gebhart/patrepeval huggingface dataset:
Modular and efficient pre-processing of single-cell RNA-seq (2019)

Abstract Analysis of single-cell RNA-seq data begins with pre-processing of sequencing reads to generate count matrices. We investigate algorithm choices for the challenges of pre-processing, and describe a workflow that balances efficiency and accuracy. Our workflow is based on the kallisto ( https://pachterlab.github.io/kallisto/ ) and bustools ( https://bustools.github.io/ ) programs, and is near-optimal in speed and memory. The workflow is modular, and we demonstrate its flexibility by showing how it can be used for RNA velocity analyses. Documentation and tutorials for using the kallisto | bus workflow are available at https://www.kallistobus.tools/ .
Role of the J-domain in the cooperation of Hsp40 with Hsp70 (1998)

The Escherichia coli Hsp40 DnaJ and Hsp70 DnaK cooperate in the binding of proteins at intermediate stages of folding, assembly, and translocation across membranes. Binding of protein substrates to the DnaK C-terminal domain is controlled by ATP binding and hydrolysis in the N-terminal ATPase domain. The interaction of DnaJ with DnaK is mediated at least in part by the highly conserved N-terminal J-domain of DnaJ that includes residues 2-75. Heteronuclear NMR experiments with uniformly 15N-enriched DnaJ2-75 indicate that the chemical environment of residues located in helix II and the flanking loops is perturbed on interaction with DnaK or a truncated DnaK molecule, DnaK2-388. NMR signals corresponding to these residues broaden and exhibit changes in chemical shifts in the presence of DnaK(MgADP). Addition of MgATP largely reversed the broadening, indicating that NMR signals of DnaJ2-75 respond to ATP-dependent changes in DnaK. The J-domain interaction is localized to the ATPase domain of DnaK and is likely to be dominated by electrostatic interactions. The results suggest that the J-domain tethers DnaK to DnaJ-bound substrates, which DnaK then binds with its C-terminal peptide-binding domain.
Biodegradable dextran hydrogels for protein delivery applications (2007)

The rapid development of protein-based pharmaceuticals over recent decades has tremendously increased the need for suitable delivery systems, guaranteeing a safe and controlled delivery of proteinacious drugs. Hydrogels offer good opportunities as protein delivery systems or tissue engineering scaffolds owing to an inherent biocompatibility. Their hydrophilic, soft and rubbery nature ensures minimal tissue irritation and a low tendency of cells and proteins to adhere to the hydrogel surface. A variety of both natural and synthetic polymers have been used for the design of hydrogels, in which network formation is established by chemical or physical crosslinking. This review introduces the general features of hydrogels and focuses on dextran hydrogels in particular. Chemically and physically crosslinked systems are described and their potential suitability as protein delivery systems, as well as tissue engineering scaffolds are discussed. Special attention is given to network properties, protein delivery, degradation behavior and biocompatibility.
Theory of double-chirped mirrors (1998)

A theory of double-chirped mirrors (DCMs) for dispersion compensation in ultrashort pulse laser sources is presented. We describe the multilayer interference coating by exact coupled-mode equations. They show that the analysis and synthesis of a coating with a slowly varying chirp in the layer thicknesses can be mapped onto a weakly inhomogeneous transmission line problem. Solutions of the transmission line equations are given using the WKB-method. Analytic expressions for reflectivity and group delay are derived. The solutions show that the main problem in chirped mirror design is the avoidance of spurious reflections, that lead to Gires-Tournois-like interference effects responsible for the oscillations in the group delay. These oscillations are due to an impedance matching problem of the equivalent transmission line. The impedance matching can be achieved by simultaneously chirping the strength of the coupling coefficient and the Bragg wavenumber of the mirror. An adiabatic increase in the coupling coefficient removes the typical oscillations in the group delay and results in broad-band mirrors with a controlled dispersion. Finally, the mirror is matched to air with a broadband antireflection coating. We discuss a complete design of a laser mirror with a reflectivity larger than 99.8% and a controlled dispersion over 300-nm bandwidth. Using such mirrors in a Ti:sapphire laser, we have demonstrated /spl ap/30-fs pulses, tunable over 300 nm, as well as 8-fs pulses from the same setup. A different design resulted in 6.5-fs pulses.
First-in-man tau vaccine targeting structural determinants essential for pathological tau–tau interaction reduces tau oligomerisation and neurofibrillary degeneration in an Alzheimer’s disease model (2014)

Current Controlled Trials NCT01850238. Registered 7 May 2013.
CpR18, a novel SAP‐domain plant transcription factor, binds to a promoter region necessary for ABA mediated expression of the <i>CDeT27‐45</i> gene from the resurrection plant <i>Craterostigma plantagineum</i> Hochst (2002)

CDeT27-45 is a lea-like gene from the resurrection plant Craterostigma plantagineum (Scrophulariaceae) which is strongly expressed in vegetative tissues in response to dehydration or treatment with abscisic acid (ABA). Expression of the gene is correlated with the acquisition of desiccation tolerance. Nuclear proteins bind to a 29-bp cis-regulatory region of the promoter which is essential for transcriptional activation of the CDeT27-45 gene by ABA. Using a yeast one-hybrid screen, the cDNA clone CpR18 was isolated, which encodes a protein with specific binding activity for the cis-regulatory element in the CDeT27-45 promoter. The protein contains an acidic region, a SAP-domain, a zinc finger of the C3H-type, and two motifs which are conserved in proteins from several plant species. One of the conserved regions is rich in basic residues and is predicted to form a helix-loop-helix structure. The R18 gene shows high similarities to genomic sequences and ESTs from other plant species. The tissue-specific expression pattern of the rare R18 mRNA and the distribution of nuclear protein binding activity for the CDeT27-45 promoter fragment are compared. The R18 protein is indeed localized in the nucleus, and activates transcription of CDeT27-45 promoter-GUS fusion constructs in tobacco protoplasts. DNA blot analysis and isolation of genomic clones reveal that two copies of R18 are present in the C. plantagineum genome.
A Structural Scaffolding of Intermediate Filaments in Health and Disease (1998)

The cytoplasm of animal cells is structured by a scaffolding composed of actin microfilaments, microtubules, and intermediate filaments. Intermediate filaments, so named because their 10-nanometer diameter is intermediate between that of microfilaments (6 nanometers) and microtubules (23 nanometers), assemble into an anastomosed network within the cytoplasm. In combination with a recently identified class of cross-linking proteins that mediate interactions between intermediate filaments and the other cytoskeletal networks, evidence is reviewed here that intermediate filaments provide a flexible intracellular scaffolding whose function is to structure cytoplasm and to resist stresses externally applied to the cell. Mutations that weaken this structural framework increase the risk of cell rupture and cause a variety of human disorders.
Effect of Pullout Lessons on the Academic Achievement of Eighth-Grade Band Students (2011)

This study examined the effect of pullout instrumental lessons on the academic achievement of eighth-grade band students. Participants ( N = 353) included 292 nonband students and 61 band students pulled once per week for music lessons in a single suburban K–8 school district in Midwestern United States. Data indicated that eighth-grade band students achieved significantly higher mean scores on the ACT Explore test than students who dropped band prior to eighth grade ( n = 58) or never enrolled in the program ( n = 234). In addition, no significant differences existed between all band students and the highest achieving nonband students, or between students who discontinued band after at least 1 year and those who never enrolled. Although band students in this study tended to be more academically successful than nonband students at the outset, these results support the assertion that pullout lessons had no negative effect on academic achievement, regardless of the number of years students participated in the program.
OnabotulinumtoxinA for chronic migraine: efficacy, safety, and tolerability in patients who received all five treatment cycles in the <scp>PREEMPT</scp> clinical program (2013)

This subgroup analysis demonstrated improvements with onabotulinumtoxinA treatment (five cycles) vs placebo (two cycles)/onabotulinumtoxinA (three cycles) for multiple headache symptom measures and suggests that at Week 56, patients treated earlier with onabotulinumtoxinA had better outcomes. These findings demonstrate the continued need and cumulative benefit over time with continued prophylaxis, an important and clinically pragmatic observation for clinicians and patients.
Mechanism of Streptococcus mutans glucosyltransferases: hybrid-enzyme analysis (1992)

Streptococcus mutans GS5 expresses three glucosyltransferases (GTFs): GTF-I and GTF-SI, which synthesize water-insoluble glucans in a primer-independent manner, and GTF-S, which is responsible for the formation of primer-dependent soluble glucan. The amino acid sequences of the GTF-I and GTF-S enzymes exhibit approximately 50% sequence identity. Various hybrid genes were constructed from the structural genes for the enzymes, and their products were analyzed. Three different approaches were used to construct the hybrid enzymes: (i) ligation of DNA fragments containing compatible endonuclease restriction sites of the two genes at homologous positions; (ii) in vivo recombination between the homologous regions of each gene; and (iii) random fusion of DNA fragments from each gene generated following exonuclease III digestion of tandemly arranged fragments corresponding to the two functional domains of each enzyme. Hybrid GTFs composed of the sucrose-binding domain of one enzyme (GTF-I or GTF-S) with the glucan-binding domain of the other synthesized insoluble glucan exclusively in the absence of primer dextran. Insoluble glucan synthesis by some, but not all, of the GTF-S:GTF-I chimeric enzymes was stimulated by primer dextran T10 addition. In addition, glucan binding by the former but not latter group of hybrid GTFs was demonstrated. These results suggest that the glucan-binding domain alone does not solely determine primer dependence or independence or the structure of the resulting glucan product, although this carboxyl-terminal domain containing direct repeating units does appear to play a significant role in primer dependence.
The Java Native interface : programmer's guide and specification (1999)

I. INTRODUCTION AND TUTORIAL. 1. Introduction. The Java Platform and Host Environment. Role of the JNI. Implications of Using the JNI. When to Use the JNI. Evolution of the JNI. Example Programs. 2. Getting Started. Overview. Declare the Native Method. Compile the HelloWorld Class. Create the Native Method Header File. Write the Native Method Implementation. Compile the C Source and Create a Native Library. Run the Program. II. PROGRAMMER'S GUIDE. 3. Basic Types, Strings, and Arrays. A Simple Native Method. Accessing Strings. Accessing Arrays. 4. Fields and Methods. Accessing Fields. Calling Methods. Invoking Constructors. Caching Field and Method Ids. Performance of JNI Field and Method Operations. 5. Local and Global References. Local and Global References. Freeing References. Rules for Managing References. 6. Exceptions. Overview. Proper Exception Handling. 7. The Invocation Interface. Creating the Java Virtual Machine. Linking Native Applications with the Java Virtual Machine. Attaching Native Threads. 8. Additional JNI Features. JNI and Threads. Writing Internationalized Code. Registering Native Methods. Load and Unload Handlers. Reflection Support. JNI Programming in C++. 9. Leveraging Existing Native Libraries. One-to-One Mapping. Shared Stubs. One-to-One Mapping versus Shared Stubs. Implementation of Shared Stubs. Peer Classes. 10. Traps and Pitfalls. Error Checking. Passing Invalid Arguments to JNI Functions. Confusing jclass with jobject. Truncating jboolean Arguments. Boundaries between Java Application and Native Code. Confusing IDs with References. Caching Field and Method Ids. Terminating Unicode Strings. Violating Access Control Rules. Disregarding Internationalization. Retaining Virtual Machine Resources. Excessive Local Reference Creation. Using Invalid Local References. Using the JNIEnv across Threads. Mismatched Thread Models. III. SPECIFICATION. 11. Overview of the JNI Design. Design Goals. Loading Native Libraries. Linking Native Methods. Calling Conventions. The JNIEnv Interface Pointer. Passing Data. Accessing Objects. Errors and Exceptions. 12. JNI Types. Primitive and Reference Types. Field and Method Ids. String Formats. Constants. 13. JNI Functions. Summary of the JNI Functions. Specification of JNI Functions. Index. 0201325772T04062001
Crystal Structure of the Tetramerization Domain of the p53 Tumor Suppressor at 1.7 Angstroms (1995)

The p53 protein is a tetrameric transcription factor that plays a central role in the prevention of neoplastic transformation. Oligomerization appears to be essential for the tumor suppressing activity of p53 because oligomerization-deficient p53 mutants cannot suppress the growth of carcinoma cell lines. The crystal structure of the tetramerization domain of p53 (residues 325 to 356) was determined at 1.7 angstrom resolution and refined to a crystallographic R factor of 19.2 percent. The monomer, which consists of a beta strand and an alpha helix, associates with a second monomer across an antiparallel beta sheet and an antiparallel helix-helix interface to form a dimer. Two of these dimers associate across a second and distinct parallel helix-helix interface to form the tetramer.
Molecular manipulations of the multidrug transporter: a new role for transgenic mice <sup>1</sup> (1991)

Multidrug resistance in human cancer is associated with overexpression of the MDR1 gene which encodes a 170,000 molecular weight membrane glycoprotein that transports cytotoxic drugs out of cancer cells. The MDR1 gene is normally expressed in intestine, kidney, liver, and adrenal glands, and in tumors derived from these tissues, but it is not expressed in normal bone marrow. Transgenic mice that express the MDR1 gene in their bone marrow have been developed, and because of this expression these mice are resistant to the bone marrow-suppressive effects of daunomycin, doxorubicin, taxol, and several other anticancer drugs. These mice can be used in several different ways to develop new types of drugs to treat human cancer.--Pastan, I.; Willingham, M. C.; Gottesman, M. Molecular manipulations of the multidrug transporter: a new role for transgenic mice.
Global regulation of gene expression in Escherichia coli (1993)

Global transcription responses of Escherichia coli to various stimuli or genetic defects were studied by measuring mRNA levels in about 400 segments of the genome. Measuring mRNA levels was done by analyzing hybridization to DNA dot blots made with overlapping lambda clones spanning the genome of E. coli K-12. Conditions examined included isopropyl-beta-D-thiogalactopyranoside (IPTG) induction, heat shock, osmotic shock, starvation for various nutrients, entrance of cells into the stationary phase of growth, anaerobic growth in a tube, growth in the gnotobiotic mouse gut, and effects of pleiotropic mutations rpoH, himA, topA, and crp. Most mapped genes known to be regulated by a particular situation were successfully detected. In addition, many chromosomal regions containing no previously known regulated genes were discovered that responded to various stimuli. This new method for studying globally regulated genetic systems in E. coli combines detection, cloning, and physical mapping of a battery of coregulated genes in one step.
Object reuse and exchange for publishing and sharing workflows (2011)

The workflow paradigm can provide the means to describe the complete functional pipeline for a scientific experiment and therefore expose the underlying scientific processes for enabling the reproducibility of results. However, current means for exposing such information are tied closely to the individual workflow engines and there is no existing method that provides a common way to share this information.
&lt;title&gt;Phase modulation using the silicon backplane spatial light modulator and transmissive glass&lt;/title&gt; (1999)

Spatial Light Modulators (SLMs) are very important components in optical systems. SLMs using arrays of phase modulating pixels are the basis of many new system proposals in adaptive optics, image processing and switching. Ferroelectric Liquid Crystals (FLCs) are especially well suited to devices requiring binary phase gratings and have been widely used. Many of the above applications have been pioneered and demonstrated using `all glass' multiplexed FLC SLMs (128 by 128 pixels) operating in transmission mode. More compact and integrated system will be built using FLC and Silicon SLMs and much work is now focused in this area due to the interest in polarization insensitive FLC binary phase modulation for beamsteering application and arrays of intensity modulator for microdisplays. Here we examine the advantages and disadvantages of a range of different implementations of FLC SLMs for applications requiring arrays of phase modulating pixels. The basis of our comparison is the spatial and temporal distribution of light in the far field diffraction pattern formed by the SLMs. The spatial field is influenced by the flatness and pixel structure of the SLMs, its topology, the surface finish of pixels, the liquid crystal alignment and so forth. Temporal variations arise because of the electronic addressing schemes used to address pixels. Both are important in most applications discussed. The devices considered are all-glass multiplexed FLC SLMs operating in transmissive mode and non- planarized silicon backplane FLC SLM with the mirror flat down on the silicon.
Focal blood-brain-barrier disruption with high-frequency pulsed electric fields (2014)

The blood-brain-barrier (BBB), a network of tight junctions that impedes large molecule transport, limits the usefulness of systemic chemotherapeutic delivery for the treatment of malignant gliomas and other neurological diseases. Here, we present a tool for BBB disruption that uses bursts of sub-microsecond bipolar pulses to enhance the transfer of large molecules to the brain. Blunt needle electrodes were advanced into the motor cortex of anesthetized adult rats, and a series of 90–900 bursts were delivered with voltage-to-distance ratios of 250 or 2000 V/cm, a total programmed energized time of 100 μs, and a repetition rate of 1 Hz. BBB disruption was assessed via a gadolinium-Evans blue albumin tracer, and all experimental conditions were found to cause BBB disruption immediately following treatment without inducing local or distal muscle contractions. The lowest energy condition, 300 bursts consisting of 850 ns bipolar pulses, resulted in significant BBB disruption (0.51 cm 3 ), without displaying necrotic or apoptotic damage to neurological tissue.
Neuromedin Beta: P73t Polymorphism in Overweight and Obese Subjects (2008)

Neuromedin beta (NMB) is a member of the bombesin-like peptide family expressed in brain, gastrointestinal tract, pancreas, adrenals and adipose tissue. The aim of our study was to compare the frequency of P73T polymorphism in overweight and obese patients (37 men: age 50.6+/-11.7 years, BMI 41.1+/-7.8 kg/m(2); 255 women: age 49.0+/-11.9 years, BMI 37.9+/-6.8 kg/m(2)) with that of healthy normal weight subjects (51 men: age 28.2+/-7.1 years, BMI 22.3+/-2.0 kg/m(2); 104 women: age 29.1+/-9.1 years, BMI 21.5+/-1.9 kg/m(2)) and to investigate the polymorphism's influence on anthropometric, nutritional and psychobehavioral parameters in overweight/obese patients both at the baseline examination and at a control visit carried out 2.5 years later, regardless of the patient s compliance with the weight reduction program. No significant differences in the genotype distribution were demonstrated between normal weight and overweight/obese subjects. Male T allele non-carriers compared to T allele carriers had higher energy (p=0.009), protein (p=0.018) and fat (p=0.002) intakes and hunger score (p=0.015) at the beginning of treatment. Male T allele non-carriers had a more favorable response to weight management at the follow-up, as they exhibited a significant reduction in waist circumference, energy intake and depression score as well as a significant increase in dietary restraint. No significant differences between carriers and non-carriers were demonstrated in women at the baseline examination. Both female T allele carriers and non-carriers demonstrated similar significant changes in nutritional parameters and in restraint score at the follow-up. Nevertheless, only female non-carriers showed a significant decrease in the hunger score.
NMR and X-ray Spectroscopy of Sodium−Silicon Clathrates (2001)

The 23Na and 29Si NMR spectra of the sodium−silicon clathrate materials Na8Si46 and NaxSi136 (1 < x < 24) and the parent Zintl phase NaSi have been studied in detail with a view to ironing out a number of ambiguities in the published literature and to determining properties of these potential thermoelectric materials. Sharp spectra are obtained only when the clathrate cages are close to fully occupied by Na, so that crystallographic symmetry is achieved. Signals from Na in the small and large cages of both structures have been unequivocally assigned. The pseudospherical cages give isotropic 23Na lines, whereas the other cages produce first-order quadrupolar line shapes. Electric field gradients derived from these spectra, and ab initio calculations are in remarkable agreement. The large Knight shifts of both types of nuclei have rather unusual temperature dependences, which reflect the changing distributions of unpaired electron density in the conduction bands. As the Na content of NaxSi136 is reduced there is drastic broadening of the 23Na and 29Si spectra due to a random distribution of vacant cages and hence of environments, and the Si spectra shift to lower frequencies, indicating a reduction in conduction s-electron density on the Si. Intensity data suggest a preferential loss of Na from the large cages. XPS results show a protective coating of silica on the surface of the clathrates. NMR, XPS, and XANES results all indicate transfer of electrons from Na to the Si framework, as predicted by calculations. XANES shows a lowering of the absorption edge, and hence of the conduction band, of both clathrates relative to crystalline Si.
Chemoprotection against cyclophosphamide-induced urotoxicity: comparison of nine thiol protective agents. (1994)

Nine thiol chemoprotective compounds were compared for their abilities to reduce the urotoxicity induced by a high dose (1.5 mmol/kg i.p.) of the cancer chemotherapeutic agent, cyclophosphamide (CTX) in male Swiss-Webster mice. Toxicity was assessed by the change in body weight at 48 h, as well as the relative bladder weight (rbw), both a macroscopic and a microscopic rating of bladder damage, and the glutathione (GSH) status of the bladder and the liver. In addition, the rbw, macroscopic assessment, and GSH measurements were also carried out at 4 h, the point of maximal damage and GSH depletion. The powerful effects of compounds with the D-configuration indicated that direct action by the thiols is their most likely mechanism of action. Indirect action through GSH is unlikely because the D-amino acid cannot support GSH's biosynthesis.