gebhart/patrepeval huggingface dataset:
100 Years and Counting: Prospects for Defeating Alzheimer's Disease (2006)

This week marks a century since the first description of Alzheimer's disease (AD). Despite approval of several drugs for AD, the disease continues to rob millions of their memories and their lives. Fortunately, many new therapies directly targeting the mechanisms underlying AD are now in the pipeline. Among the investigative AD therapies in clinical trials are several strategies to block pathogenic amyloid-beta peptides and to rescue vulnerable neurons from degeneration. Complementary but less mature strategies aim to prevent the copathogenic effects of apolipoprotein E and the microtubule-associated protein tau. New insights into selective neuronal vulnerability and the link between aging and AD may provide additional entry points for therapeutic interventions. The predicted increase in AD cases over the next few decades makes the development of better treatments a matter of utmost importance and urgency.
An integrated, low noise patch-clamp amplifier for biological nanopore applications (2010)

We present an integrated, low noise patch-clamp amplifier for biological nanopore applications. Our amplifier consists of an integrator-differentiator architecture coupled with a novel opamp design in the CMOS 0.35 µm process. The post-layout full-chip simulation shows the input referred noise of the amplifier is 0.49 pA RMS over a 5 kHz bandwidth using a verified electrical model for the biological nanopore system. In our biological nanopore experiments studying protein-DNA interactions, we encounter capacitive transients with a nominal settling time of 5 ms. Our amplifier design reduces the settling time to 0.2 ms, without requiring any compensation circuitry.
Targeted mutagenesis of simian virus 40 DNA mediated by a triple helix-forming oligonucleotide (1993)

Triple-helical DNA can be formed by oligonucleotides that bind as third strands of DNA in a sequence-specific manner in the major groove in homopurine/homopyrimidine stretches in duplex DNA. Such triple helix-forming oligonucleotides have been used to inhibit gene expression by blocking transcription factor access to promoter sites in transient expression assays. In an alternative approach to genetic manipulation using triplex DNA, we show that triplex-forming oligonucleotides can be used to produce site-specific, targeted mutations in a viral genome in order to achieve a permanent, heritable effect on gene function and expression. We use a triplex-forming oligonucleotide linked to a psoralen derivative at its 5' end to achieve targeted mutagenesis in a simian virus 40 (SV40) vector genome. Site-specific triplex formation delivers the psoralen to the targeted site in the SV40 DNA. Photoactivation of the psoralen yields adducts and thereby mutations at that site. Mutations were produced in the target gene in over 6% of the viral genomes. DNA sequence analysis of the mutations in the target gene showed that all were in the targeted region, and 55% were found to be the same T:A-to-A:T transversion precisely at the targeted base pair. In control experiments, no mutagenesis above the background frequency in the assay was produced by a non-triplex-forming, psoralen-linked oligonucleotide unless a vast excess of this oligonucleotide was used, demonstrating the specificity of the targeted mutagenesis. This frequency of targeted mutagenesis of SV40 in monkey cells represents a 30-fold increase relative to similar experiments using lambda phage in bacteria, suggesting that fixation of the triplex-directed lesion into a mutation occurs more efficiently in mammalian cells. If the ability to reproducibly and predictably target mutations to sites in viral DNA in vitro by using modified oligonucleotides can be extended to DNA in vivo, this approach may prove useful as a technique for gene therapy, as a strategy for antiviral therapeutics, and as a tool for genetic engineering.
High power vector summation switching power amplifier development (1981)

A time sequence of square waves is summed to provide minimum distortion high power voltage sinusoids. The phase difference is varied to control the resultant summed amplitude. Frequency and phase modulation is achieved through digital control of the individual square waves.
Subtilist: a relational database for the Bacillus subtilis genome (1995)

In the framework of the international collaborative project aiming to sequence the whole Bacillus subtilis chromosome, we have created a relational database for managing and analysing information associated with the molecular genetics of this bacterium: SubtiList. It allows recovery of non-redundant DNA sequences of the B. subtilis genome, as well as related information, i.e. genes, proteins, etc. A logical structure has been designed with appropriate links between the different objects, and a set of procedures has been implemented for data updating and management. The database is organized around a core constituted by all known contigs of B. subtilis, i.e. sets of non-redundant sequences created from original entries in the EMBL data library. A user-friendly interface has been developed to make the database easy to consult. Sequence analysis tools have been integrated into the database, such as a program for rapid similarity searching of protein data banks, and a powerful DNA pattern searching program. Thanks to the consistency of SubtiList, we have performed a codon usage analysis by Factorial Correspondence Analysis, and a study of the distribution of the isoelectric points of known proteins of B. subtilis. The SubtiList database is available through anonymous ftp (address 'ftp.pasteur.fr' or IP number 157.99.64.12, directory '/pub/GenomeDB/SubtiList').
Exploration of benzimidazole chemistry (2008)

Benzimidazoles have far reaching applications in the field of chemistry and beyond. The major focus of this work is on the synthesis of benzimidazoles and bis(benzimidazoles) and subsequent complexation chemistry which has been further applied to areas such as constrained geometry and catalysis. A number of new techniques, such as the facile oxidation of methylene bridged benzimidazoles, have been elucidated in this study. Many improvements in experimental conditions have also been found in the syntheses of members of this class of compounds. We report here the preparation and characterization of two systems with constrained coordination geometries. The first consists of tetrahedrally constrained complexes using bis[rac-2,2'-bis[2-(1-alkylbenzimidazol-2-yl)]biphenyl] characterized with several transition metal ions. The second consists of chiral, square-bipyramidally constrained complexes using chiral bis[1,2-bis(1-alkylbenzimidazol-2-yl)-1',2'-bis(alkoxy)ethane] with first and second row transition metal ions. The copper complexes of selected bis(benzimidazoles) have been found to catalyze the oxidative carbonylation of methanol to form dimethyl carbonate. Such complexes have also been found to be remarkable polymerization catalysts with the ability to homopolymerize and copolymerize olefins and acrylates.
Multicenter Trial of Early Hypothermia in Severe Brain Injury (2009)

The North American Brain Injury Study: Hypothermia IIR (NABIS:H IIR) is a randomized clinical trial designed to enroll 240 patients with severe brain injury between the ages of 16 and 45 years. The primary outcome measure is the dichotomized Glasgow Outcome Scale (GOS) at 6 months after injury. The study has the power to detect a 17.5% absolute difference in the percentage of patients with a good outcome with a power of 80%. All patients are randomized by waiver of consent unless family is immediately available. Enrollment is within 2.5 h of injury. Patients may be enrolled in the field by emergency medical services personnel affiliated with the study or by study personnel when the patient arrives at the emergency department. Patients who do not follow commands and have no exclusion criteria and who are enrolled in the hypothermia arm of the study are cooled to 35 degrees C as rapidly as possible by intravenous administration of up to 2 liters of chilled crystalloid. Those patients who meet the criteria for the second phase of the protocol (primarily a post-resuscitation GCS 3-8 without hypotension and without severe associated injuries) are cooled to 33 degrees C. Patients enrolled in the normothermia arm receive standard management at normothermia. As of December 2007, 74 patients had been randomized into phase II of the protocol. Patients in the hypothermia arm reached 35 degrees C in 2.7 +/- 1.1 (SD) h after injury and reached 33 degrees C at 4.4 +/- 1.5 h after injury.
Effects of growth hormone on human fluid homeostasis (2000)

Regulation of body fluid homeostasis is apparently simple since daily sodium and water intake equals daily sodium and water output. However, the mechanisms enabling the body to excrete exactly the ingested amounts of water and sodium are complex and incompletely understood, albeit thoroughly investigated. The factors regulating body fluid homeostasis may grossly be divided into neural-humoral factors and physical factors. The former group comprises among others the reinin–angiotensin–aldosterone system (RAAS), arginine vasopressin (AVP), atrial natriuretic factor (ANF), prostaglandins and renal sympathetic nerve activity. The latter group is made up by physical factors regulating cardiac function, renal blood flow and plasma protein concentration and hence osmotic pressure. The position of growth hormone (GH) in this complex scenario is not yet established, but several reports suggest that GH plays a role in body fluid regulation. More than 60 years ago anterior pituitary extracts were shown to induce fluid retention in rats (Bierring & Nielsen, 1932; Lee & Schaffer, 1934). Two decades later GH-induced sodium and fluid retention was also demonstrated in humans (Ikkos, Luft & Sjogren, 1954; Ikkos, Luft & Gemzell, 1959). Since then the sodium and water retaining effects of GH has been confirmed in several studies (Hutchings et al., 1959; Beck et al., 1960; Henneman et al., 1960; Biglieri, Watlington & Forsham, 1961; Møller et al., 1991).
Effects of dietary omega–3 fatty acids on ventricular function in dogs with healed myocardial infarctions: in vivo and in vitro studies (2010)

Since omega-3 polyunsaturated fatty acids (n-3 PUFAs) can alter ventricular myocyte calcium handling, these fatty acids could adversely affect cardiac contractile function, particularly following myocardial infarction. Therefore, 4 wk after myocardial infarction, dogs were randomly assigned to either placebo (corn oil, 1 g/day, n = 16) or n-3 PUFAs supplement [docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) ethyl esters; 1, 2, or 4 g/day; n = 7, 8, and 12, respectively] groups. In vivo, ventricular function was evaluated by echocardiography before and after 3 mo of treatment. At the end of the 3-mo period, hearts were removed and in vitro function was evaluated using right ventricular trabeculae and isolated left ventricular myocytes. The treatment elicited significant (P < 0.0001) dose-dependent increases (16.4-fold increase with 4 g/day) in left ventricular tissue and red blood cell n-3 PUFA levels (EPA + DHA, placebo, 0.42 +/- 0.04; 1 g/day, 3.02 +/- 0.23; 2 g/day, 3.63 +/- 0.17; and 4 g/day, 6.97 +/- 0.33%). Regardless of the dose, n-3 PUFA treatment did not alter ventricular function in the intact animal (e.g., 4 g/day, fractional shortening: pre, 42.9 +/- 1.6 vs. post, 40.1 +/- 1.7%; placebo: pre, 39.2 +/- 1.3 vs. post, 38.4 +/- 1.6%). The developed force per cross-sectional area, changes in length- and frequency-dependent behavior in contractile force, and the inotropic response to beta-adrenoceptor activation were also similar for trabeculae obtained from placebo- or n-3 PUFA-treated dogs. Finally, calcium currents and calcium transients were the same in myocytes from n-3 PUFA- and placebo-treated dogs. Thus dietary n-3 PUFAs did not adversely alter either in vitro or in vivo ventricular contractile function in dogs with healed infarctions.
Visualizing and Understanding Convolutional Neural Networks (2013)

Large Convolutional Neural Network models have recently demonstrated
impressive classification performance on the ImageNet benchmark \cite{Kriz12}.
However there is no clear understanding of why they perform so well, or how
they might be improved. In this paper we address both issues. We introduce a
novel visualization technique that gives insight into the function of
intermediate feature layers and the operation of the classifier. We also
perform an ablation study to discover the performance contribution from
different model layers. This enables us to find model architectures that
outperform Krizhevsky \etal on the ImageNet classification benchmark. We show
our ImageNet model generalizes well to other datasets: when the softmax
classifier is retrained, it convincingly beats the current state-of-the-art
results on Caltech-101 and Caltech-256 datasets.
High Levels of Inducible Nitric Oxide Synthase mRNA Are Associated with Increased Monocyte Counts in Blood and Have a Beneficial Role inPlasmodium falciparumMalaria (2000)

To date, there have been conflicting reports concerning the clinical significance of nitric oxide (NO) in Plasmodium falciparum malaria. Some authors have proposed that NO contributes to the development of severe and complicated malaria, while others have argued that NO has a protective role. To investigate these apparently contradictory reports, reverse transcription-coupled PCR was used to study inducible NO synthase (iNOS) in whole-blood RNA samples from patients with severe and complicated malaria or uncomplicated malaria and from healthy donors. This work produced three principal findings. First, samples of patients with severe and complicated malaria were variably positive, with weak to moderate intensity. Markedly higher iNOS RNA levels were observed in samples of patients with uncomplicated malaria than in patients with severe and complicated malaria. Samples of healthy donors were uniformly negative. Second, since we initially demonstrated iNOS expression in whole-blood RNA samples, we extended our investigations to individual blood cells such as monocytes, lymphocytes, neutrophils, and platelets to identify the cellular source of iNOS. We found that iNOS was expressed predominantly in monocytes. Third, retrospective statistical analysis of monocyte counts clearly demonstrated that patients with uncomplicated malaria had higher monocyte counts at the time of presentation than patients with severe and complicated malaria. Taken together, our findings give room to the interpretation that NO may have a beneficial rather than a deleterious role in falciparum malaria.
Activation of a consensus FNR-dependent promoter by DNR of Pseudomonas aeruginosa in response to nitrite (1998)

Expression of the enzymes for anaerobic nitrate respiration of Pseudomonas aeruginosa requires two CRP/FNR-related transcriptional regulators, ANR and DNR. Activity of the consensus CRP- or FNR-dependent promoter in the anr and dnr deficient mutants was investigated. The CRP-dependent promoter was active in the mutant strains. Both regulators could activate the promoter with a consensus FNR-binding motif. DNR-dependent activation was nitrite-dependent, whereas activation by ANR was not, suggesting that only DNR is involved in sensing nitrogen oxides.
The Oxford Handbook of Event-Related Potential Components (2011)

Preface Part One: Conceptual Bases 1. ERP Components: The Ups and Downs of Brainwave Recordings Emily S. Kappenman and Steven J. Luck 2. Beyond ERPs: Oscillatory Neuronal Dynamics Marcel Bastiaansen, Ali Mazaheri, and Ole Jensen 3. ERP Features and EEG Dynamics: An ICA Perspective Scott Makeig and Julie Onton Part Two: Commonly Studied ERP Components 4. Sensory ERP Components Hillel Pratt 5. The N170: Understanding the Time Course of Face Perception in the Human Brain Bruno Rossion and Corentin Jacques 6. The Mismatch Negativity (MMN) Risto Naatanen and Kairi Kreegipuu 7. Neuropsychology of P300 John Polich 8. Negative slow waves as indices of anticipation: The Bereitschaftspotential, the Contingent Negative Variation, and the Stimulus Preceding Negativity Cornelis H.M. Brunia, Geert J.M. van Boxtel, and Koen B.E. Bocker 9. The Lateralized Readiness Potential Fren T.Y. Smulders and Jeff O. Miller 10. The Error-Related Negativity (ERN/Ne) William J. Gehring, Yanni Liu, Joseph M. Orr, and Joshua Carp Part Three: ERP Components in Specific Cognitive Domains 11. ERP Components and Selective Attention Steven J. Luck and Emily S. Kappenman 12. Electrophysiological Correlates of the Focusing of Attention within Complex Visual Scenes: N2pc and Related Electrophysiological Correlates Steven J. Luck 13. What ERPs Can Tell Us about Working Memory Veronica B. Perez and Edward K. Vogel 14. Electrophysiological Correlates of Episodic Memory Processes Edward L. Wilding and Charan Ranganath 15. Language-Related ERP Components Tamara Y. Swaab, Kerry Ledoux, C. Christine Camblin, and Megan Boudewyn 16. ERPs and the Study of Emotion Greg Hajcak, Anna Weinberg, Annmarie MacNamara, and Dan Foti Part Four: ERPs in Special Populations 17. Event-related Potentials and Development Donna Coch and Margaret M. Gullick 18. The Components of Aging David Friedman 19. Abnormalities of Event Related Potential Components in Schizophrenia Brian F. O'Donnell, Dean F. Salisbury, Margaret A. Niznikiewicz, Colleen A. Brenner, and Jenifer L. Vohs 20. Event-related Brain Potentials in Depression: Clinical, Cognitive, and Neurophysiologic Implications Gerard E. Bruder, Jurgen Kayser, and Craig E. Tenke 21. Alterations of ERP Components in Neurodegenerative Diseases Rolf Verleger 22. Homologues of Human ERP Components in Nonhuman Primates Geoffrey F. Woodman
Three-dimensional integrated circuits (2006)

Three-dimensional (3D) integrated circuits (ICs), which contain multiple layers of active devices, have the potential to dramatically enhance chip performance, functionality, and device packing density. They also provide for microchip architecture and may facilitate the integration of heterogeneous materials, devices, and signals. However, before these advantages can be realized, key technology challenges of 3D ICs must be addressed. More specifically, the processes required to build circuits with multiple layers of active devices must be compatible with current state-of-the-art silicon processing technology. These processes must also show manufacturability, i.e., reliability, good yield, maturity, and reasonable cost. To meet these requirements, IBM has introduced a scheme for building 3D ICs based on the layer transfer of functional circuits, and many process and design innovations have been implemented. This paper reviews the process steps and design aspects that were developed at IBM to enable the formation of stacked device layers. Details regarding an optimized layer transfer process are presented, including the descriptions of 1) a glass substrate process to enable through-wafer alignment; 2) oxide fusion bonding and wafer bow compensation methods for improved alignment tolerance during bonding; 3) and a single-damascene patterning and metallization method for the creation of high-aspect-ratio (6:1 < AR < 11:1) contacts between two stacked device layers. This process provides the shortest distance between the stacked layers (<2 µm), the highest interconnection density (>10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">8</sup> vias/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ), and extremely aggressive wafer-to-wafer alignment (submicron) capability.
Measurement of prostate‐specific membrane antigen in the serum with a new antibody (1996)

Work to date has identified prostate-specific membrane antigen (PSMA) as a membrane-bound glycoprotein with high specificity for prostatic epithelial cells. PSMA reacts with the monoclonal antibody 7E11.C5, which is present in serum, seminal fluid, and prostatic epithelial cells, and is increased in its expression in the presence of a hormone refractory state associated with prostatic cancer. This report confirms these results and further documents the presence of the monoclonal antibody 3F5.4G6, which reacts with the extracellular domain of PSMA. This region of PSMA is also an element present in a truncated version of the protein, so-called PSM′. Immune precipitation with either 7E11.C5 or 3F5.4G6 yields an isolated protein species that are reactive with the reciprocal antibody in Western blot analysis. Thus, 3F5.4G6 recognizes the same PSMA protein as does 7E11.C5, but at different epitopes on essentially opposite ends of the molecule. These two antibodies are well suited for use in a sandwich immunoassay, either one as a capture or detection antibody. Current work on this is underway. This report also confirms that 7E11.C5 Western blots for PSMA are negative with normal human brain tissue. The monoclonal antibody 9H10 does not react with 3F5.4G6 or with 7E11.C5 in studies conducted herein. Moreover, 3F5.4G6 reacts with PSMA found in the LNCaP cell line, but not DU-145 or PC3, which lack PSMA. © 1996 Wiley-Liss, Inc.
Cerebrospinal fluid insulin-like growth factors IGF-1 and IGF-2 in infantile autism (2007)

There has been little exploration of major biologic regulators of cerebral development in autism. We measured insulin-like growth factors (IGF) -1 and -2 from cerebrospinal fluid (CSF) by radio immunoassay in 25 children with autism (median age 5y 5mo; range 1y 11mo-15y 10mo; 20 males, 5 females), and in 16 age-matched comparison children without disability (median age 7y 4mo; range 1y 1mo-15y 2mo; eight males, eight females). IGF-1 and -2 concentrations were further correlated with age of patients and head size. CSF IGF-1 concentration was significantly lower in patients with autism than in the comparison group. The CSF concentrations of children with autism under 5 years of age were significantly lower than their age-matched comparisons. The head circumferences correlated with CSF IGF-1 in children with autism but no such correlation was found in the comparison group. There was no difference between the two groups in CSF IGF-2 concentrations. No patients with autism had macrocephaly. We conclude that low concentrations of CSF IGF-1 at an early age might be linked with the pathogenesis in autism because IGF-1 is important for the survival of Purkinje cells of the cerebellum. The head growth might be explained by the actions of IGF-1 and -2 reflected in CSF concentrations.
Scanning attractive force microscope using photothermal vibration (1991)

An attractive force microscope using photothermal vibration is presented. A cantilever is vibrated by the optical absorption of a laser beam whose intensity modulation frequency is at resonance frequency, and the vibration is detected by an optical deflection method. The characteristics of the photothermal vibration and the attractive force gradient versus tip-sample distance have been measured with a Ni foil cantilever. Topographic images of digital memory disks made from a polycarbonate and Mg–Al alloy were recorded.
Fiber-grating pulse compressor: Performance with initially chirped pulses (1987)

Numerical simulation of a fiber-grating pulse compressor is performed assuming incident frequency chirped pulses. Characteristic fiber lengths are defined to explain qualitatively the behavior of the compression ratio curves. High compression ratios are not particularly sensitive to the input pulse chirp even for pulses of up to twice the bandwidth limit. The results are presented in normalized form with the help of optical soliton theory and can be used for a wide range of initial pulse widths.