gebhart/patrepeval huggingface dataset:
TREM2 Risk Variant and Loss of Brain Tissue (2013)

We were intrigued by reports of a discovery of a rare variant in TREM2 (1–3) that roughly triples the lifetime risk of Alzheimer’s disease (AD). The frequency of this risk variant was reported as 0.63% in the Icelandic population (1) and is somewhat variable across populations (see Supplement). Here we aimed to understand how the gene variant affects AD risk by mapping its effects on brain in 478 subjects (mean age: 75.5±6.5 years; 283M/195F; 100 with AD, 221 with mild cognitive impairment and 157 healthy controls) from the Alzheimer’s Disease Neuroimaging Initiative, scanned with brain MRI every year for 2 years (4). Using tensor-based morphometry, we computed the rates of brain tissue loss, per year, over 24 months from the baseline MRI in a statistically-defined region of interest, based on voxels with significant atrophic rates over time within the temporal lobes in AD (4). We then tested the hypothesis that annual brain loss rates, over time, in this region are associated with carrying the risk allele of rs9394721, a close proxy for the newly discovered risk variant, rs75932628, in TREM2 (r2=0.492; see Supplement). We report that TREM2 mutation carriers annually lose brain tissue up to 1.4–3.3% faster than non-carriers, in a pattern that mirrors the profile of AD pathology in the brain (Figure 1). Mutation carriers lose brain tissue twice as fast as healthy elderly people (Table 2S). After adjusting for age and sex, the risk allele was also significantly associated with smaller hippocampal volumes, elevated levels of cerebrospinal fluid (CSF) biomarker p-tau181p, which are usually observed in AD (5), and poorer cognitive performance (see Supplement) based on the standard clinical dementia rating scale (CDR) and Alzheimer’s Disease Assessment Scale (ADAS-cog), assessed at baseline MRI scan and after 24 months’ follow-up (Table 1S). The TREM2 risk variant may affect signaling by TREM2 receptors expressed on microglial cells in the brain, perhaps interfering with the anti-inflammatory functions of these cells and their removal of apoptotic tissue. This may affect brain amyloid clearance, leading to AD-like neurodegeneration and accelerated cognitive decline (2). Selection of carriers of this risk variant and probably other TREM2 risk variants for enrollment in trials of interventions to treat persons with Alzheimer’s disease, in which MRI scans are used in obtaining outcomes, should increase the power of such trials.



Figure 1

At a 24-month follow-up scan, these 3D regression coefficient maps show brain volume differences in the temporal lobe associated with carrying the TREM2 risk allele. The risk allele carriers showed significantly accelerated brain atrophy from 1.4–3.3% ...
Detection of chemical mutagens using Muta<sup>®</sup> Mouse: a transgenic mouse model (1993)

A transgenic mouse strain with a high copy number of rescuable lacZ sequences was evaluated for its effectiveness in detecting lacZ- mutations in selected tissues. Procarbazine, cyclophosphamide, ethylnitrosourea, 7,12-dimethylbenz[a]anthracene (DMBA), acrylamide and chlorambucil were tested following either single or repeated dosing regimens. Bone marrow, liver, skin and testis tissues were selected to assess as target sites for mutation. Bone marrow, liver and testis tissues were examined for mutation following exposures to ethylnitrosourea and chlorambucil. Increased mutant frequencies were found for both chemicals in all three tissues. Bone marrow tissue was examined for mutation following procarbazine, cyclophosphamide and acrylamide exposures, and skin was examined for mutation following dermal application of DMBA. Mutation induction was observed in all cases. The results obtained from this investigation demonstrate the applicability of this transgenic mouse as an effective model to detect and analyze gene mutation in selected organs including germinal tissues. Studies of organotrophic chemical mutagens and carcinogens are possible with this model as are studies of the susceptibility of germinal tissues to mutagen exposures.
Newnes Engineering Science Pocket Book Ed. 3 (2001)

Newnes Engineering Science Pocket Book is a uniquely versatile and practical tool for a wide range of engineers and students. All the fundamentals of electrical and mechanical engineering science and physics are covered, with an emphasis on concise descriptions, key methods, clear diagrams, formulae and how to use them. John Bird's presentations of this core material puts all the answers at your fingertips.The contents of this book have been carefully matched to the latest Further and Higher Education syllabuses so that it can also be used as a revision guide or a quick-access source of underpinning knowledge. Students on competence-based courses such as NVQs will find this approach particularly refreshing and practical.
RNA interference in <i>Histoplasma capsulatum</i> demonstrates a role for α‐(1,3)‐glucan in virulence (2004)

Histoplasma capsulatum is a fungal pathogen that causes respiratory and systemic disease by proliferating within macrophages. While much is known about histoplasmosis, only a single virulence factor has been defined, in part because of the inefficiency of Histoplasma reverse genetics. As an alternative to allelic replacement, we have developed a telomeric plasmid-based system for silencing gene expression in Histoplasma by RNA interference (RNAi). Episomal expression of long RNAs that form stem-loop structures triggered gene silencing. To test the effectiveness of RNAi in Histoplasma, we depleted expression of a gfp transgene as well as two endogenous genes, ADE2 and URA5, and showed significant reductions in corresponding gene function. Silencing was target gene specific, stable during macrophage infection and reversible. We used RNAi targeting AGS1 (encoding alpha-(1,3)-glucan synthase) to deplete levels of alpha-(1,3)-glucan, a cell wall polysaccharide. Loss of alpha-(1,3)-glucan by RNAi yielded phenotypes indistinguishable from an AGS1 deletion: attenuation of the ability to kill macrophages and colonize murine lungs. This demonstrates for the first time that alpha-(1,3)-glucan is an important contributor to Histoplasma virulence.
The Mechanism of Kynurenine Hydrolysis Catalyzed by Kynureninase (1979)

Several kynurenine analogs have been prepared and examined for their susceptibility to hydrolytic cleavage by bacterial kynureninase. In addition to L-kynurenine, 4-fluoro- and 5-fluoro-L-kynurenines were hydrolyzed rapidly. 3-Hydroxy-, 5-hydroxy-, 5-methyl-, and N'-formyl-L-kynurenines, and beta-benzoyl-DL-alanine were hydrolyzed slowly, whereas D-kynurenine, S-benzyl-L-cysteine, and L-asparagine were not hydrolyzed. Kinetic parameters for these kynurenine analogs indicate that a substituent on the benzene ring of kynurenine does not greatly affect the affinity of the enzyme for the substrate but does markedly affect the rate of hydrolysis. gamma-(o-Aminophenyl)-L-homoserine was converted into L-alanine and o-amino-benzaldehyde, suggesting that the sigma-bond electrons between the beta- and gamma-carbon atoms of this kynurenine analog remain in the alanyl moiety during the enzyme reaction. Aromatic compounds such as o-aminobenzaldehyde and o-aminoacetophenone strongly inhibited the kynurenine hydrolysis. It was shown that kynurenic acid is not produced by kynureninase by the use of isotopically labeled substrate. A small amount of pyruvate was definitely formed in the kynureninase reaction. On the basis of these results, a reaction mechanism is proposed for the enzymatic kynurenine cleavage, involving hydrolysis of the alpha, gamma-diketone intermediate to give anthranilic acid and the pyruvate-pyridoxamine 5'-phosphate Schiff base, which is further converted into the alanine-pyridoxal 5'-phosphate Schiff base, or directly hydrolyzed to give pyruvate and the pyridoxamine 5'-phosphate form of the enzyme.
Vessel Pattern Knowledge Discovery from AIS Data: A Framework for Anomaly Detection and Route Prediction (2013)

Understanding maritime traffic patterns is key to Maritime Situational Awareness applications, in particular, to classify and predict activities. Facilitated by the recent build-up of terrestrial networks and satellite constellations of Automatic Identification System (AIS) receivers, ship movement information is becoming increasingly available, both in coastal areas and open waters. The resulting amount of information is increasingly overwhelming to human operators, requiring the aid of automatic processing to synthesize the behaviors of interest in a clear and effective way. Although AIS data are only legally required for larger vessels, their use is growing, and they can be effectively used to infer different levels of contextual information, from the characterization of ports and off-shore platforms to spatial and temporal distributions of routes. An unsupervised and incremental learning approach to the extraction of maritime movement patterns is presented here to convert from raw data to information supporting decisions. This is a basis for automatically detecting anomalies and projecting current trajectories and patterns into the future. The proposed methodology, called TREAD (Traffic Route Extraction and Anomaly Detection) was developed for different levels of intermittency (i.e., sensor coverage and performance), persistence (i.e., time lag between subsequent observations) and data sources (i.e., ground-based and space-based receivers).
Visibility estimation from a moving vehicle using the RALPH vision system (2002)

Reduced visibility is a common casual factor in many traffic accidents. This paper describes a forward looking vision system which simultaneously tracks the lane and estimates visibility. The system estimates the visibility by measuring the attenuation of contrast between consistent road features at various distances ahead of the vehicle. Results of experiments on simulated images, as well as live vehicle tests are presented.
An Ultra-Low-Power ADPLL for BLE Applications (2014)

In recent years, wireless personal area network (WPAN) applications have triggered the needs for low-cost and low-power PLLs which also provide good performance. All-digital phased-locked loops (ADPLLs) are preferred over their analog counterparts in nanoscale CMOS technology due to their flexibility, configurability, small area and easy portability. However, fractional spurs and insufficiently low power dissipation are main problems related to conventional TDC-based structures. In this work, a sub-half mW 2.2 GHz - 3 GHz fractional-N ADPLL is presented for Bluetooth Low Energy (BLE) applications. Coarse-fine DTC based phase predictor with dynamic element matching (DEM) ability and clock gated phase error freezer are proposed to reduce the power while maintaining good phase noise and fractional spur performance. This prototype ADPLL was taped out on Sep. 11th 2014 in GlobalFoundries 40 nm Low Power (40 nm-LP) technology. Based on post-layout simulations and modelling, it is expected to consume less than 450 ?W with integrated rms jitter of 1.5 ps for the close integer channel and 800 fs for the rest of channels, leading to a potential state-of-art FoM below -240 dB. Design of the full ADPLL in terms of system level analysis, digital logic, mixed-signal and RF design is presented in the thesis.
Discriminative Reranking for Spelling Correction (2006)

Abstract. This paper proposes a novel approach to spelling correction. It reranks the output of an existing spelling corrector, Aspell. A discriminative model (Ranking SVM) is employed to improve upon the initial ranking, using additional features as evidence. These features are derived from stateof-the-art techniques in spelling correction, including edit distance, letter-based n-gram, phonetic similarity and noisy channel model. This paper also presents a new method to automatically extract training samples from the query log chain. The system outperforms the baseline Aspell greatly, as well as previous models and several off-the-shelf spelling correction systems (e.g. Microsoft Word 2003). The results on query chain pairs are comparable to that based on manually-annotated pairs, with 32.2%/32.6 % reduction in error rate, respectively. 1.
Protograph LDPC Codes over Burst Erasure Channels (2006)

In this paper we design high rate protograph based LDPC codes suitable for binary erasure channels. To simplify the encoder and decoder implementation for high data rate transmission, the structure of codes are based on protographs and circulants. These LDPC codes can improve data link and network layer protocols in support of communication networks. Two classes of codes were designed. One class is designed for large block sizes with an iterative decoding threshold that approaches capacity of binary erasure channels. The other class is designed for short block sizes based on maximizing minimum stopping set size. For high code rates and short blocks the second class outperforms the first class. A scheme is proposed to use these LDPC codes over burst erasure channels. The proposed encoding method is also applicable to cases when packets are frequency hopped over channels with partial band jamming or frequency selective fading. Various LDPC codes are compared and simulation results are provided
Architectural considerations for photonic switching networks (1991)

Photonic technologies are reviewed that could become important components of future telecommunication systems. Photonic devices and systems are divided into two classes according to the function they perform. The first class, relational, refers to devices, that map the input channels to the output channels under external control. The second class, logic, perform some type or combination of Boolean logic functions. Some of the strengths and weaknesses of operating in the photonic domain are presented. Relational devices and their applications are discussed. Optical logic devices and their potential applications are reviewed.
Aneurysm Syndromes Caused by Mutations in the TGF-β Receptor (2006)

Mutations in either TGFBR1 or TGFBR2 predispose patients to aggressive and widespread vascular disease. The severity of the clinical presentation is predictive of the outcome. Genotyping of patients presenting with symptoms like those of vascular Ehlers-Danlos syndrome may be used to guide therapy, including the use and timing of prophylactic vascular surgery.
New Compounds. p-Chlorophenyl Phenacyl Sulfide (1946)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNew Compounds. p-Chlorophenyl Phenacyl SulfideIsaiah Von and Marvin CarmackCite this: J. Am. Chem. Soc. 1946, 68, 9, 1867–1868Publication Date (Print):September 1, 1946Publication History Published online6 November 2002Published inissue 1 September 1946https://pubs.acs.org/doi/10.1021/ja01213a600https://doi.org/10.1021/ja01213a600research-articleACS PublicationsRequest reuse permissionsArticle Views32Altmetric-Citations-LEARN 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
A Unified Algorithm for Solving Key Equations for Decoding Alternant Codes (1999)

this paper. This problem may be thought of as an extension of the problem, disclem, by Berlekamp [2] and Massey [14], of finding an element of
D27-pLpxL, an Avirulent Strain of <i>Yersinia pestis</i> , Primes T Cells That Protect against Pneumonic Plague (2009)

Vaccinating with live, conditionally attenuated, pigmentation (Pgm)-deficient Yersinia pestis primes T cells that protect mice against pneumonic plague. However, Pgm-deficient strains are not considered safe for human use because they retain substantial virulence in animal models. Y. pestis strains engineered to express Escherichia coli LpxL are avirulent owing to constitutive production of lipopolysaccharide with increased Toll-like receptor 4-activating ability. We generated an LpxL-expressing Pgm-deficient strain (D27-pLpxL) and demonstrate here that this avirulent strain retains the capacity to prime protective T cells. Compared with unvaccinated controls, mice immunized intranasally with live D27-pLpxL exhibit a decreased bacterial burden and increased survival when challenged intranasally with virulent Y. pestis. T cells provide a substantial degree of this protection, as vaccine efficacy is maintained in B-cell-deficient muMT mice unless those animals are depleted of CD4 and CD8 T cells at the time of challenge. Upon challenge with Y. pestis, pulmonary T-cell numbers decline in naive mice, whereas immunized mice show increased numbers of CD44(high) CD43(high) effector T cells and T cells primed to produce tumor necrosis factor alpha and gamma interferon; neutralizing these cytokines at the time of challenge abrogates protection. Immunization does not prevent dissemination of Y. pestis from the lung but limits bacterial growth and pathology in visceral tissue, apparently by facilitating formation of granuloma-like structures. This study describes a new model for studying T-cell-mediated protection against pneumonic plague and demonstrates the capacity for live, highly attenuated, Y. pestis vaccine strains to prime protective memory T-cell responses safely.
The effects of microgravity on the skeletal system--a review. (1990)

Exposure of astronauts to microgravity leads to the loss of calcium from weightbearing bones. Prolonged exposure, e.g., during a journey to Mars, may present problems on return to Earth, with increased risk of fractures and premature osteoporosis in later life. The precise mechanisms of calcium loss have yet to be determined although a key feature is the absence of mechanical loading. Countermeasures aimed at reducing calcium loss to acceptable levels include the use of exercise, drugs, dietary modifications and inertia suits such as the Soviet "Penguin" suit. Missions of a number of years may, however, require the development of artificial gravity on a spacecraft. The country that first solves the physiological problems of man in space and, in particular, skeletal calcium loss, will almost certainly be the first to be able to put a man on Mars.
Immune tolerance for haemophilia patients with inhibitors: analysis of the western United States experience (2000)

The experience with immune tolerance (IT) induction therapy for haemophilia patients with inhibitors, instituted during 1990-97 at 17 haemophilia treatment centres in the western United States, was reviewed. IT was instituted in 104 of 139 (75%) of all identified haemophilia A and haemophilia B patients with inhibitors. Doses and schedules for IT varied but most patients were treated with a daily administration of 25-200 units kg-1 day-1. Successful immune tolerance (defined as Bethesda Unit titres < 1.0) was achieved in 57 of 81 (78%) patients who completed therapy. IT success was significantly greater for those patients with historic titres < 100 BU (P < 0.0003) and those with titres of < 10 BU at initiation of IT (P < 0.0001). IT success was uniformly achieved in 16 patients with low to moderate responding inhibitors. IT in infants < 2 years of age was problematic due to the presence of high titre inhibitors and complications of venous access. Frequent complications of IT included increased bleeding during intravenous access device insertion (20%) and infections associated with venous access devices (64%). IT is widely accepted as a treatment modality for haemophilia patients with inhibitors. Patient participation in IT regimens and management during therapy is facilitated greatly by the efforts of treatment centre nurse coordinators who are knowledgeable about haemophilia and its complications. Additional clinical trials will be necessary to define better initial dose, schedule, dose adjustment and success/failure criteria for IT.
Kinetic Basis for the Donor Nudeotide-Sugar Specificity of  l,4-N-Acetylglucosaminyltransferase III (2000)

The kinetic basis of the donor substrate specificity of beta1, 4-N-acetylglucosaminyltransferase III (GnT-III) was investigated using a purified recombinant enzyme. The enzyme also transfers GalNAc and Glc moieties from their respective UDP-sugars to an acceptor at rates of 0.1-0.2% of that for GlcNAc, but Gal is not transferred at a detectable rate. Kinetic analyses revealed that these inefficient transfers, which are associated with the specificity of the enzyme, are due to the much lower V(max) values, whereas the K(m) values for UDP-GalNAc and UDP-Glc differ only slightly from that for UDP-GlcNAc. It was also found that various other nucleotide-Glc derivatives bind to the enzyme with comparable affinities to those of UDP-GlcNAc and UDP-Glc, although the derivatives do not serve as glycosyl donors. Thus, GnT-III does not appear to distinguish UDP-GlcNAc from other structurally similar nucleotide-sugars by specific binding in the ground state. These findings suggest that the specificity of GnT-III toward the nucleotide-sugar is determined during the catalytic process. This type of specificity may be efficient in preventing a possible mistransfer when other nucleotide-sugars are present in excess over the true donor.
Influence of the regulatory protein RsmA on cellular functions in Pseudomonas aeruginosa PAO1, as revealed by transcriptome analysis (2006)

RsmA is a posttranscriptional regulatory protein in Pseudomonas aeruginosa that works in tandem with a small non-coding regulatory RNA molecule, RsmB (RsmZ), to regulate the expression of several virulence-related genes, including the N-acyl-homoserine lactone synthase genes lasI and rhlI, and the hydrogen cyanide and rhamnolipid biosynthetic operons. Although these targets of direct RsmA regulation have been identified, the full impact of RsmA on cellular activities is not as yet understood. To address this issue the transcriptome profiles of P. aeruginosa PAO1 and an isogenic rsmA mutant were compared. Loss of RsmA altered the expression of genes involved in a variety of pathways and systems important for virulence, including iron acquisition, biosynthesis of the Pseudomonas quinolone signal (PQS), the formation of multidrug efflux pumps, and motility. Not all of these effects can be explained through the established regulatory roles of RsmA. This study thus provides both a first step towards the identification of further genes under RsmA posttranscriptional control in P. aeruginosa and a fuller understanding of the broader impact of RsmA on cellular functions.