gebhart/patrepeval huggingface dataset:
Dystrophin quantification and clinical correlations in Becker muscular dystrophy: implications for clinical trials (2011)

Duchenne muscular dystrophy is caused by mutations in the DMD gene that disrupt the open reading frame and prevent the full translation of its protein product, dystrophin. Restoration of the open reading frame and dystrophin production can be achieved by exon skipping using antisense oligonucleotides targeted to splicing elements. This approach aims to transform the Duchenne muscular dystrophy phenotype to that of the milder disorder, Becker muscular dystrophy, typically caused by in-frame dystrophin deletions that allow the production of an internally deleted but partially functional dystrophin. There is ongoing debate regarding the functional properties of the different internally deleted dystrophins produced by exon skipping for different mutations; more insight would be valuable to improve and better predict the outcome of exon skipping clinical trials. To this end, we have characterized the clinical phenotype of 17 patients with Becker muscular dystrophy harbouring in-frame deletions relevant to on-going or planned exon skipping clinical trials for Duchenne muscular dystrophy and correlated it to the levels of dystrophin, and dystrophin-associated protein expression. The cohort of 17 patients, selected exclusively on the basis of their genotype, included 4 asymptomatic, 12 mild and 1 severe patient. All patients had dystrophin levels of >40% of control and significantly higher dystrophin (P = 0.013), β-dystroglycan (P = 0.025) and neuronal nitric oxide synthase (P = 0.034) expression was observed in asymptomatic individuals versus symptomatic patients with Becker muscular dystrophy. Furthermore, grouping the patients by deletion, patients with Becker muscular dystrophy with deletions with an end-point of exon 51 (the skipping of which could rescue the largest group of Duchenne muscular dystrophy deletions) showed significantly higher dystrophin levels (P = 0.034) than those with deletions ending with exon 53. This is the first quantitative study on both dystrophin and dystrophin-associated protein expression in patients with Becker muscular dystrophy with deletions relevant for on-going exon skipping trials in Duchenne muscular dystrophy. Taken together, our results indicate that all varieties of internally deleted dystrophin assessed in this study have the functional capability to provide a substantial clinical benefit to patients with Duchenne muscular dystrophy.
Artist Spotlight: Curved and Pointed (2010)

abstraction is elimination of detail and codification of information.We operate by its principles in all our systems of communication and even in our coherent thoughts.Since we must communicate in the world outside ourselves and not mind-to-mind, we have the ability to simplify our perceptions into compact, expressible forms, such as words and symbols.The ability to recognize that "bird" means any, all, or one particular bird, has a more playful side, such as seeing birds in the shapes of clouds or lines of curved wood.i find it fascinating that the essentials i pick out of a visual experience, and translate through inarticulate wood, can relate some of the feelings of that experience to another.and i find sculpture to be something altogether different from pictures.an artist making images has to create only one side of things-the side we see-and can even create something altogether imaginary.a sculptor, on the other hand, while dealing with his or her imagination, also has to deal with the physical facts of the world.Gravity, size, and relationships of placement demand a functional kind of attentionthe same kind we give to everyday objects.But sculpture further demands a special kind of attention-the importance of what it looks from every side.
A framework for algorithm deployment on cloud-based quantum computers (2018)

In recent years, the field of quantum computing has significantly developed in both the improvement of hardware as well as the assembly of various software tools and platforms, including cloud access to quantum devices. Unfortunately, many of these resources are rapidly changing and thus lack accessibility and stability for robust algorithm prototyping and deployment. Effectively leveraging the array of hardware and software resources at a higher level, that can adapt to the rapid development of software and hardware, will allow for further advancement and democratization of quantum technologies to achieve useful computational tasks. As a way to approach this challenge, we present a flexible, high-level framework called algo2qpu that is well-suited for designing and testing instances of algorithms for near-term quantum computers on the cloud. Algorithms that employ adaptive protocols for optimizations of algorithm parameters can be grouped under the umbrella of "adaptive hybrid quantum-classical" (AHQC) algorithms. We demonstrate the utility of algo2qpu for near-term algorithm development by applying the framework to implement proof-of-principle instances of two AHQC algorithms that have applications in quantum chemistry and/or quantum machine learning, namely the quantum autoencoder and the variational quantum classifier, using Rigetti Computing's Forest platform.
Particle Charging and Charge Screening in Nonpolar Dispersions with Nonionic Surfactants (2010)

The electrostatic stabilization of colloidal dispersions is usually considered the domain of polar media only because of the high energetic cost associated with introducing electric charge in nonpolar environments. Nevertheless, some surfactants referred to as "charge control agents" are known to raise the conductivity of liquids with low electric permittivity and to mediate charge stabilization of nonpolar dispersions. Here we study an example of the particularly counterintuitive charging and electrostatic interaction of colloidal particles in a nonpolar solvent caused by nonionic surfactants. PMMA particles in hexane solutions of nonionic sorbitan oleate (Span) surfactants are found to exhibit a field-dependent electrophoretic mobility. Extrapolation to zero field strength yields evidence for large electrostatic surface potentials that decay with increasing surfactant concentration in a fashion reminiscent of electrostatic screening caused by salt in aqueous solutions. The amount of surface charge and screening ions in the nonpolar bulk is further characterized via measurements of the particles' pair interaction energy. The latter is obtained by liquid structure analysis of quasi-2-dimensional equilibrium particle configurations studied with digital video microscopy. In contrast to the behavior reported for systems with ionic surfactants, we observe particle charging and a screened Coulomb type interaction both above and below the surfactant's critical micelle concentration.
[Effect of smoking on the indicators of immunity and the acute-phase reaction in persons professionally exposed to solvents]. (1992)

In 156 men, 46 non-smokers, 47 smokers, 19 non-smokers exposed to organic solvents and 41 smokers exposed also to solvents the levels of immunoglobulins, lysozyme, C3c, C4, alpha 1-acid glycoprotein, coeruloplasmin and haptoglobins were determined in serum, besides that the counts of circulating T, B and non-T non-B lymphocytes were calculated. A synergistic depressing effect of cigarette smoke and organic solvents was found on certain immunity parameters. This depression was manifested also as changes in the concentrations of IgA, IgD, IgG, lysozyme and T-lymphocyte subpopulations.
KIR: Diverse, Rapidly Evolving Receptors of Innate and Adaptive Immunity (2002)

KIR genes have evolved in primates to generate a diverse family of receptors with unique structures that enable them to recognize MHC-class I molecules with locus and allele-specificity. Their combinatorial expression creates a repertoire of NK cells that surveys the expression of almost every MHC molecule independently, thus antagonizing the spread of pathogens and tumors that subvert innate and adaptive defense by selectively downregulating certain MHC class I molecules. The genes encoding KIR that recognize classical MHC molecules have diversified rapidly in human and primates; this contrasts with conservation of immunoglobulin- and lectin-like receptors for nonclassical MHC molecules. As a result of the variable KIR-gene content in the genome and the polymorphism of the HLA system, dissimilar numbers and qualities of KIR:HLA pairs function in different humans. This diversity likely contributes variability to the function of NK cells and T-lymphocytes by modulating innate and adaptive immune responses to specific challenges.
The prepro-peptide of Mucor rennin directs the secretion of human growth hormone by Saccharomyces cerevisiae (1990)

An aspartic proteinase, Mucor pusillus rennin (MPR), of filamentous fungus Mucor pusillus, is efficiently secreted from a transformant of Saccharomyces cerevisiae containing the intact MPR gene. To test the usefulness of the MPR leader peptide in secretion of heterologous proteins from yeast cells, several plasmids encoding the fusion proteins composed of different parts of the NH2-terminal region of prepro-MPR and human growth hormone (hGH) were constructed. The parts of the leader peptide upstream of hGH were the whole prepro-peptide following the NH2-terminal region of mature MPR in JGH1, the intact pre-sequence and a part of the pro-sequence in JGH2, and the putative signal sequences of the NH2-terminal 18 and 22 amino acids in JGH3 and JGH7, respectively. When the hGH genes fused to these leader sequences were expressed in yeast cells under the control of the yeast GAL7 promoter, proteins of various sizes immunoreactive with the anti-hGH antibody were secreted into the medium. Among the plasmids mentioned above, JGH2 directed the greatest secretion of the protein of 23 kilodaltons in size, which contained the expected NH2-terminal amino acid sequence of an additional eight amino acids derived from the pro-peptide of MPR. The addition of the GAL10 terminator downstream of the hGH gene in JGH2 resulted in a greater than three- to fivefold increase in the secretion, whereas the insertion of the GAL4 gene, which is a positive regulator for the GAL system, had no significant effect. The improved yield of the total protein of hGH secreted into the medium reached approximately 10 mg/liter.
Immunoassay for human serum hemojuvelin (2010)

This enzyme-linked immunosorbent assay has a good specificity and sensitivity for the quantification of soluble hemojuvelin in human serum and could be a valuable aid to understanding the physiological role of this protein.
Pedestrian tracking from a moving vehicle (2002)

Intelligent vehicles and unattended driving systems of the future will need the ability to recognize relevant traffic participants (such as other vehicles, pedestrians, bicyclists, etc.) and detect dangerous situations ahead of time. An important component of these systems is one that is able to distinguish pedestrians and track their motion to make intelligent driving decisions. The associated computer vision problem that needs to be solved is detection and tracking of pedestrians from a moving camera, which is extremely challenging. Robust pedestrian tracking performance can be achieved by temporal integration of the data in a probabilistic setting. We employ a shape model for pedestrians and an efficient variant of the condensation tracker to achieve these objectives. The tracking is performed in the high-dimensional space of shape model parameters which consists of Euclidean transformation parameters and deformation parameters. Our condensation tracker employs sampling on quasi-random points, improving its asymptotic complexity and robustness, and making it amenable to real-time implementation.
Solution processing of transparent conductors: from flask to film (2011)

This critical review focuses on the solution deposition of transparent conductors with a particular focus on transparent conducting oxide (TCO) thin-films. TCOs play a critical role in many current and emerging opto-electronic devices due to their unique combination of electronic conductivity and transparency in the visible region of the spectrum. Atmospheric-pressure solution processing is an attractive alternative to conventional vacuum-based deposition methods due to its ease of fabrication, scalability, and potential to lower device manufacturing costs. An introduction into the applications of and material criteria for TCOs will be presented first, followed by a discussion of solution routes to these systems. Recent studies in the field will be reviewed according to their materials system. Finally, the challenges and opportunities for further enabling research will be discussed in terms of emerging oxide systems and non-oxide based transparent conductors (341 references).
A single arginine residue determines species specificity of the human growth hormone receptor. (1995)

Although growth hormone (GH) receptors (GHRs) in many species bind human (h) GH as well as their own GH, the hGHR only binds primate GH. Arg43 in hGHR interacts with Asp171 of hGH. Nonprimates have a His in the position equivalent to residue 171 of primate GH and a Leu in position 43 of primate GHR. To determine whether Arg43 accounts for the species specificity of the hGHR, point mutations that changed Leu43 to Arg were introduced into the cDNAs encoding the bovine (b) GHR or the rat GH binding protein (GHBP) and these mutants or their wild-type (WT) counterparts were expressed in mouse L cells. Binding of hGH or bGH to transfected cells or to GHBP secreted into the incubation medium was assessed by displacement of 125I-labeled hGH. WT and mutant bGHR bound hGH with similar affinity, but the affinity of the mutant receptors for bGH was reduced 200-fold. Likewise, WT and mutant GHBP bound hGH with equal affinity, but only WT GHBP bound bGH. Cross-linking of 125I-labeled hGH to WT or mutant GHR produced a 141-kDa labeled complex whose appearance was blocked by unlabeled hGH, but bGH blocked cross-linking only to WT receptors. Both hGH and bGH stimulated tyrosine phosphorylation of a 95-kDa protein in cells transfected with WT GHR, but bGH was less effective in cells expressing mutant GHR. We conclude that incompatibility of Arg43 in the hGHR with His171 in nonprimate GH is the major determinant of species specificity.
Directed evolution converts subtilisin E into a functional equivalent of thermitase (1999)

We used directed evolution to convert Bacillus subtilis subtilisin E into an enzyme functionally equivalent to its thermophilic homolog thermitase from Thermoactinomyces vulgaris. Five generations of random mutagenesis, recombination and screening created subtilisin E 5-3H5, whose half-life at 83 degrees C (3.5 min) and temperature optimum for activity (Topt, 76 degrees C) are identical with those of thermitase. The Topt of the evolved enzyme is 17 degrees C higher and its half-life at 65 degrees C is >200 times that of wild-type subtilisin E. In addition, 5-3H5 is more active towards the hydrolysis of succinyl-Ala-Ala-Pro-Phe-p-nitroanilide than wild-type at all temperatures from 10 to 90 degrees C. Thermitase differs from subtilisin E at 157 amino acid positions. However, only eight amino acid substitutions were sufficient to convert subtilisin E into an enzyme equally thermostable. The eight substitutions, which include known stabilizing mutations (N218S, N76D) and also several not previously reported, are distributed over the surface of the enzyme. Only two (N218S, N181D) are found in thermitase. Directed evolution provides a powerful tool to unveil mechanisms of thermal adaptation and is an effective and efficient approach to increasing thermostability without compromising enzyme activity.
Negotiating price/delivery date in a stochastic manufacturing environment (1999)

We study a make-to-order manufacturing system consisting of several processing centers that are subject to failures and repairs. Our objective is to build a model that can be used as a tool for negotiating the delivery date and the price of a certain upcoming order. The model takes into account the congestion level of the shop floor at the time the order is placed. Based on the workload of the processing centers, the model splits the order into lots and assigns them to the processing centers so as to determine the order completion time associated with the minimum operating cost. The efficiency of the solution method for the model allows real-time decision-making while negotiating the price and delivery date of the order to be placed. Since the decisions are made based on a snapshot of the congestion level at the shop floor, using this model will reduce the conflict between the marketing and the production activities in manufacturing organizations.
Established and Emerging Markers of Kidney Function (2012)

A variety of methods are available to assist clinicians in the assessment of kidney function and injury. Ongoing investigation will help determine the utility of several new markers and clarify their role in the care of patients with and at risk for kidney disease.
Recombinant protein purification using thermoseparating aqueous two-phase systems (1999)

The biotechnology industry has grown considerably over the past twenty years, and the revolution within the field of molecular biology has dramatically improved the possibilities of producing proteins and other important biomolecules. The product of interest will be obtained in a multi-component solution and some challenging purification work has to be performed to recover the target molecule in a pure form. The aim of this thesis is to show that an aqueous two-phase system composed of technical grade polymer(s) and recyclable polymers can be used as an efficient primary recovery step for biological material. The polymers studied are either low-cost starch derivatives or thermoseparating copolymers, e.g. ethylene oxide and propylene oxide random copolymers (EOPO polymers). Thermoseparating polymers in water solution will upon heating form a two-phase system where one phase is enriched in polymer and the other depleted. The thermoseparating polymer can be recycled and used in a number of extraction systems. Apolipoprotein A-I (Apo A-I) was chosen as target protein in this study. The protein was purified from cell-free E. coli extracts. Systems composed of EOPO/hydroxypropyl starch had high protein capacity and Apo A-I could be efficiently purified while retaining a high yield. Due to the amphiphilic properties of Apo A-I the purification of the protein could be improved by addition of surfactant. Recycling of thermoseparating polymers has been performed, and the recycled polymers have been shown to be just as efficient for protein purification as fresh polymers.
Inflammatory bowel disease susceptibility loci defined by genome scan meta-analysis of 1952 affected relative pairs (2004)

Crohn's disease and ulcerative colitis (the inflammatory bowel diseases) have a strong genetic component. Although over 20 putative susceptibility loci have been identified by individual genome scans, the majority of these loci have not been replicated. Many individual studies are at the lower limit of acceptable power for complex disease linkage analysis. Genome scan meta-analysis (GSMA), by use of sample sizes an order of magnitude greater than individual linkage studies, has increased power to detect novel loci, may confirm or refute regions detected in smaller individual studies, and enables regions to be prioritized for further gene identification efforts. Genome scan data (markers, significance scores) were obtained from 10 separate studies and meta-analysis was performed using the GSMA method. These studies comprised 1952 inflammatory bowel disease, 1068 Crohn's disease and 457 ulcerative colitis affected relative pairs. Study results were divided into 34 cM chromosomal bins, ranked, weighted by study size, summed across studies and bin-by-bin significance obtained by simulation. A region on chromosome 6p (containing the HLA) met genome wide significance for inflammatory bowel disease. Loci meeting suggestive significance for inflammatory bowel disease were 2q, 3q, 5q, 7q and 16 (NOD2/CARD15 region); Crohn's disease, 2q, 3q, 6p, 16 (NOD2/CARD15 region), 17q, 19p; and ulcerative colitis, 2q. Clustering of adjacent bins was observed for chromosomes 6p, 16, 19p. The meta-analysis has identified novel loci and prioritized genomic regions for further gene identification studies.
Quantum statistical mechanics in a closed system (1991)

A closed quantum-mechanical system with a large number of degrees of freedom does not necessarily give time averages in agreement with the microcanonical distribution. For systems where the different degrees of freedom are uncoupled, situations are discussed that show a violation of the usual statistical-mechanical rules. By adding a finite but very small perturbation in the form of a random matrix, it is shown that the results of quantum statistical mechanics are recovered. Expectation values in energy eigenstates for this perturbed system are also discussed, and deviations from the microcanonical result are shown to become exponentially small in the number of degrees of freedom.
Generation of mouse-induced pluripotent stem cells by transient expression of a single nonviral polycistronic vector (2009)

Induced pluripotent stem (iPS) cells have generated keen interest due to their potential use in regenerative medicine. They have been obtained from various cell types of both mice and humans by exogenous delivery of different combinations of Oct4, Sox2, Klf4, c-Myc, Nanog, and Lin28. The delivery of these transcription factors has mostly entailed the use of integrating viral vectors (retroviruses or lentiviruses), carrying the risk of both insertional mutagenesis and oncogenesis due to misexpression of these exogenous factors. Therefore, obtaining iPS cells that do not carry integrated transgene sequences is an important prerequisite for their eventual therapeutic use. Here we report the generation of iPS cell lines from mouse embryonic fibroblasts with no evidence of integration of the reprogramming vector in their genome, achieved by nucleofection of a polycistronic construct coexpressing Oct4, Sox2, Klf4, and c-Myc.
SINGLE CELL ENDOCRINOLOGY: ANALYSIS OF P-450scc ACTIVITY BY FLUORESCENCE DETECTION METHODS (1991)

A mechanism-based, fluorogenic probe for the cytochrome P-450scc (cholesterol side chain cleavage) enzyme, rate-limiting for the conversion of cholesterol to steroid hormones, is introduced and its application to the study of enzyme activity and regulation in single steroidogenic cells by several fluorescence detection methods is demonstrated. Reaction of the probe with P-450scc gives pregnenolone and the highly fluorescent resorufin anion. Spectroscopic changes in probe fluorescence, indicative of P-450scc activity, were monitored by steady-state fluorescence spectroscopy, flow cytometry, and microspectrofluorometry. This unique probe provides a nonradiometric indicator for real-time measurement of P-450scc activity in single living cells.