gebhart/patrepeval huggingface dataset:
Association of Cell-Free DNA Tumor Fraction and Somatic Copy Number Alterations With Survival in Metastatic Triple-Negative Breast Cancer (2018)

Purpose Cell-free DNA (cfDNA) offers the potential for minimally invasive genome-wide profiling of tumor alterations without tumor biopsy and may be associated with patient prognosis. Triple-negative breast cancer (TNBC) is characterized by few mutations but extensive somatic copy number alterations (SCNAs), yet little is known regarding SCNAs in metastatic TNBC. We sought to evaluate SCNAs in metastatic TNBC exclusively via cfDNA and determine if cfDNA tumor fraction is associated with overall survival in metastatic TNBC. Patients and Methods In this retrospective cohort study, we identified 164 patients with biopsy-proven metastatic TNBC at a single tertiary care institution who received prior chemotherapy in the (neo)adjuvant or metastatic setting. We performed low-coverage genome-wide sequencing of cfDNA from plasma. Results Without prior knowledge of tumor mutations, we determined tumor fraction of cfDNA for 96.3% of patients and SCNAs for 63.9% of patients. Copy number profiles and percent genome altered were remarkably similar between metastatic and primary TNBCs. Certain SCNAs were more frequent in metastatic TNBCs relative to paired primary tumors and primary TNBCs in publicly available data sets The Cancer Genome Atlas and METABRIC, including chromosomal gains in drivers NOTCH2, AKT2, and AKT3. Prespecified cfDNA tumor fraction threshold of ≥ 10% was associated with significantly worse metastatic survival (median, 6.4 v 15.9 months) and remained significant independent of clinicopathologic factors (hazard ratio, 2.14; 95% CI, 1.4 to 3.8; P < .001). Conclusion We present the largest genomic characterization of metastatic TNBC to our knowledge, exclusively from cfDNA. Evaluation of cfDNA tumor fraction was feasible for nearly all patients, and tumor fraction ≥ 10% is associated with significantly worse survival in this large metastatic TNBC cohort. Specific SCNAs are enriched and prognostic in metastatic TNBC, with implications for metastasis, resistance, and novel therapeutic approaches.
Transmission electron microscopy of extended crystal defects in proton bombarded and annealed gaas (1983)

Abstract The technique of cross-sectional transmission electron microscopy (TEM) has been applied to study the nature of extended defects in proton bombarded GaAs as a function of dose and post-bombardment anneal. For low doses (up to 5 × 1015 protons cm−2) the main defects were found to be Frank dislocation loops which develop after an anneal at 500°C. In high dose (1017 protons cm−2) samples damage of a diffuse structure was detectable by TEM without annealing. Upon annealing, dislocation networks interspersed with voids became visible. Models for the growth of voids and Frank loops with temperature of anneal have been developed and the experimental details analysed accordingly. From these analyses an average enthalpy for vacancy migration of 0.3 eV is deduced for GaAs.
Endovascular exclusion of abdominal aortic aneurysms: initial experience with stent-grafts in cardiology practice. (2000)

The use of an endovascular stent-graft prosthesis for the treatment of infrarenal abdominal aortic aneurysms is receiving increasing attention as an option that may avoid the significant morbidity and mortality associated with open surgical treatment. We studied the clinical effectiveness of stent-grafts in patients with infrarenal abdominal aortic aneurysms. Between October 1995 and May 1998, 33 patients underwent infrarenal abdominal aortic aneurysm exclusion with a homemade polytetrafluoroethylene-covered stent, and between November 1998 and September 1999, 56 patients underwent abdominal aortic aneurysm exclusion with the Medtronic AneuRx stent-graft. Overall, these patients represented a high-risk surgical group. The technical success rate was 100% in both groups. No patient required immediate conversion to open repair. With the polytetrafluoroethylene-covered stent, the primary success rate was 33%, and the secondary success rate was 76%. In the AneuRx group, the primary success rate was 82.8%, and the secondary success rate was 85.3% at 6 months. There was no procedural or 1-month mortality or major morbidity in either group. By showing that infrarenal abdominal aortic aneurysms can be treated safely and successfully with an endoluminal stent-graft, our early results provide additional support for the endovascular treatment of abdominal aortic aneurysms. Further follow-up studies will determine the long-term ability of such treatment to prevent aneurysmal rupture and death.
Multilayer nonnegative matrix factorisation (2006)

A multilayer approach to nonnegative matrix factorisation algorithms is proposed. It considerably improves their performance; especially if a problem is ill-conditioned, or data are badly scaled, and projected gradient algorithms are used. This is fully confirmed by extensive simulations with diverse types of data in application to blind source separation.
Animal models with construct validity for schizophrenia (1990)

Developing animal models for psychiatric disorders is a complicated process. This is principally due to our relatively limited knowledge of the processes underlying such complicated illnesses as depression and schizophrenia. Unfortunately this can lead to a vicious circle. Our limited knowledge of the disease leads to the inability to develop proper animal models, which will lead to an inability to increase our knowledge about neuronal mechanisms underlying the illness. In the present review we have tried to show that with respect to schizophrenia the situation is slowly changing. Using electrophysiological and psychological methods, clinicians begin to understand the psychopathological processes underlying the schizophrenic process. Preclinical researchers have tried to use this knowledge to develop animal models in which hypotheses can be tested and possible insight into mechanisms underlying the disease can be gained. In the present review three different animal models are presented. These are based on the construct that schizophrenic patients are disturbed in their information processing. More precisely the first two animal models are based on the construct that schizophrenic patients are less able to differentiate between relevant and irrelevant stimuli. The analysis of the literature suggests that the amphetamine-induced distruption of latent inhibition (and probably blocking), and the phencyclidine-induced disturbances in the startle response might provide two interesting animal models with construct, face and predictive validity for schizophrenia. This third model deals with the amphetamine-induced changes in the behaviour of socially living monkeys. This model seems to be related to both positive and negative symptoms of schizophrenia and is based on the construct that the negative symptoms are due to a compensatory mechanism which protects the subjects from "sensory flooding". The amphetamine-induced changes in behaviour of socially living monkeys seem to represent an example of an animal model in which both positive symptoms (stereotypy) and negative symptoms (social isolation) occurs. The construct validity of this model is still unclear, but pharmacological studies suggest that, apart from the face validity, the model also has a certain predictive validity. The models discussed in the present review can help us to increase our insight in neuronal structures underlying information processing disturbances. Structures known to be implicated in these models include the hippocampus, amygdala and ventral striatum.
Neo-Organoid of Marrow Mesenchymal Stromal Cells Secreting Interleukin-12 for Breast Cancer Therapy (2008)

Bone marrow-derived mesenchymal stromal cells (MSCs), beneficial for regenerative medicine applications due to their wide differentiation capabilities, also hold promise as cellular vehicles for the delivery of therapeutic plasma-soluble gene products due to their ease of handling, expansion, and genetic engineering. We hypothesized that MSCs, gene enhanced to express interleukin-12 (IL-12) and then embedded in a matrix, may act as an anticancer neo-organoid when delivered s.c. in autologous/syngeneic hosts. We performed such experiments in mice and noted that primary murine MSCs retrovirally engineered to secrete murine IL-12 can significantly interfere with growth of 4T1 breast cancer cells in vivo, with a more substantial anticancer action achieved when these cells are embedded in a matrix. Plasma of mice that received the IL-12 MSC-containing neo-organoids showed increased levels of IL-12 and IFN-gamma. Histopathologic analysis revealed less tumor cells in implants of 4T1 cells with IL-12 MSCs, and the presence of necrotic tumor islets and necrotic capillaries, suggesting antiangiogenesis. We also showed that the anticancer effect exerted by the IL-12 MSCs is immune mediated because it is absent in immunodeficient mice, is not due to systemic IL-12 delivery, and also occurs in a B16 melanoma model. This study therefore establishes the feasibility of using gene-enhanced MSCs in a cell-based neo-organoid approach for cancer treatment.
Expression of endothelial adhesion molecules in vivo. Increased endothelial ICAM-2 expression in lymphoid malignancies. (1992)

The authors have compared the reactivity of monoclonal antibodies (MAb) directed against endothelial adhesion molecules (ICAM-1, ICAM-2, VCAM-1, ELAM-1) in hyperplastic, nonmalignant, and malignant lymph nodes. The authors demonstrate that the reactivity with ICAM-1 MAb is stronger in the high endothelial venules (HEV) and other smaller vessels (SV) in lymphomas compared with hyperplastic lymph nodes. Similarly, the reactivity of an ICAM-2 MAb (6D5) was shown to be higher in malignant lymph nodes compared with nonmalignant ones. ICAM-2 MAb stained both the HEV and SV. VCAM-1 MAb reacted strongly with germinal centers and its endothelial reactivity was higher in the lymphoma nodes. ELAM-1 MAb stained only faintly some endothelial cells in malignant tissue. These data suggest that besides the known regulatable endothelial adhesion molecules ICAM-1 and VCAM-1, the expression of ICAM-2 can be modified.
Task adaptation in stochastic language models for continuous speech recognition (1992)

The authors describe two approaches for adapting a specific syllable trigram model to a new task. One uses a small amount of text data similar to the target task, and the other uses supervised learning using the most recent input phrases. The effect of each adaptation is verified with syllable perplexity and phrase recognition. Where the syntactic knowledge was only the syllable trigram model, the perplexity was reduced from 54.5 to 18.1 for the adaptation using 100 phrases of similar text, and was reduced to 14.6 by the supervised learning. The recognition rates were also improved from 42.3% to 46.6% and 50.9%, respectively. Text similarity for speech recognition is also studied.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Performance of digital magnetic recording with equalization and offtrack interference (1991)

The relative performance of well-equalized peak detection, partial response, and decision feedback detection in an intertrack-interference (ITI)-dominated noise environment is calculated, showing that it depends heavily on the intertrack interference. It is found that equalized peak detection performs relatively well at low linear density and extreme offtrack positions (e.g. 20%) and that partial response with Viterbi detector performs the best at small offtrack positions. However, overall, the decision feedback equalizer provides the best performance for a given amount of complexity, and its advantages are discussed. Tolerance to offtrack error as a function of linear density and, taking offtrack performance into account, tradeoffs between increasing linear or areal density are addressed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Vaccination with inactivated influenza A virus during pregnancy protects neonatal mice against lethal challenge by influenza A viruses representing three subtypes (1990)

A single intraperitoneal injection of pregnant mice with a monovalent Formalin-inactivated influenza A virus vaccine protected their offspring against a lethal challenge dose of the same influenza A virus H3N2, H2N2, and H1N1 subtypes, as well as against challenge with the other two subtypes. Degree of protection was vaccine dose related. Cross-fostering of neonates indicated that protection was conferred by breast milk antibodies. Serum virus-specific neutralizing antibodies in the mothers and neonates correlated with resistance to vaccine virus, but were detected against other subtypes only in a complement enhancement test or when high doses of vaccine were given.
Safety and Immunogenicity of Capsular Polysaccharide–Tetanus Toxoid Conjugate Vaccines for Group B Streptococcal Types Ia and Ib (1999)

About 40% of invasive group B streptococcal (GBS) isolates are capsular polysaccharide (CPS) types Ia or Ib. Because infant and maternal GBS infections may be preventable by maternal vaccination, individual GBS CPS have been coupled to tetanus toxoid (TT) to prepare vaccines with enhanced immunogenicity. Immunogenicity in rabbits and protective capacity in mice of a series of type Ia- and Ib-TT conjugates increased with the degree of polysaccharide-to-protein cross-linking. In total, 190 healthy, nonpregnant women aged 18-40 years were randomized in four trials to receive Ia- or Ib-TT conjugate (dose range, 3.75-63 microg of CPS component), uncoupled Ia or Ib CPS, or saline. All vaccines were well-tolerated. CPS-specific IgG serum concentrations peaked 4-8 weeks after vaccination and were significantly higher in recipients of conjugated than of uncoupled CPS. Immune responses to the conjugates were dose-dependent and correlated in vitro with opsonophagocytosis. These results support inclusion of Ia- and Ib-TT conjugates when formulating a multivalent GBS vaccine.
Prognostic Factors in High-Grade Osteosarcoma of the Extremities or Trunk: An Analysis of 1,702 Patients Treated on Neoadjuvant Cooperative Osteosarcoma Study Group Protocols (2002)

Tumor site and size, primary metastases, response to chemotherapy, and surgical remission are of independent prognostic value in osteosarcoma.
Dual Role of Heat Shock Proteins as Regulators of Apoptosis and Innate Immunity (2010)

Stress or heat shock proteins (HSPs) 70 and 90 are powerful chaperones whose expression is induced in response to a wide variety of physiological and environmental insults. These proteins have different functions depending on their intracellular or extracellular location. Intracellular HSPs have a protective function. They allow the cells to survive potentially lethal conditions. The cytoprotective functions of HSPs can largely be explained by their anti-apoptotic properties. HSP70 and HSP90 can directly interact with different proteins of the tightly regulated programmed cell death machinery and thereby block the apoptotic process at distinct key points. In cancer cells, where the expression of HSP70 and/or HSP90 is frequently abnormally high, they participate in oncogenesis and in resistance to chemotherapy. Therefore, the inhibition of HSPs has become an interesting strategy in cancer therapy. In contrast to intracellular HSPs, extracellularly located or membrane-bound HSPs mediate immunological functions. They can elicit an immune response providing a link between innate and adaptive immune systems. In cancer, most immunotherapeutical approaches based on extracellular HSPs exploit their carrier function for immunogenic peptides. This review will focus on the roles of HSP70 and HSP90 in apoptosis and in innate immunity and how these functions are being exploited in cancer therapy.
Strategies for light extraction from surface plasmons in organic light-emitting diodes (2011)

Organic light-emitting diodes (OLEDs) usually exhibit a low light-outcoupling efficiency of only 20%. Typically, more than 30% of the available power is lost to surface plasmons (SPs). Consequently, the overall efficiency could be strongly enhanced by recovering SP losses. Therefore, three suitable techniques for extracting SPs-index coupling, prism coupling, and grating coupling-are discussed from a theoretical point of view and investigated experimentally in simplified OLED-like structures. The basic physical processes are clarified by systematic variations of the involved layer thicknesses and by excited state lifetime measurements. In addition, the analysis of the results is supported by optical simulations based on a dipole model. Finally, the advantages and disadvantages of each method, their potential efficiency for recovering SP losses, as well as the applicability in OLEDs are compared.
The antiheparin effect of a heparinoid, pentosan polysulphate. Investigation of a mechanism (1984)

A pentosan polysulphate [a fully sulphated (1-4)-beta-D-xylopyranose with a single laterally positioned 4-O-methyl-alpha-D-glucuronic acid] has been shown to inhibit the anticoagulant activity of high-affinity heparin as observed in plasma and when using purified enzyme and inhibitor. The activity was shown to be concentration-dependent with an apparent Ki of approx. 2 microM. The antiheparin property was not shown by a number of other anionic carbohydrates when tested. The rate of thrombin inhibition at 0.33 microM-heparin was reduced from 7.1 X 10(8) M-1 X min-1 in the absence of pentosan polysulphate to 2.3 X 10(8) M-1 X min-1 at 2 microM-pentosan polysulphate and to 0.3 X 10(8)M-1 X min-1 at 20 microM. Using the random bireactant model of heparin action [Griffiths (1982) J. Biol. Chem. 257, 13899-13902] it was observed that the pentosan polysulphate had no effect on the Km for antithrombin III (150 nM) but increased the Km for thrombin from 25 nM to 450 nM. A reduction in the inhibition rate by 17.3-fold predicted by substitution of these values into the general two-substrate reaction-rate equation was confirmed experimentally.
Specificity of monoclonal antibodies elicited by mucosal infection of BALB/c mice with virulent Shigella flexneri 2a (1996)

Protective immunity against shigellosis is thought to be determined by the O-antigen side chains of the lipopolysaccharide (LPS) molecule. To study possible common protective epitopes, monoclonal antibodies reacting with Shigella flexneri 2a LPS were generated from BALB/c mice infected ocularly with the virulent serotype 2a strain S. flexneri 2457T and tested against a panel of S. flexneri LPSs by enzyme-linked immunosorbent and immunoblot assays. Four monoclonal antibodies were identified, all of which showed restricted specificity patterns. Three different patterns of reactivity to LPS possessing the 3,4 group antigen were seen: (i) 2a only, (ii) 2a and 5a, and (iii) 2a, 4a, 5a, and Y. These results have implications for designing a Shigella vaccine that will be protective against related serotypes. Electron microscopy studies showed that the monoclonal antibodies bind to the bacterial surface in a patchy pattern, suggesting their potential use for examining the LPS distribution on the surface of the bacteria.
Dominant-negative and targeted null mutations in the endothelial receptor tyrosine kinase, tek, reveal a critical role in vasculogenesis of the embryo. (1994)

The receptor tyrosine kinases (RTKs) expressed on the surface of endothelial cells are likely to play key roles in initiating the program of endothelial cell growth during development and subsequent vascularization during wound healing and tumorigenesis. Expression of the Tek RTK during mouse development is restricted primarily to endothelial cells and their progenitors, the angioblasts, suggesting that Tek is a key participant in vasculogenesis. To investigate the role that Tek plays within the endothelial cell lineage, we have disrupted the Tek signaling pathway using two different genetic approaches. First, we constructed transgenic mice expressing a dominant-negative form of the Tek receptor. Second, we created a null allele of the tek gene by homologous recombination in embryonic stem (ES) cells. Transgenic mice expressing dominant-negative alleles of Tek or homozygous for a null allele of the tek locus both died in utero with similar defects in the integrity of their endothelium. By crossing transgenic mice that express the lacZ reporter gene under the transcriptional control of the endothelial cell-specific tek promoter, we found that the extraembryonic and embryonic vasculature was patterned correctly. However, homozygous tek embryos had approximately 30% and 75% fewer endothelial cells at day 8.5 and 9.0, respectively. Homozygous null embryos also displayed abnormalities in heart development, consistent with the conclusion that Tek is necessary for endocardial/myocardial interactions during development. On the basis of the analysis of mice carrying either dominant-negative or null mutations of the tek gene, these observations demonstrate that the Tek signaling pathway plays a critical role in the differentiation, proliferation, and survival of endothelial cells in the mouse embryo.
Cross-activating c-Met/β1 integrin complex drives metastasis and invasive resistance in cancer (2017)

The molecular underpinnings of invasion, a hallmark of cancer, have been defined in terms of individual mediators but crucial interactions between these mediators remain undefined. In xenograft models and patient specimens, we identified a c-Met/β1 integrin complex that formed during significant invasive oncologic processes: breast cancer metastases and glioblastoma invasive resistance to antiangiogenic VEGF neutralizing antibody, bevacizumab. Inducing c-Met/β1 complex formation through an engineered inducible heterodimerization system promoted features crucial to overcoming stressors during metastases or antiangiogenic therapy: migration in the primary site, survival under hypoxia, and extravasation out of circulation. c-Met/β1 complex formation was up-regulated by hypoxia, while VEGF binding VEGFR2 sequestered c-Met and β1 integrin, preventing their binding. Complex formation promoted ligand-independent receptor activation, with integrin-linked kinase phosphorylating c-Met and crystallography revealing the c-Met/β1 complex to maintain the high-affinity β1 integrin conformation. Site-directed mutagenesis verified the necessity for c-Met/β1 binding of amino acids predicted by crystallography to mediate their extracellular interaction. Far-Western blotting and sequential immunoprecipitation revealed that c-Met displaced α5 integrin from β1 integrin, creating a complex with much greater affinity for fibronectin (FN) than α5β1. Thus, tumor cells adapt to microenvironmental stressors induced by metastases or bevacizumab by coopting receptors, which normally promote both cell migration modes: chemotaxis, movement toward concentrations of environmental chemoattractants, and haptotaxis, movement controlled by the relative strengths of peripheral adhesions. Tumor cells then redirect these receptors away from their conventional binding partners, forming a powerful structural c-Met/β1 complex whose ligand-independent cross-activation and robust affinity for FN drive invasive oncologic processes.
Recombinant human erythropoietin: effects on frataxin expression in vitro (2005)

Our results provide a scientific basis for further studies examining the effectiveness of this agent for the treatment of FRDA patients.
Synthesis of a Porous SiC Material from Polycarbosilane by Direct Foaming and Radiation Curing (2014)

This chapter contains sections titled: Introduction Experimental Procedure Results and Discussion Conclusion
Transcutaneous vagus and trigeminal nerve stimulation for neuropsychiatric disorders: a systematic review (2014)

TNS and tVNS improve treatment of particular neuropsychiatric disorders such as depression.