gebhart/patrepeval huggingface dataset:
Frequent mutations in the neurotrophic tyrosine receptor kinase gene family in large cell neuroendocrine carcinoma of the lung (2008)

The neurotrophic tyrosine receptor kinase (NTRK) family is potentially implicated in tumorigenesis and progression of several neoplastic diseases, including lung cancer. We investigated a large number of pulmonary neuroendocrine tumors (PNETs) and non-small cell lung carcinomas (NSCLCs) without morphological evidence of neuroendocrine differentiation for mutations in the NTRK gene family. A total of 538 primary lung carcinomas, including 17 typical carcinoids (TCs), 10 atypical carcinoids (ACs), 39 small cell lung carcinomas (SCLCs), 29 large cell neuroendocrine carcinomas (LCNECs), and 443 NSCLCs were evaluated by single-strand conformation polymorphism (SSCP) and sequencing of the tyrosine kinase domain (TKD) of NTRK1, NTRK2, and NTRK3. The NTRK1 gene was never found to be mutated. A total of 10 somatic mutations were detected in NTRK2 and NTRK3, mostly located in the activating and catalytic loops. NTRK mutations were seen in 9 (10%) out of 95 PNETs but in 0 out of 443 NSCLCs investigated. No mutations were observed in TCs, ACs, and SCLCs. Interestingly, all the mutations were restricted to the LCNEC histotype, in which they accounted for 31% of cases. A mutational analysis, performed after microdissection of LCNECs combined with adenocarcinoma (ADC), showed that only neuroendocrine areas were positive, suggesting that NTRK mutations are involved in the genesis of the neuroendocrine component of combined LCNECs. Our data indicate that somatic mutations in the TKD of NTRK genes are frequent in LCNECs. Such mutational events could represent an important step in the cancerogenesis of these tumors and may have potential implications for the selection of patients for targeted therapy.
Foxp3 interacts with nuclear factor of activated T cells and NF-κB to repress cytokine gene expression and effector functions of T helper cells (2005)

Scurfy mice, which are deficient in a functional Foxp3, exhibit a severe lymphoproliferative disorder and display generalized over-production of cytokines. Here, we show that, among the Foxp transcriptional factor family, which includes Foxp1, Foxp2, and Foxp3, only Foxp3 has the ability to inhibit IL-2, IL-4, and IFN-gamma production by primary T helper cells. We found that Foxp3 physically associates with the Rel family transcription factors, nuclear factor of activated T cells (NFAT) and NF-kappaB, and blocks their ability to induce the endogenous expression of their target genes, including key cytokine genes. More importantly, T cells derived from scurfy mice have a dramatic increase in nuclear factor of activated T cells (NFAT) and NF-kappa B transcriptional activity compared with the T cells derived from WT mice. Furthermore, complementation of Foxp3 in scurfy-derived T cells lowers the NFAT and NF-kappa B transcriptional activity to the physiological level. Finally, we show that myelin proteolipid protein-specific autoreactive T cells transduced with Foxp3 cannot mediate experimental autoimmune encephalomyelitis, providing further support that Foxp3 suppresses the effector function of autoreactive T cells. Foxp3 has already been associated with the generation of CD4(+)CD25+ regulatory T cells; our data additionally demonstrate that Foxp3 suppresses the effector functions of T helper cells by directly inhibiting the activity of two key transcription factors, NFAT and NF-kappa B, which are essential for cytokine gene expression and T cell functions.
Transcription of the E2F-1 Gene Is Rendered Cell Cycle Dependent by E2F DNA-Binding Sites within Its Promoter (1995)

The cell cycle-regulatory transcription factor E2F-1 is regulated by interactions with proteins such as the retinoblastoma gene product and by cell cycle-dependent alterations in E2F-1 mRNA abundance. To better understand this latter phenomenon, we have isolated the human E2F-1 promoter. The human E2F-1 promoter, fused to a luciferase cDNA, gave rise to cell cycle-dependent luciferase activity upon transfection into mammalian cells in a manner which paralleled previously reported changes in E2F-1 mRNA abundance. The E2F-1 promoter contains four potential E2F-binding sites organized as two imperfect palindromes. Gel shift and transactivation studies suggested that these sites can bind to E2F in vitro and in vivo. Mutation of the two E2F palindromes abolished the cell cycle dependence of the E2F-1 promoter. Thus, E2F-1 appears to be regulated at the level of transcription, and this regulation is due, at least in part, to binding of one or more E2F family members to the E2F-1 promoter.
Genetic modification of a murine fibrosarcoma to produce interleukin 7 stimulates host cell infiltration and tumor immunity. (1992)

Retroviral-mediated gene transfer was used to introduce and express the gene for murine interleukin 7 (IL-7) in a fibrosarcoma tumor (FSA). The tumorigenicity of these genetically modified FSA cells was greatly decreased in immunologically intact syngeneic mice but was unaltered in T-cell-deprived mice. IL-7-infected tumors that did grow in intact animals from large size inocula did so slowly and had a high incidence of spontaneous regression. Furthermore, mice that had rejected tumors became specifically immune to challenge with uninfected parental tumor cells. IL-7-infected FSA growing in intact mice were heavily infiltrated with host T-cells that were presumably responsible for slow growth and tumor regression, and tumor cells were in the minority. Fluorescence-activated cell sorter analysis showed that there was a 530% increase in T-cells in IL-7-infected FSA compared with control tumors. CD8+ T-cells were particularly elevated, but CD4+ lymphocytes were also increased in number, as were eosinophils and basophils. The CD4+:CD8+ ratio in IL-7-infected FSA was 1:1.7 in comparison to 1:0.6 in control tumors. Lymphocytes isolated from IL-7-producing tumors had greatly enhanced cytotoxicity towards uninfected, parental FSA cells. Killing of non-cross-reacting fibrosarcoma line was also increased but to a much lesser extent. Injection of recombinant human IL-7 directly into established FSA tumors slowed their growth and, in a significant number of instances, caused complete regression. Mice that had rejected tumor became specifically immune. The dose that was needed for this effect was, however, somewhat large: 20 micrograms twice daily for 10 days. This result contrasts with the efficacy of IL-7 gene infection in stimulating responses to the same tumor. These considerations make IL-7 a good candidate for tumor-directed cytokine gene therapy.
Correcting spelling errors by modelling their causes (2005)

This paper accounts for a new technique of correcting isolated words in typed texts. A language-dependent set of string substitutions reflects the surface form of errors that result from vocabulary incompetence, misspellings, or mistypings. Candidate corrections are formed by applying the substitutions to text words absent from the computer lexicon. A minimal acyclic deterministic finite automaton storing the lexicon allows quick rejection of nonsense corrections, while costs associated with the substitutions serve to rank the remaining ones. A comparison of the correction lists generated by several spellcheckers for two corpora of English spelling errors shows that our technique suggests the right words more accurately than the others.
Color Doppler Ultrasound and Gamma Imaging of Intratumorally Injected 500 nm Iron–Silica Nanoshells (2013)

Perfluoropentane gas filled iron-silica nanoshells have been developed as stationary ultrasound contrast agents for marking tumors to guide surgical resection. It is critical to establish their long-term imaging efficacy, as well as biodistribution. This work shows that 500 nm Fe-SiO2 nanoshells can be imaged by color Doppler ultrasound over the course of 10 days in Py8119 tumor bearing mice. The 500 nm nonbiodegradable SiO2 and biodegradable Fe-SiO2 nanoshells were functionalized with diethylenetriamine pentaacetic acid (DTPA) ligand and radiolabeled with (111)In(3+) for biodistribution studies in nu/nu mice. The majority of radioactivity was detected in the liver and kidneys following intravenous (IV) administration of nanoshells to healthy animals. By contrast, after nanoshells were injected intratumorally, most of the radioactivity remained at the injection site; however, some nanoshells escaped into circulation and were distributed similarly as those given intravenously. For intratumoral delivery of nanoshells and IV delivery to healthy animals, little difference was seen between the biodistribution of SiO2 and biodegradable Fe-SiO2 nanoshells. However, when nanoshells were administered IV to tumor bearing mice, a significant increase was observed in liver accumulation of SiO2 nanoshells relative to biodegradable Fe-SiO2 nanoshells. Both SiO2 and Fe-SiO2 nanoshells accumulate passively in proportion to tumor mass, during intravenous delivery of nanoshells. This is the first report of the biodistribution following intratumoral injection of any biodegradable silica particle, as well as the first report demonstrating the utility of DTPA-(111)In labeling for studying silica nanoparticle biodistributions.
Water-Soluble Nitric Oxide-Releasing Gold Nanoparticles (2007)

The synthesis and characterization of water-soluble nitric oxide (NO)-releasing monolayer-protected gold clusters (MPCs) are reported. Tiopronin-protected MPCs ( approximately 3 nm) were functionalized with amine ligands and subsequently exposed to 5 atm of NO to form diazeniumdiolate NO donors covalently bound to the gold MPC. Diazeniumdiolate formation conditions, NO-release, and nanoparticle stability were examined as a function of the structure of the protecting ligand, pH, and storage time. Despite their aqueous solubility, proton-initiated decomposition of the diazeniumdiolate-modified Tio-MPCs resulted in only modest NO-release (<0.023 micromol/mg) for short durations (<1.5 h). To increase the NO storage capacity of gold nanoparticles, polyamine-stabilized MPCs ( approximately 5 nm) were synthesized with significantly enhanced NO-release properties (0.386 micromol/mg) and durations (up to 16 h). Transmission electron microscopy, thermogravimetric analysis, nuclear magnetic resonance spectroscopy, elemental analysis, and UV-vis spectroscopy were used to characterize both nanoparticle systems before and after NO exposure. The MPCs represent the smallest water-soluble NO-release nanoparticles to date (3-5 nm).
Allergic reactions to oral, surgical and topical bovine collagen: Anaphylactic risk for surgeons (1996)

Clinical reactions to collagen are rare. Nevertheless, patients with a history of allergic reactions to bovine collagen-derived products should be investigated because of the widespread use of collagen-derived therapeutic devices, the potential for immunological cross-reactivity with dietary collagen (gelatin) and the potential for anaphylaxis.
Enantioselective Borohydride 1,4-Reduction of α, β-Unsaturated Carboxamides Using Optically Active Cobalt(II) Complex Catalysts (1998)

Abstract The enantioselective borohydride reduction catalyzed by cobalt(II) complex was successfully applied to 1,4-reduction of β,β-disubstituted α,β-unsaturated carboxamides. In the presence of less than 1 mol% of optically active aldiminato cobalt(II) complex catalyst, the corresponding carboxamides were obtained in high yields with high enantiomeric excesses.
XORing Elephants: Novel Erasure Codes for Big Data (2013)

Distributed storage systems for large clusters typically use replication to provide reliability. Recently, erasure codes have been used to reduce the large storage overhead of three-replicated systems. Reed-Solomon codes are the standard design choice and their high repair cost is often considered an unavoidable price to pay for high storage efficiency and high reliability. This paper shows how to overcome this limitation. We present a novel family of erasure codes that are efficiently repairable and offer higher reliability compared to Reed-Solomon codes. We show analytically that our codes are optimal on a recently identified tradeoff between locality and minimum distance. We implement our new codes in Hadoop HDFS and compare to a currently deployed HDFS module that uses Reed-Solomon codes. Our modified HDFS implementation shows a reduction of approximately 2x on the repair disk I/O and repair network traffic. The disadvantage of the new coding scheme is that it requires 14% more storage compared to Reed-Solomon codes, an overhead shown to be information theoretically optimal to obtain locality. Because the new codes repair failures faster, this provides higher reliability, which is orders of magnitude higher compared to replication.
Solid Freeform Fabrication by Electrographic Printing (2003)

A solid freeform fabrication technique is described where powder is deposited layer by layer using electrophotographic printing. In this process, powder is picked up and deposited using a charged photoconducting surface and deposited on a build platform. The paper describes a test bed that was designed and constructed to study the application of electrophotography to solid freeform fabrication. It can precisely deposit powder in the desired shape on each layer. The electric field required to transfer the powder on to the platform (or onto previously printed layers) was studied. A polymer toner powder was used to build small components by fusing each layer of printer powder using a hot compaction plate.
Demonstration of high-Q mid-infrared chalcogenide glass-on-silicon resonators (2013)

We demonstrated high-index-contrast, waveguide-coupled As2Se3 chalcogenide glass resonators monolithically integrated on silicon fabricated using optical lithography and a lift-off process. The resonators exhibited a high intrinsic quality factor of 2×10(5) at 5.2 μm wavelength, which is among the highest values reported in on-chip mid-infrared (mid-IR) photonic devices. The resonator can serve as a key building block for mid-IR planar photonic circuits.
High levels of circulating soluble receptors for tumor necrosis factor in hairy cell leukemia and type B chronic lymphocytic leukemia. (1992)

The presence of soluble tumor necrosis factor (TNF) binding proteins (BP) was investigated in the sera of healthy volunteer blood donors and cancer patients. Two distinct types of TNFBP, types A and B, which are immunologically related to the cellular 75-kD TNF receptor (TNFR) and the cellular 55-kD TNFR, respectively, were assessed by immunoassays using nonblocking anti-receptor antibodies and 125I-recombinant human TNF alpha. As compared to the titers observed in 25 healthy controls, TNFBP types A and B titers were found to be elevated in almost all sera obtained from patients with underlying malignant disease. The highest amounts of TNFBP were seen in the sera of patients with B cell malignancies including hairy cell leukemia (HCL) and type B chronic lymphocytic leukemia. Treatment of HCL patients with recombinant human interferon-alpha was associated with decrease of circulating TNFBP.
Organic Light‐Emitting Diodes Using a Neutral π Radical as Emitter: The Emission from a Doublet (2015)

Triplet harvesting is a main challenge in organic light-emitting devices (OLEDs), because the radiative decay of the triplet is spin-forbidden. Here, we propose a new kind of OLED, in which an organic open-shell molecule, (4-N-carbazolyl-2,6-dichlorophenyl)bis(2,4,6-trichlorophenyl)methyl (TTM-1Cz) radical, is used as an emitter, to circumvent the transition problem of triplet. For TTM-1Cz, there is only one unpaired electron in the highest singly occupied molecular orbital (SOMO). When this electron is excited to the lowest singly unoccupied molecular orbital (SUMO), the SOMO is empty. Thus, transition back of the excited electron to the SOMO is totally spin-allowed. Spectral analysis showed that electroluminescence of the OLED originated from the electron transition between SUMO and SOMO. The magneto-electroluminescence measurements revealed that the spin configuration of the excited state of TTM-1Cz is a doublet. Our results pave a new way to obtain 100% internal quantum efficiency of OLEDs.
Myocardial remodeling and arrhythmogenesis in moderate cardiac hypertrophy in rats (2001)

In 47 male adult Wistar rats with 4-wk aortic coarctation (AC) and 39 age-matched sham-operated rats (SO) chronically instrumented for telemetry electrocardiogram recording, we investigated the mechanisms of arrhythmogenesis in moderate cardiac hypertrophy, with an approach from "in vivo" toward the cellular level, analyzing 1) stress-induced cardiac arrhythmias in all rats and 2) myocardial fibrosis in 35 animals and action potential duration and density of hyperpolarization-activated current in 19 others at the ventricular level. Aortic banding increased arterial blood pressure, cardiac weight, and ventricular myocyte volume by 11, 25, and 14%, respectively (P < 0.001-0.05). Ventricular arrhythmias occurred at similar rates in AC and SO rats throughout the stress procedure. Action potential duration and hyperpolarization-activated current were about twice as great and myocardial fibrosis about four times greater in AC animals (P < 0.005-0.05). Electrocardiogram data also revealed more supraventricular arrhythmias in AC rats during the baseline period and after stress and fewer atrioventricular block episodes after stress (P < 0.05). Thus stress-induced supraventricular and atrioventricular nodal, but not ventricular, arrhythmias were affected in moderate cardiac hypertrophy when ventricular morphofunctional alterations were evident.
LA CENTRALIDAD DEL TRABAJO EN EL PROCESO DE CONSTRUCCIÓN DE LA IDENTIDAD DE LOS JÓVENES: UNA APROXIMACIÓN PSICOSOCIAL (1998)

The centrality of work in the process of youth identity construction: a psychosocial approach. The main goal of this research is de analysis of the centrality of work in the youth and its influence in the process of construction of their identity. From this general aim three phenomena (youth, work and identity) are approached in a critical and systematic way in the first part of the paper. Following the theoretical articulation of those concepts, and with the use of qualitative methodology (discussion groups, participant observation, in depth interviews with experts and with young people), an analysis of the conceptions, values and meanings that differents groups of young people have about work was carried out. Then, the study of how these conceptions influence the process of identity is examined. This process is decisive and of fundamental importance in this stage of the life-cycle. The research is realized with a discoursive focus and from a psychosocial approach.
New Insights into the Pathogenesis of Vitiligo: Imbalance of Epidermal Cytokines at Sites of Lesions (2002)

Vitiligo is a skin disease that is caused by selective destruction of melanocytes and is characterized by white spots. Melanocytes and keratinocytes seem to exhibit a functional close relationship, mediated at least in part by keratinocyte-derived cytokines, which seem important for survival and activity of melanocytic cells. We wanted to investigate the hypothesis that in vitiligo the expression of epidermal cytokines may be modified compared with normal skin. In 15 patients with active, non-segmental vitiligo, biopsies were obtained from lesional, perilesional and non-lesional skin; normal skin from five healthy donors was also tested. Tissue sections were tested using immunohistochemistry for the expression of keratinocyte-derived cytokines with stimulating activity, such as granulocyte-monocyte colony stimulating factor (GM-CSF), basic fibroblastic growth factor (bFGF), and stem cell factor (SCF) or with inhibiting activity, such as interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) on melanocytes. Cytokine receptors and specific melanocytic markers were also investigated. No melanocyte was identified in lesional skin by means of specific markers or c-kit receptor, whereas in perilesional, non-lesional and healthy skin, melanocytes were found in similar number. In vitiligo skin a significantly lower expression of GM-CSF, bFGF and SCF was found, and a significantly higher expression of IL-6 and TNF-alpha was detected, compared with perilesional, non-lesional and healthy skin. In conclusion, we provided evidence that a significant change of epidermal cytokines exists in vitiligo skin compared with perilesional, non-lesional and healthy skin, suggesting that the cytokine production of epidermal microenvironment may be involved in vitiligo.
Galectin-3 in diabetic patients (2014)

Galectin-3 is a versatile molecule which exerts several and sometimes opposite functions in various pathophysiological processes. Recently, galectin-3 has gained attention as a powerful predictor of heart failure and mortality, thus becoming a useful prognostic marker in clinical practice. Moreover, though not specifically investigated in diabetic cohorts, plasma levels of galectin-3 correlated with the prevalence of diabetes and related metabolic conditions, thus suggesting that pharmacological blockade of this lectin might be successful for treating heart failure especially in subjects suffering from these disorders. Indeed, galectin-3 is considered not only as a marker of heart failure, but also as a mediator of the disease, due to its pro-fibrotic action, though evidence comes mainly from studies in galectin-3 deficient mice. However, these studies have provided contrasting results, with either attenuation or acceleration of organ fibrosis and inflammation, depending on the experimental setting and particularly on the levels of advanced glycation endproducts (AGEs)/advanced lipoxidation endproducts (ALEs), of which galectin-3 is a scavenging receptor. In fact, under conditions of increased AGE/ALE levels, galectin-3 ablation was associated with tissue-specific outcomes, reflecting the AGE/ALE-receptor function of this lectin. Conversely, in experimental models of acute inflammation and fibrosis, galectin-3 deficiency resulted in attenuation of tissue injury. There is a need for prospective studies in diabetic patients specifically investigating the relation of galectin-3 levels with complications and for further animal studies in order to establish the effective role of this lectin in organ damage before considering its pharmacological blockade in the clinical setting.
Cloning and expression of the Bacillus anthracis protective antigen gene in Bacillus subtilis (1986)

The gene encoding the protective antigen (PA) moiety of the tripartite exotoxin of Bacillus anthracis was cloned from the recombinant plasmid pSE36 into Bacillus subtilis 1S53 by using the plasmid vector pUB110. Two clones, designated PA1 and PA2, were identified which produced PA in liquid cultures at levels of 20.5 to 41.9 micrograms/ml. This PA was identical to B. anthracis Sterne PA with respect to migration on sodium dodecyl sulfate-polyacrylamide gels and to Western blot antigenic reactivity. Addition of lethal factor or edema factor to PA1 and PA2 supernatants generated biologically active anthrax lethal toxin or edema-producing toxin, respectively. The recombinant plasmid in PA1 (pPA101) was 7.8 kilobases, whereas the PA2 strain plasmid (pPA102) was 6.1 kilobases. Both plasmids had deletions extending into the insert sequence but not into the DNA encoding the PA protein. Immunization with the live recombinant strains protected guinea pigs from lethal challenge with virulent B. anthracis spores, and the immunization partially or completely protected rats from intravenous challenge with anthrax lethal toxin.