gebhart/patrepeval huggingface dataset:
Prevention of pathology in mdx mice by expression of utrophin: analysis using an inducible transgenic expression system (2002)

Duchenne muscular dystrophy results from the absence of dystrophin, a cytoskeletal protein. Previously, we have shown in a transgenic mouse model of the disease (mdx) that high levels of expression of the dystrophin-related protein, utrophin can prevent pathology. We developed a new transgenic mouse model where muscle specific utrophin expression was conditioned by addition of tetracycline in water. Transgene expression was turned on at different time points: in utero, at birth, 10 and 30 days after birth. We obtained moderate levels of expression, variable from fibre to fibre (mosaicism) but sufficient to induce a correct localization of the dystro-sarcoglycan complex. Histology revealed a reduction of necrotic foci and of the percentage of centronucleated fibres, which remained still largely above the normal level. Isometric force was not improved but the resistance to eccentric contractions was significantly stronger. When utrophin expression was activated 30 days after birth, improvements were marginal, suggesting that the age at which utrophin therapy is initiated could be an important factor. Our results also provide an unexpected insight into the pathogenesis of the dystrophinopathies. We observed a complete normalization of the characteristics of the mechano-sensitive/voltage-independent Ca(2+) channels (occurrence, open probabilities and Ca(2+) currents), while the classical markers of dystrophy were still abnormal. These observations question the role of increased Ca(2+) channel activity in initiating the dystrophic process. The new model shows that utrophin therapy, initiated after birth, can be effective, but the extent of correction of the various symptoms of dystrophinopathy critically depends on the amount of utrophin expressed.
Keyframe-based visual–inertial odometry using nonlinear optimization (2014)

Combining visual and inertial measurements has become popular in mobile robotics, since the two sensing modalities offer complementary characteristics that make them the ideal choice for accurate visual–inertial odometry or simultaneous localization and mapping (SLAM). While historically the problem has been addressed with filtering, advancements in visual estimation suggest that nonlinear optimization offers superior accuracy, while still tractable in complexity thanks to the sparsity of the underlying problem. Taking inspiration from these findings, we formulate a rigorously probabilistic cost function that combines reprojection errors of landmarks and inertial terms. The problem is kept tractable and thus ensuring real-time operation by limiting the optimization to a bounded window of keyframes through marginalization. Keyframes may be spaced in time by arbitrary intervals, while still related by linearized inertial terms. We present evaluation results on complementary datasets recorded with our custom-built stereo visual–inertial hardware that accurately synchronizes accelerometer and gyroscope measurements with imagery. A comparison of both a stereo and monocular version of our algorithm with and without online extrinsics estimation is shown with respect to ground truth. Furthermore, we compare the performance to an implementation of a state-of-the-art stochastic cloning sliding-window filter. This competitive reference implementation performs tightly coupled filtering-based visual–inertial odometry. While our approach declaredly demands more computation, we show its superior performance in terms of accuracy.
Complement, Age-Related Macular Degeneration and a Vision of the Future (2010)

Age-related macular degeneration (AMD) is one of the most well-characterized late-onset, complex trait diseases. Remarkable advances in our understanding of the genetic and biological foundations of this disease were derived from a recent convergence of scientific and clinical data. Importantly, the more recent identification of AMD-associated variations in a number of complement pathway genes has provided strong support for earlier, paradigm-shifting studies that suggested that aberrant function of the complement system plays a key role in disease etiology. Collectively, this wealth of information has provided an impetus for the development of powerful tools to accurately diagnose disease risk and progression and complement-based therapeutics that will ultimately delay or prevent AMD. Indeed, we are poised to witness a new era of a personalized approach toward the assessment, management, and treatment of this debilitating, chronic disease.
Insect Cell-Derived VP2 of Infectious Bursal Disease Virus Confers Protection against the Disease in Chickens (1996)

Infectious bursal disease virus (IBDV) has become a major problem in recent years. Conventional vaccines make use of attenuated or inactivated viral strains, but these are gradually losing their effectiveness. We investigated the possibility of using purified VP2, a subunit of IBDV structural protein expressed in insect cells, as a vaccine. The VP2 gene was cloned into pAcYM1. The cloned gene was expressed in a baculovirus system, giving rise to a high quantity of recombinant VP2 (rVP2) protein. The length of the VP2 is 453 amino acids, and it contains two additional amino acids of the baculovirus at the carboxyl terminus. The molecular mass of the protein is about 48 kD. The rVP2 protein reacted with antibodies raised against viral VP2 and had a similar molecular weight. This protein was tested in a controlled vaccination experiment and compared with an inactivated commercial vaccine. High levels of antibodies were raised by the vaccinated birds. The vaccinated birds were challenged with a pathogenic viral strain. rVP2-vaccinated chickens exhibited high resistance to the virus. No mortality or weight changes in the bursa of Fabricius were observed in the vaccinated birds, whereas in the negative control birds, vaccinated with phosphate buffer, up to 50% mortality was found. Higher levels of antibodies were found by enzyme-linked immunosorbent assay in birds vaccinated with rVP2 compared with those vaccinated with the commercial vaccine. This study suggests the potential use of the isolated rVP2 as a subunit vaccine.
The Fluid Joint: The Soft Spot of Micro‐ and Nanosystems (2015)

Fluid bridges are ubiquitous soft structures of finite size that conform to and link the surfaces of neighboring objects. Fluid joints, the specific type of fluid bridge with at least one extremity constrained laterally, display even more pronounced reactivity and self-restoration, which make them remarkably suited for assembly, actuation, and manipulation purposes. Their peculiar surface and bulk properties place fluid joints at the rich intersection of diverse scientific interests, and foster their widespread use throughout micro- and nanotechnology. A critical survey of the mechanics and of the manifold applications of fluid bridges and joints in micro- and nanosystems is presented here, along with current challenges and multidisciplinary perspectives.
Characteristics of chronic gout in Northern Sulawesi, Indonesia. (2006)

Severe tophaceous gout with deformities and disability is found in North Sulawesi. Prominent risk factors include alcohol, obesity, renal impairment, diet, hypertension, and family history. Improved education about gout seems needed. Urate-lowering drugs are not available in community health centers but are needed, especially in rural areas, as studied here.
Informed mobile prefetching (2012)

Prefetching is a double-edged sword. It can hide the latency of data transfers over poor and intermittently connected wireless networks, but the costs of prefetching in terms of increased energy and cellular data usage are potentially substantial, particularly for data prefetched incorrectly. Weighing the costs and benefits of prefetching is complex, and consequently most mobile applications employ simple but sub-optimal strategies.
Experimental Tumor Therapy in Mice Using the Cyclophosphamide-Activating Cytochrome P450 2B1 Gene (1994)

Most malignant tumors of the central nervous system do not respond well to chemotherapy. The anticancer drug cyclophosphamide (CPA) is largely ineffective against these neoplasms as its conversion to DNA-alkylating, cytotoxic metabolites is restricted primarily to the liver and these metabolites do not readily cross the blood-brain barrier. Here, we show that brain tumor cells can be sensitized to the cytotoxic effects of CPA, both in culture and in vivo, by introduction of the hepatic enzyme responsible for the activation of CPA, cytochrome P450 2B1. Stable transfection of rat C6 glioma cells with the P450 2B1 gene rendered the cultured tumor cells sensitive to CPA. Further, C6 cells bearing this gene were more sensitive than parental cells to the cytotoxic action of CPA when grown subcutaneously in the flanks of athymic mice. Murine fibroblasts producing a retrovirus vector encoding P450 2B1 and expressing this enzyme were then prepared and grafted into the brains of athymic mice seeded with rat C6 gliomas. Intrathecal administration of CPA prevented the development of meningeal neoplasia and led to partial regression of the parenchymal tumor mass. By contrast, C6 glioma-bearing mice receiving fibroblasts expressing the Escherichia coli lacZ gene and CPA exhibited extensive meningeal tumors and parenchymal solid brain tumors. The in situ activation of CPA by cytochrome P450 2B1 provides a novel approach not only for brain tumor gene therapy, but also for negative, drug-conditional selection of other defined cell populations.
Peroxisome proliferator and retinoid signalingpathways co-regulate preadipocyte phenotype and survival. (1994)

Culture of mouse 3T3-L1 preadipocytes in medium containing delipidated bovine calf serum caused the cells to elongate and divide after reaching confluency. The continued proliferation correlated with sustained expression of the c-myc gene, which was repressed in control cells. Exposure of the cells to activators of peroxisome proliferator-activated receptor (PPAR), including clofibrate, WY-14,643, and 5,8,11,14-eicosatetraynoic acid, reversed and prevented the effects of culturing preadipocytes in delipidated serum. Continued exposure to PPAR activators led to adipose conversion, during which PPAR and its heterodimerization partner (retinoid X receptor) were induced. Retinoic acid (RA) had no effect on the growth or survival of preadipocytes grown in the presence of normal bovine serum. However, treatment of cells cultured in delipidated serum with RA caused death of the cells by apoptosis. Thus, preadipocyte phenotype and survival are regulated by activators of nuclear hormone receptors.
CYR61, a product of a growth factor-inducible immediate early gene, promotes angiogenesis and tumor growth (1998)

CYR61 is a secreted, cysteine-rich, heparin-binding protein encoded by a growth factor-inducible immediate-early gene. Acting as an extracellular, matrix-associated signaling molecule, CYR61 promotes the adhesion of endothelial cells through interaction with the integrin alphaVbeta3 and augments growth factor-induced DNA synthesis in the same cell type. In this study, we show that purified CYR61 stimulates directed migration of human microvascular endothelial cells in culture through an alphaV beta3-dependent pathway and induces neovascularization in rat corneas. Both the chemotactic and angiogenic activities of CYR61 can be blocked by specific anti-CYR61 antibodies. Whereas most human tumor-derived cell lines tested express CYR61, the gastric adenocarcinoma cell line RF-1 does not. Expression of the CYR61 cDNA under the regulation of a constitutive promoter in RF-1 cells significantly enhances the tumorigenicity of these cells as measured by growth in immunodeficient mice, resulting in tumors that are larger and more vascularized than those produced by control RF-1 cells. Taken together, these results identify CYR61 as an angiogenic inducer that can promote tumor growth and vascularization; the results also suggest potential roles for CYR61 in physiologic and pathologic neovascularization.
The β -Adrenoceptor (1998)

The human beta-adrenoceptor is a member of the seven-transmembrane family of receptors, encoded by a gene on chromosome 5. beta-Adrenoceptors have been classified into beta1, beta2, and beta3 subgroups, with beta2-receptors being widely distributed in the respiratory tract, particularly in airway smooth muscle. Intracellular signaling following beta2-adrenoceptor activation is largely affected through a trimeric Gs protein coupled to adenylate cyclase. Cyclic AMP (cAMP) induces airway relaxation through phosphorylation of muscle regulatory proteins and attenuation of cellular Ca2+ concentrations. Alternative cAMP-independent pathways involving activation of membrane maxi-K+ channels and coupling through Gi to the MAP kinase system have also been described. Site-directed mutagenesis has identified Asp 113 and Ser 204/207 within the third and fourth membrane domains as the active site of the beta2-receptor, critical for beta2-agonist binding and activity. beta2-Agonists have been characterized as those that directly activate the receptor (albuterol), those that are taken up into a membrane depot (formoterol), and those that interact with a receptor-specific auxiliary binding site (salmeterol). These differences in mechanism of action are reflected in the kinetics of airway smooth muscle relaxation and bronchodilation in patients with asthma. beta-Adrenoceptor desensitization associated with beta2-agonist activation is a consequence of phosphorylation by beta-ARK and uncoupling of the receptor from Gs following beta-arrestin binding, of internalization and recycling of the receptor through processes of sequestration and resensitization and downregulation, modulated by an effect on receptor gene expression. The degree of receptor desensitization appears to differ, depending on the cell or tissue type, and is reflected in the different profiles of clinical tolerance to chronic beta2-agonist therapy. A number of polymorphisms of the beta2-receptor have been described that appear to alter the behavior of the receptor following agonist exposure. These include Arg-Gly 16, Glu-Gln 27, and Thr-lle 164. The Gly 16 receptor downregulates to a greater extent and is associated with increased airway hyperreactivity, nocturnal symptoms, and more severe asthma. The Glu 27 form appears to protect against downregulation and is associated with less reactive airways. An individual can be homozygous or heterozygous for given polymorphisms, and large populations will have to be studied to determine their importance to the asthma phenotype.
A Review of Standards and Statistics Used to Describe Blood Glucose Monitor Performance (2010)

Glucose performance is reviewed in the context of total error, which includes error from all sources, not just analytical. Many standards require less than 100% of results to be within specific tolerance limits. Analytical error represents the difference between tested glucose and reference method glucose. Medical errors include analytical errors whose magnitude is great enough to likely result in patient harm. The 95% requirements of International Organization for Standardization 15197 and others make little sense, as up to 5% of results can be medically unacceptable. The current American Diabetes Association standard lacks a specification for user error. Error grids can meaningfully specify allowable glucose error. Infrequently, glucose meters do not provide a glucose result; such an occurrence can be devastating when associated with a life-threatening event. Nonreporting failures are ignored by standards. Estimates of analytical error can be classified into the four following categories: imprecision, random patient interferences, protocol-independent bias, and protocol-dependent bias. Methods to estimate total error are parametric, nonparametric, modeling, or direct. The Westgard method underestimates total error by failing to account for random patient interferences. Lawton's method is a more complete model. Bland-Altman, mountain plots, and error grids are direct methods and are easier to use as they do not require modeling. Three types of protocols can be used to estimate glucose errors: method comparison, special studies and risk management, and monitoring performance of meters in the field. Current standards for glucose meter performance are inadequate. The level of performance required in regulatory standards should be based on clinical needs but can only deal with currently achievable performance. Clinical standards state what is needed, whether it can be achieved or not. Rational regulatory decisions about glucose monitors should be based on robust statistical analyses of performance.
Identification of the Regulatory Subunit ofArabidopsis thalianaAcetohydroxyacid Synthase and Reconstitution with Its Catalytic Subunit (2001)

Acetohydroxyacid synthase (EC 4.1.3.18; AHAS) catalyzes the initial step in the formation of the branched-chain amino acids. The enzyme from most bacteria is composed of a catalytic subunit, and a smaller regulatory subunit that is required for full activity and for sensitivity to feedback regulation by valine. A similar arrangement was demonstrated recently for yeast AHAS, and a putative regulatory subunit of tobacco AHAS has also been reported. In this latter case, the enzyme reconstituted from its purified subunits remained insensitive to feedback inhibition, unlike the enzyme extracted from native plant sources. Here we have cloned, expressed in Escherichia coli, and purified the AHAS regulatory subunit of Arabidopsis thaliana. Combining the protein with the purified A. thaliana catalytic subunit results in an activity stimulation that is sensitive to inhibition by valine, leucine, and isoleucine. Moreover, there is a strong synergy between the effects of leucine and valine, which closely mimics the properties of the native enzyme. The regulatory subunit contains a sequence repeat of approximately 180 residues, and we suggest that one repeat binds leucine while the second binds valine or isoleucine. This proposal is supported by reconstitution studies of the individual repeats, which were also cloned, expressed, and purified. The structure and properties of the regulatory subunit are reminiscent of the regulatory domain of threonine deaminase (EC 4.2.1.16), and it is suggested that the two proteins are evolutionarily related.
Ancient ubiquitous protein-1 mediates sterol-induced ubiquitination of 3-hydroxy-3-methylglutaryl CoA reductase in lipid droplet–associated endoplasmic reticulum membranes (2012)

Sterol-induced binding to Insigs in endoplasmic reticulum (ER) membranes triggers ubiquitination of the cholesterol biosynthetic enzyme 3-hydroxy-3-methylglutaryl CoA reductase. This ubiquitination, which is mediated by Insig-associated ubiquitin ligases gp78 and Trc8, is obligatory for extraction of reductase from lipid droplet-associated ER membranes into the cytosol for proteasome-mediated, ER-associated degradation (ERAD). In this study, we identify lipid droplet-associated, ancient, ubiquitous protein-1 (Aup1) as one of several proteins that copurify with gp78. RNA interference (RNAi) studies show that Aup1 recruits the ubiquitin-conjugating enzyme Ubc7 to lipid droplets and facilitates its binding to both gp78 and Trc8. The functional significance of these interactions is revealed by the observation that RNAi-mediated knockdown of Aup1 blunts sterol-accelerated ubiquitination of reductase, which appears to occur in lipid droplet-associated membranes and subsequent ERAD of the enzyme. In addition, Aup1 knockdown inhibits ERAD of Insig-1, another substrate for gp78, as well as that of membrane-bound precursor forms of sterol-regulatory, element-binding protein-1 and -2, transcription factors that modulate expression of genes encoding enzymes required for cholesterol synthesis. Considered together, these findings not only implicate a role for Aup1 in maintenance of intracellular cholesterol homeostasis, but they also highlight the close connections among ERAD, lipid droplets, and lipid droplet-associated proteins.
Rho1 regulatesDrosophilaadherens junctions independently of p120ctn (2005)

During animal development, adherens junctions (AJs) maintain epithelial cell adhesion and coordinate changes in cell shape by linking the actin cytoskeletons of adjacent cells. Identifying AJ regulators and their mechanisms of action are key to understanding the cellular basis of morphogenesis. Previous studies linked both p120catenin and the small GTPase Rho to AJ regulation and revealed that p120 may negatively regulate Rho. Here we examine the roles of these candidate AJ regulators during Drosophila development. We found that although p120 is not essential for development, it contributes to morphogenesis efficiency, clarifying its role as a redundant AJ regulator. Rho has a dynamic localization pattern throughout ovarian and embryonic development. It preferentially accumulates basally or basolaterally in several tissues, but does not preferentially accumulate in AJs. Further, Rho1 localization is not obviously altered by loss of p120 or by reduction of core AJ proteins. Genetic and cell biological tests suggest that p120 is not a major dose-sensitive regulator of Rho1. However, Rho1 itself appears to be a regulator of AJs. Loss of Rho1 results in ectopic accumulation of cytoplasmic DE-cadherin, but ectopic cadherin does not accumulate with its partner Armadillo. These data suggest Rho1 regulates AJs during morphogenesis, but this regulation is p120 independent.
Pediatric nutrition surveillance system--United States, 1980-1991. (1992)

The CDC Pediatric Nutrition Surveillance System (PedNSS) monitors the general health and nutritional characteristics of low-income U.S. children who participate in multiple public health programs. This system is intended to characterize trends and patterns in key indicators of nutritional status so that the information can be used for program planning and targeting. The indicators monitored by PedNSS are birth weight, childhood growth status, anemia, and breast-feeding patterns. From 1980 through 1991, the trends for low birth weight, low height-for-age (shortness), low weight-for-height (thinness), and high weight-for-height (overweight) were stable for all children monitored by the PedNSS, with the exception of Asian children, who were predominantly of Southeast Asian refugee background. In the early 1980s, the prevalence of low birth weight and shortness was higher among Asian children than among children of other racial or ethnic groups who were monitored by the PedNSS. However, these prevalences declined steadily from 1980 through 1991. By 1991, the prevalences of low birth weight and shortness for Asian children were similar to those observed for children of other races/ethnic groups. Overall, low-income U.S. children had a slightly lower height-for-age than expected, indicating that some of these children were at a health and nutritional disadvantage. The prevalence of overweight varied among different racial/ethnic groups; Hispanic and Native American children had the highest prevalences of overweight. The 20%-30% prevalence of anemia among low-income children monitored by the PedNSS was higher than among the general population, reflecting in part the preferential enrollment and retention of anemic children by public health nutrition programs and also indicating that many children had inadequate iron nutrition. From 1980 through 1991, the prevalence of anemia declined > 5% for most of the age- and race/ethnicity-specific groups monitored by PedNSS. That decline represents an improvement in iron nutritional status. PedNSS is a useful system for the monitoring and characterization of the nutrition status of low-income children at both state and national levels.