gebhart/patrepeval huggingface dataset:
Evidence for a gene influencing the TG/HDL-C ratio on chromosome 7q32.3-qter: a genome-wide scan in the Framingham Study (2000)

Some studies show that plasma triglyceride (TG) levels are a significant independent risk factor for cardiovascular disease (CVD). TG levels are inversely correlated with high density lipoprotein cholesterol (HDL-C) levels, and their metabolism may be closely interrelated. Therefore, the TG/HDL-C ratio may be a relevant CVD risk factor. Our analysis of families in the Framingham Heart Study gave a genetic heritability estimate for log(TG) of 0.40 and for log(TG/HDL-C) of 0.49, demonstrating an important genetic component for both. A 10 cM genome-wide scan for log(TG) level and log(TG/HDL-C) was carried out for the largest 332 extended families of the Framingham Heart Study (1702 genotyped individuals). The highest multipoint variance component LOD scores obtained for both log(TG) and log(TG/HDL-C) were on chromosome 7 (at 155 cM), where the results for the two phenotypes were 1.8 and 2.5, respectively. The 7q32.3-qter region contains several candidate genes. Four other regions with multipoint LOD scores greater than one were identified on chromosome 3 [LOD score for log(TG/HDL-C) = 1.8 at 140 cM], chromosome 11 [LOD score for log(TG/HDL-C) = 1.1 at 125 cM], chromosome 16 [LOD score for log(TG) = 1.5 at 70 cM, LOD score for log(TG/HDL-C) = 1.1 at 75 cM] and chromosome 20 [LOD score for log(TG/HDL-C) = 1.7 at 35 cM, LOD score for log(TG) = 1.3 at 40 cM]. These results identify loci worthy of further study.
Programming floating-gate circuits with UV-activated conductances (2001)

A programming technique for controlling the floating gates (FGs) in ultra-low-voltage (ULV) floating-gate circuits is presented. Simple ULV PG current-scaling and level-shifting circuits are discussed. The current scaling and level shifting are accomplished using only minimum sized transistors and floating capacitors. Floating-gate current multiplier and divider circuits are described. Measured results are provided,.
The c-fms gene complements the mitogenic defect in mast cells derived from mutant W mice but not mi (microphthalmia) mice. (1991)

Mutations at three loci in the mouse--W, Steel Sl), and microphthalmia (mi)--can lead to a deficiency in melanocytes and mast cells. As well, W and Sl mutants can be anemic and sterile, whereas mi mice are osteopetrotic due to a monocyte/macrophage defect. Recent data have shown that the c-kit receptor tyrosine kinase is the gene product of the W locus, whereas Sl encodes the ligand for this growth factor receptor. We show here that ectopic expression of c-fms, a gene that encodes a macrophage growth factor receptor that is closely related to the c-kit receptor, complements mutations at the W locus in an in vitro mast cell/fibroblast coculture system but is unable to reverse the inability of mi/mi mast cells to survive under these conditions. Furthermore, mast cells expressing the c-fms receptor survive on a monolayer of fibroblasts homozygous for the Sl mutation. These results suggest that ligand binding to the c-kit or c-fms receptor activates identical or overlapping signal transduction pathways. Furthermore, they suggest that mi encodes a protein necessary for transducing signals mediated by way of either the c-kit or c-fms receptor.
Evaluating therapeutic vaccines in patients infected with HIV (2004)

Long-term survival of HIV infection can mean decades of treatment for a patient, with major side effects and costs that limit their efficacy and accessibility. Although antiretroviral therapy remains the only standard of care, alternative therapeutic strategies must be found to ensure efficient and safe clinical management of the disease in the long term. Therapeutic immunization against HIV might be a significant approach to enhancing immune control of the virus and limiting disease progression and thus the requirement for medication. Several anti-HIV vaccines are currently being evaluated in attempts to prolong periods of treatment interruption in HIV patients. The design and end-points of clinical trials, and the clinical settings in which these new strategies should be evaluated and will be of benefit, have yet to be defined and are the focus of this review.
A Superfamily of Voltage-gated Sodium Channels in Bacteria (2004)

NaChBac, a six-alpha-helical transmembrane-spanning protein cloned from Bacillus halodurans, is the first functionally characterized bacterial voltage-gated Na(+)-selective channel. As a highly expressing ion channel protein, NaChBac is an ideal candidate for high resolution structural determination and structure-function studies. The biological role of NaChBac, however, is still unknown. In this report, another 11 structurally related bacterial proteins are described. Two of these functionally expressed as voltage-dependent Na(+) channels (Na(V)PZ from Paracoccus zeaxanthinifaciens and Na(V)SP from Silicibacter pomeroyi). Na(V)PZ and Na(V)SP share approximately 40% amino acid sequence identity with NaChBac. When expressed in mammalian cell lines, both Na(V)PZ and Na(V)SP were Na(+)-selective and voltage-dependent. However, their kinetics and voltage dependence differ significantly. These single six-alpha-helical transmembrane-spanning subunits constitute a widely distributed superfamily (Na(V)Bac) of channels in bacteria, implying a fundamental prokaryotic function. The degree of sequence homology (22-54%) is optimal for future comparisons of Na(V)Bac structure and function of similarity and dissimilarity among Na(V)Bac proteins. Thus, the Na(V)Bac superfamily is fertile ground for crystallographic, electrophysiological, and microbiological studies.
Efficient search, mapping, and optimization of multi‐protein genetic systems in diverse bacteria (2014)

Developing predictive models of multi-protein genetic systems to understand and optimize their behavior remains a combinatorial challenge, particularly when measurement throughput is limited. We developed a computational approach to build predictive models and identify optimal sequences and expression levels, while circumventing combinatorial explosion. Maximally informative genetic system variants were first designed by the RBS Library Calculator, an algorithm to design sequences for efficiently searching a multi-protein expression space across a > 10,000-fold range with tailored search parameters and well-predicted translation rates. We validated the algorithm's predictions by characterizing 646 genetic system variants, encoded in plasmids and genomes, expressed in six gram-positive and gram-negative bacterial hosts. We then combined the search algorithm with system-level kinetic modeling, requiring the construction and characterization of 73 variants to build a sequence-expression-activity map (SEAMAP) for a biosynthesis pathway. Using model predictions, we designed and characterized 47 additional pathway variants to navigate its activity space, find optimal expression regions with desired activity response curves, and relieve rate-limiting steps in metabolism. Creating sequence-expression-activity maps accelerates the optimization of many protein systems and allows previous measurements to quantitatively inform future designs.
Hydrolysis of corn oil using subcritical water (2006)

This work presents the results of a study on the use of subcritical water as both solvent and reactant for the hydrolysis of corn oil without the use of acids or alkalis at temperatures of 150-280 °C. Corn oil hydrolysis leads to the formation of its respective fatty acids with the same efficiency of conventional methods. Fatty acids form an important group of products, which are used in a range of applications. The confirmation and identification of the hydrolysis products was done by HT-HRGC-FID and HRGC/MS.
Hepatitis E Virus Transmission from Wild Boar Meat (2005)

We investigated a case of hepatitis E acquired after persons ate wild boar meat. Genotype 3 hepatitis E virus (HEV) RNA was detected in both patient serum and wild boar meat. These findings provided direct evidence of zoonotic foodborne transmission of HEV from a wild boar to a human.
Melanoma patients immunized with melanoma cell vaccine induce antibody responses to recombinant MAGE-1 antigen. (1995)

Abstract The MAGE-1 gene was recently characterized to encode an immunogenic tumor Ag on several types of human tumors, including melanoma. This Ag is expressed in a wide variety of human tumors and not in normal cells, except testicular tissue, as assessed through specific mRNA analysis. In this study we cloned the MAGE-1 gene exon 3 region from a colon carcinoma cell line and expressed it in Escherichia coli. The recombinant MAGE-1 protein was affinity purified. By using Western blot analysis, IgG and IgM anti-MAGE-1 Abs were detected in the sera of melanoma patients. Fifty-three patients immunized with a melanoma cell vaccine (MCV) were assessed for anti-MAGE-1 IgG responses by using a MAGE-1 Ag-specific ELISA. The MCV consisted of three melanoma cell lines that expressed MAGE-1. Comparisons of anti-MAGE-1 IgG response pre-MCV treatment with 12- to 16-wk post-MCV treatment were made. Fifty-seven percent of the patients immunized with the MCV showed significant enhancement of IgG response to recombinant MAGE-1 protein. Patients who responded had no particular HLA-A or -B allele expression pattern. Melanoma patients immunized with whole cell MCV containing MAGE-1 can enhance anti-MAGE-1 IgG Abs. Recombinant MAGE-1 protein can be used to assess patient response to MAGE-1 and will be investigated as a potential cancer vaccine against a wide variety of human tumors that express MAGE-1.
Laser‐Assisted Vas Anastomosis: A Preliminary Report (1983)

A new technique is described for performing vas anastomoses in experimental animal (rats). A low-power CO2 laser appears to be effective in welding together the cut ends of the divided vas deferens.
Estrogen replacement therapy mitigates the loss of joint cartilage proteoglycans and bone mineral density induced by ovariectomy and osteoarthritis (2003)

Abstract Aims: To investigate the effects of ovariectomy and estrogen replacement therapy (ERT) on the structural integrity and proteoglycan (PG) content of articular cartilage (AC) and bone mineral density (BMD) in an ovine model of osteoarthritis (OA) induced by meniscectomy. Method: Thirty aged ewes were used for the study. Six had ovariectomy alone (OVX), 6 meniscectomy alone (OA) and 12 ovariectomy and meniscectomy (OVX + OA). Six of the (OVX + OA) sheep received Femtran‐50 (3M) estrogen (50 µg/day) patches (OVX + OA + ERT). Six animals were used as non‐operated controls (NOC). Three months post‐surgery all animals were sacrificed, the stifle joints dissected through the site of lesions, and coronal sections of the lateral femoral condyle (LFC) and lateral tibial plateau (LTP) were cut which were each subdivided into inner (I), middle (M) and outer (O) zones. Toluidine blue stained sections were examined using a modified Mankin scoring system, and AC–PG content determined via computer image analysis. Results: There were no significant differences between lesion scores among the OA, OVX + OA and OVX + OA + ERT groups, yet all had significantly higher scores than NOC and OVX in each region ( P &lt; 0.005). Computer image analysis of PG content in stained sections showed no difference between OVX and NOC. However, in LFC‐AC the loss of PG was highest in the OVX + OA group ( P &lt; 0.005) compared to the NOC or OVX groups. The bone mineral density (BMD) of the LFC averaged for all zones was higher in the OVX + OA + ERT group than the OVX + OA group ( P &lt; 0.02) with the most significant rise being in the I‐zone ( P &lt; 0.002). Significantly in this same zone of the OVX + OA + ERT group the AC‐PG content was higher than in the corresponding zone of the OVX + OA group ( P &lt; 0.05). Conclusions: While ERT did not reduce the focal AC lesions scores in the lateral compartment of this OA model it did mitigate the loss of PG from adjacent joint cartilage and increase the bone mineral density (BMD), especially in the I‐zone. These findings are consistent with epidemiological studies which suggest that ERT may slow the progression of OA in postmenopausal women.
Binding of Rituximab, Trastuzumab, Cetuximab, or mAb T101 to Cancer Cells Promotes Trogocytosis Mediated by THP-1 Cells and Monocytes (2008)

More than 20 years ago clinical investigations in the immunotherapy of cancer revealed that infusion of certain immunotherapeutic mAbs directed to tumor cells induced loss of targeted epitopes. This phenomenon, called antigenic modulation, can compromise mAb-based therapies. Recently we reported that rituximab (RTX) treatment of chronic lymphocytic leukemia patients induced substantial loss of targeted CD20 on B cells found in the circulation after RTX infusion; this "shaving" of RTX-CD20 complexes from B cells is also promoted in vitro by THP-1 monocytes and by PBMC in a reaction mediated by Fcgamma receptors. The mechanism responsible for shaving appears to be trogocytosis, a process in which receptors on effector cells remove and internalize cognate ligands and cell membrane fragments from target cells. We now report that three therapeutic mAbs approved by the U.S. Food and Drug Administration for the treatment of cancer, RTX, cetuximab, and trastuzumab, as well as mAb T101, which has been shown to induce antigenic modulation in the clinic, promote trogocytosis in vitro upon binding to their respective target cells. Trogocytosis of the mAb-opsonized cells is mediated by THP-1 monocytes and by primary monocytes isolated from PBMC. In view of these results, it is likely that these mAbs and possibly other anticancer mAbs now used in the clinic may promote trogocytic removal of the therapeutic mAbs and their cognate Ags from tumor cells in vivo. Our findings may have important implications with respect to the use of mAbs in cancer immunotherapy.
CD137 costimulatory T cell receptor engagement reverses acute disease in lupus-prone NZB × NZW F1 mice (2003)

Systemic lupus erythematosus (SLE) is a CD4+ T cell–dependent, immune complex–mediated, autoimmune disease that primarily affects women of childbearing age. Generation of high-titer affinity-matured IgG autoantibodies, specific for double-stranded DNA and other nuclear antigens, coincides with disease progression. Current forms of treatment of SLE including glucocorticosteroids are often inadequate and induce severe side effects. Immunological approaches for treating SLE in mice using anti-CD4 mAb's or CTLA4-Ig and anti-CD154 mAb's have proven to be effective. However, like steroid treatment, these regimens induce global immunosuppression, and their withdrawal allows for disease progression. In this report we show that lupus-prone NZB × NZW F1 mice given three injections of anti-CD137 (4-1BB) mAb's between 26 and 35 weeks of age reversed acute disease, blocked chronic disease, and extended the mice's lifespan from 10 months to more than 2 years. Autoantibody production in recipients was rapidly suppressed without inducing immunosuppression. Successful treatment could be traced to the fact that NZB × NZW F1 mice, regardless of their age or disease status, could not maintain pathogenic IgG autoantibody production in the absence of continuous CD4+ T cell help. Our data support the hypothesis that CD137-mediated signaling anergized CD4+ T cells during priming at the DC interface.
Dynamic changes in the human methylome during differentiation (2010)

DNA methylation is a critical epigenetic regulator in mammalian development. Here, we present a whole-genome comparative view of DNA methylation using bisulfite sequencing of three cultured cell types representing progressive stages of differentiation: human embryonic stem cells (hESCs), a fibroblastic differentiated derivative of the hESCs, and neonatal fibroblasts. As a reference, we compared our maps with a methylome map of a fully differentiated adult cell type, mature peripheral blood mononuclear cells (monocytes). We observed many notable common and cell-type-specific features among all cell types. Promoter hypomethylation (both CG and CA) and higher levels of gene body methylation were positively correlated with transcription in all cell types. Exons were more highly methylated than introns, and sharp transitions of methylation occurred at exon-intron boundaries, suggesting a role for differential methylation in transcript splicing. Developmental stage was reflected in both the level of global methylation and extent of non-CpG methylation, with hESC highest, fibroblasts intermediate, and monocytes lowest. Differentiation-associated differential methylation profiles were observed for developmentally regulated genes, including the HOX clusters, other homeobox transcription factors, and pluripotence-associated genes such as POU5F1, TCF3, and KLF4. Our results highlight the value of high-resolution methylation maps, in conjunction with other systems-level analyses, for investigation of previously undetectable developmental regulatory mechanisms.
Rituximab-CHOP Versus CHOP Alone or With Maintenance Rituximab in Older Patients With Diffuse Large B-Cell Lymphoma (2006)

Rituximab administered as induction or maintenance with CHOP chemotherapy significantly prolonged FFS in older DLBCL patients. After R-CHOP, no benefit was provided by MR. These results, which are consistent with an additive effect of rituximab, suggest that future studies could focus on maintenance strategies with novel agents as well as new induction therapies.
Automatic construction of 3-D statistical deformation models of the brain using nonrigid registration (2003)

In this paper, we show how the concept of statistical deformation models (SDMs) can be used for the construction of average models of the anatomy and their variability. SDMs are built by performing a statistical analysis of the deformations required to map anatomical features in one subject into the corresponding features in another subject. The concept of SDMs is similar to statistical shape models (SSMs) which capture statistical information about shapes across a population, but offers several advantages over SSMs. First, SDMs can be constructed directly from images such as three-dimensional (3-D) magnetic resonance (MR) or computer tomography volumes without the need for segmentation which is usually a prerequisite for the construction of SSMs. Instead, a nonrigid registration algorithm based on free-form deformations and normalized mutual information is used to compute the deformations required to establish dense correspondences between the reference subject and the subjects in the population class under investigation. Second, SDMs allow the construction of an atlas of the average anatomy as well as its variability across a population of subjects. Finally, SDMs take the 3-D nature of the underlying anatomy into account by analysing dense 3-D deformation fields rather than only information about the surface shape of anatomical structures. We show results for the construction of anatomical models of the brain from the MR images of 25 different subjects. The correspondences obtained by the nonrigid registration are evaluated using anatomical landmark locations and show an average error of 1.40 mm at these anatomical landmark positions. We also demonstrate that SDMs can be constructed so as to minimize the bias toward the chosen reference subject.
Intensive versus Conventional Glucose Control in Critically Ill Patients (2009)

In this large, international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose target of 180 mg or less per deciliter resulted in lower mortality than did a target of 81 to 108 mg per deciliter. (ClinicalTrials.gov number, NCT00220987.)
Preventing congestive heart failure. (1998)

The morbidity, mortality and health care costs associated with congestive heart failure make prevention a more attractive public health strategy than treatment. Aggressive management of etiologic factors, including hypertension, coronary artery disease, valvular disease and excessive alcohol intake, can prevent the left ventricular remodeling and dysfunction that lead to heart failure. Early intervention with angiotensin converting enzyme inhibitors in patients with chronic left ventricular dysfunction can prevent, as well as treat, the syndrome. Several intervention strategies in patients with acute myocardial infarction can slow or prevent the left ventricular remodeling process that antedates congestive heart failure. The primary care physician must be alert to the need for aggressive intervention to reduce the burden of heart failure syndrome on the patient and on society.
Unusual vertebral artery origins: Examples and related pathology (2003)

Anomalies of the vertebral arteries are uncommon, but important to recognize in the diagnosis and catheter based evaluation and treatment of patients suffering cerebrovascular disease. This article illustrates our experience with such anomalies. These include the vertebral artery arising as the fourth and most distal branch of the aortic arch, as a right subclavian artery branch arising distal to the right thyrocervical trunk, as a right common carotid artery branch in a patient with an aberrant right subclavian artery, and a case of left vertebral artery proximal duplication, with both aortic and left subclavian vertebral arteries present in the same patient; the latter join to form a single distal cervical vertebral artery.
Pulsed-Laser Testing for Single-Event Effects Investigations (2013)

The application of pulsed lasers to the study of Single-Event Effects (SEEs) in integrated circuits and devices is described. The role of a pulsed laser is to provide spatial and temporal information about SEEs, information that is not available when broad-beam ion sources are used. A detailed description is given of the mechanisms involved, including light propagation and absorption by both linear and non-linear processes. Numerous examples highlight the versatility and usefulness of the technique in the study of SEEs.
Mechanical properties of nanotube sheets: Alterations in joint morphology and achievable moduli in manufacturable materials (2004)

Nanotube sheets, or “bucky papers,” have been proposed for use in actuating, structural and electrochemical systems, based in part on their potential mechanical properties. Here, we present results of detailed simulations of networks of nanotubes/ropes, with special emphasis on the effect of joint morphology. We perform detailed simulations of three-dimensional joint deformation, and use the results to inform simulations of two-dimensional (2D) networks with intertube connections represented by torsion springs. Upper bounds are established on moduli of nanotube sheets, using the 2D Euler beam-network simulations. Comparisons of experimental and simulated response for HiPco-nanotube and laser-ablated nanotube sheets, indicate that ∼2–30-fold increases in moduli may be achievable in these materials. Increasing the numbers of interrope connections appears to be the best target for improving nanotube sheet stiffnesses in materials containing straight segments.
Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock* (2006)

Effective antimicrobial administration within the first hour of documented hypotension was associated with increased survival to hospital discharge in adult patients with septic shock. Despite a progressive increase in mortality rate with increasing delays, only 50% of septic shock patients received effective antimicrobial therapy within 6 hrs of documented hypotension.