gebhart/patrepeval huggingface dataset:
Quantum-assisted learning of graphical models with arbitrary pairwise connectivity (2016)

There is increasing interest in the potential advantages of using quantum computing technologies as sampling engines to speedup machine learning and probabilistic programming tasks. However, some pressing challenges in state-of-the-art quantum annealers have to be overcome before we can assess their actual performance. Most notably, the effective temperature at which samples are generated is instance-dependent and unknown, the interaction graph is sparse, the parameters are noisy, and the dynamic range of the parameters is finite. Of all these limitations, the sparse resulting from the local interaction between quantum bits in physical hardware implementations, is considered the most severe limitation to the quality of constructing powerful machine learning models. Here we show how to surpass this curse of limited connectivity bottleneck and illustrate our findings by training probabilistic generative models with arbitrary pairwise connectivity. Our model can be trained in quantum hardware without full knowledge of the effective parameters specifying the corresponding Boltzmann-like distribution. Therefore, inference of the effective temperature is avoided and the effect of noise in the parameters is mitigated. We illustrate our findings by successfully training hardware-embedded models with all-to-all on a real dataset of handwritten digits and two synthetic datasets. In each of these datasets we show the generative capabilities of the models learned with the assistance of the quantum annealer in experiments with up to 940 quantum bits. Additionally, we show a visual Turing test with handwritten digit data, where the machine generating the digits is a quantum processor. Such digits, with a remarkable similarity to those generated by humans, are extracted from the experiments with 940 quantum bits.
Structural Analysis of Substrate Binding by the Molecular Chaperone DnaK (1996)

DnaK and other members of the 70-kilodalton heat-shock protein (hsp70) family promote protein folding, interaction, and translocation, both constitutively and in response to stress, by binding to unfolded polypeptide segments. These proteins have two functional units: a substrate-binding portion binds the polypeptide, and an adenosine triphosphatase portion facilitates substrate exchange. The crystal structure of a peptide complex with the substrate-binding unit of DnaK has now been determined at 2.0 angstroms resolution. The structure consists of a beta-sandwich subdomain followed by alpha-helical segments. The peptide is bound to DnaK in an extended conformation through a channel defined by loops from the beta sandwich. An alpha-helical domain stabilizes the complex, but does not contact the peptide directly. This domain is rotated in the molecules of a second crystal lattice, which suggests a model of conformation-dependent substrate binding that features a latch mechanism for maintaining long lifetime complexes.
Ganglioside and neurotrophic growth factor interactions in retinal neuronal and glial cells. (1997)

Ganglioside (GG) and neurotrophic growth factor (GF) interactions in retinal neuronal and glial cells have been very little studied. Rat retinas were mechanically separated into outer (photoreceptor or PR) and inner (other neurons, IR) halves by planar vibratome sectioning and retinal Müller glial (RMG) cells were isolated and cultured according to previously published methods. The distribution on a percent molar basis of individual GG was different between the two halves: PR were dominated by GD3 (48% total GG) and contained only trace amounts (< 4%) of complex species (GT1b, GQ); IR was more typical of mature brain tissue, exhibiting substantial amounts (approximately 25%) of more complex GG. The GG profile of RMG cells was also simple, dominated by GM3 (60%) and GD1a (20%). A single addition to the medium of 500 pM bFGF or EGF for 48 hr to cultured RMG cells led to significant increases in total GG levels of 30-40%. Such treatments by both growth factors induced increases in GM3, whereas longer exposure (96 hr) of confluent RMG to these factors additionally stimulated synthesis of more complex GG. Incubations of RMG with [3H]-glucosamine showed that GG synthesis was 2-fold stimulated by growth factors. We also tested the effect of GM3 on one of the bFGF receptor transduction pathways, namely PI-3 kinase activation. To our knowledge these data constitute the first demonstration of neurotrophic factor stimulation of GG levels in cells of CNS in vitro. Such complex interactions may have particularly important consequences for neural physiopathology.
Characterization of Factor VIII B-Cell Inhibitory Epitopes (1999)

Introduction Factor VIII contains three epitopes that are the usual targets of clinically significant antibody inhibitors. Two of these epitopes are located in the A2 and C2 domains of factor VIII. The third epitope appears to be in the A3 domain. Ongoing studies continue to provide higher resolution maps of these epitopes and to understand the mechanism by which inhibitors produce a bleeding diathesis. The manipulation of inhibitor epitopes using recombinant DNA technology may lead to improved forms of factor VIII that have lower antigenicity and/or lower immunogenicity.
Example-based synthesis of 3D object arrangements (2012)

We present a method for synthesizing 3D object arrangements from examples. Given a few user-provided examples, our system can synthesize a diverse set of plausible new scenes by learning from a larger scene database. We rely on three novel contributions. First, we introduce a probabilistic model for scenes based on Bayesian networks and Gaussian mixtures that can be trained from a small number of input examples. Second, we develop a clustering algorithm that groups objects occurring in a database of scenes according to their local scene neighborhoods. These contextual categories allow the synthesis process to treat a wider variety of objects as interchangeable. Third, we train our probabilistic model on a mix of user-provided examples and relevant scenes retrieved from the database. This mixed model learning process can be controlled to introduce additional variety into the synthesized scenes. We evaluate our algorithm through qualitative results and a perceptual study in which participants judged synthesized scenes to be highly plausible, as compared to hand-created scenes.
Chromosome Coordinating Meeting 1992 (CCM92) (1992)

The Chromosome Coordinating Meeting, CCM 92, was held in Baltimore on November 15--17, 1992. The two major features of the workshop were entry of gene mapping data into databases and construction of consensus data sets (a process called chromosome editing).
Protein Arginine Methyltransferase 5 Suppresses the Transcription of the RB Family of Tumor Suppressors in Leukemia and Lymphoma Cells (2008)

The proper epigenetic modification of chromatin by protein arginine methyltransferases (PRMTs) is crucial for normal cell growth and health. The human SWI/SNF-associated PRMT5 is involved in the transcriptional repression of target genes by directly methylating H3R8 and H4R3. To further understand the impact of PRMT5-mediated histone methylation on cancer, we analyzed its expression in normal and transformed human B lymphocytes. Our findings reveal that PRMT5 protein levels are enhanced in various human lymphoid cancer cells, including transformed chronic lymphocytic leukemia (B-CLL) cell lines. PRMT5 overexpression is caused by the altered expression of the PRMT5-specific microRNAs 19a, 25, 32, 92, 92b, and 96 and results in the increased global symmetric methylation of H3R8 and H4R3. An evaluation of both epigenetic marks at PRMT5 target genes such as RB1 (p105), RBL1 (p107), and RBL2 (p130) showed that promoters H3R8 and H4R3 are hypermethylated, which in turn triggers pocket protein transcriptional repression. Furthermore, reducing PRMT5 expression in WaC3CD5 B-CLL cells abolishes H3R8 and H4R3 hypermethylation, restores RBL2 expression, and inhibits cancer cell proliferation. These results indicate that PRMT5 overexpression epigenetically alters the transcription of key tumor suppressor genes and suggest a causal role of the elevated symmetric methylation of H3R8 and H4R3 at the RBL2 promoter in transformed B-lymphocyte pathology.
Establishment of mouse cell lines which constitutively secrete large quantities of interleukin 2, 3, 4 or 5, using modified cDNA expression vectors (1988)

Mouse cell lines of different lineages have been established which constitutively secrete large quantities of recombinant mouse interleukins (mIL2, mIL3, mIL4 or mIL5). An existing bovine papilloma virus-based expression vector, pBV-1MTHA, was modified to allow transformed X63Ag8-653 myeloma cells, NIH 3T3 fibroblasts and C127 mammary tumor cells to stably carry multiple copies of the vector, to express the inserted cDNA encoding a single interleukin constitutively, and to secrete the interleukin in high quantities. Cell lines transformed with mIL2 cDNA stably carried 30-100 copies of the plasmid per cell and constitutively secreted biologically active mIL2 in quantities similar to those produced by murine EL4 thymoma cells or rat spleen cells stimulated with mitogens. Deletion of the 3' untranslated region containing AT-rich sequences from the mIL2 cDNA resulted in a 100-fold increase in the constitutive production and secretion of mIL2 by the transformants. Addition of a heavy metal further increased the production 2 to 6-fold. Cells transformed with 3'-deleted mIL3 cDNA constitutively secreted 300-1000 times higher activities of mIL3 than the myelomonocytic leukemia line WEHI3. mIL4 produced by the similar transformants induced [3H]thymidine uptake of a T cell line, a mast cell line and B leukemia cells, and enhanced the production of IgG1 by B cells. IL4 titers were 150 times higher than those produced by the concanavalin A-stimulated T cell line 2.19. mIL5 was secreted by similar transformants at 10-fold higher titers than those produced by concanavalin A-stimulated 2.19 T cells, as judged by the proliferation and maturation of B cell leukemia BCL1. The expression vectors should be useful in establishing eukaryotic cell lines producing proteins from full length cDNA clones at higher rates. The established cell lines secreting IL2, 3, 4 or 5 at high rate should be useful sources for these interleukins in the investigation of their function in the immune system.
A Custom CMOS Integrated Circuit For PET Tomograph Front-end Applications (2005)

A custom CMOS integrated circuit has been designed, prototyped, and evaluated for PET tomograph front-end applications. The integrated circuit reduces the size. cost, and power consumption of existing PET frontend circuits by Over a factor of two. The integrated circuit, fabricated in a standard digital, 2 p, double-metal, double-poly, n-well CMOS process, has a die size of 6.6mmx6.4mm and power consumption of under 600 mW. The PET front-end CMOS integrated circuit processes energy, position, and timing information from a BGO block detector containing four photomultiplier tubes. Photomultiplier preamplifiers and variable gain amplifiers are co~ected to summing circuits and gated integrators to provide energy and position (x and y) signals. A constantfraction discriminator, requiring no external delay line, provides a timing output derived from the sum of the four photomultiplier signals. Eight 7- and 8-bit digital-to-analog converters. connected to a readwrite serial data interface, provide gain-control and threshold levels. The measured position, energy, and timing performance (3.05ns FWHM) of the integrated circuit is comparable to existing discrete PET frontend circuits.
Activity of Retapamulin (SB-275833), a Novel Pleuromutilin, against Selected Resistant Gram-Positive Cocci (2006)

Retapamulin (SB-275833), the first pleuromutilin to be developed for human topical use, was tested against a selected population of staphylococci and beta-hemolytic streptococci. The MIC90 results for retapamulin were 0.12 microg/ml for Staphylococcus aureus and < or = 0.03 microg/ml for Streptococcus pyogenes; no cross-resistance was observed for organism subsets resistant to oxacillin, erythromycin, or mupirocin.
Maturation Stages of Mouse Dendritic Cells in Growth Factor–dependent Long-Term Cultures (1997)

The signals controlling the checkpoints of dendritic cells (DC) maturation and the correlation between phenotypical and functional maturational stages were investigated in a defined model system of growth factor-dependent immature mouse DC. Three sequential stages of DC maturation (immature, mature, and apoptotic) were defined and characterized. Immature DC (stage 1) had low expression of costimulatory molecules, highly organized cytoskeleton, focal adhesion plaques, and slow motility; accordingly, they were very efficient in antigen uptake and processing of soluble proteins. Further, at this stage most of major histocompatibility complex class II molecules were within cytoplasmic compartments consistent with a poor allostimulatory capacity. Bacteria or cytokines were very efficient in inducing progression from stage 1 towards stage 2 (mature). Morphological changes were observed by confocal analysis including depolymerization of F-actin and loss of vinculin containing adhesive structures which correlates with acquisition of high motility. Antigen uptake and presentation of native protein antigen was reduced. In contrast, presentation of immunogenic peptides and allostimulatory activity became very efficient and secretion of IL-12 p75 was detectable after antigen presentation. This functional DC maturation ended by apoptotic cell death, and no reversion to the immature phenotype was observed.
Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals (2016)

Efforts at elimination of scourges, such as malaria, are limited by the logistic challenges of reaching large rural populations and ensuring patient adherence to adequate pharmacologic treatment. We have developed an oral, ultra-long-acting capsule that dissolves in the stomach and deploys a star-shaped dosage form that releases drug while assuming a geometry that prevents passage through the pylorus yet allows passage of food, enabling prolonged gastric residence. This gastric-resident, drug delivery dosage form releases small-molecule drugs for days to weeks and potentially longer. Upon dissolution of the macrostructure, the components can safely pass through the gastrointestinal tract. Clinical, radiographic, and endoscopic evaluation of a swine large-animal model that received these dosage forms showed no evidence of gastrointestinal obstruction or mucosal injury. We generated long-acting formulations for controlled release of ivermectin, a drug that targets malaria-transmitting mosquitoes, in the gastric environment and incorporated these into our dosage form, which then delivered a sustained therapeutic dose of ivermectin for up to 14 days in our swine model. Further, by using mathematical models of malaria transmission that incorporate the lethal effect of ivermectin against malaria-transmitting mosquitoes, we demonstrated that this system will boost the efficacy of mass drug administration toward malaria elimination goals. Encapsulated, gastric-resident dosage forms for ultra-long-acting drug delivery have the potential to revolutionize treatment options for malaria and other diseases that affect large populations around the globe for which treatment adherence is essential for efficacy.
Use of EDTA derivatization to characterize interactions between oligodeoxyribonucleoside methylphosphonates and nucleic acids (1989)

EDTA-derivatized oligonucleoside methylphosphonates were prepared and used to characterize hybridization between the oligomers and single-stranded DNA or RNA. The melting temperatures of duplexes formed between an oligodeoxyribonucleotide 35-mer and complementary methylphosphonate 12-mers were 4-12 degrees C higher than those of duplexes formed by oligodeoxyribonucleotide 12-mers as determined by spectrophotometric measurements. Derivatization of the methylphosphonate oligomers with EDTA reduced the melting temperature by 5 degrees C. Methylphosphonate oligomer-nucleic acid complexes were stabilized by base stacking interactions between the terminal bases of the two oligomers binding to adjacent binding sites on the target. In the presence of Fe2+ and DTT, the EDTA-derivatized oligomers produce hydroxyl radicals that cause degradation of the sugar-phosphate backbone of both targeted DNA and RNA. Degradation occurs specifically in the region of the oligomer binding site and is approximately 20-fold more efficient for single-stranded DNA than for RNA. In comparison to the presence of one oligomer, the extent of target degradation was increased considerably by additions of two oligomers that bind at adjacent sites on the target. For example, the extent of degradation of a single-stranded DNA 35-mer caused by two contiguously binding oligomers, one of which was derivatized by EDTA, was approximately 2 times greater than that caused by the EDTA-derivatized oligomer alone. Although EDTA-derivatized oligomers are stable for long periods of time in aqueous solution, they undergo rapid autodegradation in the presence of Fe2+ and DTT with half-lives of approximately 30 min. This autodegradation reaction renders the EDTA-derivatized oligomers unable to cause degradation of their complementary target nucleic acids.(ABSTRACT TRUNCATED AT 250 WORDS)
Neurotrophic Factors and Receptors in the Immature and Adult Spinal Cord after Mechanical Injury or Kainic Acid (2001)

Delivery of neurotrophic factors to the injured spinal cord has been shown to stimulate neuronal survival and regeneration. This indicates that a lack of sufficient trophic support is one factor contributing to the absence of spontaneous regeneration in the mammalian spinal cord. Regulation of the expression of neurotrophic factors and receptors after spinal cord injury has not been studied in detail. We investigated levels of mRNA-encoding neurotrophins, glial cell line-derived neurotrophic factor (GDNF) family members and related receptors, ciliary neurotrophic factor (CNTF), and c-fos in normal and injured spinal cord. Injuries in adult rats included weight-drop, transection, and excitotoxic kainic acid delivery; in newborn rats, partial transection was performed. The regulation of expression patterns in the adult spinal cord was compared with that in the PNS and the neonate spinal cord. After mechanical injury of the adult rat spinal cord, upregulations of NGF and GDNF mRNA occurred in meningeal cells adjacent to the lesion. BDNF and p75 mRNA increased in neurons, GDNF mRNA increased in astrocytes close to the lesion, and GFRalpha-1 and truncated TrkB mRNA increased in astrocytes of degenerating white matter. The relatively limited upregulation of neurotrophic factors in the spinal cord contrasted with the response of affected nerve roots, in which marked increases of NGF and GDNF mRNA levels were observed in Schwann cells. The difference between the ability of the PNS and CNS to provide trophic support correlates with their different abilities to regenerate. Kainic acid delivery led to only weak upregulations of BDNF and CNTF mRNA. Compared with several brain regions, the overall response of the spinal cord tissue to kainic acid was weak. The relative sparseness of upregulations of endogenous neurotrophic factors after injury strengthens the hypothesis that lack of regeneration in the spinal cord is attributable at least partly to lack of trophic support.
<B> <I>Varroa destructor</I> </B> Infestation in Untreated Honey Bee (Hymenoptera: Apidae) Colonies Selected for Hygienic Behavior (2001)

Honey bee (Apis mellifera L.) colonies bred for hygienic behavior were tested in a large field trial to determine if they were able to resist the parasitic mite Varroa destructor better than unselected colonies of"Starline" stock. Colonies bred for hygienic behavior are able to detect, uncap, and remove experimentally infested brood from the nest, although the extent to which the behavior actually reduces the overall mite-load in untreated, naturally infested colonies needed further verification. The results indicate that hygienic colonies with queens mated naturally to unselected drones had significantly fewer mites on adult bees and within worker brood cells than Starline colonies for up to 1 yr without treatment in a commercial, migratory beekeeping operation. Hygienic colonies actively defended themselves against the mites when mite levels were relatively low. At high mite infestations (>15% of worker brood and of adult bees), the majority of hygienic colonies required treatment to prevent collapse. Overall, the hygienic colonies had similar adult populations and brood areas, produced as much honey, and had less brood disease than the Starline colonies. Thus, honey bees bred for hygienic behavior performed as well if not better than other commercial lines of bees and maintained lower mite loads for up to one year without treatment.
Reduced adherence to traumatized rat heart valves by a low-fibronectin-binding mutant of Staphylococcus aureus (1989)

Isogenic strains of Staphylococcus aureus, differing in fibronectin binding, were constructed for studies of the contribution of fibronectin binding to the in vivo pathogenesis of staphylococcal disease. Mutagenesis of S. aureus 879R4S was accomplished by mating with Enterococcus faecalis FA378 that carried the transposon Tn918. Four low-fibronectin-binding mutants were identified that bound 24- to 35-fold less fibronectin than the parent strain did. A spectinomycin-resistant strain, R4SSp, was transduced by a bacteriophage (80 alpha) lysate propagated on a low-binding mutant of 879R4S to produce R4SSp/1536, which bound less fibronectin, contained a single copy of the transposon, and grew on spectinomycin-containing medium. Using a rat model of endocarditis, we determined the distribution of S. aureus R4SSp and its transductant in normal and cardiac catheterized rats. Cultures of heart tissue showed that catheterized rats challenged with the fibronectin-binding parent strain had over 250-fold more organisms in the left heart than did rats challenged with the low-binding transductant. The ability to bind fibronectin had no effect on the number of S. aureus cells cultured from other tissues. These data suggest that the ability of S. aureus to bind fibronectin is an important factor in establishing adherence to damaged heart valves in vivo.
The Three-Year Medical Curriculum (1970)

For several years, medical educators have been carefully examining the length of time it takes to become a practicing physician. There are points along the educational path where appropriate shortcuts might be made by students who are both interested and endowed with adequate aptitudes. The more apparent of these are (1) reducing the calendar years spent in college to less than four, (2) reducing the calendar years spent in medical college to less than four, (3) elimination of the internship, and (4) decreasing the years spent in residency training. In this presentation, I will give prime consideration to the shortening of the medical school curriculum. I will also briefly discuss the reduction of other portions of prepractitioner education. In 1967, Paul Sanazaro and I organized a conference entitled "The Optimal Preparation for the Study of Medicine," which, in essence, examined the college-medical school relationship.<sup>1</sup>As a result of that