gebhart/patrepeval huggingface dataset:
Streaming, Distributed Variational Inference for Bayesian Nonparametrics (2015)

This paper presents a methodology for creating streaming, distributed inference algorithms for Bayesian nonparametric (BNP) models. In the proposed framework, processing nodes receive a sequence of data minibatches, compute a variational posterior for each, and make asynchronous streaming updates to a central model. In contrast to previous algorithms, the proposed framework is truly streaming, distributed, asynchronous, learning-rate-free, and truncation-free. The key challenge in developing the framework, arising from the fact that BNP models do not impose an inherent ordering on their components, is finding the correspondence between minibatch and central BNP posterior components before performing each update. To address this, the paper develops a combinatorial optimization problem over component correspondences, and provides an efficient solution technique. The paper concludes with an application of the methodology to the DP mixture model, with experimental results demonstrating its practical scalability and performance.
P3‐388: CORTICAL DISARRAY MEASUREMENT USING DIFFUSION MRI CORRELATES WITH BRAAK STAGING AND IMPROVES AMYLOID PET PREDICTION OF AD PROGRESSION (2018)

Existing brain imaging methods often assess amyloid and tau using PET scans. However, AD diagnosis still depends on post-mortem microscopic assessment of cerebral cortex. The erosion of micro-columnar architecture in the cortical grey matter at post-mortem correlates with cognitive decline and with another traditional marker of AD pathology – amyloid plaque load. The aim here was to validate a brain imaging measure of the underlying cortical cytoarchitecture that is responsible for cognitive function and to test its correspondence with the accumulation of the standard hallmarks of AD pathology, B-amyloid and tau tangles. Cortical disarray measurements (CDM) were assessed in diffusion MRI scans from the ADNI multi-centre in vivo dataset, and in 11 post-mortem brains 6 controls, 5 dementia brains from the UK brains for dementia research initiative. The CDM image analysis was designed to measure alterations in cortical diffusion signal due to erosion and disruption of the micro-column structure. Whole brain mean values were derived for each subject in vivo, and sub-regional values were calculated for the post-mortem scans, corresponding to three brain regions that were studied histologically, prefrontal cortex, inferior parietal cortex and parahippocampal gyrus. CDM values correlated with histological micro-column measures and showed a graded effect which reflected the neuropathological rating of Alzheimer's disease severity (Braak staging) in post-mortem confirmed cases. A highly significant positive correlation between CDM values and Braak staging from 0 to 6 (from controls to AD) was found, particularly in the parahippocampal gyrus. In the set of in vivo ADNI scans, which also had amyloid PET scan data available, CDM correctly selected out over 50% of the PET false positive cases. The search for new drugs for dementia is hampered by an inability to identify subjects for drug trials with sufficiently known risk of progression to dementia, to accurately stratify them, effectively measure pathological progression, or quantify the benefit of a drug. The results indicate that CDM analysis may be a useful tool to complement other measures of pathology in order to improve the detection of brain damage at the cellular level, monitor disease severity and predict progression.
Intelligent information-sharing systems (1987)

The Information Lens system is a prototype intelligent information-sharing system that is designed to include not only good user interfaces for supporting the problem-solving activity of individuals, but also good organizational interfaces for supporting the problem-solving activities of groups.
Synthesis and Characterization of a Peptide Identified as a Functional Element in αA-crystallin (2000)

Eye lens alpha-crystallin is a member of the small heat shock protein (sHSP) family and forms large multimeric structures. Earlier studies have shown that it can act like a molecular chaperone and form a stable complex with partially unfolded proteins. We have observed that prior binding of the hydrophobic protein melittin to alpha-crystallin diminishes its chaperone-like activity toward denaturing alcohol dehydrogenase, suggesting the presence of mutually exclusive sites for these proteins in alpha-crystallin. To investigate the mechanism of the interaction between alpha-crystallin and substrate proteins, we determined the melittin-binding sites in alpha-crystallin by cross-linking studies. Localization of melittin-binding sites in alpha-crystallin resulted in the identification of RTLGPFYPSR and FVIFLDVKHFSPEDLTVK of alphaA-crystallin and FSVNLDVK of alphaB-crystallin as the chaperone sites. Of these sites, FVIFLDVKHFSPEDLTVK and FSVNLDVK were identified earlier as 1,1'-bi(4-anilino) naphthalene-5,5'-disulfonic acid (bis-ANS)-binding hydrophobic sites. Here we also report the synthesis and characterization of the peptide, KFVIFLDVKHFSPEDLTVK, having the melittin as well as bis-ANS-binding sequence of alphaA-crystallin. We show that this peptide has characteristics similar to that of alphaA-crystallin by in vitro thermal aggregation assay, gel filtration study, CD spectroscopy, and bis-ANS interaction studies. The peptide sequence corresponds to the beta3 and beta4 region present in the alpha-crystallin domain of sHSP 16.5. We hypothesize that the alpha-crystallin domain in other sHSPs may have a similar function and would likely possess the anti-aggregation property even when separated from the native protein.
Seismic Behavior and Design of High-Strength Square Concrete-Filled Steel Tube Beam Columns (2004)

The behavior of high strength square concrete filled steel tube (CFT) beam columns subjected to constant axial load and cyclically varying flexural loading was investigated experimentally. The effects of the width-to-thickness (b/t) ratio, the yield stress (σy) of the steel tube, and the level of axial load on the behavior (stiffness, strength, ductility, and energy dissipation) of high strength square CFT beam columns were studied. Eight cyclic beam-column specimens were tested. Crushing of concrete and cyclic local buckling in the steel tube affected the cyclic strength and stiffness of the CFT specimens. The elastic section flexural stiffness under cyclic loading decreases rapidly due to tension cracking of the concrete infill and local buckling of the steel tube. The total energy dissipated by the cyclic specimens is dominated by the flexural energy dissipated in the failure segment (plastic hinge region). Both the current American Concrete Institute code provisions and the modified Architectural Institute of Japan method predict the moment capacities of the high strength square CFT specimens accurately. The cyclic curvature ductility (μϕ-c) decreases significantly with an increase in the axial load level. At higher axial load levels, the steel tube b/t ratio and σy have a small influence on μϕ-c. However, at lower axial load levels, increasing the steel tube b/t ratio or σy reduces μϕ-c.
Regulation of Neuronal M-Channel Gating in an Isoform-Specific Manner: Functional Interplay between Calmodulin and Syntaxin 1A (2011)

Whereas neuronal M-type K(+) channels composed of KCNQ2 and KCNQ3 subunits regulate firing properties of neurons, presynaptic KCNQ2 subunits were demonstrated to regulate neurotransmitter release by directly influencing presynaptic function. Two interaction partners of M-channels, syntaxin 1A and calmodulin, are known to act presynaptically, syntaxin serving as a major protein component of the membrane fusion machinery and calmodulin serving as regulator of several processes related to neurotransmitter release. Notably, both partners specifically modulate KCNQ2 but not KCNQ3 subunits, suggesting selective presynaptic targeting to directly regulate exocytosis without interference in neuronal firing properties. Here, having first demonstrated in Xenopus oocytes, using analysis of single-channel biophysics, that both modulators downregulate the open probability of KCNQ2 but not KCNQ3 homomers, we sought to resolve the channel structural determinants that confer the isoform-specific gating downregulation and to get insights into the molecular events underlying this mechanism. We show, using optical, biochemical, electrophysiological, and molecular biology analyses, the existence of constitutive interactions between the N and C termini in homomeric KCNQ2 and KCNQ3 channels in living cells. Furthermore, rearrangement in the relative orientation of the KCNQ2 termini that accompanies reduction in single-channel open probability is induced by both regulators, strongly suggesting that closer N-C termini proximity underlies gating downregulation. Different structural determinants, identified at the N and C termini of KCNQ3, prevent the effects by syntaxin 1A and calmodulin, respectively. Moreover, we show that the syntaxin 1A and calmodulin effects can be additive or blocked at different concentration ranges of calmodulin, bearing physiological significance with regard to presynaptic exocytosis.
Peripheral vs central squamous cell carcinoma of the lung. A comparison of clinical features, histopathology, and survival. (1990)

We reviewed the clinical features and histopathologic findings of 21 peripheral pulmonary squamous cell carcinomas (SCC) resected at our institution between 1961 and 1981 and compared them with 19 central SCCs. Histologic features were scored semiquantitatively from 0 to 3+. Peripheral SCC represented 16% of all resected SCCs. The proportion of patients with multiple symptoms was lower and survival during the 5 years after surgery was better in the peripheral group. Tumor size, mitoses per high-power field (2.4 +/- 0.3 vs 4.1 +/- 0.6 [SEM]), prevalence of lymphatic invasion (19% vs 58%), and lymph node metastases (5% vs 37%) were lower, while chest wall invasion was more frequent (25% vs 0) for peripheral SCCs. Peripheral tumors also had more intense (2 or 3+) lymphoplasmacytic (86% vs 47%) and desmoplastic (95% vs 68%) reactions. Cox regression analysis did not support a significant relationship between tumor location and survival. We conclude that, compared with the central SCC, peripheral SCC is associated with fewer symptoms at presentation and better survival. Morphologically, peripheral SCCs are smaller, have fewer mitoses, less prevalent lymphatic invasion, and a more intense stromal reaction. Improved survival in patients with peripheral SCC may be due to a more favorable stage at the time of initial treatment.
Author response to: Comment on: Randomized controlled trial of plain English and visual abstracts for dissemination surgical research via social media (2020)

The correspondence by Pringle and colleagues was received with much interest 1 .We agree that more consideration as to how we translate the context, limitations and impact of research studies in visual or adjunctive formats is needed 2 .This must be considered prior to academic publishers committing to investing in these formats going forward.On the other hand, adjunctive formats of information delivery have the potential to be powerful tools to convey information to broad audiences.This has already been demonstrated with the use of visual abstracts in surgical research 3 .Such formats are not simply limited to pictures and captions, but rather the image design, colour palate and format of delivery can provide psychological cues to facilitate understanding.Indeed, the limitations described by the authors are similarly shared by traditional text-based abstracts, which are often limited to 250 words.At present, visual abstracts offer novel opportunities for information delivery.Arguably, they may offer superior opportunities if their potential is harnessed appropriately in the future.
A Duchenne Muscular Dystrophy Gene Hot Spot Mutation in Dystrophin-Deficient Cavalier King Charles Spaniels Is Amenable to Exon 51 Skipping (2010)

Given the small size of the breed, the amiable temperament and the nature of the mutation, we propose that CKCS-MD is a valuable new model for clinical trials of antisense oligonucleotide-induced exon skipping and other therapeutic approaches for DMD.
Analysis of the autonomous replication behavior in human cells of the dihydrofolate reductase putative chromosomal origin of replication (1992)

Chinese hamster genomic DNA sequences from the region downstream of the dihydrofolate reductase (DHFR) gene reported to contain a chromosomal origin of bidirectional DNA replication (OBR-1) were tested for their ability to support autonomous DNA replication in human cells. A 13.3 kilobase fragment containing OBR-1 and surrounding sequences supported replication in short-term and long-term replication assays, while a 4.5 kb fragment containing OBR-1 did not support substantial replication in either assay. These results are consistent with our previous observations that large fragments of human DNA support replication, while smaller fragments are less efficient. The replication activities of plasmids containing OBR-1 were no greater than those of randomly chosen human fragments of similar size. Furthermore, two-dimensional gel analysis of plasmids containing OBR-1 indicated that initiation does not preferentially occur within the OBR-1 region. These results suggest that in the context of autonomous replication, the DHFR sequences tested do not contain genetic information specifying site-specific replication initiation. Possible implications of these results for chromosomal replication are discussed.
Mice Lacking a Myc Enhancer That Includes Human SNP rs6983267 Are Resistant to Intestinal Tumors (2012)

Multiple cancer-associated single-nucleotide polymorphisms (SNPs) have been mapped to conserved sequences within a 500-kilobase region upstream of the MYC oncogene on human chromosome 8q24. These SNPs may affect cancer development through altered regulation of MYC expression, but this hypothesis has been difficult to confirm. We generated mice deficient in Myc-335, a putative MYC regulatory element that contains rs6983267, a SNP accounting for more human cancer-related morbidity than any other genetic variant or mutation. In Myc-335 null mice, Myc transcripts were expressed in the intestinal crypts in a pattern similar to that in wild-type mice but at modestly reduced levels. The mutant mice displayed no overt phenotype but were markedly resistant to intestinal tumorigenesis induced by the APCmin mutation. These results establish that a cancer-associated SNP identified in human genome-wide association studies has a functional effect in vivo.
Cleavage activates Dispatched for Sonic Hedgehog ligand release (2018)

Hedgehog ligands activate an evolutionarily conserved signaling pathway that provides instructional cues during tissue morphogenesis, and when corrupted, contributes to developmental disorders and cancer. The transmembrane protein Dispatched is an essential component of the machinery that deploys Hedgehog family ligands from producing cells, and is absolutely required for signaling to long-range targets. Despite this crucial role, regulatory mechanisms controlling Dispatched activity remain largely undefined. Herein, we reveal vertebrate Dispatched is activated by proprotein convertase-mediated cleavage at a conserved processing site in its first extracellular loop. Dispatched processing occurs at the cell surface to instruct its membrane re-localization in polarized epithelial cells. Cleavage site mutation alters Dispatched membrane trafficking and reduces ligand release, leading to compromised pathway activity in vivo. As such, convertase-mediated cleavage is required for Dispatched maturation and functional competency in Hedgehog ligand-producing cells.
The Phenol‐Phenothiazine Coupling: an Oxidative Click Concept (2019)

Abstract The phenol‐phenothiazine coupling reaction is attracting increasing attention, in part due to its enabling character of innovative radical, photochemical, and electrochemical concepts. Indeed, this C−N bond forming cross dehydrogenative coupling accommodates almost any oxidizing strategy, often with mild reaction conditions. This concept paper analyses the particularity of this simple, cheap, and reliable coupling reaction, and discusses some of its probable future applications.
[Measurement of the body temperature of adults by rectal digital thermometer and the infrared tympanic thermometer: equally good results in the department of internal medicine]. (1997)

The results of this study show good agreement between the infrared tympanic thermometer and the rectal digital thermometer so that they may be regarded as interchangeable. The patients had a clear preference for the tympanic thermometer, which also took less time.
Transcriptional Activation of pBR322 DNA Can Lead to Duplex DNA Unwinding Catalyzed by the Escherichia coli Preprimosome (1989)

Mechanisms that could operate to initiate pBR322 DNA replication in the absence of RNase H and DNA polymerase I are described. Two different pathways leading to extensive unwinding of pBR322 DNA have been observed under DNA replication reaction conditions in vitro. In the presence of RNA polymerase and DNA gyrase, specifically initiated RNA II (the leading-strand primer precursor) can form an RNA-DNA hybrid with the template that starts just upstream of the origin of DNA replication and continues for about 3 kilobases. Subsequent digestion of the RNA in this RNA-pBR322 DNA hybrid results in the formation of a highly unwound DNA termed form I. If DNA gyrase is absent during the RNA polymerase-catalyzed elongation of RNA II, a stable RNA-pBR322 DNA hybrid can still form that is localized to the origin region of the genome. Formation of this hybrid activates the primosome assembly site present on the lagging-strand DNA template, by displacing it to a single-stranded conformation, thereby allowing preprimosome assembly. Once assembled, the DNA helicase activity of the preprimosome, in the presence of the single-stranded DNA binding protein and DNA gyrase but in the absence of any further transcription, can also result in extensive unwinding of pBR322 DNA. The product of this reaction, form I DNA, is more unwound than form I DNA. The formation of both form I and form I DNA is inhibited by the presence of excess RNA I, as well as by RNase H at concentrations sufficient to catalyze the normal processing of RNA II required for initiation of leading-strand DNA synthesis. These results suggest that RNA II-pBR322 DNA hybrid formation is essential to permit preprimosome assembly during pBR322 DNA replication under conditions where both RNase H and DNA polymerase I are absent.
Activation of NF-κB by hepatitis B virus X protein through an IκB kinase-independent mechanism (2001)

pX, the hepatitis B virus-encoded transcription coactivator, is involved in viral infection in vivo. pX stimulates the activity of several transcription factors including nuclear factor-kappaB (NF-kappaB), but the mechanism of activation is poorly understood. The IkappaB kinase complex (IKK) mediates activation of NF-kappaB in response to various extracellular stimuli, including inflammatory cytokines like tumor necrosis factor and interleukin 1, human T cell lymphoma virus 1 Tax protein, and tumor promoters like phorbol esters. It is not known whether IKK also mediates activation of NF-kappaB by pX. Here we report that IKK was not essential for activation of NF-kappaB by pX. Expression of pX resulted in the degradation of IkappaBalpha in the absence of its phosphorylation at Ser(32) and Ser(36) residues. Although pX stimulated the activity of cotransfected IKK-beta when it was overexpressed, it failed to activate endogenous IKK. Furthermore, expression of pX stimulated NF-kappaB nuclear translocation and transcriptional activity in IKK-gamma-null fibroblast 5R cells. Our data indicate that pX stimulates NF-kappaB activity through a mechanism that is dependent on IkappaBalpha degradation but not on IKK activation.
Tracing the Historical Culture of Spalting in Spain to Its Potential Influence on Peru (2021)

Abstract In Europe, from the fifteenth to the eighteenth century, intarsia and marquetry woodworks relied heavily on the use of spalted wood (wood colored by fungi) especially the blue-green stained wood from the Chlorociboria species. Although the use of spalted wood is well documented in Italy, Germany, Switzerland, and England, little is known about how guild traditions migrated from Spain during European colonization. This research sought to determine if the techniques or woodworks of the time moved to the viceroyalty of Peru. While numerous examples of spalted marquetry have previously been found in Spain, all were made by German artisans and imported to the country. For this research, only one piece of spalted furniture was found in Peru, and it was of English origin. Noting Spain’s lack of production of spalted woodworks and the few pieces found in Peru, it is likely that this niche product did not move to Peru with Spanish colonists and may have instead come over later with English colonists in the 1800s when spalted wood was popular in that region.
ChemInform Abstract: Studies Towards the Synthesis of Diazonamide A. Unexpected Formation of a 3,4‐Bridged Indole. (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Auditory processing in the vegetative state (2000)

H(2)(15)O-PET was used to investigate changes in regional cerebral blood flow in response to auditory stimulation in patients in the vegetative state. Five patients in a vegetative state of hypoxic origin were compared with 18 age-matched controls. In addition, the cerebral metabolism of these patients and 53 age-matched controls was studied using [(18)F]fluorodeoxyglucose. In control subjects, auditory click stimuli activated bilateral auditory cortices [Brodmann areas (BA) 41 and 42] and the contralateral auditory association cortices (BA 22). In the patients, although resting metabolism was decreased to 61% of normal values, bilateral auditory areas 41 and 42 showed activation as seen in the controls, but the temporoparietal junction cortex (BA 22) failed to be activated. Moreover, the auditory association cortex was functionally disconnected from the posterior parietal association area (BA 40), the anterior cingulate cortex (BA 24) and the hippocampus, as revealed by psychophysiological interaction analysis. Thus, despite altered resting metabolism, the auditory primary cortices were still activated during external stimulation, whereas hierarchically higher-order multi- modal association areas were not. Such a cascade of functional disconnections along the auditory cortical pathways, from the primary auditory areas to multimodal and limbic areas, suggests that the residual cortical processing observed in the vegetative state cannot lead to the integrative processes that are thought to be necessary for the attainment of the normal level of awareness.
ChemInform Abstract: SYNTH. VON CYCLISCHEN DISILADERIVATEN (1971)

Abstract Das Siloxan (IIIa) reagiert in Hexamethylphosphortriamid in Gegenwart von Mg mit den Äthylenverbindungen (II) zu den Disilacyclopentanen (I).