gebhart/patrepeval huggingface dataset:
Suppressed intrinsic catalytic activity of GLUT1 glucose transporters in insulin-sensitive 3T3-L1 adipocytes. (1991)

Previous studies indicated that the erythroidtype (GLUT1) glucose transporter isoform contributes to basal but not insulin-stimulated hexose transport in mouse 3T3-L1 adipocytes. In the present studies it was found that basal hexose uptake in 3T3-L1 adipocytes was about 50% lower than that in 3T3-L1 or CHO-K1 fibroblasts. Intrinsic catalytic activities of GLUT1 transporters in CHO-K1 and 3T3-L1 cells were compared by normalizing these hexose transport rates to GLUT1 content on the cell surface, as measured by two independent methods. Cell surface GLUT1 levels in 3T3-L1 fibroblasts and adipocytes were about 10- and 25-fold higher, respectively, than in CHO-K1 fibroblasts, as assessed with an anti-GLUT1 exofacial domain antiserum, delta. The large excess of cell surface GLUT1 transporters in 3T3-L1 adipocytes relative to CHO-K1 fibroblasts was confirmed by GLUT1 protein immunoblot analysis and by photoaffinity labelling (with 3-[125I]iodo-4-azidophenethylamido-7-O-succinyldeacetylforskoli n) of glucose transporters in isolated plasma membranes. Thus, GLUT1 intrinsic activity is markedly reduced in 3T3-L1 fibroblasts compared with the CHO-K1 fibroblasts, and further reduction occurs upon differentiation to adipocytes. Intrinsic catalytic activities specifically associated with heterologously expressed human GLUT1 protein in transfected CHO-K1 versus 3T3-L1 cells were determined by subtracting appropriate control cell values for hexose transport and delta-antibody binding from those determined in the transfected cells expressing high levels of human GLUT1. The results confirmed a greater than 90% inhibition of the intrinsic catalytic activity of human GLUT1 transporters on the surface of mouse 3T3-L1 adipocytes relative to CHO-K1 fibroblasts. We conclude that a mechanism that markedly suppresses basal hexose transport catalyzed by GLUT1 is a major contributor to the dramatic insulin sensitivity of glucose uptake in 3T3-L1 adipocytes.
Emerging applications of kinetic biomarkers in preclinical and clinical drug development. (2005)

The cost of drug discovery and development is increasing, while the rate of new drug approvals is declining. In contrast to major technological advances with in silico and in vitro screening tools, there have been almost no advances in the tools available for establishing the actions of agents in the complex biochemical networks characteristic of fully assembled living systems. The resulting poor capacity to predict clinical response underlies the high attrition rate of leads at every step of drug development. A potential solution would be provided by kinetic biomarkers (in vivo measurement of fluxes though the key pathways that drive disease processes and therapeutic response). Novel approaches using stable isotope labeling with mass spectrometric analysis have recently emerged for measuring molecular kinetics relevant to drug targets with some applications to drug development. This review discusses the general principles of kinetic biomarkers, providing examples where kinetics have generated meaningful insights into drug activity and highlighting areas where the application of kinetic biomarkers may be particularly useful for future drug discovery and development. Stable isotope mass spectrometric technologies may provide a parallel efficiency for converting molecules into approved drugs with sufficient throughput and reproducibility to maintain pace with the modern engine for generating leads.
The macrophage in MS: just a scavenger after all? Pathology and pathogenesis of the acute MS lesion (2006)

Advances in the neuropathology of multiple sclerosis (MS) have contributed greatly to our understanding of the mechanisms of tissue injury in the condition. Particular interest has focussed on the active MS lesion, defined by macrophage activity in the presence of partially demyelinated axons. This has led to the prevailing consensus that a T-cell dependent, macrophage-mediated, autoimmune attack on constituents in the normal myelin sheath underlies the disease. This hypothesis, which has been largely supported by comparisons with the animal model, experimental allergic encephalomyelitis, has recently been questioned by an analysis of the pathological events preceding myelin phagocytosis in nascent MS lesions. The prephagocytic changes in evolving lesions examined shortly after the onset of an MS relapse raise the possibility that oligodendrocyte cell death and associated changes within the myelin sheath initiate local macrophage scavenger activity, with subsequent amplification of the inflammatory response. The presence of such lesions in patients with a spectrum of pathological changes in nearby or distant active phagocytic plaques suggests that pathological heterogeneity in MS is largely due to evolution of lesional pathology, rather than pathogenic heterogeneity.
CD28 Controls Differentiation of Regulatory T Cells from Naive CD4 T Cells (2008)

CD28 is required for the development of regulatory T cells (Tregs; CD4(+)CD25(+)Foxp3(+)) in the thymus and also contributes to their survival and homeostasis in the periphery. We studied whether and how CD28 and ICOS control the differentiation of Tregs from naive T cells. By using wild-type, CD28-, ICOS-, or CD28/ICOS-double knockout mice on C57BL/6 background as T cell sources, we found that CD28 is essential, whereas ICOS is dispensable, for the development and homeostasis of Tregs. Furthermore, the differentiation of Tregs from naive CD4(+)CD25(-) T cells in vivo also depends on CD28. The requirement of CD28 for Treg differentiation was mediated by IL-2, because neutralization of IL-2 with its specific mAb-blocked Treg differentiation from wild-type CD4(+)CD25(-) T cells and addition of IL-2 restored Treg differentiation from CD28(-/-) T cells. Other common gamma-chain cytokines, IL-4, IL-7, or IL-15, do not share such a role with IL-2. Although CD28 is required for the differentiation of Tregs from naive T cells, already generated Tregs do not depend on CD28 to exert their suppressive function. Our study reveals a new aspect of CD28 function in regulating T cell response.
Statistical predicate invention (2007)

We propose statistical predicate invention as a key problem for statistical relational learning. SPI is the problem of discovering new concepts, properties and relations in structured data, and generalizes hidden variable discovery in statistical models and predicate invention in ILP. We propose an initial model for SPI based on second-order Markov logic, in which predicates as well as arguments can be variables, and the domain of discourse is not fully known in advance. Our approach iteratively refines clusters of symbols based on the clusters of symbols they appear in atoms with (e.g., it clusters relations by the clusters of the objects they relate). Since different clusterings are better for predicting different subsets of the atoms, we allow multiple cross-cutting clusterings. We show that this approach outperforms Markov logic structure learning and the recently introduced infinite relational model on a number of relational datasets.
Role of the intracellular domains of LRP5 and LRP6 in activating the Wnt canonical pathway (2005)

LDL-receptor related proteins 5 and 6 (LRP5/6) are co-receptors of Frizzled receptors that mediate Wnt-induced activation of the transcription factor family TCF/LEF-1. Even though LRP5 and LRP6 are highly homologous, LRP6, but not LRP5, is expressed primarily in the nervous system and deletion of the LRP6 gene results in significant brain abnormalities, while deletion of LRP5 results in primarily decreased bone density. Additionally, the exact function of LRP5 and LRP6 have not been clearly defined, although it is clear that they both play key roles in the Wnt canonical pathway. In this study the role of the intracellular domains of LRP5/6 in mediating Wnt signaling was examined. In the absence of exogenous Wnt 3a, full-length (FL) LRP6, but not LRP5, increased TCF/LEF-1 transcriptional activity, however both significantly potentiated Wnt 3a-induced TCF/LEF-1 activation. In contrast to the findings with the FL constructs, the intracellular domains (membrane-anchored and cytosolic) of both LRP5 and LRP6 significantly increased TCF/LEF-1 activation in the absence of Wnt 3a, and potentiated the Wnt 3a-induced decrease in beta-catenin phosphorylation, increase in free beta-catenin levels and the increase in TCF/LEF-1 activity. These findings demonstrate that: (1) LRP5 and LRP6 differentially modulate TCF/LEF-1 activation in the absence of Wnt 3a and (2) the intracellular C-terminal domains of LRP5/6 potentiate Wnt 3a-induced TCF/LEF-1 activation whether or not they are membrane-anchored. These findings provide significant new insights into the roles of LRP5/6 in modulating canonical Wnt signaling.
Comproportionation versus Disproportionation in the Initiation Step of Cu(0)-Mediated Living Radical Polymerization (2012)

We present a study of the initiation step in copper(0)-mediated atom transfer radical polymerization (also known as SET-LRP or SARA ATRP), in which a nitroxide free radical, N-tert-butyl-N-[1-diethylphosphono-(2,2-dimethylpropyl)] nitroxide (SG1), is used to trap radicals derived from ethyl 2-bromoisobutyrate (EBiB), copper metal and pentamethyl diethylene triamine (PMDETA) ligand. A kinetic model was developed relating the rate of conversion of EBiB to the rate constants of activation by copper metal (ka0) and comproportionation of Cu0 and CuII (kcomp). This allowed the determination of these parameters in several solvents, including dimethyl sulfoxide (DMSO), dimethylformamide (DMF), ethanol (EtOH), and acetonitrile (MeCN), in which significant levels of comproportionation were observed, leading to autoacceleration of the reaction. A similar treatment of copper-mediated polymerization kinetics predicts 1/2 order dependence on initiator concentration and copper surface area, in accordance with previously published experimental data.
Improved fractal geometry based texture segmentation technique (1993)

The problem of natural texture segmentation is considered. The technique is based on four texture features derived using the fractal geometry of images. These four features are fractal dimension (FD) of the original image, FD of above average (high) gray level image, FD of below (low) gray level image, and multifractal of order two. A modified box-counting approach is proposed to estimate the FD and computed features all are normalised in the same range [0, 1]. A feature domain smoothing is activated to reduce the spurious segmentation. Next, a nonsupervised clustering approach is used to segment a scene into the desired number of classes. Some supervised techniques like minimum distance classifier and k-nearest neighbour classifier are also considered. Mosaics of various natural textures are generated and the segmentation results are presented to show the efficiency of the technique.
Metal-catalyzed direct alkylations of (hetero)arenes via C–H bond cleavages with unactivated alkyl halides (2010)

Significant progress has been made in direct alkylations of (hetero)arenes with unactivated alkyl halides. Thus, C-H bond functionalizations were accomplished with beta-hydrogen-containing alkyl halides in the presence of palladium, nickel or ruthenium catalysts under basic reaction conditions. A valuable asset of these methodologies is represented by their excellent regio- and chemoselectivities, along with remarkable mild reaction conditions, rendering this approach an attractive alternative to traditional alkylation strategies.
Branch folding in the CRISP microprocessor: reducing branch delay to zero (1987)

A new method of implementing branch instructions is presented. This technique has been implemented in the CRISP Microprocessor. With a combination of hardware and software techniques the execution time cost for many branches can be effectively reduced to zero. Branches are folded into other instructions, making their execution as separate instructions unnecessary. Branch Folding can reduce the apparent number of instructions needed to execute a program by the number of branches in that program, as well as reducing or eliminating pipeline breakage. Statistics are presented demonstrating the effectiveness of Branch Folding and associated techniques used in the CRISP Microprocessor.
Design of a 7 Degree-of-Freedom Upper-Limb Powered Exoskeleton (2006)

The exoskeleton is an external structural mechanism with joints and links corresponding to those of the human body. Worn by the human, the exoskeleton transmits torques from proximally located actuators through rigid exoskeletal links to the human joints. This paper presents the development of an anthropometric seven degree-of-freedom powered exoskeleton for the upper limb. The design was based on a database defining the kinematics and dynamics of the upper limb during daily living activities, as well as joint physiological and upper limb anatomical considerations, workspace analyses, and joint ranges of motion. Proximal placement of motors and distal placement of pulley reductions were incorporated into the design of a cable-driven wearable robotic arm. This design led to low inertias, high-stiffness links, and back-drivable transmissions with zero backlash. Potential applications of the exoskeleton as a wearable robot include use as: (1) a therapeutic and diagnostics device for physiotherapy, (2) an assistive (orthotic) device for human power amplifications, (3) a haptic device in virtual reality simulation, and (4) a master device for teleoperation
An Internally-controlled Double Blind Trial of Thalidomide in Severe Erythema Nodosum Leprosum (1971)

A double-blind, internally-controlled, clinical trial of thalidpmide in severe, chronic, histologically-proven erythema nodosum leprosum (ENL) is reported. A total of 10 adult male patients were admitted to the trial, all of whom were receiving continuous treatment with steroids and whose minimum daily requirement just to suppress the reaction was in no case less than 15 mg of prednisolone or 18 international units of corticotrophin. The trial wa s divided into 4 equal parts (of either 4 or 6 weeks' duration) consisting of an initial control period, first and second trial periods, and a final control period. Throughout the trial all patients received DDS, 100 mg twice weekly ; thalidomide, 300 mg daily, wa s given during one trial period and identical placebo tablets during the other. As judged by the red uction in their steroid requirements, 9 of the 10 patients showed a very significant improvement while they were receiving thalidomide, although 7 subsequently relapsed after stopping the drug. There was no dose-for-dose relationship between thalidomide and prednisolone. Two patients developed a mild allergic dermatitis.
Generation of polarization entangled photon pairs using silicon wire waveguide (2008)

We report the experimental generation of polarization entangled photon pairs based on spontaneous four-wave mixing in a silicon waveguide. Using a nano-scale silicon wire waveguide placed in a fiber loop, we obtained 1.5-microm band polarization entanglement with two-photon interference visibilities of >83%.
The Fanconi Anemia Protein FANCC Binds to and Facilitates the Activation of STAT1 by Gamma Interferon and Hematopoietic Growth Factors (2000)

Hematopoietic progenitor cells from Fanconi anemia (FA) group C (FA-C) patients display hypersensitivity to the apoptotic effects of gamma interferon (IFN-gamma) and constitutively express a variety of IFN-dependent genes. Paradoxically, however, STAT1 activation is suppressed in IFN-stimulated FA cells, an abnormality corrected by transduction of normal FANCC cDNA. We therefore sought to define the specific role of FANCC protein in signal transduction through receptors that activate STAT1. Expression and phosphorylation of IFN-gamma receptor alpha chain (IFN-gammaRalpha) and JAK1 and JAK2 tyrosine kinases were equivalent in both normal and FA-C cells. However, in coimmunoprecipitation experiments STAT1 did not dock at the IFN-gammaR of FA-C cells, an abnormality corrected by transduction of the FANCC gene. In addition, glutathione S-transferase fusion genes encoding normal FANCC but not a mutant FANCC bearing an inactivating point mutation (L554P) bound to STAT1 in lysates of IFN-gamma-stimulated B cells and IFN-, granulocyte-macrophage colony-stimulating factor- and stem cell factor-stimulated MO7e cells. Kinetic studies revealed that the initial binding of FANCC was to nonphosphorylated STAT1 but that subsequently the complex moved to the receptor docking site, at which point STAT1 became phosphorylated. The STAT1 phosphorylation defect in FA-C cells was functionally significant in that IFN induction of IFN response factor 1 was suppressed and STAT1-DNA complexes were not detected in nuclear extracts of FA-C cells. We also determined that the IFN-gamma hypersensitivity of FA-C hematopoietic progenitor cells does not derive from STAT1 activation defects because granulocyte-macrophage CFU and erythroid burst-forming units from STAT1(-/-) mice were resistant to IFN-gamma. However, BFU-E responses to SCF and erythropoietin were suppressed in STAT(-/-) mice. Consequently, because the FANCC protein is involved in the activation of STAT1 through receptors for at least three hematopoietic growth and survival factor molecules, we reason that FA-C hematopoietic cells are excessively apoptotic because of an imbalance between survival cues (owing to a failure of STAT1 activation in FA-C cells) and apoptotic and mitogenic inhibitory cues (constitutively activated in FA-C cells in a STAT1-independent fashion).
Preparation of Bruch's membrane and analysis of the age-related changes in the structural collagens. (1995)

Changes in the constituent collagens may contribute to the accumulation of debris in Bruch's membrane with age and interfere with the function of the retinal pigment epithelium, with subsequent consequences for the overlying photoreceptors.
Effect of Hormone Replacement Therapy on Breast Cancer Risk: Estrogen Versus Estrogen Plus Progestin (2000)

This study provides strong evidence that the addition of a progestin to HRT enhances markedly the risk of breast cancer relative to estrogen use alone. These findings have important implications for the risk-benefit equation for HRT in women using CHRT.
Macrophage-derived IL-10 mediates mucosal repair by epithelial WISP-1 signaling (2017)

In response to injury, epithelial cells migrate and proliferate to cover denuded mucosal surfaces and repair the barrier defect. This process is orchestrated by dynamic crosstalk between immune cells and the epithelium; however, the mechanisms involved remain incompletely understood. Here, we report that IL-10 was rapidly induced following intestinal mucosal injury and was required for optimal intestinal mucosal wound closure. Conditional deletion of IL-10 specifically in CD11c-expressing cells in vivo implicated macrophages as a critical innate immune contributor to IL-10-induced wound closure. Consistent with these findings, wound closure in T cell- and B cell-deficient Rag1-/- mice was unimpaired, demonstrating that adaptive immune cells are not absolutely required for this process. Further, following mucosal injury, macrophage-derived IL-10 resulted in epithelial cAMP response element-binding protein (CREB) activation and subsequent synthesis and secretion of the pro-repair WNT1-inducible signaling protein 1 (WISP-1). WISP-1 induced epithelial cell proliferation and wound closure by activating epithelial pro-proliferative pathways. These findings define the involvement of macrophages in regulating an IL-10/CREB/WISP-1 signaling axis, with broad implications in linking innate immune activation to mucosal wound repair.
HELP (High Efficiency Liquid Phase) new oligonucleotide synthesis on soluble polymeric support (1990)

A simple, rapid and high-yielding method for the synthesis of oligonucleotides by the phosphotriesters approach is described. The use of polyethylene glycol (PEG) as soluble polymeric support preserves some convenient features of the solid-phase synthesis with new interesting advantages. Short oligonucleotides in hundred milligrams scale can be obtained from few grams of functionalized PEG.
The direct conversion of xylan to lactic acid by Lactobacillus brevis transformed with a xylanase gene (2011)

A xylanase gene (xynR8), obtained from the DNA of a pool of uncultured rumen microbes, was introduced via a plasmid into Lactobacillus brevis. The recombinant xylanase, with an estimated molecular weight of 32 KDa, was expressed in the transformants and showed obvious xylanase activity (0.412 U ml−1) against oat-spelt xylan in broth when compared to the wild-type Lactobacillus brevisATCC367. The transformants all shared a similar ability to utilize and metabolize xylooligosaccharides. When a selected transformant was inoculated into modified MRS medium containing xylan as the main carbon source, the cell density reached 2.20 × 109 CFU ml−1 on day 4, while the wild-type strain without the plasmid containing the recombinant xylanase did not grow at all under the same conditions. After fermentation, 1.70 g l−1 of lactic acid and 0.44 g l−1 of ethanol were present in the culture supernatant of the strain containing the recombinant xylanase. These results indicate that Lactobacillus brevis containing the xylanase gene is capable of directly saccharifying and fermenting xylan to produce lactic acid in one step. This strain will enable the development of a feasible and economical approach to the production of lactic acid directly from xylan.
Utilization of a Protein “Shuttle” To Load Vault Nanocapsules with Gold Probes and Proteins (2009)

Vaults are large protein nanocapsules that may be useful as drug delivery vehicles due to their normal presence in humans, their large interior volume, their simple structural composition consisting of multiple copies of one protein, and a recombinant production system that also provides a means to tailor their structure. However, for vaults to be effective in such applications, efficient means to load the interiors of the capsules must be demonstrated. Here we describe the use of a domain derived from a vault lumen-associated protein as a carrier to target both gold nanoclusters and heterologous His-tagged proteins to specific binding sites on the vault interior wall.
An analysis of variance test for normality (complete samples) (1965)

Journal Article An analysis of variance test for normality (complete samples) Get access S. S. SHAPIRO, S. S. SHAPIRO General Electric Co. and Bell Telephone Laboratories, Inc. Search for other works by this author on: Oxford Academic Google Scholar M. B. WILK M. B. WILK General Electric Co. and Bell Telephone Laboratories, Inc. Search for other works by this author on: Oxford Academic Google Scholar Biometrika, Volume 52, Issue 3-4, December 1965, Pages 591–611, https://doi.org/10.1093/biomet/52.3-4.591 Published: 01 December 1965
Manufacturing methods for high density micro-channel arrays (2000)

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2000.
Photovoltaic Power Systems and the National Electrical Code: Suggested Practices (2001)

This suggested practices manual examines the requirements of the National Electrical Code (NEC) as they apply to photovoltaic (PV) power systems. The design requirements for the balance of systems components in a PV system are addressed, including conductor selection and sizing, overcurrent protection ratings and location, and disconnect ratings and location. PV array, battery, charge controller, and inverter sizing and selection are not covered, as these items are the responsibility of the system designer, and they in turn determine the items in this manual. Stand-alone, hybrid, and utility-interactive PV systems are all covered.