Miracle-dz/UniFAR-FTUs huggingface dataset:
Missense mutations in the WD40 domain of AHI1 cause non-syndromic retinitis pigmentosa

Background Recent findings suggesting that Abelson helper integration site 1 (AHI1) is involved in non-syndromic retinal disease have been debated, as the functional significance of identified missense variants was uncertain. We assessed whether AHI1 variants cause non-syndromic retinitis pigmentosa (RP). Methods Exome sequencing was performed in three probands with RP. The effects of the identified missense variants in AHI1 were predicted by three-dimensional structure homology modelling. Ciliary parameters were evaluated in patient’s fibroblasts, and recombinant mutant proteins were expressed in ciliated retinal pigmented epithelium cells. Results In the three patients with RP, three sets of compound heterozygous variants were detected in AHI1 (c.2174G>A; p.Trp725* and c.2258A>T; p.Asp753Val, c.660delC; p.Ser221Glnfs*10 and c.2090C>T; p.Pro697Leu, c.2087A>G; p.His696Arg and c.2429C>T; p.Pro810Leu). All four missense variants were present in the conserved WD40 domain of Jouberin, the ciliary protein encoded by AHI1, with variable predicted implications for the domain structure. No significant changes in the percentage of ciliated cells, nor in cilium length or intraflagellar transport were detected. However, expression of mutant recombinant Jouberin in ciliated cells showed a significantly decreased enrichment at the ciliary base. Conclusions This report confirms that mutations in AHI1 can underlie autosomal recessive RP. Moreover, it structurally and functionally validates the effect of the RP-associated AHI1 variants on protein function, thus proposing a new genotype–phenotype correlation for AHI1 mutation associated retinal ciliopathies.
SECAM: a supervisory equipment control application model for integrated semiconductor manufacturing equipment

This paper describes SECAM (Supervisory Equipment Control Application Model), an object-oriented application prototype for SECs (supervisory equipment controller) for integrated semiconductor manufacturing equipment based on a high-level fieldbus PROFIBUS-FMS. It also features a layered architecture based on some key objects including service objects (SOs), command objects, and virtual control device (VCD) objects, which facilitate complex supervisory control application design and implementation based on highlevel fieldbus services. The proposed approach is demonstrated for a CTC for semiconductor manufacturing.
Oxygen‐enhanced MR imaging of mice lungs

Inhaled molecular oxygen has been widely used in humans to evaluate pulmonary ventilation using MRI. MR imaging has recently played a greater role in examining the morphologic and physiologic characteristics of mouse models of lung disease where structural changes are highly correlated to abnormalities in respiratory function. The motivation of this work is to develop oxygen‐enhanced MR imaging for mice. Conventional human MR techniques cannot be directly applied to mouse imaging due to smaller dimensions and faster cardiac and respiratory physiology. This study examines the development of oxygen‐enhanced MR as a noninvasive tool to assess regional ventilation in spontaneously breathing mice. An optimized cardiac‐triggered, respiratory‐gated fast spin‐echo imaging sequence was developed to address demands of attaining adequate signal from the parenchyma, maintaining practical acquisition times, and compensating for rapid physiological motion. On average, a 20% T1‐shortening effect was observed in mice breathing 100% oxygen as compared to air. The effect of ventilation was shown as a significant signal intensity increase of 11% to 16% in the mouse parenchyma with 100% oxygen inhalation. This work demonstrates that adequate contrast and resolution can be achieved using oxygen‐enhanced MR to visualize ventilation, providing an effective technique to study ventilation defects in mice. Magn Reson Med, 2008. © 2008 Wiley‐Liss, Inc.
LDA Based Similarity Modeling for Question Answering

We present an exploration of generative modeling for the question answering (QA) task to rank candidate passages. We investigate Latent Dirichlet Allocation (LDA) models to obtain ranking scores based on a novel similarity measure between a natural language question posed by the user and a candidate passage. We construct two models each one introducing deeper evaluations on latent characteristics of passages together with given question. With the new representation of topical structures on QA datasets, using a limited amount of world knowledge, we show improvements on performance of a QA ranking system.
Role of the General Base Glu-268 in Nitroglycerin Bioactivation and Superoxide Formation by Aldehyde Dehydrogenase-2*

Mitochondrial aldehyde dehydrogenase-2 (ALDH2) plays an essential role in nitroglycerin (GTN) bioactivation, resulting in formation of NO or a related activator of soluble guanylate cyclase. ALDH2 denitrates GTN to 1,2-glyceryl dinitrate and nitrite but also catalyzes reduction of GTN to NO. To elucidate the relationship between ALDH2-catalyzed GTN bioconversion and established ALDH2 activities (dehydrogenase, esterase), we compared the function of the wild type (WT) enzyme with mutants lacking either the reactive Cys-302 (C302S) or the general base Glu-268 (E268Q). Although the C302S mutation led to >90% loss of all enzyme activities, the E268Q mutant exhibited virtually unaffected rates of GTN denitration despite low dehydrogenase and esterase activities. The nucleotide co-factor NAD caused a pronounced increase in the rates of 1,2-glyceryl dinitrate formation by WT-ALDH2 but inhibited the reaction catalyzed by the E268Q mutant. GTN bioactivation measured as activation of purified soluble guanylate cyclase or release of NO in the presence of WT- or E268Q-ALDH2 was markedly potentiated by superoxide dismutase, suggesting that bioavailability of GTN-derived NO is limited by co-generation of superoxide. Formation of superoxide was confirmed by determination of hydroethidine oxidation that was inhibited by superoxide dismutase and the ALDH2 inhibitor chloral hydrate. E268Q-ALDH2 exhibited ∼50% lower rates of superoxide formation than the WT enzyme. Our results suggest that Glu-268 is involved in the structural organization of the NAD-binding pocket but is not required for GTN denitration. ALDH2-catalyzed superoxide formation may essentially contribute to oxidative stress in GTN-exposed blood vessels.
Dual-baseline SAR interferometry from correlated phase signals

In this paper we consider the problem of the estimation of the digital elevation model (DEM) of a ground scene starting from dual baseline interferometric synthetic aperture radar (SAR) signals. classical maximum likelihood (ML) estimation techniques require the knowledge of the joint probability density function (PDF) of the two measured interferometric phases. Usually the joint PDF expression is derived assuming that the two interferograms are statistically independent. This assumption is not verified for dual baseline configurations based on three image acquisitions. In this paper we compute the dual baseline joint pdf of the interferometric phases in a closed form, taking into account the mutual correlation of all the involved SAR images and without using any approximation. This expression can be exploited for the computation of the maximum likelihood function and for the method accuracy assessment by means of the Cramer Rao lower bound (CRLB) evaluation.
Association between Secondary and Primary Sjögren's Syndrome in a Large Collection of Lupus Families

Objective. Systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) share clinical and immunogenetic features and may occur together. We undertook this study to determine the risk of primary SS among SLE-unaffected relatives of SLE patients and whether or not primary and secondary SS tended to occur in the same families. Methods. We collected clinical and serological data on 2694 SLE patients, 7390 SLE-unaffected relatives of the SLE patients, and 1470 matched controls. Results. Of the 2694 subjects with SLE, 548 had secondary SS, while 71 of their 7390 SLE-unaffected relatives had primary SS. None of the 1470 controls had SS as defined herein (p = 5 × 10−5 compared to SLE-unaffected relatives). Of the 71 SLE-unaffected relatives with primary SS, 18 (25.3%) had an SLE-affected family member with secondary SS, while only 530 of the 7319 (7.2%) SLE-unaffected relatives without SS did so (p = 1 × 10−8). Conclusion. Among families identified for the presence of SLE, primary and secondary SS tend to occur within the same families. These results highlight the commonalities between these two forms of SS, which in fact correspond to the same disease.
The double-layered hydroxide 3CaO.Al2O3.0.5CaBr2.0.5CaCl2.10H2O.

The title compound, calcium oxide–dialuminium trioxide–calcium dibromide–calcium dichloride hydrate (3/1/0.5/0.5/10), also formulated as Ca2Al(OH)6Br0.478Cl0.522·2H2O (dicalcium aluminium hydro­xide hemibromide hemichloride dihydrate), is a double-layered hydro­xide which belongs to the solid solution Ca2Al(OH)6BrxCl1−x·2H2O, where x can vary from 0 to 1. Chloride and bromide anions of the negatively charged interlayer [Br0.5Cl0.5·2H2O]− share statistically the same crystallographic site. Al3+ and Ca2+ cations are coordinated by six and seven O atoms, respectively. All water mol­ecules are bonded to Ca2+ cations and assume the seventh coordination position. Anions in the interlayer are surrounded by ten H atoms. Br− and Cl− are therefore connected to the main layer by ten hydrogen bonds, six of 2.74 (2) A and four of 2.52 (5) A, where the donors are hydroxyl groups and water mol­ecules, respectively. Like the chloride equivalent, the title compound is a 6R polytype with trigonal space group R\overline 3c and lattice parameters a = 5.7537 (4) A and c = 48.108 (4) A.
Transforming Growth Factor (cid:98) 1, in the Presence of Granulocyte/Macrophage Colony-stimulating Factor and Interleukin 4, Induces Differentiation of Human Peripheral Blood Monocytes into Dendritic Langerhans Cells

Langerhans cells (LCs) are dendritic cells (DCs) that are present in the epidermis, bronchi, and mucosae. Although LCs originate in bone marrow, little is known about their lineage of origin. In this study, we demonstrate that in vitro LCs may originate from monocytes. Adult peripheral blood CD14 (cid:49) monocytes differentiate into LCs (CD1a (cid:49) , E-cadherin (cid:49) , cutaneous lympho-cyte-associated antigen (cid:49) , Birbeck granules (cid:49) , Lag (cid:49) ) in the presence of granulocyte/macrophage colony-stimulating factor, interleukin 4, and transforming growth factor (cid:98) 1 (TGF- (cid:98) 1). This process occurs with virtually no cell proliferation and is not impaired by 30 Gy irradiation. Selection of monocyte subpopulations is ruled out since monocyte-derived DCs can further differentiate into LCs. Our data suggest that in vivo LC differentiation may be induced periph-erally, from a nonproliferating myeloid precursor, i.e., the monocyte, in response to a TGF- (cid:98) 1–rich microenvironment, as found in the skin and epithelia. Therefore, the monocyte may represent a circulating precursor critical to the immune response in vivo. Dallas, TX). Ultrastructural Study. Cells to be processed for electron microscopy were fixed overnight at 4 (cid:56) C in 2.5% glutaraldehyde (Sigma Chemical Co.) in 0.1 M cacodylate buffer, pH 7.4, fol-lowed by postfixation for 1–2 h in 0.1 M cacodylate-buffered 2% osmium tetraoxide (Merck, Darmstadt, Germany). After dehydra-tion in a series of graded ethanol and propylene oxide solutions, cells were embedded in epoxy resin (Epon 812; TAAB, Janning, Vanves, France). Ultrathin sections were stained with uranyl acetate and lead citrate and examined with a JEOL.1200 EX2 electron mi-croscope (JEOL, Croissy sur Seine, France).
The postoperative lumbar spine: enhanced MR evaluation of the intervertebral disk.

PURPOSE To document the pattern of enhancement and morphologic changes on MR images that occur in the intervertebral disk and adjacent vertebral bodies after diskectomy and to correlate the presence of intervertebral disk enhancement with the preoperative and postoperative clinical findings. METHODS Preoperatively, and at 3 months and 6 months after surgery, 94 adults who had first-time surgery for a herniated lumbar intervertebral disk that was associated with radiculopathy, expressed as leg symptoms or signs (with or without lower back pain), were asked to respond to a questionnaire regarding pain, were given serial physical examinations, and were examined with contrast-enhanced MR imaging. The measures of clinical outcome that were evaluated included the straight leg raise sign, radicular pain, and lower back pain. Type of disk herniation, intervertebral disk enhancement, disk space height, and degenerative end-plate changes were also assessed. RESULTS Of the 94 patients evaluated, 19 (20%) had postoperative intervertebral disk enhancement that was not present on the preoperative study. The pattern of enhancement was remarkably consistent, with 18 of the cases showing linear enhancement within the intervertebral disk, manifested as two thin bands paralleling the end plates. End-plate enhancement was present in 7 (37%) of the 19 patients with disk enhancement. There were no significant associations between disk enhancement and specific clinical symptoms before or after surgery. CONCLUSION Our group of asymptomatic postoperative patients had anular enhancement (curette site), disk enhancement, and vertebral end-plate enhancement on MR images without evidence of disk space infection. This finding points out the need to understand asymptomatic postoperative changes that are sequelae of surgery and not necessarily indicators of infection.
N‐Methyl‐D‐Aspartate antagonist reduces stroke size and regional glucose metabolism

Pharmacological inhibition of cell excitation during focal ischemia was studied in the rat middle cerebral artery occlusion model. The potent and selective N‐methyl‐D‐aspartate antagonist CGS 19755, administered 5 minutes prior to or 5 minutes following permanent middle cerebral artery occlusion, caused a substantial decrease in infarct size, which was associated with reduction of postischemic cerebral glucose hypermetabolism. These data support a role for excitation‐induced hypermetabolism in the pathogenesis of infarction following focal cerebrovascular occlusion.
Marine Rare Actinobacteria: Isolation, Characterization, and Strategies for Harnessing Bioactive Compounds

Actinobacteria are prolific producers of thousands of biologically active natural compounds with diverse activities. More than half of these bioactive compounds have been isolated from members belonging to actinobacteria. Recently, rare actinobacteria existing at different environmental settings such as high altitudes, volcanic areas, and marine environment have attracted attention. It has been speculated that physiological or biochemical pressures under such harsh environmental conditions can lead to the production of diversified natural compounds. Hence, marine environment has been focused for the discovery of novel natural products with biological potency. Many novel and promising bioactive compounds with versatile medicinal, industrial, or agricultural uses have been isolated and characterized. The natural compounds cannot be directly used as drug or other purposes, so they are structurally modified and diversified to ameliorate their biological or chemical properties. Versatile synthetic biological tools, metabolic engineering techniques, and chemical synthesis platform can be used to assist such structural modification. This review summarizes the latest studies on marine rare actinobacteria and their natural products with focus on recent approaches for structural and functional diversification of such microbial chemicals for attaining better applications.
Search for the electric dipole moment of the electron with thorium monoxide

The electric dipole moment of the electron (eEDM) is a signature of CP-violating physics beyond the standard model. We describe an ongoing experiment to measure or set improved limits to the eEDM, using a cold beam of thorium monoxide (ThO) molecules. The metastable H 3Δ1 state in ThO has important advantages for such an experiment. We argue that the statistical uncertainty of an eEDM measurement could be improved by as much as three orders of magnitude compared to the current experimental limit, in a first-generation apparatus using a cold ThO beam. We describe our measurements of the H state lifetime and the production of ThO molecules in a beam, which provide crucial data for the eEDM sensitivity estimate. ThO also has ideal properties for the rejection of a number of known systematic errors; these properties and their implications are described.
Genetic History of Hepatitis C Virus in East Asia

ABSTRACT The hepatitis C virus (HCV), which currently infects an estimated 3% of people worldwide, has been present in some human populations for several centuries, notably HCV genotypes 1 and 2 in West Africa and genotype 6 in Southeast Asia. Here we use newly developed methods of sequence analysis to conduct the first comprehensive investigation of the epidemic and evolutionary history of HCV in Asia. Our analysis includes new HCV core (n = 16) and NS5B (n = 14) gene sequences, obtained from serum samples of jaundiced patients from Laos. These exceptionally diverse isolates were analyzed in conjunction with all available reference strains using phylogenetic and Bayesian coalescent methods. We performed statistical tests of phylogeographic structure and applied a recently developed “relaxed molecular clock” approach to HCV for the first time, which indicated an unexpectedly high degree of rate variation. Our results reveal a >1,000-year-long development of genotype 6 in Asia, characterized by substantial phylogeographic structure and two distinct phases of epidemic history, before and during the 20th century. We conclude that HCV lineages representing preexisting and spatially restricted strains were involved in multiple, independent local epidemics during the 20th century. Our analysis explains the generation and maintenance of HCV diversity in Asia and could provide a template for further investigations of HCV spread in other regions.
TSV reveal process developments for 2.5D integration

2.5D integration using TSV silicon interposer has attracted much attention in recent years for both front-end foundries and back-end packaging houses. TSV back revealing is one of the key process modules for the fabrication of 2.5D interposer. Two kinds of process flows for TSV revealing are introduced and compared in this paper. The first one uses Si-Cu co-polishing for copper revealing, which can compensate the total thickness variation (TTV) of TSV tips, but the passivation opening on the back side of the TSVs becomes more and more difficult when the TSV size is scaling down. The second one reopens the backside of the TSVs after backside polymer passivation by mask-free plasma etching, which is advantageous for small TSVs but needs to control the TTV strictly. Fabrication results using these two process flows are given and discussed.
Multimodal MRI for Ischemic Stroke: From Acute Therapy to Preventive Strategies

Background and Purpose Conventional therapies for ischemic stroke include thrombolytic therapy, prevention of inappropriate coagulation and thrombosis, and surgery to repair vascular abnormalities. Over 10 years have passed since the US Food and Drug Administration approved intravenous tissue plasminogen activator for use in acute stroke patients, but most major clinical trials have failed during the last 2 decades, including large clinical trials for secondary prevention and neuroprotection. These results suggest the presence of heterogeneity among stroke patients. Neuroimaging techniques now allow changes to be observed in patients from the acute to the recovery phase. The role of MRI in stroke evaluation and treatment is discussed herein. Main Contents Three MRI strategies are discussed with relevant examples. First, the following MRI strategies for acute ischemic stroke are presented: diffusion-perfusion mismatch, deoxygenation (oxygen extraction and cerebral metabolic rate of oxygen), and blood-brain barrier permeability derangement in selected patients for recanalization therapy. Second, multimodal MRI for identifying stroke mechanisms and the specific causes of stroke (i.e., patent foramen ovale, infective endocarditis, and nonbacterial thrombotic endocarditis) are presented, followed by MRI strategies for prevention of recurrent stroke: plaque images and flow dynamics for carotid intervention. Expectations The studies reviewed herein suggest that using MRI to improve the understanding of individual pathophysiologies will further promote the development of rational stroke therapies tailored to the specifics of each case.
Evaluating Rater Competency for CNS Clinical Trials

Abstract: Clinical trials rely on ratings accuracy to document a beneficial drug effect. This study examined rater competency with clinical nervous system rating instruments relative to previous clinical experience and participation in specific rater training programs. One thousand two hundred forty-one raters scored videotaped interviews of the Hamilton Anxiety Scale (HAM-A), Hamilton Depression Scale (HAM-D), and Young Mania Rating Scale (YMRS) during rater training programs conducted at 9 different investigator meetings. Scoring deviations relative to established acceptable scores were used to evaluate individual rater competency. Rater competency was not achieved by clinical experience alone. Previous clinical experience with mood-disordered patients ranged from none at all (18%) to 40 years in 1 rater. However, raters attending their first-ever training session (n = 485) were not differentiated on the basis of clinical experience on the HAM-A (P = 0.054), HAM-D (P = 0.06), or YMRS (P = 0.66). Alternatively, participation in repeated rater training sessions significantly improved rater competency on the HAM-A (P = 0.002), HAM-D (P < 0.001), and YMRS (P < 0.001). Furthermore, raters with clinical experience still improved with rater training. Using 5 years of clinical experience as a minimum cutoff (n = 795), raters who had participated in 5 or more training sessions significantly outperformed comparably experienced raters attending their first-ever training session on the HAM-A (P = 0.003), HAM-D (P < 0.001), and YMRS (P < 0.001). The findings show that rater training improves rater competency at all levels of clinical experience. Furthermore, more stringent criteria for rater eligibility and comprehensive rater training programs can improve ratings competency.