gebhart/patrepeval huggingface dataset:
Mice, men and the relatives: cross-species studies underpin innate immunity (2012)

The innate immune response is the first line of defence against infection. Germ-line-encoded receptors recognize conserved molecular motifs from both exogenous and endogenous sources. Receptor activation results in the initiation of a pro-inflammatory immune response that enables the resolution of infection. Understanding the inner workings of the innate immune system is a fundamental requirement in the search to understand the basis of health and disease. The development of new vaccinations, the treatment of pathogenic infection, the generation of therapies for chronic and auto-inflammatory disorders, and the ongoing battle against cancer, diabetes and atherosclerosis will all benefit from a greater understanding of innate immunity. The rate of knowledge acquisition in this area has been outstanding. It has been underpinned and driven by the use of model organisms. Information obtained from Drospohila melanogaster, knock-out and knock-in mice, and through the use of forward genetics has resulted in discoveries that have opened our eyes to the functionality and complexity of the innate immune system. With the current increase in genomic information, the range of innate immune receptors and pathways of other species available to study is rapidly increasing, and provides a rich resource to continue the development of innate immune research. Here, we address some of the highlights of cross-species study in the innate immune field and consider the benefits of widening the species-field further.
Proteomic Analysis of Ductal Carcinoma of the Breast Using Laser Capture Microdissection, LC−MS, and 16O/18O Isotopic Labeling (2004)

The goal of this study was the development of a method for quantitative expression proteomics on the limited sample amounts obtained through laser capture microdissection (LCM) of tissues, e.g., approximately 10 000 cells, which typically contain roughly 1-4 microg protein. The 16O/18O labeling method was selected as an approach to measure differential expression. A sample preparation protocol including lysis, digestion and 16O/18O labeling was first developed for LCM cell samples. The selected protocol was examined using two LCM caps of 10 000 cells from invasive ductal carcinoma of the breast and shown to be repeatable. A further test of LC-IT-MS/MS in combination with the 16O/18O post-digestion labeling method for studying low level samples was conducted first on a single protein (BSA) and then on a 5-standard protein mixture digest of different protein amounts, each with a total content approximately 1 microg. Next, protein expression was compared between 10 000 cells, each of microdissected normal ductal epithelium and metastatic ductal carcinoma, using the developed method. The proteins from the microdissected cells were extracted, precipitated, digested with trypsin and then 16O/18O labeled. The normal and metastatic cell samples were analyzed using reversed phase LC-ESI-MS/MS on the ion trap mass spectrometer. A total of 76 proteins were identified. Some, such as mitochondrial isocitrate dehydrogenase, actin and 14-3-3 protein xi/delta were found to be significantly up-regulated in the breast tumor cells.
Theoretical Foundation and Design Formulae for Channel and Pillar Type Propped Fractures – A Method to Increase Fracture Conductivity (2014)

Abstract A mathematical formulation and solution methodology for placing proppant to create open channels and propped pillar packs in hydraulic fractures is presented. The advantage of this methodology is increased fracture conductivity by creating open channels and/or pillars that support the unpropped (or open) fracture region. The technique requires reduced proppant mass and results in enhanced fracture conductivity. The work illustrates that high conductivity proppant is not required. The paper presents the governing equations, assumptions and a solution methodology for designing open channels and for flow around pillars in propped fractures. The governing equations and assumptions for calculating the surface displacement (in the loaded and unloaded regions) for pressure loading of a strip and circular region in an elastic half-space are formulated in the appendices. Four cases are presented: 1) uniform pressure distribution over an infinite strip, 2) uniform (constant) distribution (i.e., rigid line punch) over an infinite strip, 3) uniform pressure applied to a circular region, and 4) uniform normal displacement over a circular region. The effects of the closure stress on the proppant and the formation modulus on embedment are discussed and illustrate the advantage of this methodology in formations with high Young's modulus and low confining stress contrasts. Disadvantages and limitations of the procedure are also discussed. A formulation for the equivalent fracture permeability for flow through channel and pillar type propped fractures is also presented and demonstrates the advantage of creating pillars and open channels for enhanced fracture conductivity. Fractures with open channels and pillars have much greater permeability than traditionally propped fractures. However, proppant permeability is not important in pillar and channel type fracture designs. A proppant that is more ductile and one that creates few fines when crushed is more advantageous for channel and pillar type designs. The design formulae present a simple methodology to allow for easy field implementation based on a volumetric ratio of fluid to proppant stages. The treatment design can be accomplished with standard industry pumping equipment and methods are provided for the fracture design engineer to create treatment schedules that can be employed by current hydraulic pumping technology. The methodology, if implemented correctly, will greatly increase the dimensionless fracture conductivity (by orders of magnitude) resulting in enhanced production while minimizing operational costs associated with proppant quality.
Phosphorylation of FTDP-17 Mutant tau by Cyclin-dependent Kinase 5 Complexed with p35, p25, or p39 (2005)

One of the major pathological hallmarks of Alzheimer disease is neurofibrillary tangles. Neurofibrillary tangles are bundles of paired helical filaments composed of hyperphosphorylated tau. Cyclin-dependent kinase 5 (Cdk5) is one of the tau protein kinases that increase paired helical filament epitopes in tau by phosphorylation. Recently, various mutations of tau have been identified in frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). Here, we investigated the phosphorylation of FTDP-17 mutant tau proteins, K257T, P301L, P301S, and R406W, by Cdk5 complexed with p35, p25, or p39 in vitro and in cultured cells. The extent of phosphorylation by all Cdk5 species was slightly lower in mutant tau than in wild-type tau. Major phosphorylation sites, including Ser202, Ser235, and Ser404, were the same among the wild-type, K257T, P301L, and P301S tau proteins phosphorylated by any Cdk5. On the other hand, R406W tau was less phosphorylated at Ser404 than were the other variants. This was not due to the simple replacement of amino acid Arg406 with Trp close to the phosphorylation site, because Ser404 in a R406W peptide was equally phosphorylated in a wild-type peptide. The decreased phosphorylation of mutant tau by Cdk5s was canceled when tau protein bound to microtubules was phosphorylated. These results indicate that FTDP-17 mutations do not affect the phosphorylatability of tau by Cdk5 complexed with p35, p25, or p39 and may explain part of the discrepancy reported previously between in vivo and in vitro phosphorylation of FTDP-17 tau mutants.
Afasi og lingvistikk – til gjensidig glede og nytte? (2004)

Afasi er kanskje den mest prototypiske formen for språkvanske vi kjenner til, og lingvistisk kunnskap bør ha en naturlig plass i utforskning av denne og andre typer språkvansker. I artikkelen drøftes forholdet mellom afasi og lingvistikk gjennom å se på hvordan lingvistikken kan fungere som et metaspråk, både i kartlegging av språkvanskene og i planlegging og evaluering av afasiundervisning, og å se på hvordan afasirammedes språkbruk kan bidra til å utvikle kunnskapen vår om språk generelt.
Mechanical injury potentiates proteoglycan catabolism induced by interleukin‐6 with soluble interleukin‐6 receptor and tumor necrosis factor α in immature bovine and adult human articular cartilage (2009)

Our findings indicate that mechanical injury potentiates the catabolic effects of TNFalpha and IL-6/sIL-6R in causing proteoglycan degradation in human and bovine cartilage. The temporal and spatial evolution of degradation suggests the importance of transport of biomolecules, which may be altered by overload injury. The catabolic effects of injury plus TNFalpha appeared partly due to endogenous IL-6, since GAG loss was partially abrogated by an IL-6-blocking Fab.
Preliminary report: correct diagnosis of sex in fetal cells isolated from cervical mucus during early pregnancy (2005)

The aim of this study was to determine the accuracy of sexing fetal cells isolated from cervical mucus. Immunopositive cells identified using a fetal-specific antibody were isolated and subjected to genetic analysis. Fetal sex was predicted in all 22 samples, as confirmed by analysis of the corresponding placental tissue. This study validates the accuracy of our test for sex diagnosis and confirms the ability to effectively recover and analyse fetal cells from the cervical mucus during early pregnancy.
Difference of ultra-drying tolerance and heat-stable proteins in seeds of different rice cultivars (2001)

The difference of ultra drying tolerance and the heat stable proteins were studied among different rice cultivars, and two ideas inferred from the results. (1) The germination rate and vigor index of japonica rice seeds (Chunjiang 15 and Chunjiang 683) decreased rapidly when their moisture content fell to 4.5%. On the contrary, the germination rate and vigor index of indica rice (J174 and J106) seeds changed little even when their moisture content fell to 3.5%, which indicated that indica rice had strong ultra drying tolerance. While the seeds' tolerance of waxy rice and hybrid rice (Shanyou 63) were intervened in japonica rice's and indica rice's. (2) SDS PAGE electrophoresis showed that a 36.3 kD heat stable protein appeared only in seeds of rice cultivars (indica rice, waxy rice and hybrid rice) with ultra drying tolerance. These results suggested that the special heat stable proteins might be related to ultra drying tolerance.
Comparison of Usability and Patient Preference for Insulin Pen Needles Produced with Different Production Techniques: “Thin-Wall” Needles Compared to “Regular-Wall” Needles: An Open-Label Study (2009)

Pen and pen needle handling, preparation, and execution of injections should be a part of repeated diabetes education and be re-evaluated on a regular basis. The "thin-wall" 31-gauge needle was found to be more user-friendly and consequently preferred by the patients. Additional larger-scale trials using blinded and randomized study designs are needed to validate these findings.
Brain-Selective Overexpression of Angiotensin (AT 1 ) Receptors Causes Enhanced Cardiovascular Sensitivity in Transgenic Mice (2002)

To examine the physiological importance of brain angiotensin II type 1 (AT1) receptors, we developed a novel transgenic mouse model with rat AT1a receptors targeted selectively to neurons of the central nervous system (CNS). A transgene consisting of 2.8 kb of the rat neuron-specific enolase (NSE) 5' flanking region fused to a cDNA encoding the full open-reading frame of the rat AT1a receptor was constructed and transgenic mice (NSE-AT1a) were generated. Two of six transgenic founder lines exhibited brain-selective expression of the transgene at either moderate or high levels. Immunohistochemistry revealed widespread distribution of AT1 receptors in neurons throughout the CNS. This neuron-targeted overexpression of AT1a receptors resulted in enhanced cardiovascular responsiveness to intracerebroventricular (ICV) angiotensin II (Ang II) injection but not to other central pressor agents, demonstrating functional overexpression of the transgene in NSE-AT1a mice. Interestingly, baseline blood pressure (BP) was not elevated in either transgenic line. However, blockade of central AT1 receptors with ICV losartan caused significant falls in basal BP in NSE-AT1a mice but had no effect in nontransgenic controls. These results suggest that whereas there is an enhanced contribution of central AT1 receptors to the maintenance of baseline BP in NSE-AT1a mice, particularly effective baroreflex buffering prevents hypertension in this model. Used both independently, and in conjunction with mice harboring gene-targeted deletions of AT1a receptors, this new model will permit quantitative and relevant investigations of the role of central AT1a receptors in cardiovascular homeostasis in health and disease.
Pole-Zero Cancellation Circuit With Pulse Pile-Up Tracking System for Low Noise Charge-Sensitive Amplifiers (2008)

Modern X-ray imaging systems require low noise high-count-rate multichannel front-end electronics. Such systems widely use charge-sensitive amplifiers (CSA) with pole-zero cancellation (PZC) circuits for sensor readout. CSAs in multichannel ASICs often include continuous reset systems based on MOS transistors discharging the integrating capacitance. Noise requirements for such front-end electronics put the effective CSA feedback resistance in the range of hundreds of MOmega. On the other hand, the high input pulse rate generates a dc voltage shift at the CSA output that modifies the CSA feedback resistance and degrades the PZC circuit performance. In the paper we analyze these problems and propose a novel circuit solution to bias transistors in the CSA feedback and in the PZC circuit. This bias circuit tracks the above mentioned voltage shift at the CSA output and ensures proper cancellation of the CSA feedback pole even in the case of high rates of input pulses. We present measurements of a test structure for the continuous CSA feedback discharge and implementation of this circuit in a fast multichannel ASIC manufactured in the 0.35 mum CMOS technology. The circuit performance for the high input pulse rate is described in detail.
The Electrochemical Reduction of Carbon Dioxide, Formic Acid, and Formaldehyde (1977)

The prospects for the electrochemical reduction of carbon dioxide to methanol were examined by investigating the intermediate reactions. The reduction of carbon dioxide was carried out in a neutral electrolyte at a mercury electrode. The high overvoltage observed for carbon dioxide reduction to the formate anion reflects a low value for the efficiency of electric energy utilization for this process. Formic acid can be reduced to methanol in a perchloric acid electrolyte (at a lead electrode) or in a buffered formic acid electrolyte (at a tin electrode). The faradaic efficiency for methanol formation is close to 100% at the tin electrode in a narrow potential region corresponding to a low current density. The potential dependence of formic acid reduction to methanol suggests that the adsorption of formic acid on the electrode, near the pzc, may be the rate‐controlling step in the over‐all reaction. The reduction of formaldehyde to methanol occurs with a faradaic efficiency exceeding 90% in a basic solution. The Tafel slope decreases when either the formaldehyde concentration is increased (at constant pH) or when thepH of the solution is increased (at constant concentration). The polyoxymethylene glycols present as impurities in formaldehyde solutions may influence the mechanism of the electrode process through interaction with formaldehyde molecules and/or other adsorbed species resulting in small changes of the Tafel slope.
The age‐related attenuation in long‐term potentiation is associated with microglial activation (2006)

It is well established that inflammatory changes contribute to brain ageing, and an increased concentration of proinflammatory cytokine, interleukin-1beta (IL-1beta), has been reported in the aged brain associated with a deficit in long-term potentiation (LTP) in rat hippocampus. The precise age at which changes are initiated is unclear. In this study, we investigate parallel changes in markers of inflammation and LTP in 3-, 9- and 15-month-old rats. We report evidence of increased hippocampal concentrations of the proinflammatory cytokines IL-1alpha, IL-18 and interferon-gamma (IFNgamma), which are accompanied by deficits in LTP in the older rats. We also show an increase in expression of markers of microglial activation, CD86, CD40 and intercellular adhesion molecules (ICAM). Associated with these changes, we observed a significant impairment of hippocampal LTP in the same rats. The importance of microglial activation in the attenuation of long-term potentiation (LTP) was demonstrated using an inhibitor of microglial activation, minocycline; partial restoration of LTP in 15-month-old rats was observed following administration of minocycline. We propose that signs of neuroinflammation are observed in middle age and that these changes, which are characterized by microglial activation, may be triggered by IL-18.
Atomic scale imaging of alkanethiolate monolayers at gold surfaces with atomic force microscopy (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAtomic scale imaging of alkanethiolate monolayers at gold surfaces with atomic force microscopyCarla A. Alves, Earl L. Smith, and Marc D. PorterCite this: J. Am. Chem. Soc. 1992, 114, 4, 1222–1227Publication Date (Print):February 1, 1992Publication History Published online1 May 2002Published inissue 1 February 1992https://pubs.acs.org/doi/10.1021/ja00030a015https://doi.org/10.1021/ja00030a015research-articleACS PublicationsRequest reuse permissionsArticle Views1217Altmetric-Citations277LEARN 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
Improved Route To Chiral Amines (2014)

RETURN TO ISSUEPREVNewsNEXTImproved Route To Chiral AminesCite this: Chem. Eng. News 2014, 92, 35, 13Publication Date (Print):September 1, 2014Publication History Published online31 March 2015Published inissue 1 September 2014https://pubs.acs.org/doi/10.1021/cen-09235-notw8https://doi.org/10.1021/cen-09235-notw8newsACS PublicationsCopyright © 2014 Chemical & Engineering NewsArticle Views12Altmetric-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:Amines Get e-Alerts
Imaging and Photodynamic Therapy: Mechanisms, Monitoring, and Optimization (2010)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTImaging and Photodynamic Therapy: Mechanisms, Monitoring, and OptimizationJonathan P. Celli†, Bryan Q. Spring†, Imran Rizvi†‡, Conor L. Evans†, Kimberley S. Samkoe‡, Sarika Verma†, Brian W. Pogue†‡, and Tayyaba Hasan*†View Author Information Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, and Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755* To whom correspondence should be addressed. E-mail: [email protected]†Massachusetts General Hospital and Harvard Medical School.‡Dartmouth College.Cite this: Chem. Rev. 2010, 110, 5, 2795–2838Publication Date (Web):March 30, 2010Publication History Received4 September 2009Published online30 March 2010Published inissue 12 May 2010https://pubs.acs.org/doi/10.1021/cr900300phttps://doi.org/10.1021/cr900300preview-articleACS PublicationsCopyright © 2010 American Chemical SocietyRequest reuse permissionsArticle Views23102Altmetric-Citations1936LEARN 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 SUBJECTS:Biological imaging,Cancer,Fluorescence,Fluorescence imaging,Tumors Get e-Alerts
A repeated measures model for analysis of continuous outcomes in sequential parallel comparison design studies (2013)

Previous authors have proposed the sequential parallel comparison design (SPCD) to address the issue of high placebo response rate in clinical trials. The original use of SPCD focused on binary outcomes, but recent use has since been extended to continuous outcomes that arise more naturally in many fields, including psychiatry. Analytic methods proposed to date for analysis of SPCD trial continuous data included methods based on seemingly unrelated regression and ordinary least squares. Here, we propose a repeated measures linear model that uses all outcome data collected in the trial and accounts for data that are missing at random. An appropriate contrast formulated after the model has been fit can be used to test the primary hypothesis of no difference in treatment effects between study arms. Our extensive simulations show that when compared with the other methods, our approach preserves the type I error even for small sample sizes and offers adequate power and the smallest mean squared error under a wide variety of assumptions. We recommend consideration of our approach for analysis of data coming from SPCD trials.