed multiple integrants, more in 15445 than in 88049. Using a simplified technique (FLEA-PCR) for generating libraries of Integrant-Host-Junctions (IHJ), we studied leukemia samples from these two (primates 15545 and 88049). So far we have characterized 52 different flanking sequences from primate 15545 of which we could match 43 genomic loci. We have isolated 39 different flanking sequences from primate 88049 of which we could match 29 genomic loci. Of the characterized integration sites from 15445 the following potential oncogenes could be affected: DKK3, CUTL1, RUNX1, RUNX3, TCF7L2, FOXP1, MTIF2, GAB1, CST7, CABIN1 and RHOH. Of the characterized integration sites from 88049 the following potential oncogenes could be affected: LY86, JARID2, TNIK(TRAF2 and NCK interacting kinase), SMT3H2, PTK2B, MSF, FBXL10 and RAPH1. Both primate leukemia samples contain an integration site just 5 to the gene for Neuronal acetylcholine receptor protein (CHRNA9). RNA derived from leukemic bone marrow from both animals and involved thymic tissue from one was subjected to microarray analysis and compared to that of control tissue using the Affymetrix human genome U133 plus 2 array. The gene expression profile was similar among diseased tissues, and efforts to correlate the expression profile with genes potentially dysregulated by integration events is ongoing. Together with some subjects of the recent X-SCID study, these macaques represent the only cases of leukemogenesis caused by vector induced insertional mutagenesis in primates. Our findings confirm the assumption that with an inert transgene (NEO, RCR), multiple integrations effecting different oncogenes are required to result in malignant transformation of transduced cells.
A Bayesian hierarchical nonlinear model for assessing the association between genetic variation and drug cytotoxicity (2009)

Non-tumor cell-based model systems have recently gained interest in pharmacogenetic research as a hypothesis generating tool. The hypotheses generated from these model systems can be followed up in functional studies, or tested in individuals taking the same investigational agents. The current cellular phenotypes (e.g. cytotoxicity) of interest in these studies are based on the effects of an individual dosage of a drug on the cell lines, or a summary of results at many dosages of a drug (e.g. dose that inhibits 50 per cent of cell growth, GI 50). A more complete analysis of the impact of genetic variation on all aspects of the dose-response curve may lend additional insight into the pharmacogenomics of a particular drug. This paper illustrates the use of a Bayesian hierarchical nonlinear model for the analysis of pharmacogenomic data with cytotoxicity endpoints. The model is illustrated with cytotoxicity and expression data collected on cell lines from a pharmacogenomic study of the drug gemcitabine. By completing an analysis based on the entire dose-response curve, we were able to detect additional genes that affect not only the GI 50, but also the slope of the curve, which reflects the therapeutic index of the drug. Simulation studies also demonstrate that in comparison with the analyses based on the commonly used summary measure GI 50, investigation of the impact of genetic variation on all aspects of the cytotoxicity dose-response curve is more informative, and more powerful with respect to detecting the effect of gene expression on cytotoxicity.
A multisensor data fusion approach for the volcanic ash granulometry classification (2014)

In this paper a methodology to be adopted for volcanic ash average granulometry estimation is presented. The main idea is to count the number of ash particles in a known volume. To this purpose a piezoelectric transducer was used to convert ash particles impacts into electrical signals, which provide information about the number of ash particles. Moroever, a couple of infrared (IR) diode-phototransistors allows for the monitoring of the ash level in the instrumented tank. Information from this sensor should be used in a multisensor data fusion approach with information on the ash granulometry gained by the methodology proposed by authors in a previous work. Experimental results showing the suitability of the proposed approach are presented.
Long-term labeling and imaging of synaptically-connected neuronal networks <i>in vivo</i> using double-deletion-mutant rabies viruses (2021)

Abstract Monosynaptic tracing is a widely-used technique for mapping neural circuitry, but its cytotoxicity has confined it primarily to anatomical applications. Here we present a second-generation system for labeling direct inputs to targeted neuronal populations with minimal toxicity, using double-deletion-mutant rabies viruses. Spread of the viruses requires expression of both deleted viral genes in trans in postsynaptic source cells; suppressing this expression with doxycycline following an initial period of viral replication reduces toxicity to postsynaptic cells. Longitudinal two-photon imaging in vivo indicated that over 90% of both presynaptic and source cells survived for the full twelve-week course of imaging. Ex vivo whole-cell recordings at 5 weeks postinfection showed that the second-generation system perturbs input and source cells much less than does the first-generation system. Finally, two-photon calcium imaging of labeled networks of visual cortex neurons showed that their visual response properties appeared normal for 10 weeks, the longest we followed them.
Examination of four HLA class I pseudogenes. Common events in the evolution of HLA genes and pseudogenes (1992)

The HLA class I gene family in lymphoblastoid cell line 721 has been studied in detail and a number of sequences in addition to the classical genes have been identified. The cloning, characterization, and nucleotide sequences of four sequences, all full length HLA class I pseudogenes, are described in this report. These pseudogenes, contained within 5.4-, 5.9-, 7.0-, and 9.2-kb HindIII fragments, each have the class I exon-intron structure as well as class I homology in their 5' and 3' flanking regions. However, all four sequences have one or more substitutions that perturb the coding region, leaving little doubt that they are in fact pseudogenes. Comparisons among these sequences and the HLA class I genes revealed that their homology with the class I genes is patchwork. Thus, although some regions have diverged, other contiguous intron-exon sequences are highly conserved. Comparisons in the 5' regions indicate that the pseudogene promoters more closely resemble the classical HLA promoters than the nonclassical promoters as none of the unique structural features found in the HLA-E, -F, or -G regulatory regions are present in any of the pseudogene promoters. Further comparisons revealed that at least two putative gene conversion events, similar to those hypothesized to have occurred in the evolution of some HLA genes, may have occurred in the evolution of some of the pseudogenes. These and other hypothetical events in the evolution of the class I gene family are discussed.
ChemInform Abstract: COPPER(I) AND COPPER(II) COMPLEXES OF BIOLOGICALLY RELEVANT TRIDENTATE LIGANDS (1985)

Abstract Die Reaktionen der entsprechenden Dicarbonsäuren (II) mit dem Diamin (I) liefern die dreizähnigen Liganden (IIIa)‐(IIIc), die zwei Benzimidazolgruppen enthalten.
Dynamic oxygen changes during status epilepticus and subsequent endogenous kindling (2020)

Induced SE and self-generated recurrent epileptiform activity can have profound and opposing effects on brain tissue oxygenation that may serve as a biomarker for ongoing pathological activity in the brain.
Origin of genetic code: A needle in the haystack of tRNA sequences. (1996)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Desloratadine for allergic rhinitis (2006)

Seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR) affect up to 40% of the population (depending on geographical area), and are associated with significant morbidity, socioeconomic costs and reductions in quality of life. Antihistamines are a first-line therapy, with newer nonsedating agents having superseded sedating first-generation drugs. Desloratadine is a nonsedating, nonimpairing antihistamine that is effective in relieving nasal and non-nasal symptoms of SAR and PAR, including nasal congestion. Desloratadine has a 24-h duration of action, enabling once-daily dosing and providing relief of morning symptoms. Clinical trials have demonstrated that it has no performance impairment, cardiovascular effects or clinically relevant interactions with other tested medications. This article reviews the use of desloratadine in the treatment of SAR and PAR.
Proceedings of the Oxygen Homeostasis/Hypoxia Meeting (2004)

Abstract The first Oxygen Homeostasis/Hypoxia Meeting was held on February 12, 2003, at the Sheraton National Hotel, Washington, D.C. The meeting was hosted by Drs. S. Percy Ivy and Giovanni Melillo of the National Cancer Institute, NIH. The purpose of the meeting was to stimulate collaborations among the participants who are engaged in different areas of hypoxia research and application, including basic research on hypoxia, and its induction and consequences; the development of drugs targeting hypoxia and factors involved in pathways leading to (or controlled by) hypoxia; and the development and application of hypoxia imaging techniques and reagents.
Microbiological Analysis of Fluids in Postsurgical Gastroesophageal Intrathoracic Leaks Obtained by Endoscopy: A New Way to Optimize Antibiotic Therapy (2015)

The microbiological colonization of postsurgical gastroesophageal intrathoracic leaks in patients is frequent. Only the direct microbiological analysis of fluids from intrathoracic leaks, but not of blood cultures, is effective for optimizing an antibiotic therapy in such patients.
A Sulphonylthiourea (BM 20) Related to Torasemide: a new Loop Diuretic with Relative Potassium-sparing Properties (1993)

A series of sulphonylthioureas related to torasemide, a high ceiling loop diuretic, were synthesized and found to inhibit the Na+ 2Cl- K+ co-transporter of the thick ascending limb of the loop of Henlé. Their diuretic properties were studied (30 mg kg-1) after oral administration to rats. Lipophilic derivatives, very active in-vitro, were found inactive orally and intraperitoneally in rats. The four most active compounds were examined for their dose-dependent diuresis. Three of them showed a potency, water and electrolyte excretion similar to torasemide. The fourth molecule, a sulphonylthiourea (BM 20), exhibited relative potassium-sparing properties and a minimal diuretic dose of 0.001 mg kg-1, 200 times lower than torasemide.
Role of stearoyl‐CoA desaturase‐1 expression in cancer proliferation (2008)

Tumors are dependent on endogenous saturated fatty acids (SFA) which can be lipotoxic unless desaturated via stearoyl‐CoAdesaturase‐1 (SCD‐1). While inhibiting SCD‐1 activity induces apoptosis in cancer cells, the link between SFA and proliferation via SCD‐1 has not been shown. We hypothesize that desaturation of SFA through SCD‐1 is necessary for proliferation of cancer cells. Cancer cell lines were assessed for viability in the presence of SFA or oleate +/− Cerulenin. The variance in cell death following SFA +/− Cerulenin treatment was correlated with SCD‐1 expression. Next, HeLa cells overexpressing SCD‐1 were assessed for SFA and MUFA sensitivity +/− Cerulenin: SCD‐1 overexpression increased viability in the presence of SFA and Cerulenin. To determine the downstream effects of SCD‐1 expression variance, classification of lipogenic pathway members as well as lipid raft expression of Cav‐1, Akt, and cSrc was determined. Increased SCD‐1 was associated with higher SREPB‐1c and lower Cav‐1. Furthermore, SCD‐1 overexpression in HeLa cells resulted in a loss of Cav‐1 in lipid rafts. Oleate treatment increased Akt and p53 signaling and SCD‐1 expression. We can conclude that cancer cells rely on SCD‐1 for SFA mediated proliferation. Furthermore, SCD‐1 expression is associated with a loss of Cav‐1 expression that may augment membrane composition and lipid raft regulation of signaling. NIH RO1 DK62388 JM Ntambi (PI)
Abstract 1388: Loss of TGFβ signaling increases alternative end-joining and could sensitize high-grade serous ovarian cancer to PARP inhibitors (2020)

Abstract Defective DNA damage repair (DDR) is an important therapeutic target in high-grade serous ovarian cancer (HGSOC). This is exemplified by the efficacy of platinum analogues in this disease, as well as the advent of PARP inhibitors that exhibit synthetic lethality when applied to BRCA-mutated tumors. We recently found that loss of transforming growth factor β (TGFβ) signaling in head and neck squamous cell carcinoma causes dysregulation of BRCA1 and hence defective homologous recombination, which pushes cells to rely on error-prone alternative end-joining (alt-EJ) for DDR (Liu et al. Clin Ca Res 2018). To examine this link in ovarian cancer, here we interrogated the transcriptomes from 562 HGSOC patients from The Cancer Genome Atlas Consortium (TCGA) using a 50-gene signature of chronic TGFβ signaling and a 30-gene signature of alt-EJ competency. Our study unveiled a highly significant (p&amp;lt;0.00001) inverse correlation between TGFβ and alt-EJ in HGSOC. Alt-EJ is error prone, thus we examined the fraction of the genome altered as a function of TGFβ/alt-EJ; the TGFβ/alt-EJ pathway index score was negatively associated with the fraction of genome altered (Pearson correlation coefficient: -0.3288887; P-value = 2.9e-15), with tumors with low TGFβ/high alt-EJ exhibiting more genomic alterations. Alt-EJ increases tumor cell sensitivity to radiation and chemotherapy. Patients with low TGFβ/high alt-EJ profile were associated with an overall survival advantage (p=0.02) and a disease-free survival advantage (p=0.03). Consistent with this, patients with low TGFβ/high alt-EJ profile showed a significantly better response to primary treatment with cisplatin (p=0.038). These data support combinations of TGFβ inhibitors that could boost response to chemotherapy in HGSOC. Because PARP enzymes are key to alt-EJ, which sensitizes cells to PARP inhibition (ibid), these data suggest a novel means to identify patients that will likely be responsive to PARP inhibitors independently of BRCA mutational status. Citation Format: Ines Guix, Qi Liu, Luis Palomero, Jade Moore, Miquel Angel Pujana, Mary Helen Barcellos-Hoff. Loss of TGFβ signaling increases alternative end-joining and could sensitize high-grade serous ovarian cancer to PARP inhibitors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1388.
Microenvironmental modulation of asymmetric cell division in human lung cancer cells (2010)

Normal tissue homeostasis is maintained through asymmetric cell divisions that produce daughter cells with differing self-renewal and differentiation potentials. Certain tumor cell subfractions can self-renew and repopulate the heterogeneous tumor bulk, suggestive of asymmetric cell division, but an equally plausible explanation is that daughter cells of a symmetric division subsequently adopt differing cell fates. Cosegregation of template DNA during mitosis is one mechanism by which cellular components are segregated asymmetrically during cell division in fibroblast, muscle, mammary, intestinal, and neural cells. Asymmetric cell division of template DNA in tumor cells has remained elusive, however. Through pulse-chase experiments with halogenated thymidine analogs, we determined that a small population of cells within human lung cancer cell lines and primary tumor cell cultures asymmetrically divided their template DNA, which could be visualized in single cells and in real time. Template DNA cosegregation was enhanced by cell-cell contact. Its frequency was density-dependent and modulated by environmental changes, including serum deprivation and hypoxia. In addition, we found that isolated CD133(+) lung cancer cells were capable of tumor cell repopulation. Strikingly, during cell division, CD133 cosegregated with the template DNA, whereas the differentiation markers prosurfactant protein-C and pan-cytokeratins were passed to the opposing daughter cell, demonstrating that segregation of template DNA correlates with lung cancer cell fate. Our results demonstrate that human lung tumor cell fate decisions may be regulated during the cell division process. The characterization and modulation of asymmetric cell division in lung cancer can provide insight into tumor initiation, growth, and maintenance.
New antibiotics 4181-A and B from Streptomyces griseus; Taxonomy, fermentation, isolation and characterization. (1988)

The new antibiotics 4181-A and B were isolated from the fermentation broth of Streptomyces griseus, a soil isolate. Their molecular formulae were determined as C29H21NO9 and C28H19NO9, respectively. The UV, IR and NMR spectra suggest that they possess a quinone moiety in their structures. They were found to have antibacterial, antifungal and antitumor activity.
Role of CXCR4 Chemokine Receptor Blockade Using AMD3100 for Mobilization of Autologous Hematopoietic Progenitor Cells (2005)

G-CSF mobilization of hematopoietic progenitor cells (HPCs) is mediated through enzyme release from maturing myeloid cells, leading to digestion of adhesion molecules, trophic chemokines and their receptors, and the extracellular matrix. HPCs traffic to and are retained in the marrow through the trophic effects of the chemokine SDF-1alpha/CXCL12 binding to its receptor, CXCR4. AMD3100 reversibly inhibits SDF-1alpha/CXCR4 binding, and AMD3100 administration mobilizes CD34+ cells into the circulation. AMD3100 has been tested in several clinical trials which demonstrate that it improves the number of CD34+ cells mobilized including patients failing to mobilize with G-CSF alone. Engraftment of AMD3100-mobilized cells is prompt and durable. Toxicities are mild and infrequent. Lymphoma and myeloma cells do not appear to be mobilized. AMD3100 appears to be a promising agent for HPC mobilization.
Methods for forming pitting resistant carbon coating (2023)

A method for making a pitting resistant carbon coating that includes a hydrogenated diamond-like coating (“H-DLC”). The H-DLC is relatively soft and elastic. Unlike hard and/or inelastic coatings in the prior art, the present coatings do not exhibit a loss of adhesion (delamination). A bonding layer may be deposited on a metallic substrate and the deposited H-DLC on the bonding layer.
Aspiration Thrombectomy in Patients Undergoing Primary Angioplasty for ST Elevation Myocardial Infarction: An Updated Meta‐Analysis (2015)

Routine AT prior to PPCI in STEMI is associated with higher risk of stroke. There is no statistical difference in clinical outcome parameters of mortality, major adverse cardiac events, target vessel revascularization, stent thrombosis, and net clinical benefit between AT and PCI alone.
Signal transduction pathways initiated by catecholamines in takotsubo syndrome: focus on nitrosative stress and energetic impairment (2018)

Takotsubo syndrome reflects an ‘aberrant’ response to acute catecholamine stimulation, largely but not entirely as a manifestation of increased sensitivity to β‎<sub>2</sub>-adrenoceptor stimulation and signal transduction via Gi proteins, especially in ageing female hearts. It is now apparent that prolonged impairment of quality of life and slow recovery of echocardiographic parameters such as global longitudinal strain after episodes of takotsubo syndrome reflect ongoing myocardial inflammation and associated oedema, together with impairment of cardiac energetics on phosphorus magnetic resonance spectroscopy.
Thoracoscopic ablation of blebs using PDS-endoloop in recurrent spontaneous pneumothorax. (1991)

Thoracoscopy has specific advantages over traditional open thoracotomy, including shorter hospitalization, decreased recovery time, and an earlier return to the work force. Thoracoscopy and bleb ablation using sophisticated lasers has been successful in treating spontaneous pneumothorax. We have recently completed thoracoscopy bleb ablation with PDS Endoloop (Polyclioxanone, Ethicon, Inc., Somerville, NJ, U.S.A.) and pleurodesis in a patient with a recurrent spontaneous pneumothorax. The chest tube was removed and the patient discharged on the 3rd postoperative day. He returned to work on the 7th postoperative day. This new procedure can be used on selected patients with small blebs.
Metrology and Standardization of High Speed Pluggable Optical Interconnects (2021)

This paper describes research carried out under EURAMET project 14IND13 on the characterization of shortrange\noptical interconnect technology. This paper aims to disseminate to the wider communications sector the\nprimary importance of metrology and the need for standards associated with these emerging technologies.\nThe focus of the research is the functional performance of embedded polymer waveguides. The results of\nvarious crucial parameters are described and their relevance and influence upon existing national and\ninternational standards discussed.
High quality ZnO:Al transparent conducting oxide films synthesized by pulsed filtered cathodic arc deposition (2009)

Aluminum-doped zinc oxide, ZnO:Al or AZO, is a well-known n-type transparent conducting oxide with great potential in a number of applications currently dominated by indium tin oxide (ITO). In this study, the optical and electrical properties of AZO thin films deposited on glass and silicon by pulsed filtered cathodic arc deposition are systematically studied. In contrast to magnetron sputtering, this technique does not produce energetic negative ions, and therefore ion damage can be minimized. The quality of the AZO films strongly depends on the growth temperature while only marginal improvements are obtained with post-deposition annealing. The best films, grown at a temperature of about 200?C, have resistivities in the low to mid 10-4 Omega cm range with a transmittance better than 85percent in the visible part of the spectrum. It is remarkable that relatively good films of small thickness (60 nm) can be fabricated using this method.
Spectroscopic and lasing properties of Ho:Tm:LuAG (1993)

Ho:Tm:LuAG has been grown, examined spectroscopically, and lased at 2.1 microm. Ho:Tm:LuAG was selected for this experimental investigation when quantum-mechanical modeling predicted that it would be a good laser material for Ho laser operation on one of the (5)I(7) to (5)I(8) transitions. Lasing was achieved at 2.100 microm, one of the three wavelengths predicted to be most probable for laser action.