gebhart/patrepeval huggingface dataset:
Silencing Myostatin Using Cholesterol-conjugated siRNAs Induces Muscle Growth (2016)

Short interfering RNAs (siRNAs) are a valuable tool for gene silencing with applications in both target validation and therapeutics. Many advances have recently been made to improve potency and specificity, and reduce toxicity and immunostimulation. However, siRNA delivery to a variety of tissues remains an obstacle for this technology. To date, siRNA delivery to muscle has only been achieved by local administration or by methods with limited potential use in the clinic. We report systemic delivery of a highly chemically modified cholesterol-conjugated siRNA targeting muscle-specific gene myostatin (Mstn) to a full range of muscles in mice. Following a single intravenous injection, we observe 85-95% knockdown of Mstn mRNA in skeletal muscle and >65% reduction in circulating Mstn protein sustained for >21 days. This level of Mstn knockdown is also accompanied by a functional effect on skeletal muscle, with animals showing an increase in muscle mass, size, and strength. The cholesterol-conjugated siRNA platform described here could have major implications for treatment of a variety of muscle disorders, including muscular atrophic diseases, muscular dystrophy, and type II diabetes.
Dynamic Modeling With Correlated Inputs: Theory, Method, and Experimental Demonstration (2015)

When modeling dynamic processes for several inputs with freely existing data, such as data collected with normal process operations, the ability to accurately model the output response for a given input change is impeded when inputs are cross-correlated (i.e., pairwise) as this adversely affects accurate estimation of the causative effects of inputs on the response variable. The causative effects of the inputs can be evaluated functionally and analytically via the Jacobian matrix which is done in this work for NARMAX and Wiener structures that are linear and nonlinear in model parameters. This analysis shows that the Wiener structure with physically based nonlinear parametrization is superior. This conclusion is also supported in this work by a modeling study on a real distillation column consisting of eight test runs over a period of three years.
Induction of Autoantigen-Specific Th2 and Tr1 Regulatory T Cells and Modulation of Autoimmune Diabetes (2003)

Autoantigen-based immunotherapy can modulate autoimmune diabetes, perhaps due to the activation of Ag-specific regulatory T cells. Studies of these regulatory T cells should help us understand their roles in diabetes and aid in designing a more effective immunotherapy. We have used class II MHC tetramers to isolate Ag-specific T cells from nonobese diabetic (NOD) mice and BALB/c mice treated with glutamic acid decarboxylase 65 peptides (p206 and p221). Based on their cytokine secretion profiles, immunization of NOD mice with the same peptide induced different T cell subsets than in BALB/c mice. Treatment of NOD mice induced not only Th2 cells but also IFN-gamma/IL-10-secreting T regulatory type 1 (Tr1) cells. Adoptive transfer experiments showed that isolated tetramer(+) T cells specific for p206 or p221 could inhibit diabetes development. These cells were able to suppress the in vitro proliferation of other NOD mouse T cells without cell-cell contact. They performed their regulatory functions probably by secreting cytokines, and Abs against these cytokines could block their suppressive effect. Interestingly, the presence of both anti-IL-10 and anti-IFN-gamma could enhance the target cell proliferation, suggesting that Tr1 cells play an important role. Further in vivo experiments showed that the tetramer(+) T cells could block diabetogenic T cell migration into lymph nodes. Therefore, treatment of NOD mice with autoantigen could induce Th2 and Tr1 regulatory cells that can suppress the function and/or block the migration of other T cells, including diabetogenic T cells, and inhibit diabetes development.
Genetics and molecular biology of carotenoid pigment biosynthesis (1996)

The crucial roles of carotenoids and their metabolites in photooxidative protection and photosynthesis, not to mention nutrition, vision, and cellular differentiation, make them an important and complex class of biological pigments. Significant advances within the last few years have enhanced our understanding of the genetics and molecular biology of carotenoid biosynthesis in bacteria, fungi, algae, and plants. All of the genes involved in carotenoid biosynthesis from Rhodobacter capsulatus, an anoxygenic photosynthetic bacterium, and from several species of Erwinia, nonphotosynthetic bacteria, have been molecularly characterized. Recent studies have revealed that two early enzymes of carotenoid biosynthesis, geranylgeranyl pyrophosphate synthase and phytoene synthase, are structurally and functionally related in all carotenogenic organisms. In contrast, the subsequent conversion of phytoene, the first C(40) carotenoid, to beta-carotene requires two desaturases and one cyclase in oxygenic photosynthetic organisms (cyanobacteria, algae, and higher plants) but only one structurally distinct desaturase and a structurally distinct cyclase in other carotenogenic bacteria and in fungi. Studies of the enzymes that introduce oxygen-containing functional groups into carotenes to produce xanthophylls, the vast majority of all carotenoids, are still in their infancy. This review summarizes the most recent developments in carotenoid biosynthesis from a molecular genetic standpoint.
Ischaemic preconditioning limits infarct size in the rat heart (1992)

These results show that rat hearts can be ischaemically preconditioned and suggest that the protective mechanism involved in this phenomenon is not mediated through the endogenous inhibition of mitochondrial ATPase. An overall reduction in mitochondrial ATP "wastage" may not be the sole mechanism in the protection seen in ischaemic preconditioning.
Vinylogous Ureas as a Novel Class of Inhibitors of Reverse Transcriptase-Associated Ribonuclease H Activity (2008)

High-throughput screening of National Cancer Institute libraries of synthetic and natural compounds identified the vinylogous ureas 2-amino-5,6,7,8-tetrahydro-4 H-cyclohepta[ b]thiophene-3-carboxamide (NSC727447) and N-[3-(aminocarbonyl)-4,5-dimethyl-2-thienyl]-2-furancarboxamide (NSC727448) as inhibitors of the ribonuclease H (RNase H) activity of HIV-1 and HIV-2 reverse transcriptase (RT). A Yonetani-Theorell analysis demonstrated that NSC727447, and the active-site hydroxytropolone RNase H inhibitor beta-thujaplicinol were mutually exclusive in their interaction with the RNase H domain. Mass spectrometric protein footprinting of the NSC727447 binding site indicated that residues Cys280 and Lys281 in helix I of the thumb subdomain of p51 were affected by ligand binding. Although DNA polymerase and pyrophosphorolysis activities of HIV-1 RT were less sensitive to inhibition by NSC727447, protein footprinting indicated that NSC727447 occupied the equivalent region of the p66 thumb. Site-directed mutagenesis using reconstituted p66/p51 heterodimers substituted with natural or non-natural amino acids indicates that altering the p66 RNase H primer grip significantly affects inhibitor sensitivity. NSC727447 thus represents a novel class of RNase H antagonists with a mechanism of action differing from active site, divalent metal-chelating inhibitors that have been reported.
Effect of Gasoline Quality on Throttle Response of Engines During Warm-Up (1990)

&lt;div class="htmlview paragraph"&gt;An investigation of throttle response of engines during warm-up was conducted using various gasolines. Test data were obtained from an engine on a test bench at intermediate temperature around 20∼ 30 °C. By using the engine test bench data, correlation coefficients between engine response time and gasoline characteristics were calculated.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;The result shows that the middle range of distillation temperature is an important factor in gasoline characteristics for warm-up driveability of fuel injected engines. It also shows that 50% distillation temperature can be used as one indication of warm-up driveability. This indication is effective only for hydrocarbon type gasolines. In the case of MTBE blended gasoline, the distillation temperature becomes low when MTBE is blended to gasoline, but throttle response was not improved.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;It is also found that the effect of gasoline distillation on throttle response is enhanced by intake valve deposits. Hence effect of gasoline detergent additive in Japanese market was investigated. Some of the detergents produced more intake valve deposits than no detergent.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;It is concluded that distillation characteristics and detergent additive are important factors of gasoline quality for engine response, in other words, vehicle driveability.&lt;/div&gt;
Intelligence Science (2011)

Intelligence Science is an interdisciplinary subject dedicated to joint research on basic theory and technology of intelligence by brain science, cognitive science, artificial intelligence and others. Brain science explores the essence of brain research on the principle and model of natural intelligence at the molecular, cell and behavior level. Cognitive science studies human mental activity, such as perception, learning, memory, thinking, consciousness etc. In order to implement machine intelligence, artificial intelligence attempts simulation, extension and expansion of human intelligence using artificial methodology and technology. Research scientists from the above three disciplines work together to explore new concepts, new theories and methodologies. This book will introduce the concept and methodology of intelligence science systematically. The whole book is divided into 18 chapters altogether. It can be regarded as a textbook in courses of intelligence science, cognitive science, cognitive informatics etc. for senior and graduate students. It has important reference value for researchers engaged in fields such as intelligence science, brain science, cognitive science, neural science, artificial intelligence, psychology and so on
AsianWORKs (2001)

ABSTRACT Achieving economic self-sufficiency through employment is the ultimate goal of recent changes to the welfare program. The Asian American and Pacific Islander (AAPI) population is most vulnerable to failing in this goal because of language difficulty, low education levels and lack of job skills in the labor market. Many AAPI immigrants, and Southeast Asian Americans in particular, suffer from adjustment and mental health problems due to their experiences as refugees. These are but a few of the obstacles for AAPI welfare recipients to become self-sufficient, making them one of the most “hard-to-serve” populations. The goal of self-sufficiency through employment can be reached if culturally appropriate and adequate support services are provided to meet the unique needs of the population. Few programs, however, are targeted at AAPIs. Using key-informant interviews and the case material review method, this article highlights the difficulties of AAPI welfare recipients and describes a unique program serving the Southeast Asian American, particularly the Cambodian, population. The article focuses on the program components of outreach and engagement, day socialization and job readiness, and family support services, and it discusses improvement to service access and lessons learned for the practice of cultural competence.
Protection Elicited by a Double Leucine and Pantothenate Auxotroph of Mycobacterium tuberculosis in Guinea Pigs (2004)

We developed a live, fully attenuated Mycobacterium tuberculosis vaccine candidate strain with two independent attenuating auxotrophic mutations in leucine and pantothenate biosynthesis. The deltaleuD deltapanCD double auxotroph is fully attenuated in the SCID mouse model and highly immunogenic and protective in the extremely sensitive guinea pig tuberculosis model, reducing both bacterial burden and disease pathology.
Deconvolution of images and spectra (1997)

ngineering, The University of Washington Seattle, Washington I. II. III. IV. V. VI. Introduction 478 Geometrical POCS 478 A. Convex Sets 479 B. Projecting onto a Convex Set 480 c. 482 Convex Sets of Signals 484 A. The Signal Space 484 B. Some Commonly Used Convex Sets of Signals 486 Examples 490 A. Von Neumann&amp;apos;s Alternating Projection Theorem 490 B. The Papoulis-Gerchberg Algorithm 490 C. Algorithm 494 D. Restoration of Linear Degradation 494 Notes 497 Conclusions 498 References 499 List of Symbols E BE BS sets of vectors or functions the universal set multidimensional vectors vectors in the sets A and B functions of
Organosilicon Dendritic Networks in Porous Ceramics for Water Purification (2005)

Triethoxysilyl-functionalized poly(propylene imine) (DAB32) dendrimer and poly(ethylene imine) (PEI5) hyperbranched polymer were conveniently prepared in chloroform and were subsequently allowed to impregnate porous ceramic filters. Following hydrolysis of triethoxysilyl moieties to Si−OH, polycondensation occurred affording networks containing Si−O−Si bridges with simultaneous formation of Si−O−M bridges resulting from the interaction of Si−OH with M−OH of the ceramic surface. In this manner, covalent binding of the organosilicon dendritic polymers is achieved at the ceramic surface. These porous ceramic filters, impregnated with organosilicon dendritic polymers, were employed for water purification. The concentration of polycyclic aromatic compounds in water was reduced to the level of a few ppb by continuous filtration of contaminated water through these filters. The filters loaded with pollutants were effectively regenerated by treatment with acetonitrile.
Presence and Growth of Naturalized Escherichia coli in Temperate Soils from Lake Superior Watersheds (2006)

The presence of Escherichia coli in water is used as an indicator of fecal contamination, but recent reports indicate that soil populations can also be detected in tropical, subtropical, and some temperate environments. In this study, we report that viable E. coli populations were repeatedly isolated from northern temperate soils in three Lake Superior watersheds from October 2003 to October 2004. Seasonal variation in the population density of soilborne E. coli was observed; the greatest cell densities, up to 3 x 10(3) CFU/g soil, were found in the summer to fall (June to October), and the lowest numbers, < or =1 CFU/g soil, occurred during the winter to spring months (February to May). Horizontal, fluorophore-enhanced repetitive extragenic palindromic PCR (HFERP) DNA fingerprint analyses indicated that identical soilborne E. coli genotypes, those with > or =92% similarity values, overwintered in frozen soil and were present over time. Soilborne E. coli strains had HFERP DNA fingerprints that were unique to specific soils and locations, suggesting that these E. coli strains became naturalized, autochthonous members of the soil microbial community. In laboratory studies, naturalized E. coli strains had the ability to grow and replicate to high cell densities, up to 4.2 x 10(5) CFU/g soil, in nonsterile soils when incubated at 30 or 37 degrees C and survived longer than 1 month when soil temperatures were < or =25 degrees C. To our knowledge, this is the first report of the growth of naturalized E. coli in nonsterile, nonamended soils. The presence of significant populations of naturalized populations of E. coli in temperate soils may confound the use of this bacterium as an indicator of fecal contamination.
The Constrained Amino Acid β‐Acc Confers Potency and Selectivity to Integrin Ligands (2007)

Complete opposites: The incorporation of the rigid building block (+)-β-Acc (Acc=aminocyclopropane carboxylic acid) into cyclic RGD peptides results in a high affinity towards the integrin αvβ3. The peptides 1 and 2 are composed of the enantiomeric building blocks (+)- (blue) and (−)-β-Acc (red). The active peptide 1 inhibits integrin αvβ3 mediated cell adhesion to vitronectin with an IC50 value of 20 nM. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2007/z605248_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Probabilistic Algorithms in Finite Fields (1980)

We present probabilistic algorithms for the problems of finding an irreducible polynomial of degree n over a finite field, finding roots of a polynomial, and factoring a polynomial into its irreducible factors over a finite field. All of these problems are of importance in algebraic coding theory, algebraic symbol manipulation, and number theory. These algorithms have a very transparent, easy to program structure. For finite fields of large characteristic p, so that exhaustive search through ${\text{Z}}_p $, is not feasible, our algorithms are of lower order in the degrees of the polynomial and fields in question, than previously published algorithms.
KGF induces lipogenic genes through a PI3K and JNK/SREBP-1 pathway in H292 cells (2005)

Lipid synthesis is required for cell growth and is subject to pharmacologic regulation. Keratinocyte growth factor (KGF) stimulates proliferation and lipogenesis in H292 cells, a pulmonary epithelial cancer cell line, but the signaling pathways are not known. KGF stimulated the expression of the transcription factors sterol-regulatory element binding protein-1 (SREBP-1), CCAAT/enhancer binding protein alpha (C/EBPalpha), and C/EBPdelta and two key enzymes involved in lipogenesis, FAS and stearoyl coenzyme A desaturase-1 (SCD-1). We found that KGF induced rapid activation of Akt, p70 S6K, JNK, and extracellular signal-regulated (ERK). Induction of SREBP-1, SCD-1, and FAS by KGF was inhibited by the JNK inhibitor SP600125 and the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 but not by the ERK inhibitor PD98059. Using FAS and SCD-1-luciferase promoter constructs, we observed that KGF stimulated the transcription of these promoters and that exogenous cholesterol inhibited the induction. Mutation of the SREBP-1 binding site in the SCD-1 promoter abolished the effect of KGF on SCD-1 transcription. In addition, overexpression of active SREBP-1 directly stimulated SCD-1 and FAS. Conversely, adenovirus-mediated overexpression of a dominant negative form of SREBP-1 inhibited the KGF effect on FAS and SCD-1 expression. In summary, we conclude that KGF requires both PI3K and JNK signaling pathways to induce SREBP-1, which in turn induces SCD-1 and FAS expression in H292 cells.
Quantitative demonstration of spontaneous metastasis by MCF-7 human breast cancer cells cotransfected with fibroblast growth factor 4 and LacZ. (1993)

We recently established transfectants of MCF-7 human breast cancer cells with fibroblast growth factor 4 (fgf-4) that showed rapid growth and spontaneous metastasis in ovariectomized and tamoxifen-treated nude mice. To establish a spontaneous metastatic model of human breast cancer cells in nude mice with a sensitive marker for detection of micrometastasis, the transfection of fgf-4 was combined with transfection of the bacterial lacZ gene encoding beta-galactosidase. MKL-4 cells, a lacZ transfectant of an fgf-4-transfected cell line, showed the same level of fgf-4 expression as parental cells and expressed a high level of beta-galactosidase activity. When MKL-4 cells were injected s.c. into female nude mice, rapidly growing tumors developed. Whole organ staining for beta-galactosidase activity was able to detect even small numbers of metastatic tumor cells. Micrometastases in lymph nodes, lung, and brain were detected 3 weeks after the tumor cell injections, the first time point tested. Within 12 weeks, metastases were observed in lymph nodes, lung, brain, kidney, perirenal fatty tissues, liver, spleen, retroperitoneum, heart, and gallbladder. The frequency of metastasis and number of foci were correlated with the volume of the primary tumors. The distribution of metastatic sites was similar to that in breast cancer patients. MKL-4 cells may be a useful model for studying the malignant progression of hormone-dependent breast cancer, antimetastatic drugs, or early events in metastasis.
Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex (2016)

Systematic interrogation of gene function requires the ability to perturb gene expression in a robust and generalizable manner. Here we describe structure-guided engineering of a CRISPR-Cas9 complex to mediate efficient transcriptional activation at endogenous genomic loci. We used these engineered Cas9 activation complexes to investigate single-guide RNA (sgRNA) targeting rules for effective transcriptional activation, to demonstrate multiplexed activation of ten genes simultaneously, and to upregulate long intergenic non-coding RNA (lincRNA) transcripts. We also synthesized a library consisting of 70,290 guides targeting all human RefSeq coding isoforms to screen for genes that, upon activation, confer resistance to a BRAF inhibitor. The top hits included genes previously shown to be able to confer resistance, and novel candidates were validated using individual sgRNA and complementary DNA overexpression. A gene expression signature based on the top screening hits correlated with markers of BRAF inhibitor resistance in cell lines and patient-derived samples. These results collectively demonstrate the potential of Cas9-based activators as a powerful genetic perturbation technology.
Very High-Order Microring Resonator Filters for WDM Applications (2004)

High-order microring resonators having from 1 to 11 coupled cavities are demonstrated. These filters exhibit low loss, flat tops, and out-of-band rejection ratios that can exceed 80 dB. They achieve performance that is suitable for commercial applications.
CD8 T Cell-Intrinsic GITR Is Required for T Cell Clonal Expansion and Mouse Survival following Severe Influenza Infection (2010)

The regulation of T cell expansion by TNFR family members plays an important role in determining the magnitude of the immune response to pathogens. As several members of the TNFR family, including glucocorticoid-induced TNFR-related protein (GITR), are found on both regulatory and effector T cells, there is much interest in understanding how their effects on these opposing arms of the immune system affect disease outcome. Whereas much work has focused on the role of GITR on regulatory T cells, little is known about its intrinsic role on effector T cells in an infectious disease context. In this study, we demonstrate that GITR signaling on CD8 T cells leads to TNFR-associated factor (TRAF) 2/5-dependent, TRAF1-independent NF-κB induction, resulting in increased Bcl-x(L). In vivo, GITR on CD8 T cells has a profound effect on CD8 T cell expansion, via effects on T cell survival. Moreover, GITR is required on CD8 T cells for enhancement of influenza-specific CD8 T cell expansion upon administration of agonistic anti-GITR Ab, DTA-1. Remarkably, CD8 T cell-intrinsic GITR is essential for mouse survival during severe, but dispensable during mild respiratory influenza infection. These studies highlight the importance of GITR as a CD8 T cell costimulator during acute viral infection, and argue that despite the similarity among several TNFR family members in inducing T lymphocyte survival, they clearly have nonredundant functions in protection from severe infection.