gebhart/patrepeval huggingface dataset:
Evidence‐Based Recommendations for the Assessment and Management of Sleep Disorders in Older Persons (2009)

Sleep-related disorders are most prevalent in the older adult population. A high prevalence of medical and psychosocial comorbidities and the frequent use of multiple medications, rather than aging per se, are major reasons for this. A major concern, often underappreciated and underaddressed by clinicians, is the strong bidirectional relationship between sleep disorders and serious medical problems in older adults. Hypertension, depression, cardiovascular disease, and cerebrovascular disease are examples of diseases that are more likely to develop in individuals with sleep disorders. Conversely, individuals with any of these diseases are at a higher risk of developing sleep disorders. The goals of this article are to help guide clinicians in their general understanding of sleep problems in older persons, examine specific sleep disorders that occur in older persons, and suggest evidence- and expert-based recommendations for the assessment and treatment of sleep disorders in older persons. No such recommendations are available to help clinicians in their daily patient care practices. The four sections in the beginning of the article are titled, Background and Significance, General Review of Sleep, Recommendations Development, and General Approach to Detecting Sleep Disorders in an Ambulatory Setting. These are followed by overviews of specific sleep disorders: Insomnia, Sleep Apnea, Restless Legs Syndrome, Circadian Rhythm Sleep Disorders, Parasomnias, Hypersomnias, and Sleep Disorders in Long-Term Care Settings. Evidence- and expert- based recommendations, developed by a group of sleep and clinical experts, are presented after each sleep disorder.
Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity (2013)

Obesity and type 2 diabetes are characterized by altered gut microbiota, inflammation, and gut barrier disruption. Microbial composition and the mechanisms of interaction with the host that affect gut barrier function during obesity and type 2 diabetes have not been elucidated. We recently isolated Akkermansia muciniphila, which is a mucin-degrading bacterium that resides in the mucus layer. The presence of this bacterium inversely correlates with body weight in rodents and humans. However, the precise physiological roles played by this bacterium during obesity and metabolic disorders are unknown. This study demonstrated that the abundance of A. muciniphila decreased in obese and type 2 diabetic mice. We also observed that prebiotic feeding normalized A. muciniphila abundance, which correlated with an improved metabolic profile. In addition, we demonstrated that A. muciniphila treatment reversed high-fat diet-induced metabolic disorders, including fat-mass gain, metabolic endotoxemia, adipose tissue inflammation, and insulin resistance. A. muciniphila administration increased the intestinal levels of endocannabinoids that control inflammation, the gut barrier, and gut peptide secretion. Finally, we demonstrated that all these effects required viable A. muciniphila because treatment with heat-killed cells did not improve the metabolic profile or the mucus layer thickness. In summary, this study provides substantial insight into the intricate mechanisms of bacterial (i.e., A. muciniphila) regulation of the cross-talk between the host and gut microbiota. These results also provide a rationale for the development of a treatment that uses this human mucus colonizer for the prevention or treatment of obesity and its associated metabolic disorders.
G Protein-coupled Receptor Kinases Promote Phosphorylation and β-Arrestin-mediated Internalization of CCR5 Homo- and Hetero-oligomers (2005)

Expression levels of the chemokine receptor, CC chemokine receptor 5 (CCR5), at the cell surface determine cell susceptibility to HIV entry and infection. Cellular activation by CCR5 itself, but also by unrelated receptors leads to cross-phosphorylation and cross-internalization of CCR5. This study addresses the underlying molecular mechanisms of homologous and heterologous CCR5 regulation. As shown by bioluminescence resonance energy transfer experiments, CCR5 formed constitutive homo- as well as heterooligomeric complexes together with C5aR but not with the unrelated AT(1a)R in living cells. Stimulation with CCL5 of RBL cells, which co-expressed CCR5 together with an N-terminally truncated CCR5-DeltaNT mutant, resulted in both protein kinase C (PKC)- and G protein-coupled receptor (GPCR) kinase (GRK)-mediated cross-phosphorylation of the mutant unligated receptor, as determined by phosphosite-specific monoclonal antibody. Similarly, both PKC and GRK cross-phosphorylated CCR5 in a heterologous manner after C5a stimulation of RBL-CCR5/C5aR cells, whereas AT(1a)R stimulation resulted only in classical PKC-mediated CCR5 phosphorylation. Co-expression of CCR5-DeltaNT together with a phosphorylation-deficient CCR5 mutant that neither binds beta-arrestin nor undergoes internalization partially restored the CCL5-induced association of beta-arrestin with the homo-oligomeric receptor complex and augmented cellular uptake of (125)I-CCL5. Co-expression of C5aR, but not of AT(1a)R, promoted CCR5 co-internalization upon agonist stimulation by a mechanism independent of CCR5 phosphorylation. Co-internalization of phosphorylated CCR5 was also observed in C5a-stimulated macrophages. Finally, co-expression of a constitutively internalized C5aR-US28(CT) mutant led to intracellular accumulation of CCR5 in the absence of ligand stimulation. These results show that GRKs and beta-arrestin are involved in heterologous receptor regulation by cross-phosphorylating and co-internalizing unligated receptors within homo- or hetero-oligomeric protein complexes.
Deformation of carbon nanotubes by surface van der Waals forces (1998)

The strength and effect of surface van der Waals forces on the shape of multiwalled and single-walled carbon nanotubes is investigated using atomic-force microscopy, continuum mechanics, and molecular-mechanics simulations. Our calculations show that depending on the tube diameter and number of shells, the van der Waals interaction between nanotubes and a substrate results in high binding energies, which has also been determined experimentally. Nanotubes on a substrate may consequently experience radial and axial deformations, which significantly modify the idealized geometry of free nanotubes. These findings have implications for electronic transport and the tribological properties of adsorbed nanotubes.
Towards enterprise software as a service in the cloud (2010)

For traditional data warehouses, mostly large and expensive server and storage systems are used. In particular, for small- and medium size companies, it is often too expensive to run or rent such systems. These companies might need analytical services only from time to time, for example at the end of a billing period. A solution to overcome these problems is to use Cloud Computing. In this paper, we report on work-in-progress towards building an OLAP cluster of multi-tenant main memory column databases on the Amazon EC2 cloud computing environment, for which purpose we ported SAP's in-memory column database TREX to run in the Amazon cloud. We discuss early findings on cost/performance tradeoffs between reliably storing the data of a tenant on a single node using a highly-available network attached storage, such as Amazon EBS, vs. replication of tenant data to a secondary node where the data resides on less resilient storage. We also describe a mechanism to provide support for historical queries across older snapshots of tenant data which is lazy-loaded from Amazon's S3 near-line archiving storage and cached on the local VM disks.
Solid-phase enzyme-immunoassay for detection of hepatitis B surface antigen. (1976)

The preliminary results of a solid-phase enzyme-immunoassay (EIA) for the detection of hepatitis B surface antigen (HBsAg) are presented. This method has been compared with the solid-phase radioimmunoassay (RIA) for HBsAg in dilution series of four HBsAg positive sera four national reference panels (The Laboratory Panel of the Central Laboratory of the Blood Transfusion Service of the Netherlands Red Cross, USA BOB Reference Panels Nos 2 and 3, and the 1st Panel of the National Reference Centre for virus Hepatitis at the Institute of Hygiene of the University of Göttingen, West Germany). In addition, the two test methods were compared in a weekly (up to 16 weeks) follow-up of 14 patients with acute viral hepatitis B. It was seen that, both by reading EIA test results with the naked eye and by colorimetric reading, the sensitivity and specificity of this test method compared very favourably with those of the RIA. EIA may have a slightly lower sensitivity than RIA for the subtype ad, while its sensitivity for the subtype ay may be slightly higher than that of RIA. These minor sensitivity differences may be due to the specificity profiles of the antisera used.
The CRISPR endoribonuclease Csy4 utilizes unusual sequence- and structure-specific mechanisms to recognize and process crRNAs (2012)

Many prokaryotes contain clustered regularly interspaced short palindromic repeats (CRISPRs) that together with CRISPR-associated (&lt;italic&gt;cas&lt;/italic&gt;) genes confer resistance to invasive genetic elements. Central to this immune system is the production of CRISPR-derived RNAs (crRNAs) via enzymatic cleavage of CRISPR locus transcripts. These crRNAs serve as guides for foreign nucleic acid targeting and degradation. Here we identify Csy4 as the endoribonuclease responsible for CRISPR transcript processing in &lt;italic&gt;Pseudomonas aeruginosa&lt;/italic&gt; UCBPP-PA14. Biochemical assays and six co-crystal structures of Csy4 bound to substrate and product crRNAs reveal the complex mechanisms Csy4 utilizes to recognize, position, and cleave its cognate RNA substrate in order to generate mature crRNAs. Csy4 makes sequence-specific contacts to the major groove of its cognate RNA stem-loop and makes extensive electrostatic interactions with the phosphate backbone that are highly sensitive to the helical geometry of the substrate, resulting in an extremely high affinity binding interaction (&lt;italic&gt;K&lt;/italic&gt;&lt;sub&gt;d&lt;/sub&gt; &amp;#8776; 50 pM). Csy4 has equally tight affinity for both its substrate and product RNAs and therefore functions &lt;italic&gt;in vivo&lt;/italic&gt; as a single turnover catalyst. Phylogenetically conserved serine and histidine residues constitute a catalytic dyad in which the serine pins the ribosyl 2&amp;#8242;-hydroxyl nucleophile in place, allowing the histidine to deprotonate the active site 2&amp;#8242;-hydroxyl, leading to nucleophilic attack on the scissile phosphate. The Csy4 active site lacks a general acid to protonate the leaving group and positively charged residues to stabilize the transition state, explaining why the observed catalytic rate constant is ~10&lt;super&gt;4&lt;/super&gt;-fold slower than that of RNase A. The RNA cleavage step carried out by Csy4 is essential for assembly of the Csy protein-crRNA complex that facilitates target recognition. Considering that Csy4 recognizes a single cellular substrate and subsequently sequesters the cleavage product, evolutionary pressure has likely selected for substrate specificity and high-affinity crRNA interactions at the expense of rapid cleavage kinetics.A major goal of synthetic biology is to construct reliable and predictable genetic circuits. However, synthetic genetic systems often perform unpredictably due to structural interactions between DNA, RNA, and protein components. Here we present a novel synthetic RNA processing platform utilizing Csy4 and its cognate target RNA to physically separate otherwise linked genetic elements such as promoters, ribosome binding sites, &lt;italic&gt;cis&lt;/italic&gt; regulatory elements, and riboregulators. Implementation of this platform provides a general approach for creating context-free standard genetic elements that can be readily applied to the bottom-up construction of increasingly complex biological systems in a plug-and-play manner.
Monitoring integrated networks for performance management (1990)

An object-oriented model for network independent monitoring and performance evaluation in real-time is presented. the model describes the behavior of network objects by a set of state variables and a set of invariants. The model is used to evaluate quality-of-service characteristics of different classes of traffic in an integrated network testbed. An objective-driven measurement strategy to establish the dynamic database of the network is discussed. A statistical database derived from the dynamic database is also obtained.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Hearables: Multimodal physiological in-ear sensing (2017)

Future health systems require the means to assess and track the neural and physiological function of a user over long periods of time, and in the community. Human body responses are manifested through multiple, interacting modalities - the mechanical, electrical and chemical; yet, current physiological monitors (e.g. actigraphy, heart rate) largely lack in cross-modal ability, are inconvenient and/or stigmatizing. We address these challenges through an inconspicuous earpiece, which benefits from the relatively stable position of the ear canal with respect to vital organs. Equipped with miniature multimodal sensors, it robustly measures the brain, cardiac and respiratory functions. Comprehensive experiments validate each modality within the proposed earpiece, while its potential in wearable health monitoring is illustrated through case studies spanning these three functions. We further demonstrate how combining data from multiple sensors within such an integrated wearable device improves both the accuracy of measurements and the ability to deal with artifacts in real-world scenarios.
Targeted disruption of the PD78 gene (traF) reduces pheromone-inducible conjugal transfer of the bacteriocin plasmid pPD1 in Enterococcus faecalis (1995)

Bacterial sex pheromone, cPD1, induces sexual aggregation of Enterococcus faecalis harboring the bacteriocin plasmid, pPD1, and enables pPD1 to transfer at high frequency in a liquid culture. PD78 is a cPD1-inducible cell surface protein encoded by pPD1. The PD78 gene, traF, was disrupted by homologous recombination between pPD1 and an artificial vector having a deletion in the middle portion of traF. The disruption of traF did not affect the cPD1-inducible aggregation but reduced the transfer frequency of pPD1 to 2% of the wild-type level.
The Direct Binding of Insulin-like Growth Factor-1 (IGF-1) to Integrin αvβ3 Is Involved in IGF-1 Signaling (2009)

It has been proposed that ligand occupancy of integrin alphavbeta3 with extracellular matrix ligands (e.g. vitronectin) plays a critical role in insulin-like growth factor-1 (IGF-1) signaling. We found that expression of alphavbeta3 enhanced IGF-1-induced proliferation of Chinese hamster ovary cells in serum-free conditions (in the absence of vitronectin). We hypothesized that the direct integrin binding to IGF-1 may play a role in IGF-1 signaling. We demonstrated that alphavbeta3 specifically and directly bound to IGF-1 in cell adhesion, enzyme-linked immunosorbent assay-type binding, and surface plasmon resonance studies. We localized the amino acid residues of IGF-1 that are critical for integrin binding by docking simulation and mutagenesis. We found that mutating two Arg residues at positions 36 and 37 in the C-domain of IGF-1 to Glu (the R36E/R37E mutation) effectively reduced integrin binding. Interestingly, although the mutant still bound to IGF1R, it was defective in inducing IGF1R phosphorylation, AKT and ERK1/2 activation, and cell proliferation. Furthermore wild type IGF-1 mediated co-precipitation of alphavbeta3 and IGF1R, whereas the R36E/R37E mutant did not, suggesting that IGF-1 mediates the interaction between alphavbeta3 and IGF1R. These results suggest that the direct binding to IGF-1 to integrin alphavbeta3 plays a role in IGF-1 signaling through ternary complex formation (alphavbeta3-IGF-IGF1R), and integrin-IGF-1 interaction is a novel target for drug discovery.
Use of RFLPs larger than 100 kbp to map the position and internal organization of the nucleolus organizer region on chromosome 2 in Arabidopsis thaliana (1995)

Summary In Arabidopsis thaliana ribosomal RNA genes (rRNA genes or rDNA) are grouped in two nucleolus organizer regions (NORs) that together comprise approximately 6% of the genome. The map positions of the NORs relative to other genetic markers are unknown. It was found that the restriction endonuclease Hin dIII cuts once in some but not all rRNA genes to yield strain‐specific RFLPs of 100–700 kb that could be visualized by pulsed‐field gel electrophoresis and Southern blotting. The Hin dIII RFLPs of the A. thaliana strains Columbia and Landsberg segregated among recombinant inbred lines derived from a cross between these two strains. Linkage analysis placed the NOR bearing the polymorphic Hin dIII sites to the top of the upper arm of chromosome 2. The name NOR2 is suggested for this locus. Hin dIII‐bearing rRNA genes are interspersed with clusters of Hin dIII‐less genes throughout NOR2 . The observed clustering is most consistent with unequal crossing‐over, or nearest‐neighbor gene conversion, as the mechanism(s) that spread rRNA gene variants throughout an NOR. No meiotic cross‐over events yielding a ‘hybrid’ NOR with multiple RFLPs from both parents were observed among the 47 recombinant inbred lines examined. However, the appearance of novel Hin dIII profiles in approximately 40% of the recombinant inbred lines demonstrates that fluctuations in the distribution of rRNA gene variants occur frequently and can be readily detected on pulsed‐field gels.
Localization of neurons expressing substance P and neurokinin B gene transcripts in the human hypothalamus and basal forebrain (1997)

In situ hybridization histochemistry was used to map the distribution of neurons expressing the substance P (SP) or neurokinin B (NKB) genes in the human hypothalamus and basal forebrain. Hypothalami from five adult males were frozen in isopentane at -30 degrees C and serially sectioned at 20 jm thickness. Every 20th section was hybridized with [35S]-labeled, 48-base synthetic cDNA probes that were complementary to either SP or NKB mRNAs. Slides were dipped into nuclear emulsion for visualization of mRNAs at the single-cell level. The location of labeled neurons (greater than x 5 background) was mapped by using an image-combining computer microscope system. A distinct and complementary distribution pattern of SP and NKB neurons was observed in the human hypothalamus and basal forebrain. NKB was the predominant tachykinin in the rostral hypothalamus, whereas SP mRNA predominated in the posterior hypothalamus. Numerous NKB neurons were identified in the magnocellular basal forebrain, the bed nucleus of stria terminalis, and the anterior hypothalamic area. Scattered NKB neurons were present in the infundibular and paraventricular nuclei, paraolfactory gyrus, posterior hypothalamic area, lateral division of the medial mammillary nucleus, and amygdala. Numerous neurons expressing SP mRNAs were identified in the premammillary, supramammillary, and medial mammillary nuclei; the posterior hypothalamic area; and the corpus striatum. Scattered SP neurons were also observed in the preoptic area; the infundibular, intermediate, dorsomedial, and ventromedial nuclei; the infundibular stalk; the amygdala; the bed nucleus of stria terminalis; and the paraolfactory gyrus. These studies provide the first description of the location of neurons that express tachykinin gene transcripts in the human hypothalamus.
MERCURY SENSOR (2007)

RETURN TO ISSUEPREVNewsNEXTMERCURY SENSORANALYTICAL CHEMISTRY: Colorimetric method is sensitive and selectiveMITCH JACOBYCite this: Chem. Eng. News 2007, 85, 19, 15Publication Date (Print):May 7, 2007Publication History Published online29 October 2010Published inissue 7 May 2007https://pubs.acs.org/doi/10.1021/cen-v085n019.p015https://doi.org/10.1021/cen-v085n019.p015newsACS PublicationsCopyright © 2007 American Chemical SocietyArticle Views38Altmetric-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 options SUBJECTS:Colorimetry,Environmental pollution,Mercury Get e-Alerts
DNA Fusion Vaccine Designed to Induce Cytotoxic T Cell Responses Against Defined Peptide Motifs: Implications for Cancer Vaccines (2001)

DNA vaccination offers a strategy to induce immune attack on cancer cells, but tumor Ags are often weak. Inclusion of a "foreign" protein increases immunogenicity, and we found previously that fusion of the fragment C (FrC) of tetanus toxin to the tumor Ag sequence promotes Ab and CD4(+) responses against B cell tumors. For CTL responses, use of the full two-domain FrC may be less helpful, because known immunogenic MHC class I-binding peptides in the second domain could compete with attached tumor-derived epitopes. Therefore, we removed the second domain, retaining the N-terminal domain, which contains a "universal" helper epitope. We investigated the ability to induce CTL responses of candidate peptides placed at the C terminus of this domain. As test peptides, we repositioned the two known CTL motifs from the second domain to this site. Strong CTL responses to each peptide were induced by the engineered construct, as compared with the native FrC construct. Induced CTLs were able to specifically kill tumor cells transfected with FrC as a surrogate tumor Ag both in vitro and in vivo. Further reduction of the domain to a short helper epitope generated only weak CTL responses against fused peptides, and synthetic peptides mixed with the plasmid containing the first domain were ineffective. The single FrC domain-peptide vaccine design also was able to induce high levels of CTLs against a known epitope from carcinoembryonic Ag. Response to peptide was suppressed if two FrC domains were present, consistent with immunodominance. These principles and designs may have relevance for cancer vaccines delivered via DNA.
Optimal training and redundant precoding for block transmissions with application to wireless OFDM (2002)

The adoption of orthogonal frequency-division multiplexing by wireless local area networks and audio/video broadcasting standards testifies to the importance of recovering block precoded transmissions propagating through frequency-selective finite-impulse response (FIR) channels. Existing block transmission standards invoke bandwidth-consuming error control codes to mitigate channel fades, and training sequences to identify the FIR channels. To enable block-by-block receiver processing, we design redundant precoders with cyclic prefix and superimposed training sequences for optimal channel estimation and guaranteed symbol detectability, regardless of the underlying frequency-selective FIR channels. Numerical results are presented to access the performance of the designed training and precoding schemes.