gebhart/patrepeval huggingface dataset:
Precision genome-editing with CRISPR/Cas9 in human induced pluripotent stem cells (2017)

Abstract Genome engineering in human induced pluripotent stem cells (iPSCs) represent an opportunity to examine the contribution of pathogenic and disease modifying alleles to molecular and cellular phenotypes. However, the practical application of genome-editing approaches in human iPSCs has been challenging. We have developed a precise and efficient genome-editing platform that relies on allele-specific guideRNAs (gRNAs) paired with a robust method for culturing and screening the modified iPSC clones. By applying an allele-specific gRNA design strategy, we have demonstrated greatly improved editing efficiency without the introduction of additional modifications of unknown consequence in the genome. Using this approach, we have modified nine independent iPSC lines at five loci associated with neurodegeneration. This genome-editing platform allows for efficient and precise production of isogenic cell lines for disease modeling. Because the impact of CRISPR/Cas9 on off-target sites remains poorly understood, we went on to perform thorough off-target profiling by comparing the mutational burden in edited iPSC lines using whole genome sequencing. The bioinformatically predicted off-target sites were unmodified in all edited iPSC lines. We also found that the numbers of de novo genetic variants detected in the edited and unedited iPSC lines were similar. Thus, our CRISPR/Cas9 strategy does not specifically increase the mutational burden. Furthermore, our analyses of the de novo genetic variants that occur during iPSC culture and genome-editing indicate an enrichment of de novo variants at sites identified in dbSNP. Taken together, we propose that this enrichment represents regions of the genome more susceptible to mutation. Herein, we present an efficient and precise method for allele-specific genome-editing in iPSC and an analyses pipeline to distinguish off-target events from de novo mutations occurring with culture.
Autoxidation of 5-methyl-5,6,7,8-tetrahydrofolic acid (1975)

The autoxidation of 5-Methyl-5,6,7,8-tetrahydrofolic acid has been studied by kinetic methods and product analysis. The yields of the two major products, 5-methyl-5,6-dihydrofolic acid and 4a-hydroxy-5-methyl-4a,5,6,7-tetrahydrofolic acid, were determined under a variety of conditions. Attempts to observe or isolate possible intermediate organic hydroperoxides failed. A mechanistic interpretation is considered.
A robust wireless infrared system with channel reciprocity (1998)

Mobile computing devices require reliable wireless communication links, whereby data rates, transmission range, and power consumption fit the particular needs of the various types of devices. Proper designs of physical layer functions and medium access control mechanisms are crucial for efficient connectivity and coexistence among all participants in a communication cell. We describe a solution for reliable wireless infrared connectivity based on infrared channel reciprocity. Robust header signalling, and variable data rate coding.
Combining Structural Information and the Use of Priors in Mixed Named-Page and Homepage Finding. (2003)

This paper presents Carnegie Mellon University’s experiments on the mixed named-page and homepage finding task of the TREC 12 Web Track. Our results were strong; we achieved the success using language models estimated from combining information from document text, in-link text, and information present in the structure of the documents. We also present experiments using expectations about posterior distributions to create class-based prior probabilities. We find that priors do provide a large gain for our official runs, but we do further experiments that show the priors do not always help. Some preliminary analysis shows that the prior probabilities are not providing the desired posterior distributions. In cases where applying the priors harm performance, the observed posterior distributions in the rankings are far off of the desired posterior distributions. 1.
Synthesis of Pentafluorosulfanylpyrazole and Pentafluorosulfanyl-1,2,3-triazole and Their Derivatives as Energetic Materials by Click Chemistry (2007)

1-Pentafluorosulfanyl acetylene and its derivatives react with azide or diazomethane giving rise to an SF5-substituted 1,2,3-triazole or pyrazole. The SF5 group increases density remarkably and as a result enhances the detonation performance of the energetic materials relative to the CF3 group.
Performance evaluation of an ultra-low power receiver for body area networks (BAN) (2010)

The main bottleneck to achieve energy autonomy in body area networks (BAN) is the design of an ultra low power yet reliable wireless system. In this paper, we first demonstrate the feasibility of an ultra low power receiver by presenting our implemented receiver chip that could operate on a total power of 479.5 uW, which is more than one order of magnitude lower than commercially available low power transceivers working at 2.4 GHz. We then show the reliability of this chip, which can achieve a receiver sensitivity of -72 dBm for a data rate of 1 Mbps. We further demonstrate that this receiver sensitivity is sufficient to guarantee reliability by evaluating this chip in different to-body communication in BAN environments. By using typical BAN channels, simulation results show that our system can provide a reliable link in both the standing and walking situations. With the measured data, we show that a transmit power of -15 dBm is sufficient for our receiver to achieve reliable communication link in different BAN environments. This transmit power requirement is 15 dB lower than the widely known low power Zigbee system. It could thus significantly facilitate the ultra low power transmitter design, and minimize the human exposure to radio frequency electromagnetic fields. The design and evaluation of our receiver presented in this paper therefore provides a way to move towards the energy autonomy of BAN, and opens access to many new applications in BAN.
ELECTRONICALLY TUNABLE ACOUSTO-OPTIC FILTER (1969)

Experimental results on a new type of electronically tunable optical filter are described. Tuning from 7000 to 5500 Å has been obtained by changing an acoustic driving frequency from 750 to 1050 MHz. A band pass of less than 2 Å, a corrected peak transmission of 50%, and an average skirt rejection ratio of about 45 dB have been obtained.
Experimental support for the evolution of symmetric protein architecture from a simple peptide motif (2010)

The majority of protein architectures exhibit elements of structural symmetry, and "gene duplication and fusion" is the evolutionary mechanism generally hypothesized to be responsible for their emergence from simple peptide motifs. Despite the central importance of the gene duplication and fusion hypothesis, experimental support for a plausible evolutionary pathway for a specific protein architecture has yet to be effectively demonstrated. To address this question, a unique "top-down symmetric deconstruction" strategy was utilized to successfully identify a simple peptide motif capable of recapitulating, via gene duplication and fusion processes, a symmetric protein architecture (the threefold symmetric β-trefoil fold). The folding properties of intermediary forms in this deconstruction agree precisely with a previously proposed "conserved architecture" model for symmetric protein evolution. Furthermore, a route through foldable sequence-space between the simple peptide motif and extant protein fold is demonstrated. These results provide compelling experimental support for a plausible evolutionary pathway of symmetric protein architecture via gene duplication and fusion processes.
Quantitative Determination of Creatine Kinase Isoenzyme Catalytic Concentrations in Serum Using Immunological Methods (1977)

For the determination of creatine kinase isoenzyme catalytic concentrations in serum two methods based on immunological reactions are presented: One method uses inhibiting antibodies, which selectively block the activity of creatine kinase M subunits ("Inhibition Test"). This test is used for routine measurements of creatine kinase MB catalytic concentration; Another method uses precipitating antibodies, which allows a quantitative differentiation of creatine kinase isoenzymes MM, MB and BB ("Precipitation Test"). This test is used as a control for the Inhibition Test for the possible presence of creatine kinase BB activities in doubtful cases. Procedures, specificity, correlation and application of these methods are discussed.
Genetic Mapping of Factors Affecting Quantitative Variation for Flowering in Sunflower (2000)

The number of days from seedling emergence to flowering (DTF) is a major consideration in sunflower ( Helianthus annuus L.) breeding because the maximum yield of the crop can only be achieved if the cultivars are phenologically adapted to the production environment. Identification of genetic factors that affect flowering could create opportunities for improved breeding methods and for more fundamental investigations of this important trait and its interactions with the environment. The objectives of this study were to locate quantitative trait loci (QTL) for DTF in an elite sunflower population evaluated in four environments. Two hundred thirty‐five F 2 ‐generation plants and their F 3 progeny of a single‐cross population of two divergent inbred lines were evaluated in four environments (Fargo, ND and Venado Tuerto, Daireaux, and Balcarce in Argentina). Detection of QTL was facilitated with a genetic linkage map of 205 loci defined by restriction fragment length polymorphism (RFLP) and composite interval mapping. Five QTL of five linkage groups accounted for 89% of the genetic variation for DTF. Gene action was additive at four QTL and dominant at the other locus. Three QTL were detected in all environments and generations. The parental effects and the relative magnitudes of the genetic effects of those QTL were consistent across generations and environments.
A low-power 128-tap digital adaptive equalizer for broadband modems (1997)

This paper describes a modem receiver chip containing two 64-tap adaptive finite impulse response (FIR) filters configured in parallel as in-phase and quadrature-phase filters. Each filter has a span of 16 symbols and can be configured for T/2, T/3, or T/4 fractional spacing. A zero-latency pipeline technique is used that allows adaptive filters of arbitrary length without degrading the speed. Power is saved at the algorithmic, architectural, and circuit levels. The chip has support for dynamically tuning coefficient precision, updating rates and filter lengths to reduce power consumption. The chip was fabricated in 0.5-/spl mu/m CMOS technology and consumes 535 mW of power when operating at 50 MHz with 128 taps, T/4 spacing, and symbol-rate power-of-two LMS updating. This can be further reduced to 280 mW using dynamic power reduction techniques. The power in the FIR filter is 162 mW with maximum precision converged coefficients which corresponds to 5.1 mW per multiply-accumulate operation.
Glycolipid Antigen Processing for Presentation by CD1d Molecules (2001)

The requirement for processing glycolipid antigens in T cell recognition was examined with mouse CD1d-mediated responses to glycosphingolipids (GSLs). Although some disaccharide GSL antigens can be recognized without processing, the responses to three other antigens, including the disaccharide GSL Gal(alpha1-->2)GalCer (Gal, galactose; GalCer, galactosylceramide), required removal of the terminal sugars to permit interaction with the T cell receptor. A lysosomal enzyme, alpha-galactosidase A, was responsible for the processing of Gal(alpha1-->2)GalCer to generate the antigenic monosaccharide epitope. These data demonstrate a carbohydrate antigen processing system analogous to that used for peptides and an ability of T cells to recognize processed fragments of complex glycolipids.
Reverse engineering of dependency graphs via dynamic analysis (2011)

Reverse engineering of software systems often employs static analysis of a program's source code. In this invited talk, I will present our approach to reverse engineering of software systems via analyzing monitoring data of a programs operational use; thus, via dynamic analysis. Our Kieker monitoring framework generates dependency graphs from observed monitoring data. It is used in several industrial cooperations on which I'll report.
Rifabutin‐based <i>Helicobacter pylori</i> eradication ‘rescue therapy’ (2001)

SIRS, We read with interest the work by Perri et al. on the efficacy of a rifabutin-based Helicobacter pylori eradication regimen in patients who remained positive after three or more courses of 7-day standard therapies.1 In order to verify rifabutin efficacy and tolerability, we carried out a 10-day trial with the following regimen: omeprazole (20 mg b.d.), amoxicillin (1 g b.d.), rifabutin (300 mg o.m.). All 10 patients (7 male, mean age 36 years) had multiple unsuccessful eradication attempts, and agreed to be submitted to the therapy. We obtained good eradication rates: 77% of patients (7/9) by per protocol analysis and 70% by intention-to-treat analysis (7/10). However, one patient withdrew after 6 days of therapy: he developed fever with a severe leukopenia and trombocytopenia that continued for several days after discontinuation of rifabutin. His absolute WBC count fell below 2000/mm3, and his platelet count fell below 100 000/mm3 at day 7. His bone marrow aspirate indicated that neutropenia was a result of myelotoxicity. His white blood cell count returned to normal at day 15 after discontinuation of therapy. Our results confirm the efficacy of rifabutin in eradicating H. pylori in patients ‘resistant’ to standard regimens, nevertheless physicians should be aware of the risk of major side-effects arising during a rifabutin-based regimen. The myelotoxicity of rifabutin has been described during longer exposure (> 10 days) and at a higher dosage (> 600 mg/day).2, 3 Important drug interactions with commonly-used antibiotics can also be speculated—for example, with clarithromycin in combination therapy, because rifabutin induces cytochrome P-450.4 Finally, since the Italian Ministry of Health and the FDA indications for the use of rifabutin are restricted to prevention or cure of Mycobacterium avium complex disease in HIV-infected patients, the use of this drug outside this indication is questionable.
Development and characteristics of myrosinase in <i>Brassica napus</i> during early seedling growth (1991)

Myrosinase (β‐thioglucoside glucohydroase, E. C. 3.2.3.1) proteins with different physical, but similar kinetic characteristics exist in oilseed rape ( Brassica napus L. cv. Bienvenu) seedlings. Two protein fractions have been described which are immunologically, and therefore likely to be structurally, related. Myrosinase I, a dimeric 156 kDa glycosylated protein was purified to apparent homogeneity, and polyclonal antibodies were raised against this protein. Myrosinase II, in comparison, was significantly less glycosylated. The native protein had a molecular weight of approximately 188 kDa, with subunit M r 's of mainly 62 kDa and also 68 kDa. Total ‘potential’enzyme activity (assayed in the presence of ascorbic acid activator) increased during early seedling growth. Immunoblot analysis of seedling proteins showed that this is directly related to an increase in the amount of myrosinase protein itself , predominantly myrosinase II proteins, which are not present in the dry seed. Myrosinase II protein is located exclusively in the cotyledons of 5‐day‐old seedlings, whilst myrosinase I is distributed throughout the seedling.
Ubiquilin Modifies TDP-43 Toxicity in a Drosophila Model of Amyotrophic Lateral Sclerosis (ALS) (2010)

TDP-43 (43-kDa TAR DNA-binding protein) is a major constituent of ubiquitin-positive cytosolic aggregates present in neurons of patients with amyotrophic lateral sclerosis (ALS) and ubiquitin-positive fronto-temporal lobar degeneration (FTLD-U). Inherited mutations in TDP-43 have been linked to familial forms of ALS, indicating a key role for TDP-43 in disease pathogenesis. Here, we describe a Drosophila melanogaster model of TDP-43 proteinopathy. Expression of wild-type human TDP-43 protein in Drosophila motor neurons led to motor dysfunction and dramatic reduction of life span. Interestingly, coexpression of ubiquilin 1, a previously identified TDP-43-interacting protein with suspected functions in autophagy and proteasome targeting, reduced steady-state TDP-43 expression but enhanced the severity of TDP-43 phenotypes. Finally, ectopically expressed TDP-43 was largely localized to motor neuron nuclei, suggesting that expression of wild-type TDP-43 alone is detrimental even in the absence of cytosolic aggregation. Our findings demonstrate that TDP-43 exerts cell-autonomous neurotoxicity in Drosophila and further imply that dose-dependent alterations of TDP-43 nuclear function may underlie motor neuron death in ALS.
Reactions of spin-label crosslinking reagents with red blood cell proteins (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReactions of spin-label crosslinking reagents with red blood cell proteinsGary L. Willingham and Betty Jean GaffneyCite this: Biochemistry 1983, 22, 4, 892–898Publication Date (Print):February 15, 1983Publication History Published online1 May 2002Published inissue 15 February 1983https://pubs.acs.org/doi/10.1021/bi00273a028https://doi.org/10.1021/bi00273a028research-articleACS PublicationsRequest reuse permissionsArticle Views45Altmetric-Citations15LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Phenol oxidation and biosynthesis. Part 26. Isonitriles in the synthesis of benzylisoquinoline derivatives (1979)

Lithiomethyl and toluene-4-sulphonyl(potassiomethyl)isonitriles have been applied in short high-yield homologations of O-benzylvanillin, O-benzylisovanillin, and veratraldehyde giving N-(2-arylethyl)-2-arylacetamides and subsequently isoquinoline derivatives. These experiments are relevant to the preparation of alkaloids including papaverine and reticuline.
Oxygen-induced mitochondrial damage and aging (1992)

Although the views of Harman and Gerschman provide a reasonable explanation for many of the effects of aging, they fail to explain why many cell types, from amoebae to mammalian spermatogonia, do not show a time-related involution, while other cells (especially the neurons) change with age. We feel that a better understanding of senescence (from the molecular to the organ and organismic levels) can be gained by integrating the free radical theory of aging with the classic concepts of Minot and Pearl on the role of cell differentiation and metabolic rate in, respectively, triggering and pacing senescence. In agreement with the above, we maintain that aging is the non-programmed but unavoidable "side effect" of oxy-radical damage to the membrane and genome of the mitochondria of irreversibly differentiated cells. If oxy-radical damage to mtDNA occurs, it will block the rejuvenation of the mitochondrial population by the process of organelle division, thus leading to bioenergetic decline and cellular death.
Multilayer silicon cavity mirrors for the far-infrared p-Ge laser (2005)

Multilayer mirrors capable of > 99.9% reflectivity in the far infrared (70-200 microm wavelengths) were constructed using thin silicon etalons separated by empty gaps. Calculations indicate that only three periods are required to produce 99.9% reflectivity because of the large difference between the index of refraction of silicon (3.384) and the vacuum (1). The mirror was assembled from high-purity silicon wafers, with resistivity over 4000 omega cm to reduce free-carrier absorption. Wafers were double-side polished with faces parallel within 10 arc sec. The multilayer mirror was demonstrated as a cavity mirror for the far-infrared p-Ge laser. Dependence of reflectivity on design accuracy was considered.
Frequency and voltage planning for multi-core processors under thermal constraints (2008)

Clock frequency and transistor density increases have resulted in elevated chip temperatures. In order to meet temperature constraints while still exploiting the performance opportunities enabled by continued scaling, chip designers have migrated towards multi-core architectures. Multi-core architectures use multiple cores running at moderate clock frequencies to run several threads concurrently, which increases overall system throughput. In this work, we propose novel methods to find the optimal operating parameters, i.e., frequency and voltage, that maximize a multi-core system throughput under thermal constraints. By adjusting core clock frequencies and voltages, on-chip power dissipation can be spatially and temporally distributed to maximize the chippsilas physical performance during runtime. We propose a simple, yet efficient model that accurately characterize the effects that changes in clock frequency and voltage have on on-chip temperatures. Using the model, we find the optimal operating conditions for the following scenarios: (1) standard processor performance, where various cores operate using identical operating parameters, (2) optimal processor performance where each core can have its own frequency and voltage, and (3) optimal processor performance with thread priorities, where each core runs a thread of varied importance. We run several experiments across six different technology nodes to validate the work, assuring that our models and methods are accurate. Our methods demonstrate the total physical performance of a multi-core system can be increased by up to 33.4% without violating the maximum temperature constraints.