gebhart/patrepeval huggingface dataset:
Phosphorodiamidate morpholino oligomers suppress mutant huntingtin expression and attenuate neurotoxicity (2014)

Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin (HTT) gene. Disease pathogenesis derives, at least in part, from the long polyglutamine tract encoded by mutant HTT. Therefore, considerable effort has been dedicated to the development of therapeutic strategies that significantly reduce the expression of the mutant HTT protein. Antisense oligonucleotides (ASOs) targeted to the CAG repeat region of HTT transcripts have been of particular interest due to their potential capacity to discriminate between normal and mutant HTT transcripts. Here, we focus on phosphorodiamidate morpholino oligomers (PMOs), ASOs that are especially stable, highly soluble and non-toxic. We designed three PMOs to selectively target expanded CAG repeat tracts (CTG22, CTG25 and CTG28), and two PMOs to selectively target sequences flanking the HTT CAG repeat (HTTex1a and HTTex1b). In HD patient-derived fibroblasts with expanded alleles containing 44, 77 or 109 CAG repeats, HTTex1a and HTTex1b were effective in suppressing the expression of mutant and non-mutant transcripts. CTGn PMOs also suppressed HTT expression, with the extent of suppression and the specificity for mutant transcripts dependent on the length of the targeted CAG repeat and on the CTG repeat length and concentration of the PMO. PMO CTG25 reduced HTT-induced cytotoxicity in vitro and suppressed mutant HTT expression in vivo in the N171-82Q transgenic mouse model. Finally, CTG28 reduced mutant HTT expression and improved the phenotype of Hdh(Q7/Q150) knock-in HD mice. These data demonstrate the potential of PMOs as an approach to suppressing the expression of mutant HTT.
Fetuses in a Thai Buddhist Temple as Chaotic Irruption and Public Embarrassment (2012)

Abstract In late 2010, about 2000 human fetuses were discovered in the mortuary of a Buddhist temple in Bangkok. This article examines the subsequent affair from two perspectives: the magico-religious and the socio-political. The first deals with the fetuses as a symbol: it examines the beliefs regarding fetuses in Buddhism and Thai folk religion, and the manner with which the irruption of the fetuses into the Buddhist temple was dealt with. The second deals with the fetuses as an exposure of a widespread social problem with complex legal and social policy implications, and the way the authorities treated it. The two perspectives are related through Buddhism, which helped to resolve the magico-religious issue of dispatching the fetuses’ spirits, while constituting a barrier to the resolution of the socio-political issue of change in the Thai abortion law. This created an irresolvable conundrum: the issue of abortion cannot be resolved in a sustainable way without affecting some of the fundamental premises on which Thailand's abortion law and its “regime of images” is based. The authorities preferred to uphold the law and sustain the image, rather than to resolve the basic underlying problem of which the discovered fetuses were just the most blatant symptom. This problem is the discrepancy between the restrictive abortion law and current sexual practices, which have engendered a growing demand for abortions by the younger generation of Thai urbanites.
Apolipoprotein A-I charge and conformation regulate the clearance of reconstituted high density lipoprotein in vivo (1999)

While low apolipoprotein A-I (apoA-I) levels are primarily associated with increased high density lipoprotein (HDL) fractional catabolic rate (FCR), the factors that regulate the clearance of HDL from the plasma are unclear. In this study, the effect of lipid composition of reconstituted HDL particles (LpA-I) on their rate of clearance from rabbit plasma has been investigated. Sonicated LpA-I containing 1 to 2 molecules of purified human apoA-I and 5 to 120 molecules of palmitoyl-oleoyl phosphatidylcholine (POPC) exhibit similar charge and plasma FCR to that for lipid free apoA-I, 2.8 pools/day. Inclusion of 1 molecule of apoA-II to an LpA-I complex increases the FCR to 3.5 pools/day, a value similar to that observed for exchanged-labeled HDL3. In contrast, addition of 40 molecules of triglyceride, diglyceride, or cholesteryl ester to a sonicated LpA-I containing 120 moles of POPC and 2 molecules of apoA-I increases the negative charge of the particle and reduces the FCR to 1.8 pools/day. Discoidal LpA-I are the most positively charged lipoprotein particles and also have the fastest clearance rates, 4.5 pools/day. Immunochemical characterization of the different LpA-I particles shows that the exposure of an epitope at residues 98 to 121 of the apoA-I molecule is associated with an increased negative particle charge and a slower clearance from the plasma. We conclude that the charge and conformation of apoA-I are sensitive to the lipid composition of LpA-I and play a central role in regulating the clearance of these lipoproteins from plasma. conformation regulate the clearance of reconstituted high density lipoprotein in vivo.
The interaction of activated factor VII with tissue factor: insight into the mechanism of cofactor-mediated activation of activated factor VII. (1998)

The structure solution of the complex of tissue factor (TF) and activated factor VII (FVIIa) and extensive mutagenesis analysis of the FVIIa protease domain have recently provided a detailed, novel insight into the function of the extrinsic activation complex. This overview relates the functional data to the known molecular interactions defined by crystallography, arriving at a hypothesis of how FVIIa is 'switched on' through specific contacts with TF. Combining these findings with the results of mutational analysis of TF, a picture emerges whereby multiple domains of both cofactor and enzyme provide contacts for the assembly of macromolecular substrate.
Gene Cloning and Expression ofLeifsoniaAlcohol Dehydrogenase (LSADH) Involved in Asymmetric Hydrogen-Transfer Bioreduction to Produce (R)-Form Chiral Alcohols (2006)

The gene encoding Leifsonia alcohol dehydrogenase (LSADH), a useful biocatalyst for producing (R)-chiral alcohols, was cloned from the genomic DNA of Leifsonia sp. S749. The gene contained an opening reading frame consisting of 756 nucleotides corresponding to 251 amino acid residues. The subunit molecular weight was calculated to be 24,999, which was consistent with that determined by polyacrylamide gel electrophoresis. The enzyme was expressed in recombinant Escherichia coli cells and purified to homogeneity by three column chromatographies. The predicted amino acid sequence displayed 30-50% homology to known short chain alcohol dehydrogenase/reductases (SDRs); moreover, the NADH-binding site and the three catalytic residues in SDRs were conserved. The recombinant E. coli cells which overexpressed lsadh produced (R)-form chiral alcohols from ketones using 2-propanol as a hydrogen donor with the highest level of productivity ever reported and enantiomeric excess (e.e.).
Capillary Electrophoresis (1999)

This review covers the clinical chemistry applications of capillary electrophoresis published during the period of October 1996 to October 1998. The search method for the literature has been CA Selects for Capillary Electrophoresis from the Chemical Abstracts Service. Although the implementation of CE methods in routine clinical laboratories has been slow, there has been a rapid expansion of CE in clinically related research. This review is not intended to provide readers a detailed description of the published papers; rather, the author has tried to summarize the important research activities in clinical chemistry into several categories (Tables 1-6). The author feels that he may give a fair coverage to a variety of clinical chemistry applications, while allowing the readers to search for a specific application and get to its original publications quickly.
Interactive local adjustment of tonal values (2006)

This paper presents a new interactive tool for making local adjustments of tonal values and other visual parameters in an image. Rather than carefully selecting regions or hand-painting layer masks, the user quickly indicates regions of interest by drawing a few simple brush strokes and then uses sliders to adjust the brightness, contrast, and other parameters in these regions. The effects of the user's sparse set of constraints are interpolated to the entire image using an edge-preserving energy minimization method designed to prevent the propagation of tonal adjustments to regions of significantly different luminance. The resulting system is suitable for adjusting ordinary and high dynamic range images, and provides the user with much more creative control than existing tone mapping algorithms. Our tool is also able to produce a tone mapping automatically, which may serve as a basis for further local adjustments, if so desired. The constraint propagation approach developed in this paper is a general one, and may also be used to interactively control a variety of other adjustments commonly performed in the digital darkroom.
Immunoblotting and dot immunobinding. Emerging techniques in protein immunochemistry. (1988)

Immunoblotting (also known as Western blot) and dot immunobinding (also known as dot blot) immunoassays, used extensively in immunochemical research, have great potential significance for diagnostic testing in the clinical laboratory. Immunoblotting has distinct versatility in immunochemical test applications. Immunoblotting combines the power of gel electrophoresis for resolving the electrophoretic variants of immunologically cross-reacting proteins with the ease and sensitivity of immunodetection on a solid-phase immunoassay. The potential for diagnostic applications includes: assay of antigens from pathologic serum samples, body fluids, and tissue; assay of patient serum samples for antibody against known antigen; and separation and assay of patient immunoglobulin. The usefulness of these applications is enhanced by the possibility of simultaneous use of nonantibody ligand, reversible protein staining, or, in the case of enzyme proteins, the use of substrate to detect activity. Dot immunobinding, in a similar fashion, permits assays of multiple specimens simultaneously on single strips of blotting media using sample sizes as small as 0.1 microL. Also, both immunoblotting and dot immunobinding techniques permit sequential probing of antigens with different antisera, with subsequent elution and recovery of specific antibody probes.
Phage display selection of hairpin loop soyacystatin variants that mediate high affinity inhibition of a cysteine proteinase (2001)

Two hairpin-loop domains in cystatin family proteinase inhibitors form an interface surface region that slots into the active site cleft of papain-like cysteine proteinases, and determine binding affinity. The slot region surface architecture of the soybean cysteine proteinase inhibitor (soyacystatin N, scN) was engineered using techniques of in vitro molecular evolution to define residues that facilitate interaction with the proteinase cleft and modulate inhibitor affinity and function. Combinatorial phage display libraries of scN variants that contain mutations in the essential motifs of the first (QVVAG) and second (EW) hairpin-loop regions were constructed. Approximately 1010-1011 phages expressing recombinant scN proteins were subjected to biopanning selection based on binding affinity to immobilized papain. The QVVAG motif in the first hairpin loop was invariant in all functional scN proteins. All selected variants (30) had W79 in the second hairpin-loop motif, but there was diversity for hydrophobic and basic amino acids in residue 78. Kinetic analysis of isolated scN variants identified a novel scN isoform scN(LW) with higher papain affinity than the wild-type molecule. The variant contained an E78L substitution and had a twofold lower Ki (2.1 pM) than parental scN, due to its increased association rate constant (2.6 +/- 0.09 x 107 M-1sec-1). These results define residues in the first and second hairpin-loop regions which are essential for optimal interaction between phytocystatins and papain, a prototypical cysteine proteinase. Furthermore, the isolated variants are a biochemical platform for further integration of mutations to optimize cystatin affinity for specific biological targets.
Dye-Sensitized Solar Cells with Conversion Efficiency of 11.1% (2006)

Dye-sensitized solar cells (DSCs) using titanium dioxide (TiO2) electrodes with different haze were investigated. It was found that the incident photon to current efficiency (IPCE) of DSCs increases with increase in the haze of the TiO2 electrodes, especially in the near infrared wavelength region. Conversion efficiency of 11.1%, measured by a public test center, was achieved using high haze TiO2 electrodes. This indicates that raising the haze of TiO2 electrodes is an effective technique for improvement of conversion efficiency.
Speaker overlap detection with prosodic features for speaker diarisation (2012)

The handling of overlapping speech in the context of speaker diarisation attracted in recent years the interest of the scientific community, since speaker overlap was identified as one of the factors degrading the performance of conventional diarisation systems. In this study, the authors are discussing the possibility of using long-term prosodic features for the detection of overlapping speech, which is subsequently employed in speaker diarisation to improve the baseline system. The most relevant subset from the set of candidate prosodic features is determined in two steps. First, a ranking according to minimal-redundancy-maximal-relevance criterion is obtained, and then a hill-climbing wrapper strategy is applied for determining the optimal number of prosodic features, which should accompany short-term spectral features for overlap detection. In experiments on the augmented multi-party interaction (AMI) meeting distant-channel data, the authors show that the addition of prosodic features decreased overlap detection error. Detected overlap segments were used in speaker diarisation to recover missed speech by assigning multiple speaker labels and to increase the purity of speaker clusters. Improvements of the baseline diarisation system are reported in both single- and multi-site data conditions. However, the extension of the diarisation system with TDOAs showed its incompatibility with the overlap exclusion technique.
Multiple Chromosomes in Bacteria: The Yin and Yang of trp Gene Localization in Rhodobacter sphaeroides 2.4.1 (1999)

The existence of multiple chromosomes in bacteria has been known for some time. Yet the extent of functional solidarity between different chromosomes remains unknown. To examine this question, we have surveyed the well-described genes of the tryptophan biosynthetic pathway in the multichromosomal photosynthetic eubacterium Rhodobacter sphaeroides 2.4.1. The genome of this organism was mutagenized using Tn5, and strains that were auxotrophic for tryptophan (Trp(-)) were isolated. Pulsed-field gel mapping indicated that Tn5 insertions in both the large (3 Mb CI) and the small (0.9 Mb CII) chromosomes created a Trp(-) phenotype. Sequencing the DNA flanking the sites of the Tn5 insertions indicated that the genes trpE-yibQ-trpGDC were at a locus on CI, while genes trpF-aroR-trpB were at locus on CII. Unexpectedly, trpA was not found downstream of trpB. Instead, it was placed on the CI physical map at a locus 1.23 Mb away from trpE-yibQ-trpGDC. To relate the context of the R. sphaeroides trp genes to those of other bacteria, the DNA regions surrounding the trp genes on both chromosomes were sequenced. Of particular significance was the finding that rpsA1, which encodes ribosomal protein S1, and cmkA, which encodes cytidylate monophosphate kinase, were on CII. These genes are considered essential for translation and chromosome replication, respectively. Southern blotting suggested that the trp genes and rpsA1 exist in single copy within the genome. To date, this topological organization of the trp "operon" is unique within a bacterial genome. When taken with the finding that CII encodes essential housekeeping functions, the overall impression is one of close regulatory and functional integration between these chromosomes.
Electrospun PCL nanofibers with anisotropic mechanical properties as a biomedical scaffold (2008)

To design an ideal scaffold, various factors should be considered, such as pore size and morphology, mechanical properties versus porosity, surface properties and appropriate biodegradability. Of these factors, the importance of mechanical properties on cell growth is particularly obvious in tissues such as bone, cartilage, blood vessels, tendons and muscles. Although electrospun nanofibers provide easily applicable nano-sized structures which could be used as biomedical scaffolds, the mechanical properties are poor since an increased pore size and porosity are generally accompanied by a decrease in mechanical properties. In addition, the general electrospinning has been limited to the fabrication of a variety of anisotropic mechanical properties, which are extremely important parameters for designing a musculoskeletal system. In this study, scaffolds consisting of variously oriented nanofibers were produced using an electrospinning process modified with an auxiliary electrode and a two-axis robot collecting system. Using an auxiliary electrode, a stable Taylor cone and initial spun jets were obtained. The influence of the electrode was evaluated with electric field simulation. Using the modified electrospinning process, various directions of orientation of electrospun fibers could be acquired and the fabricated oriented nanofiber webs showed a mechanically anisotropic behavior and a higher hydrophilic property compared to randomly distributed fibrous mats.
Rapid and sensitive method for detection of Shiga-like toxin-producing Escherichia coli in ground beef using the polymerase chain reaction (1992)

A rapid and sensitive method for detection of Shiga-like toxin (SLT)-producing Escherichia coli (SLT-EC) with the polymerase chain reaction (PCR) is described. Two pairs of oligonucleotide primers homologous to SLTI and SLTII genes, respectively, were used in multiplex PCR assays. The first pair generated a ca. 600-bp PCR product with DNA from all SLTI-producing E. coli tested but not from E. coli strains that produce SLTII or variants of SLTII. The second pair generated a ca. 800-bp PCR product with DNA from E. coli strains that produce SLTII or variants of SLTII but not from SLTI-producing E. coli. When used in combination, the SLTI and SLTII oligonucleotide primers amplified DNA from all of the SLT-EC tested. No PCR products were obtained with SLT primers with DNA from 28 E. coli strains that do not produce SLT or 44 strains of 28 other bacterial species. When ground beef samples were inoculated with SLT-EC strains 319 (O157:H7; SLTI and SLTII), H30 (O26:H11; SLTI), and B2F1/3 (O91:H21; SLTII variants VT2ha and VT2hb) and cultured in modified Trypticase soy broth for 6 h at 42 degrees C, an initial sample inoculum of as few as 1 CFU of these SLT-EC strains per g could be detected in PCR assays with DNA extracted from the broth cultures.
The pre-vaccination epidemiology of measles, mumps and rubella in Europe: implications for modelling studies (2000)

Data on the pre-vaccination patterns of infection for measles, mumps and rubella are collated from a number of European countries in order to compare the epidemiology of the three viruses. Key epidemiological parameters, such as the age-specific force of infection and the basic reproduction number (R0) are estimated from case notification or serological data using standard techniques. A method is described to compare force of infection estimates derived from serological data. Analysis suggests that the pre-vaccination patterns of measles and mumps infection in the different countries were similar. In contrast, the epidemiology of rubella was highly variable between countries. This suggests that it may be acceptable to use parameter values estimated from other countries to model measles and mumps transmission, but that this approach to modelling rubella transmission requires more caution. Estimates of R0 depend on underlying mixing assumptions. Constraints were placed on R0 estimates by utilising knowledge of likely mixing patterns. The estimates for R0 were highest for measles, intermediate for mumps, and generally lowest for rubella. Analysis of within- and between-age-group transmission rates suggested that mumps transmission tends to be more concentrated within young children than the other two viruses. The implications for the design of immunization programmes are that mumps may be the easiest to control via infant immunization since it is predominantly transmitted between the very young and the variability in rubella epidemiology requires that careful consideration of the possible effects of vaccination options should be made using local data when planning rubella immunization programmes.
Behavioral recovery from traumatic brain injury after membrane reconstruction using polyethylene glycol (2008)

Polyethylene glycol (PEG; 2000 MW, 30% by volume) has been shown to mechanically repair damaged cellular membranes and reduce secondary axotomy after traumatic brain and spinal cord injury (TBI and SCI respectively). This repair is achieved following spontaneous reassembly of cell membranes made possible by the action of targeted hydrophilic polymers which first seal the compromised portion of the plasmalemma, and secondarily, allow the lipidic core of the compromised membranes to resolve into each other. Here we compared PEG-treated to untreated rats using a computer-managed open-field behavioral test subsequent to a standardized brain injury. Animals were evaluated after a 2-, 4-, and 6-hour delay in treatment after TBI. Treated animals receive a single subcutaneous injection of PEG. When treated within 2 hours of the injury, injured PEG-treated rats showed statistically significant improvement in their exploratory behavior recorded in the activity box when compared to untreated but brain-injured controls. A delay of 4 hours reduced this level of achievement, but a statistically significant improvement due to PEG injection was still clearly evident in most outcome measures compared at the various evaluation times. A further delay of 2 more hours, however, eradicated the beneficial effects of PEG injection as revealed using this behavioral assessment. Thus, there appears to be a critical window of time in which PEG administration after TBI can provide neuroprotection resulting in an enhanced functional recovery. As is often seen in clinically applied acute treatments for trauma, the earlier the intervention can be applied, the better the outcome.