gebhart/patrepeval huggingface dataset:
Gene therapy to human diseases (1996)

The identification of defective genes associated with a number of human disorders (tyrosine hydroxylase for Parkinson's disease, aspartylglucosaminidase in lysosomal storage disease, CFTR in cystic fibrosis, and LDL receptor in familial hypercholesterolemia) has promoted the development of strategies aimed at transferring to the somatic cells of the patient or of animal models vectors carrying the corrected gene. The obstacles to overcome include targeting the specific cell type or organ (liver for Factors VIII and IX in hemophilia), enhancing entry to cells into non-lysosomal compartments, nuclear import, percentage of cells transduced with the therapeutic gene, sustained expression of the transgene in human tissues, and immunogenicity of the transduced cells expressing the recombinant or viral proteins. Improvements in each single of these steps are likely to enhance enormously the potential of gene transfer for the treatment of human diseases. A number of human diseases including HIV infections and hypertension are approached by somatic gene transfer. VEGF regulating vascular permeability, growth of endothelial cells and angiogenesis, and TGF-B implicated in wound healing and in stimulation in synthesis of extracellular matrix, are potential targets for restenosis, atherosclerosis, and cancer.
Quantitative cerebral anatomy of the aging human brain (1992)

Seventy-six healthy adults underwent magnetic resonance imaging (1.5 T) to investigate the effects of age on regional cerebral volumes and on the frequency and severity of cortical atrophy, lateral ventricular enlargement, and subcortical hyperintensity. Increasing age was associated with (1) decreasing volumes of the cerebral hemispheres (0.23% per year), the frontal lobes (0.55% per year), the temporal lobes (0.28% per year), and the amygdalahippocampal complex (0.30% per year); (2) increasing volumes of the third ventricle (2.8% per year) and the lateral ventricles (3.2% per year); and (3) increasing odds of cortical atrophy (8.9% per year), lateral ventricular enlargement (7.7% per year), and subcortical hyperintensity in the deep white matter (6.3% per year) and the pons (8.1% per year). Many elderly subjects did not exhibit cortical atrophy or lateral ventricular enlargement, however, indicating that such changes are not inevitable consequences of advancing age. These data should provide a useful clinical context within which to interpret changes in regional brain size associated with “abnormal” aging.
Distributed large-scale natural graph factorization (2013)

Natural graphs, such as social networks, email graphs, or instant messaging patterns, have become pervasive through the internet. These graphs are massive, often containing hundreds of millions of nodes and billions of edges. While some theoretical models have been proposed to study such graphs, their analysis is still difficult due to the scale and nature of the data.
Efficient gossip protocols for verifying the consistency of Certificate logs (2015)

The level of trust accorded to certification authorities has been decreasing over the last few years as several cases of misbehavior and compromise have been observed. Log-based approaches, such as Certificate Transparency, ensure that fraudulent TLS certificates become publicly visible. However, a key element that log-based approaches still lack is a way for clients to verify that the log behaves in a consistent and honest manner. This task is challenging due to privacy, efficiency, and deployability reasons. In this paper, we propose the first (to the best of our knowledge) gossip protocols that enable the detection of log inconsistencies. We analyze these protocols and present the results of a simulation based on real Internet traffic traces. We also give a deployment plan, discuss technical issues, and present an implementation.
Activation of Macrocyclic Biaryl‐Enediynes by Metal Ion Coordination (1995)

The cyclization temperature drops by 100 °C when the 2,2′-bipyridine moiety of enediyene 1 is coordinated by a Hg2+ ion (as in 2). This noncovalent interaction induces a change in conformation that is translated into a significantly increased proclivity for Bergman cyclization. This approach could be used, in principle, to activate strained, inactive enediyne prodrugs for cytotoxic action. tfa = F3CCO2
Bioprinting: inkjet printing proteins and hybrid cell-containing materials and structures (2008)

Inkjet printing is a powerful tool for precision patterning and manufacture. Recently there have been significant developments in the use of inkjet printing for applications in biology, biomaterials and sensor structures that have used the technique to directly print enzymes and living cells. Despite impressive progress, the approach to date has been empirical. This Highlight article reviews some key advances in recent years and outlines potential future areas that require research and development.
A novel oncolytic viral therapy and imaging technique for gastric cancer using a genetically engineered vaccinia virus carrying the human sodium iodide symporter (2014)

GLV-1 h153 is an effective oncolytic virus expressing the hNIS protein that can efficiently regress gastric tumors and allow deep-tissue imaging. These data encourages its continued investigation in clinical settings.
A PSO-SVM Method for Parameters and Sensor Array Optimization in Wound Infection Detection based on Electronic Nose (2012)

In this paper a new method based on the support vector machine (SVM) combined with particle swarm optimization (PSO) is proposed to analyze signals of wound infection detection based on electronic nose (enose). Owing to the strong impact of sensor array optimization and SVM parameters selection on the classification accuracy of SVM, PSO is used to realize a synchronization optimization of sensor array and SVM model parameters. The results show that PSO-SVM method combined with sensor array optimization greatly improves the classification accuracy of mice wound infection compared with radical basis function (RBF) network and genetic algorithms (GA) with/without sensor array optimization. Meanwhile, the proposed sensor array optimization method which weights sensor signals by importance factors also obtain better classification accuracy than that of weighting sensor signals by 0 and 1.
Beiträge zum Reaktionsverhalten von 2‐Aminovinylcarbonylverbindungen (1972)

Abstract 2‐Chlorvinylcarbonylverbindungen reagieren mit Sarkosinäthylester unter Substitution des Chloratoms. Im Falle der 2‐Chlorvinylaldehyde cyclisieren die Substitutionsprodukte sofort zu 1‐Methylpyrrol‐2‐carbonsäureestern. Im Falle der Chlorvinylketone dagegen können die 2‐[N‐(Äthoxycarbonylmethyl)‐N‐methyl‐amino]‐vinylketone isoliert werden. Sie sind auch durch Umsetzung von Hydroxymethylenketonen mit Sarkosinäthylester zugänglich. Die substituierte Aminogruppe wird relativ leicht wieder abgespalten, in einigen Fällen gelingt jedoch ebenfalls eine Cyclisierung zu 1‐Methylpyrrolderivaten.
Heterotransplantation of Human Malignant Tumors in “Nude” Thymusless Mice. II. Malignant Tumors Induced by Injection of Cell Cultures Derived From Human Solid Tumors 2 (1974)

Journal Article Heterotransplantation of Human Malignant Tumors in "Nude" Thymusless Mice. II. Malignant Tumors Induced by Injection of Cell Cultures Derived From Human Solid Tumors Get access B. C. Giovanella, B. C. Giovanella Search for other works by this author on: Oxford Academic PubMed Google Scholar J. S. Stehlin, J. S. Stehlin Search for other works by this author on: Oxford Academic PubMed Google Scholar L. J. Williams, Jr. L. J. Williams, Jr. 3Cancer Research Laboratory and Department of Pathology , St. Joseph Hospital, Houston, Tex. 77002. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 3, March 1974, Pages 921–930, https://doi.org/10.1093/jnci/52.3.921 Published: 01 March 1974 Article history Received: 20 September 1973 Accepted: 21 November 1973 Published: 01 March 1974
Cardiac gated ventilation (1995)

There are several theoretic advantages to synchronizing positive pressure breaths with the cardiac cycle, including the potential for improving distribution of pulmonary and myocardial blood flow and enhancing cardiac output. We evaluated the effects of synchronizing respiration to the cardiac cycle using a programmable ventilator and electron beam CT (EBCT) scanning. The hearts of anesthetized dogs were imaged during cardiac gated respiration with a 50msec scan aperture. Multislice, short axis, dynamic image data sets spanning the apex to base of the left ventricle were evaluated to determine the volume of the left ventricular chamber at end-diastole and end-systole during apnea, systolic and diastolic cardiac gating. We observed an increase in cardiac output of up to 30% with inspiration gated to the systolic phase of the cardiac cycle in a nonfailing model of the heart.
From RNA to DNA, Why So Many Ribonucleotide Reductases? (1993)

It is generally accepted that DNA appeared after RNA during the chemical evolution of life. To synthesize DNA, deoxyribonucleotides are required as building blocks. At present, these are formed from the corresponding ribonucleotides through the enzymatic action of ribonucleotide reductases. Three classes of enzymes are present in various organisms. There is little sequence similarity among the three classes of reductases. However, enzymic mechanisms and the allosteric behavior of the enzymes from various organisms are strongly conserved, suggesting that the enzymes might have evolved from a common ancestor, with the class III anaerobic Escherichia coli reductase as its closest relative.
Pulsed Electromagnetic Fields in Experimental Cutaneous Wound Healing in Rats (1996)

Electromagnetic fields are now being used in many diseases such as osseous, ligamental, cartilaginous, or nervous reparation, diabetes, and myocardial or cerebral ischemia. Although many publications show the usefulness of magneto-therapy, discrepancies exist about the utility of electromagnetic fields in skin wound healing. The objective of this work was to study the effect of pulsed electromagnetic fields on wound healing in rats. Twenty-two male Wistar rats were used; a circular lesion was made in the back of each animal. They were divided into three groups: group C (control) with sham treatment (n = 8), group NF, treated with topical nitrofurazone solution (n = 7), and group PEMF, treated with pulsed electromagnetic fields of 20 mT (n = 7). The treatments were 35 minutes twice a day. The absolute and relative values of the area and perimeter of the wounds showed significantly lower values in the PEMF group at days 7, 14, and 21 compared with those in group C (p < 0.01, analysis of variance), whereas the PEMF group showed significantly lower values at day 21 only compared with the NF group (p < 0.01, analysis of variance). The results suggest a significant beneficial stimulation in the wound healing process in rats treated with PEMF, which could lead to the development of a practical tool for research and clinical use.
[Expression of core-binding factor a1 by human skin fibroblasts induced in vitro]. (2002)

Human skin fibroblast could be induced into pro-osteoblast expressing Cbfa1, an osteoblast-specific transcription factor and a regulation of osteoblast differentiation, and combined use of TNF-alpha and BMP-2 was one of the regulating factors.
Spectral passband filter with independently variable center wavelength and bandwidth (2006)

We introduce a new class of compact grating-based spectral filters and demonstrate a two-port spectral filter that uses a single two-axis microelectromechanical systems tilt mirror to continuously tune the center wavelength across 36 nm and independently tune the passband 3-dB spectral width from 28 to 210 GHz. We also demonstrate the principle of a three-port channel-drop switch
Efficient Catalysis of Polysiloxane Synthesis by Silicatein α Requires Specific Hydroxy and Imidazole Functionalities (1999)

A protein isolated from a biosilica (shown schematically) catalyzes alkoxysilane polycondensation at neutral pH values and low temperatures. Replacement of either of two specific side chain functionalities (Ser-26 and His-165) significantly diminishes catalysis, supporting a reaction mechanism analogous to that of a well-known enzyme that is highly homologous to the silica protein. These results may be useful in the development of synthetic catalysts for environmentally benign synthesis of polysiloxanes.
Antioxidants Inhibit Stimulation of HIV Transcription (1993)

In studies presented here, we demonstrate that antioxidants regulate NF-kappa B activation and signal transduction pathways leading to HIV expression. We show (1) that N-acetyl-L-cysteine (NAC), an antioxidant and an efficient glutathione (GSH) precursor, inhibits NF-kappa B activation and HIV expression under conditions in which GSH is depleted and NAC cannot be converted to GSH, (2) that the D-stereoisomer of NAC and a wide variety of chemically unrelated antioxidants also inhibit NF-kappa B activation and/or transcription directed by the HIV LTR, and (3) that depletion of GSH, the principal intracellular antioxidant, augments HIV production in an acute infection model. Taken together, these findings suggest direct antioxidant action as the mechanism for inhibition of HIV transcription by NAC. They also confirm that GSH, acting in its capacity as an antioxidant, regulates HIV expression and that exogenous antioxidants can potentiate this regulation.
Semaphorin CD100 from Activated T Lymphocytes Induces Process Extension Collapse in Oligodendrocytes and Death of Immature Neural Cells (2004)

An inappropriate cross talk between activated T lymphocytes infiltrating the CNS and neural cells can sustain the onset and progression of demyelination and axonal degeneration in neuroinflammatory diseases. To mimic this deleterious cross talk, we designed an experimental paradigm consisting of transient cocultures of T lymphocytes chronically activated by retrovirus infection (not virus productive) with human multipotent neural precursors or primary oligodendrocytes from rat brain. We showed that activated T lymphocytes induced apoptotic death of multipotent neural progenitors and immature oligodendrocytes after a progressive collapse of their process extensions. These effects were reminiscent of those induced by brain semaphorin on neural cells. Blockade by specific Abs of soluble CD100 (sCD100)/semaphorin 4D released by activated T cells, or treatment with rsCD100, demonstrated that this immune semaphorin has the ability to collapse oligodendrocyte process extensions and to trigger neural cell apoptosis, most likely through receptors of the plexin family. The specific presence of sCD100 in the cerebrospinal fluid and of CD100-expressing T lymphocytes in the spinal cord of patients suffering with neuroinflammatory demyelination pointed to the potential pathological effect of sCD100 in the CNS. Thus, our results show that CD100 is a new important element in the deleterious T cell-neural cell cross talk during neuroinflammation and suggest its role in demyelination or absence of remyelination in neuroinflammatory diseases including multiple sclerosis and human T lymphotropic virus type 1-associated myelopathy.
33—THE SNARLING OF HIGHLY TWISTED MONOFILAMENTS. PART II: CYLINDRICAL SNARLING (1972)

An account is given of an experimental investigation of the cylindrical snarling of highly twisted monofilaments. The theory underlying cylindrical snarling is set out, and an expression is derived for calculating the critical twist level at which normal snarling will be replaced by cylindrical snarling. Experiments on rubber filaments are described, and it is shown that there is good agreement between the theoretical and experimental results. Further experiments, in which the specimen was allowed to contract freely or forced into other forms, are also described. It is shown from these experiments that it is difficult to establish the true equilibrium behaviour, since the situation appears to be dominated by frictional effects or by direct barriers to relative movement.
Discrimination of rising and falling simulated single-formant frequency transitions: Practice and transition duration effects (1989)

Two experiments evaluated discrimination of simulated single-formant frequency transitions. In the first experiment, listeners received practice with trial-by-trial feedback in discriminating either rising or falling frequency transitions of three different durations (30, 60, and 120 ms). Transitions either occurred in isolation or were followed by a steady-state sound matched in frequency to the transition end point. Some improvement in discrimination over practice runs occurred for the shortest transitions. Whether performance was evaluated at the beginning or end of practice, there were no differences attributable to transition direction or to whether transitions were followed by steady-state sound. Discrimination, however, was significantly better for the longest transitions. Just noticeable differences (jnd’s) for the longest transitions, measured in Hz at transition onsets, were of approximately the same magnitude as jnd’s for steady-state sounds that were equal in frequency to the midpoints of the transitions. Subjects of the second experiment discriminated the longer rising and falling transitions, but did not receive extensive practice. Results of experiment 2 replicated results of experiment 1 in showing similar jnd’s. Experiment 2 also showed no differences attributable to transition direction or to the presence of the steady-state sound following transitions.
Resveratrol: A multitargeted agent for age-associated chronic diseases (2008)

Extensive research within the last decade has revealed that most chronic illnesses such as cancer, cardiovascular and pulmonary diseases, neurological diseases, diabetes, and autoimmune diseases exhibit dysregulation of multiple cell signaling pathways that have been linked to inflammation. Thus mono-targeted therapies developed for the last two decades for these diseases have proven to be unsafe, ineffective and expensive. Although fruits and vegetables are regarded to have therapeutic potential against chronic illnesses, neither their active component nor the mechanism of action is well understood. Resveratrol (trans-3, 5, 4'-trihydroxystilbene), a component of grapes, berries, peanuts and other traditional medicines, is one such polyphenol that has been shown to mediate its effects through modulation of many different pathways. This stilbene has been shown to bind to numerous cell-signaling molecules such as multi drug resistance protein, topoisomerase II, aromatase, DNA polymerase, estrogen receptors, tubulin and F1-ATPase. Resveratrol has also been shown to activate various transcription factor (e.g; NFkappaB, STAT3, HIF-1alpha, beta-catenin and PPAR-gamma), suppress the expression of antiapoptotic gene products (e.g; Bcl-2, Bcl-X(L), XIAP and survivin), inhibit protein kinases (e.g; src, PI3K, JNK, and AKT), induce antioxidant enzymes (e,g; catalase, superoxide dismutase and hemoxygenase-1), suppress the expression of inflammatory biomarkers (e.g., TNF, COX-2, iNOS, and CRP), inhibit the expression of angiogenic and metastatic gene products (e.g., MMPs, VEGF, cathepsin D, and ICAM-1), and modulate cell cycle regulatory genes (e.g., p53, Rb, PTEN, cyclins and CDKs). Numerous animal studies have demonstrated that this polyphenol holds promise against numerous age-associated diseases including cancer, diabetes, Alzheimer, cardiovascular and pulmonary diseases. In view of these studies, resveratrol's prospects for use in the clinics are rapidly accelerating. Efforts are also underway to improve its activity in vivo through structural modification and reformulation. Our review describes various targets of resveratrol and their therapeutic potential.
Sustained growth and three-dimensional organization of primary mammary tumor epithelial cells embedded in collagen gels. (1979)

We have developed a method for embedding cells within a collagen matrix which allows sustained growth of mouse mammary tumor epithelial cells in primary culture. A characteristic and reproducible pattern of organization and growth occurs: the cells rearrange themselves and produce duct-like structures extending into the matrix, resulting in a three-dimensional outgrowth. Autoradiography showed continuous [3H]thymidine incorporation during 8 weeks in culture. An increase in DNA content of the cultured cells as a function of time was observed. Mouse mammary tumor cells cultured in the conventional monolayer system failed to show any significant increase in cell number during a culture period of 6 weeks. In addition, in such monolayer systems, cells progressively became detached from the dishes in long-term culture. The mammary epithelial cell origin of the collagen gel cell outgrowths was shown by electron microscopic demonstration of polarized cells containing tight junctions and budding mammary tumor virus particles. In addition, in vivo transplantation of collagen gel outgrowths resulted in the development of mammary adenocarcinoma histologically similar to the donor tumor. Cellular outgrowth patterns resembling those from tumor cells were also seen in similar collagen gel cultures of normal mammary cells from mouse and human and of hyperplastic alveolar nodule cells from mouse. The significance and usefulness of this system in comparison to the conventional monolayer system are discussed.
C-Myc- Dependent Stabilization of Hif-1alpha in MM: Therapeutic Implications (2008)

Abstract Bone marrow (BM) angiogenesis has been associated with multiple myeloma (MM) progression. Here we demonstrate that oncogenic c-Myc, also prominently associated with adverse prognosis in MM, regulates Hif-1α promoter activity, Hif-1alpha protein levels, and consequently the expression of pro-angiogenic target genes such as VEGF in MM cells. As observed with c-Myc knockdown, anti-MM agents with known anti-angiogenic activity including bortezomib, lenalidomide, and enzastaurin also downregulate Hif-1alpha and VEGF. Moreover, tyrophostin adaphostin induces similar effects, associated with anti-angiogenic activity, in a zebrafish model. The correlation between c-Myc, Hif-1alpha and tumor angiogenesis was further confirmed in a xenograft mouse model of human MM. Mechanistically, our in vitro data show that oncogenic c-Myc stabilizes caspase-8, and thereby protects Hif-1alpha against caspase-8- dependent degradation and attenuation of VEGF secretion. These sequelae also contribute to enhanced VEGF secretion triggered by MM cell-bone marrow stromal cell binding. Indeed, conditioned media from adaphostin- treated co-cultures inhibit endothelial cell growth and tubule formation. In addition, HIF1alpha gene demonstrated significant increased expression (p=0.02, Mann Whitney test) in tumor cells versus plasma cells derived from healthy donors. Importantly, when tested on a dataset of 559 patients, a significant link between HIF1alpha overexpression and poor prognosis was found (p=0,0069). These data further point to the possible relevance of HIF1alpha in the progression of a subset of MM patients. In summary, our data provide strong evidence of a key role of Hif-1alpha in MM angiogenesis and the therapeutic potential of specific Hif-1alpha and c-Myc inhibitors. Moreover they demonstrate additional biologic sequelae of novel MM therapies.