gebhart/patrepeval huggingface dataset:
A connexin 43 mutant lacking the carboxyl cytoplasmic domain inhibits both growth and motility of mouse 3T3 fibroblasts (2000)

Connexins have been shown to inhibit the growth of a wide number of communication-deficient cells both in vivo and in vitro, but the molecular mechanism remains largely unknown. In previous work we have shown that stable transfectants of 3T3 A31 fibroblasts, which express a Connexin 43 (Cx43) mutant (Cx43-256M) consisting of amino acids 1-256 of rat Cx43 fused to a c-myc tag, exhibit a decreased basal growth rate and weakened mitogenic response to platelet derived growth factor compared with either the parent cell line or cells transfected with an expression vector that did not encode a functional protein. Here we have investigated further the growth characteristics of these cells in order to establish the mechanism by which this protein suppresses cell growth. Analysis of DNA synthesis in individual cells by immunofluorescence staining of bromodeoxyuridine incorporation demonstrated that the slow growth of Cx43-256M cells was due to a decrease in the number of cells that undergo DNA synthesis following growth factor stimulation. This was associated with an increased proportion of the cell population in the G2/M phases of the cell cycle suggesting growth may be arrested during G2 or metaphase. In addition to effects on cell growth, Cx43-256M expression inhibited cell motility as assayed both in a wounding assay and in a Boyden chamber assay. These results now raise the question as to whether the primary effect of the Cx43-256M protein is on cell growth or cell motility.
In vitro characterization of T cells from Mycobacterium w-vaccinated mice (1992)

Tuberculosis caused by the intracellular bacterial pathogen Mycobacterium tuberculosis still represents a major health problem, and its effective control would best be accomplished by active vaccination. Although vaccination with M. bovis BCG has proven highly effective in certain parts of the world, in several developing countries it has been found to confer only marginal protection. Hence, novel vaccination strategies are warranted. Mycobacterium w is a saprophytic cultivable mycobacterium which shares several antigens with M. tuberculosis. In the murine system, vaccination with killed M. w was found to protect against subsequent tuberculosis. In order to characterize the responsible immune mechanisms more precisely, mice were vaccinated with killed M. w and T cells restimulated in vitro with mycobacterial antigens. These T cells produced interleukin 2 and gamma interferon but no detectable interleukin 4 and interleukin 5. Killed M. w induced significantly stronger T-cell responses than killed M. tuberculosis, and both vaccination regimes were markedly improved by administration in a mild adjuvant, i.e., the Ribi adjuvant containing trehalose dimycolate, monophosphoryl lipid A, and mycobacterial cell wall skeleton. Our data suggest that M. w-induced immunity against M. tuberculosis rests primarily on TH1 cells, which are thought to be of major relevance for acquired antituberculosis resistance. Our study therefore provides a further step toward the identification of a novel tuberculosis vaccine.
Fifteen percent of myocardial infarctions and coronary revascularizations explained by family history unrelated to conventional risk factors. The Reykjavik Cohort Study (2002)

Aims To examine the relationship between history of myocardial infarction in first-degree relatives and the risk of developing coronary heart disease (myocardial infarction or coronary revascularization). Methods and Results A total of 9328 males and 10062 females, randomly selected residents of the Reykjavik area, aged 33-81 years, were examined in the period from 1967 to 1996 in a prospective cohort study. Cardiovascular risk assessment was based on characteristics at baseline. Information on history of myocardial infarction in first-degree relatives was obtained from a health questionnaire. Mean follow-up was 18 and 19 years for men and women, respectively. During follow-up 2700 men and 1070 women developed coronary heart disease. Compared with subjects without a family history, the hazard ratio of coronary heart disease was 1.75 (95% confidence interval, CI, 1.59-1.92) for men and 1.83 (95% CI, 1.60-2.11) for women, with one or more first-degree relatives with myocardial infarction. The risk factor profile was significantly worse in individuals with a positive family history. After allowance for these risk factors, the hazard ratio was still highly significant, 1.66 (CI, 1.51-1.82) and 1.64 (CI, 1.43-1.89) for men and women, respectively. Family history of myocardial infarction was attributed to 15.1% of all cases of coronary heart disease in men and 16.6% in women, independent of other known risk factors. Conclusion Family history of myocardial infarction increases the risk of developing coronary heart disease in both men and women and is largely independent of other classic risk factors. Approximately 15% of all myocardial infarctions can be attributed to familial factors that have not been measured in the study or remain to be elucidated.
Brain Grafts Reduce Motor Abnormalities Produced by Destruction of Nigrostriatal Dopamine System (1979)

In order to determine if brain tissue grafts can provide functional input to recipient central nervous system tissue, fetal rat dopamine-containing neurons were implanted adjacent to the caudate nucleus of adult recipients whose endogenous dopaminergic input had been destroyed. The grafts showed good survival and axonal outgrowth. Motor abnormalities, which had been induced by the destruction of the endogenous dopaminergic input to the caudate, were significantly reduced after grafting of the fetal brain tissue. These data suggest that such implants may be potentially useful in reversing deficits after circumscribed destruction of brain tissue.
Patents on SELEX and Therapeutic Aptamers (2008)

Aptamers, the oligonucleotides (DNA/RNA) that bind to target molecules with high specificity and affinity, have been a focus of therapeutic research for the last two decades. The magnitude of scientific and commercial interest shown for aptamers is not surprising because aptamers have several advantages over other curative modalities, especially antibodies. Patent activity in this field has also shown an exponential growth. Aptamers against a broad range of diseasecausing pathogens and proteins have been patented. These have potential use as a biomarker, therapeutics and diagnostics. As drugs they have shown commendable results in cell and animal models, a few of them undergoing clinical trials. In this review, we discuss upon all important patents filed on therapeutic aptamers and SELEX technology employed to synthesize them. We have classified them in categories based upon their target or the diseased condition they apt for. These patents provide insight into the development that occurred in transformation of aptamers as therapeutic entities and reinforces the potential they have.
Multiple Eccrine Hidrocystomas (2003)

BACKGROUND Multiple eccrine hidrocystomas are benign cystic lesions that are associated with a chronic course and seasonal variability. Even though in the literature it is presented as a very infrequent pathology, we think this is more a lack of knowledge of the existence of said pathology and the fact that patients confuse it with comedo. OBJECTIVE To treat multiple eccrine hidrocystomas of the face. RESULTS We present a case of multiple eccrine hidrocystomas of the face in a cook man. Hidrocystoma is a benign cystic tumor of the sweat glands eccrine or apocrine. Multiple eccrine hidrocystomas are benign cystic lesions that are associated with a chronic course and seasonal variability. They appear like multiple shining small papule. Although a solitary eccrine hidrocystoma can be treated easily with surgical excision, the elimination of multiple lesions is problematic because of their number and location. CONCLUSION The benefits of BTX-A treatment for multiple eccrine hidrocystomas include ease of application, no risk of scarring, and a good postoperative course. Because of the blockage produced by BTX-A on cholinergic terminals of the parasympathetic system that governs sweat glands secretion, it is suggested that periodic doses of BTX-A are injected in the superficial epidermis in order to treat multiple eccrine hidrocystomas.
Natriuretic peptides: Physiology, therapeutic potential, and risk stratification in ischemic heart disease (1998)

The natriuretic peptides are counterregulatory hormones with prognostically important levels. They are similarly upregulated in heart failure and counteract neurohormones that induce vasoconstriction and fluid retention. BNP may be the superior prognosticator for risk stratification after myocardial infarction and is independent of left ventricular ejection fraction. Lastly, experimental trials suggest that administration of exogenous natriuretic peptides or inhibitors of their catabolism to patients with ischemic heart disease may be clinically beneficial.
Role of DnaK in In Vitro and In Vivo Expression of Virulence Factors ofVibrio cholerae (1999)

The dnaK gene of Vibrio cholerae was cloned, sequenced, and used to construct a dnaK insertion mutant which was then used to examine the role of DnaK in expression of the major virulence factors of this important human pathogen. The central regulator of several virulence genes of V. cholerae is ToxR, a transmembrane DNA binding protein. The V. cholerae dnaK mutant grown in standard laboratory medium exhibited phenotypes characteristic of cells deficient in ToxR activity. Using Northern blot analysis and toxR transcriptional fusions, we demonstrated a reduction in expression of the toxR gene in the dnaK mutant strain together with a concomitant increase in expression of a htpG-like heat shock gene that is located immediately upstream and is divergently transcribed from toxR. This may be due to increased heat shock induction in the dnaK mutant. In vivo, however, although expression from heat shock promoters in the dnaK mutant was similar to that observed in vitro, expression of both toxR and htpG was comparable to that by the parental strain. In both strains, in vivo expression of toxR was significantly higher than that observed in vitro, but no reciprocal decrease in htpG expression was observed. These results suggest that the modulation of toxR expression in vivo may be different from that observed in vitro.
Phase Ib dose-escalation study of MetMAb, a monovalent antagonist antibody to the receptor MET, in combination with bevacizumab in patients with locally advanced or metastatic solid tumors. (2010)

e13050 Background: Crosstalk between the Met and vascular endothelial growth factor (VEGF) pathways may be important during tumorigenesis. Aberrant activation of the HGF/Met pathway may promote angiogenesis via tumor cell secretion of angiogenic factors or directly activating endothelial cells. The combination of Met and VEGF inhibition resulted in enhanced antitumor activity in multiple preclinical models than either treatment alone. MetMAb is a recombinant, humanized, monovalent (one-armed) monoclonal antibody antagonist of HGF-induced Met signaling. In phase Ia, MetMAb was generally well tolerated up to 30 mg/kg IV Q3W. Herein, we describe results from a phase Ib study in which we tested MetMAb in combination with bevacizumab. Methods: The phase Ib trial tested the combination of MetMAb with bevacizumab in two cohorts: 3 patients in cohort 1 received MetMAb, 10 mg/kg, and bevacizumab, 15 mg/kg, IV Q3W; and 6 patients in cohort 2 received MetMAb,15 mg/kg, and bevacizumab,15 mg/kg IV Q3W. Pre- and post-dose sera were collected for evaluation of pharmacodynamic (PD) biomarkers that could be affected by inhibition of Met and/or VEGF signaling. Results: The combination of MetMAb with bevacizumab was generally well tolerated at all doses tested. No Gr3-5 drug- related toxicities were observed. One DLT of Gr1 hemoptysis in cohort 2 was observed in a patient who had central-necrosis of pulmonary metastases. Gr2 drug-related toxicities included peripheral edema and hypoalbuminemia. The most frequently observed toxicities (>30 %) included fatigue and increased weight. The best response was stable disease, with 3 patients receiving ≥ 6 cycles. PD biomarker data will be discussed. MetMAb PK was similar to that from phase Ia and no apparent interaction with bevacizumab was observed. Conclusions: This phase Ib trial demonstrated that the combination of MetMAb and bevacizumab is generally safe and well tolerated at the recommended dose of 15mg/kg Q3W for each agent. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech
CellMiner: a relational database and query tool for the NCI-60 cancer cell lines (2009)

CellMiner is a relational database tool for storing, querying, integrating, and downloading molecular profile data on the NCI-60 and other cancer cell types. More broadly, it provides a template to use in providing such functionality for other molecular profile data generated by academic institutions, public projects, or the private sector. CellMiner is available online at (http://discover.nci.nih.gov/cellminer/).
Murine model of food allergy after epicutaneous sensitization: Role of mucosal mast cell protease-1 (2006)

A murine model of food allergy based on sensitization via epicutaneous exposure to allergen without immunostimulatory adjuvants was developed. Effective production of MMCP-1 together with specific IgE and IgG1 suggests a breakdown in oral tolerance to the allergen. Intragastric challenges were accompanied by mast cell-dependent immunopathological changes and diarrhea.
Using the Augmented Data Manipulator Network in PASM (1981)

The ADM network, with its multiple paths between given inputs and outputs, could bring fast, cost-effective communications to PASM and other distributed/parallel systems.
Performance Portable Optimizations for Loops Containing Communication Operations (2007)

As high end computing systems continue to scale in CPU computational power and overall node count, optimization techniques that can reduce communication overhead have proven important. We present a loop optimization framework designed to achieve both efficient communication/computation overlap and performance portability. The framework has been implemented in the Berkeley UPC compiler and uses a combination of compile time analysis and runtime mechanisms. We extend the compiler to perform message vectorization and message strip mining optimizations. At compile time loop nests are analyzed, their communication requirements are determined, and the computation overhead is estimated. The compiler passes analysis information to the runtime and performance portability is achieved by decoupling data movement from local computation. We generate template code that uses the transferred data without making any assumptions about the communication mechanism.
Macrophage colony‐stimulating factor gene transfer into tumor cells induces macrophage infiltration but not tumor suppression (1993)

In order to analyze the effect of a high local concentration of macrophage colony-stimulating factor (M-CSF; CSF-1) on tumor growth, the plasmacytoma cell line J558L was transfected with the human M-CSF gene and injected into syngeneic BALB/c mice. In contrast to the parental tumors, M-CSF transfectants were heavily infiltrated by macrophages as evidenced by immunohistochemistry with antibodies to Mac-1 and Mac-3 and by isolation of the macrophages from the tumor. Nevertheless, tumor growth was only slightly affected by M-CSF and M-CSF-producing cells grew as tumor in all cases. The growth retardation of M-CSF-producing cells varied depending on the experiment and seemed to be due to an indirect effect because the growth rate of the cells in vitro had not changed upon gene transfer. Attempts to activate the tumor-infiltrating macrophages for tumor suppression by systemic application of interferon-gamma and/or lipopolysaccharide were not successful. Altogether, our results suggest that M-CSF is a potent chemoattractant for macrophages in vivo but alone is not sufficient to activate these macrophages for tumoricidal activity.
A Magnetically Sprung Generator for Energy Harvesting Applications (2012)

The use of vibration energy harvesting systems for supplying energy to wireless sensor nodes is becoming increasingly popular. This paper presents a magnetically sprung vibration energy harvester that has a broadband response and is tunable. The system comprises three annular magnets longitudinally arranged along a shaft, resulting in a nonlinear hardening suspension and consequential “jump” phenomenon characteristic. This paper presents and validates a toolbox that can be used to develop such systems using a time step model and prototype. It comprises accurate models of the magnetic suspension force and electromagnetic coupling coefficient, which links the mechanical and electrical domains. The system is compared with those in the literature using power density and effectiveness metrics. The nonoptimized prototype has an average power density of 600 W·m <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-3</sup> and is comparable to those in the literature.
The action of gastric juice on beef muscle-globulin, with reference to anaemia (1934)

PERNICIOUs anaemia results from a failure of the supply of healthy red cells to the circulating blood. No way was known of restoring this lost power of regeneration of healthy red cells until Minot and Murphy [1926] observed that by feeding liver to persons suffering from this type of anaemia increased numbers of reticulocytes, or young red blood cells, appeared in the circulation, with the result that the blood was gradually restored to its normal condition.
A General Nickel-Catalyzed Hydroamination of 1,3-Dienes by Alkylamines:  Catalyst Selection, Scope, and Mechanism (2002)

A simple colorimetric assay of various transition-metal catalysts showed that the combination of DPPF, Ni(COD)(2), and acid is a highly active catalyst system for the hydroamination of dienes by alkylamines to form allylic amines. The scope of the reaction is broad; various primary and secondary alkylamines react with 1,3-dienes in the presence of these catalysts. Detailed mechanistic studies revealed the individual steps involved in the catalytic process. These studies uncovered unexpected thermodynamics for the addition of amines to pi-allyl nickel complexes: instead of the thermodynamics favoring the reaction of a nickel allyl with an amine to form an allylic amine, the thermodynamics favored reaction of a nickel(0) complex with allylic amine in the presence of acid to form a Ni(II) allyl. The realization of these thermodynamics led us to the discovery that nickel and some palladium complexes in the presence or absence of acid catalyze the exchange of the amino groups of allylic amines with free amines. This exchange process was used to reveal the relative thermodynamic stabilities of various allylic amines. In addition, this exchange reaction leads to racemization of allylic amines. Therefore, the relative rate for C-N bond formation and cleavage influences the enantioselectivity of diene hydroaminations.
Synthesis, Decomposition Pathways and "In Vitro" Evaluation of Bioreversible Phosphotriesters of Azt (1995)

Abstract The synthesis, pharmacokinetic data and biological evaluation of a series of phosphotriesters containing S-acyl-2-thioethyl groups as enzyme-labile phosphate protecting groups and AZT as a model are described. A comparison of pharmacokinetic data and “in vitro” experiments show that such bioreversible phosphotriesters of AZT are able to cross cell membranes and deliver the corresponding nucleoside monophosphate inside the cell. Moreover, kinetic data show that modification of the protecting groups can allow to modulate both the extracellular stability of the parent compond and the delivery of nucleoside monophosphate inside the cell.
Depth determination of chromophores in human skin by pulsed photothermal radiometry (1996)

We report on the application of pulsed photothermal radiometry (PPTR) to determine the depth of in-vitro and in-vivo subsurface chromophores in biological materials. Measurements provided by PPTR in combination with a nonnegative constrained conjugate-gradient algorithm are used to determine the initial temperature distribution in a biological material immediately following pulsed laser irradiation. Within the experimental error, chromophore depths (50–450 μm) in 55 in-vitro collagen phantoms determined by PPTR and optical low-coherence reflectometry are equivalent. The depths of port-wine-stain blood vessels determined by PPTR correlate very well with their locations found by computer-assisted microscopic observation of histologic sections. The mean blood-vessel depth deduced from PPTR and histologic observation is statistically indistinguishable (p &gt; 0.94).
The physics of three-dimensional radiation therapy : conformal radiotherapy, radiosurgery, and treatment planning (2001)

3D radiation therapy treatment planning: Planning tools. Computer systems. Beams. Image registration. Structures from images. Dose calculation. Biological response. Treatment plan optimization: Inverse CT. Convolution dosimetry. Analytic and iterative deconvolution theory. Stereotactic radiosurgery and radiotherapy. The physics of proton radiotherapy. Conformal radiotherapy with a multileaf collimator. Megavoltage portal imaging. Treatment machine features. Imaging for conformal radiotherapy planning: X-ray CT. MRI. SPECT. PET. CT simulators. Epilogue. Appendices: Numerical questions. Glossary. Important historical developments for contextual framing of conformal radiotherapy. Index.
Realizing Majorana zero modes in superconductor-semiconductor heterostructures (2017)

Realizing topological superconductivity and Majorana zero modes in the laboratory is one of the major goals in condensed matter physics. We review the current status of this rapidly-developing field, focusing on semiconductor-superconductor proposals for topological superconductivity. Material science progress and robust signatures of Majorana zero modes in recent experiments are discussed. After a brief introduction to the subject, we outline several next-generation experiments probing exotic properties of Majorana zero modes, including fusion rules and non-Abelian exchange statistics. Finally, we discuss prospects for implementing Majorana-based topological quantum computation in these systems.