Miracle-dz/UniFAR-FTUs huggingface dataset:
Probe-level measurement error improves accuracy in detecting differential gene expression

MOTIVATION Finding differentially expressed genes is a fundamental objective of a microarray experiment. Numerous methods have been proposed to perform this task. Existing methods are based on point estimates of gene expression level obtained from each microarray experiment. This approach discards potentially useful information about measurement error that can be obtained from an appropriate probe-level analysis. Probabilistic probe-level models can be used to measure gene expression and also provide a level of uncertainty in this measurement. This probe-level measurement error provides useful information which can help in the identification of differentially expressed genes. RESULTS We propose a Bayesian method to include probe-level measurement error into the detection of differentially expressed genes from replicated experiments. A variational approximation is used for efficient parameter estimation. We compare this approximation with MAP and MCMC parameter estimation in terms of computational efficiency and accuracy. The method is used to calculate the probability of positive log-ratio (PPLR) of expression levels between conditions. Using the measurements from a recently developed Affymetrix probe-level model, multi-mgMOS, we test PPLR on a spike-in dataset and a mouse time-course dataset. Results show that the inclusion of probe-level measurement error improves accuracy in detecting differential gene expression. AVAILABILITY The MAP approximation and variational inference described in this paper have been implemented in an R package pplr. The MCMC method is implemented in Matlab. Both software are available from http://umber.sbs. man.ac. uk/resources/puma.
Biology of Streptococcus mutans-Derived Glucosyltransferases: Role in Extracellular Matrix Formation of Cariogenic Biofilms

The importance of Streptococcus mutans in the etiology and pathogenesis of dental caries is certainly controversial, in part because excessive attention is paid to the numbers of S. mutans and acid production while the matrix within dental plaque has been neglected. S. mutans does not always dominate within plaque; many organisms are equally acidogenic and aciduric. It is also recognized that glucosyltransferases from S. mutans (Gtfs) play critical roles in the development of virulent dental plaque. Gtfs adsorb to enamel synthesizing glucans in situ, providing sites for avid colonization by microorganisms and an insoluble matrix for plaque. Gtfs also adsorb to surfaces of other oral microorganisms converting them to glucan producers. S. mutans expresses 3 genetically distinct Gtfs; each appears to play a different but overlapping role in the formation of virulent plaque. GtfC is adsorbed to enamel within pellicle whereas GtfB binds avidly to bacteria promoting tight cell clustering, and enhancing cohesion of plaque. GtfD forms a soluble, readily metabolizable polysaccharide and acts as a primer for GtfB. The behavior of soluble Gtfs does not mirror that observed with surface-adsorbed enzymes. Furthermore, the structure of polysaccharide matrix changes over time as a result of the action of mutanases and dextranases within plaque. Gtfs at distinct loci offer chemotherapeutic targets to prevent caries. Nevertheless, agents that inhibit Gtfs in solution frequently have a reduced or no effect on adsorbed enzymes. Clearly, conformational changes and reactions of Gtfs on surfaces are complex and modulate the pathogenesis of dental caries in situ, deserving further investigation.
FASL rs763110 Polymorphism Contributes to Cancer Risk: An Updated Meta-Analysis Involving 43,295 Subjects

Background Published studies investigating the association between genetic polymorphism -884C/T (rs763110) of the FAS ligand (FASL) promoter and cancer risk reported inconclusive results. To derive a more precise estimation of the relationship, we performed an updated meta-analysis of all eligible studies. Methodology/Principal Findings We carried out a meta-analysis, including 47 studies with 19,810 cases and 23,485 controls, to confirm a more conclusive association between the FASL rs763110 polymorphism and cancer susceptibility. Overall, significantly reduced cancer risk was associated with the variant -884T when all studies were pooled (TC vs. CC: OR = 0.83, 95%CI = 0.75–0.92; Pheterogeneity<0.001; TT+TC vs. CC: OR = 0.85, 95%CI = 0.77–0.94; Pheterogeneity<0.001). Stratified analysis revealed that there was a statistically reduced cancer risk in Asians (TC vs. CC: OR = 0.76, 95%CI = 0.67–0.87; Pheterogeneity<0.001; TT+TC vs. CC: OR = 0.79, 95%CI = 0.70–0.90; Pheterogeneity<0.001) and in patients with cancers of head and neck (TC vs. CC: OR = 0.87, 95%CI = 0.77–0.99; Pheterogeneity = 0.118; TT+TC vs. CC: OR = 0.88, 95%CI = 0.78–0.99; Pheterogeneity = 0.168) and ovarian cancer (TC vs. CC: OR = 0.67, 95%CI = 0.49–0.90; Pheterogeneity = 0.187; TT+TC vs. CC: OR = 0.64, 95%CI = 0.48–0.86; Pheterogeneity = 0.199). Meta-regression showed that ethnicity (p = 0.029) and genotyping method (p = 0.043) but not cancer types (p = 0.772), sample size (p = 0.518), or source of controls (p = 0.826) were the source of heterogeneity in heterozygote comparison. Conclusion Our results suggest that the FASL polymorphism rs763110 is associated with a significantly reduced risk of cancer, especially in Asian populations.
The Predominant Vestibular Uptake of Gadolinium Through the Oval Window Pathway Is Compromised by Endolymphatic Hydrops in Ménière’s Disease

Objective Intratympanic administration of gentamicin is becoming a common therapy to control vertigo in Ménière’s disease (MD). Drug entry through an oval window pathway was recently demonstrated in rats. The present study aimed to evaluate the permeability of the oval window to gadolinium in MD patients. Methods Eight patients with MD and other inner ear diseases received a transtympanic injection of 5-fold diluted gadopentetate dimeglumine (Gd-DTPA). Three-dimensional fluid-attenuated inversion-recovery (3D-FLAIR) and 3D inversion recovery turbo spin echo with real reconstruction (3D-real IR) imaging was performed using a 3-Tesla MRI scanner at 3, 6, 12, and 24 h after injection. The extent of vestibular endolymphatic hydrops (EH) was determined, and the dynamics of the signal changes in the vestibule and the cochlear basal turn were evaluated. Results Transtympanically injected Gd-DTPA entered the cochlea of all 8 of the patients and entered the vestibule of 7 of the 8 patients. EH was demonstrated in 2 patients with MD and the patient with idiopathic sensorineural hearing loss or idiopathic vertigo. In the patients lacking EH, the vestibules exhibited more efficient uptake of Gd-DTPA than did the cochleae. In the patients with vestibular EH, the Gd-DTPA signal in the vestibule was less intense than that in the cochlear basal turn. Conclusion In patients with inner ear diseases, the vestibular distribution of Gd-DTPA was compromised by vestibular EH, suggesting oval window passage of Gd-DTPA is reduced in the presence of EH.
An Realization of Chua ’ s Circuit Family

In this brief, we consider a Wien bridge-based resistance–capacitance ( ) chaotic oscillator. We show that this circuit realizes the well-known Chua’s oscillator under some conditions. We also show that this circuit is linearly conjugate, hence equivalent, to a large class of three-dimensional (3-D) systems when the parameters are appropriately chosen. We also present some experimental results.
Scaling limits for shortest path lengths along the edges of stationary tessellations

We consider spatial stochastic models, which can be applied to, e.g. telecommunication networks with two hierarchy levels. In particular, we consider Cox processes X L and X H concentrated on the edge set T (1) of a random tessellation T, where the points X L,n and X H,n of X L and X H can describe the locations of low-level and high-level network components, respectively, and T (1) the underlying infrastructure of the network, such as road systems, railways, etc. Furthermore, each point X L,n of X L is marked with the shortest path along the edges of T to the nearest (in the Euclidean sense) point of X H . We investigate the typical shortest path length C * of the resulting marked point process, which is an important characteristic in, e.g. performance analysis and planning of telecommunication networks. In particular, we show that the distribution of C * converges to simple parametric limit distributions if a scaling factor κ converges to 0 or ∞. This can be used to approximate the density of C * by analytical formulae for a wide range of κ.
Tumor site concordance and genetic toxicology test correlations in NTP 2-year gavage, drinking water, dermal, and intraperitoneal injection studies

The National Toxicology Program has conducted 594, 2-year studies exposing various strains of rats and mice via different routes of exposure. In the current study, we analyze the results from 108 chemicals tested in 106, 2-year studies conducted by exposing F334/N rats and B6C3F1 mice via gavage. An additional 18, 2-year gavage studies have been conducted in Osborne–Mendel rats and B6C3F1 mice on 19 different chemicals. We analyze the results from 23 chemicals tested in 21, 2-year studies conducted by exposing F334/N rats and B6C3F1 mice via drinking water; 18 chemicals tested in 18, 2-year studies conducted by exposing F334/N rats and B6C3F1 mice via dermal application; and 11 chemicals tested in 11, 2-year studies conducted by exposing F334/N rats and B6C3F1 mice via intraperitoneal injection. The results from these 174 studies are analyzed and discussed separately. The neoplasticity of each chemical was analyzed for tumor incidence by species–sex category, tumor site concordance across species, and tumor site concordance across sex within species. When available the Ames Salmonella mutagenicity assay results, and any results from a test for genotoxicity other than the Ames test, were correlated with the neoplasticity results. Tumor site concordance across sex within species is generally higher than tumor site concordance across species. In addition, the high degree of variability of Ames test results suggests that historical Ames test data are less reliable than recent results conducted under good laboratory practices and employing Organization for Economic Cooperation and Development protocols relevant to the physicochemical characteristics of the test chemical.
Quantum Gravity as the Natural Regulator of Matter Quantum Field Theories

It is an old speculation in physics that, once the gravitational field is successfully quantized, it should serve as the natural regulator of infrared and ultraviolet singularities that plague quantum field theories in a background metric. We demonstrate that this idea is implemented in a precise sense within the framework of four-dimensional canonical Lorentzian quantum gravity in the continuum. Specifically, we show that the Hamiltonian of the standard model supports a representation in which finite linear combinations of Wilson loop functionals around closed loops, as well as along open lines with fermionic and Higgs field insertions at the end points are densely defined operators. This Hamiltonian, surprisingly, does not suffer from any singularities, it is completely finite without renormalization. This property is shared by string theory. In contrast to string theory, however, we are dealing with a particular phase of the standard model coupled to gravity which is entirely non-perturbatively defined and second quantized.
Granulocyte colony-stimulating factor for acute ischemic stroke: a randomized controlled trial

Background: Because granulocyte colony-stimulating factor (G-CSF) has anti-inflammatory and neuroprotective properties and is known to mobilize stem cells, it may be useful in the treatment of acute ischemic stroke. We sought to examine the feasibility, safety and efficacy of using G-CSF to treat acute stroke. Methods: We conducted a randomized, blinded controlled trial involving 10 patients with acute cerebral infarction (middle cerebral artery territory as documented by the admission MRI) who presented within 7 days of onset and whose scores on the National Institutes of Health Stroke Scale (NIHSS) were between 9 and 20. Patients were assigned to either G-CSF therapy or usual care. The G-CSF group (n = 7) received subcutaneous G-CSF injections (15 μg/kg per day) for 5 days. The primary outcome was percentage changes between baseline and 12-month follow-up in mean group scores on 4 clinical scales: the NIHSS, European Stroke Scale (ESS), ESS Motor Subscale (EMS) and Barthel Index (BI). We also assessed neurologic functioning using PET to measure cerebral uptake of fluorodeoxyglucose in the cortical areas surrounding the ischemic core. Results: All of the patients completed the 5-day course of treatment, and none were lost to follow-up. No severe adverse effects were seen in patients receiving G-CSF. There was greater improvement in neurologic functioning between baseline and 12-month follow-up in the G-CSF group than in the control group (NIHSS: 59% change in the mean G-CSF group score v. 36% in the mean control group score, ESS: 33% v. 20%, EMS: 106% v. 58%, BI: 120% v. 60%). Although at 12 months there was no difference between the 2 groups in cerebral uptake of fluorodeoxyglucose in the ischemic core, uptake in the area surrounding the core was significantly improved in the G-CSF group compared with the control group. There was positive correlation between metabolic activity and EMS score following simple linear correlation analysis. Interpretation: Our preliminary evidence suggests that using G-CSF as therapy for acute stroke is safe and feasible and leads to improved neurologic outcomes.
CAPC: A Road-Departure Prevention System

he Crewman’s Associate for Path Control (CAPC) is an automatic road-departure warning system for motor vehicle drivers. This article presents the design of, and preliminary field results from, the CAPC prototype vehicle, a modified 1995 Ford Taurus SHO. The CAPC system is intended for highway drivers who are drifting off the roadway at a shallow angle of departure due to inattention, drowsiness, intoxication, or other causes. A camera senses the roadway ahead, and a suite of transducers provide measurements of vehicle motion and driver steering commands. These are used to anticipate unintended road departures and wam the driver. Warning and intervention functions for CAPC have been developed during ongoing research at the University of Michigan; the algorithms are reviewed here in the context of the prototype. The prototype hardware and software are described in detail, and preliminary experimental data from the field is presented.
Diurnality and nocturnality in nonhuman primates: comparative chronobiological studies in laboratory and nature

Looking for differences in circadian clock characteristics of diurnal and nocturnal nonhuman primates, this article summarizes results of chronobiological studies carried out in various nocturnal, diurnal, and cathemeral prosimian and anthropoid primate species under controlled laboratory conditions, under seminatural conditions, and in the wild. In almost all circadian parameters investigated, no differences were discernible between the two main chrono-ecotypes, either in circadian period length and the influence upon it of after-effects, of light intensity, and ambient temperature, or in the PRC, re-entrainment behavior, rhythm splitting, and internal desynchronization. Diurnal and nocturnal or cathemeral species differed only in the phase of artificial or natural LDs to which their circadian activity phase was adjusted as well as in the characteristics of masking activity upon the rhythms produced by the direct inhibiting or enhancing effects of light. Pronounced lunar periodicity—observed in the activity rhythm of nocturnal neotropical owl monkeys, genus Aotus, in seminatural and natural environments as well as in wild cathemeral Malagasy lemurs, genus Eulemur—is shown to result from masking effects of moonlight. In captive Eulemur fulvus albifrons, a change from dark-active over cathemeral to light-active behavior, without concurrently changing the circadian phase-setting of activity to D, was produced by direct masking effects of a stepwise reduction of darktime luminosity on an LD 12:12 cycle. Long-term activity recordings carried out in wild diurnal Malagasy sifakas (Propithecus verreauxi) and cathemeral redfronted lemurs (Eulemur fulvus rufus), as well as in wild nocturnal owl monkeys (Aotus a. azarai) of the North Argentinean Chaco, yielded in all species distinct bimodal long- and short-day activity patterns with pronounced peaks during dusk and dawn. Applying Pittendrigh's two-oscillator concept to these results, it is hypothesized that the differences in chrono-ecotype behavior may result from variations in internal coupling and external phase-setting of morning and evening oscillators (m, e) to dawn and dusk, interacting with direct masking effects of light.
Parallel Reaction Monitoring: A Targeted Experiment Performed Using High Resolution and High Mass Accuracy Mass Spectrometry

The parallel reaction monitoring (PRM) assay has emerged as an alternative method of targeted quantification. The PRM assay is performed in a high resolution and high mass accuracy mode on a mass spectrometer. This review presents the features that make PRM a highly specific and selective method for targeted quantification using quadrupole-Orbitrap hybrid instruments. In addition, this review discusses the label-based and label-free methods of quantification that can be performed with the targeted approach.
Dissecting the cellular functions of plant microtubules using mutant tubulins

α‐ and β‐tubulins, the building blocks of the microtubule (MT) polymer, are encoded by multiple genes that are largely functionally redundant in plants. Null tubulin mutants are thus phenotypically indistinguishable from the wild type, but miss‐sense or deletion mutations of critical amino acid residues that are important for the assembly, stability, or dynamics of the polymer disrupt the proper organization and function of the resultant MT arrays. Mutant tubulins co‐assemble with wild‐type tubulins into mutant MTs with compromised functions, and thus mechanistically act as dominant‐negative MT poisons. Cortical MT arrays in interphase plant cells are most sensitive to tubulin mutations, and are transformed into helical structures or random orientation, which produce twisted or radially swollen cells. Mutant plants resistant to MT‐targeted herbicides may possess tubulin mutations at the binding sites of the herbicides. Tubulin mutants are valuable tools for investigating how individual MTs are organized into particular patterns in cortical arrays, and for defining the functional contribution of MTs to various MT‐dependent or ‐assisted cellular processes in plant cells. 2013 Wiley Periodicals, Inc
A computerised tailored intervention for increasing intakes of fruit, vegetables, brown bread and wholegrain cereals in adolescent girls

Abstract Objective To evaluate the effectiveness of a computer-generated tailored intervention leaflet compared with a generic leaflet aimed at increasing brown bread, wholegrain cereal, fruit and vegetable intakes in adolescent girls. Design Clustered randomised controlled trial. Dietary intake was assessed via three 24 h dietary recalls. Setting Eight secondary schools in areas of low income and/or high ethnic diversity, five in London and three in the West Midlands, UK. Subjects Girls aged 12–16 years participated (n 823) and were randomised by school class to receive either the tailored intervention (n 406) or a generic leaflet (n 417). Results At follow-up 637 (77 %) participants completed both baseline and follow-up dietary recalls. The tailored intervention leaflet had a statistically significant effect on brown bread intake (increasing from 0·39 to 0·51 servings/d) with a smaller but significant increase in the control group also (increasing from 0·28 to 0·35 servings/d). The intervention group achieved 0·05 more servings of brown bread daily than the control group (P < 0·05), which is equivalent to 0·35 servings/week. For the other foods there were no significant effects of the tailored intervention. Conclusions The intervention group consumed approximately 0·35 more servings of brown bread weekly than the control group from baseline. Although this change between groups was statistically significant the magnitude was small. Evaluation of the intervention was disappointing but the tailored leaflet was received more positively in some respects than the control leaflet. More needs to be done to increase motivation to change dietary intake in adolescent girls.
Gastric adenocarcinoma in children and adolescents

Gastric adenocarcinoma (GAC) is an extremely rare cancer in children with very limited information on the clinical presentation and outcome. We report five pediatric patients with GAC‐treated between 1990 and 2008 at our institution. Median age at diagnosis was 17 years (range: 8–17). Our case series suggests that pediatric GAC patients present with diffuse metastatic disease (four patients) and with patterns of spread similar to adult GAC. Initial chemotherapy was mainly platinum‐based. Median time to progression was 4 months. The only long‐term survivor was a patient with localized disease who had complete surgical removal of primary tumor. Pediatr Blood Cancer 2011; 57: 524–527. © 2011 Wiley‐Liss, Inc.
Disruption of kinematic coordination in throwing under stress

The present study tested the conscious-control theory of the relationship between stress and performance. Performers under stress conditions consciously attempted to control their movements, disrupting the automaticity of control. Twenty-two male subjects (11 in Experiment 1 and 11 in Experiment 2) performed an underhand ball-throwing task using the non-dominant hand. The inter-trial variability of two kinematic measures was analyzed, namely arm-joint coordination during the throw and hand position at release (release point). Experiment 1 confirmed the validity of regarding these variability measures as indices of automaticity, as they did not vary in spite of resource shortage induced by a dual-task paradigm. In Experiment 2, in which stress led to a detriment in performance, the variability of joint coordination increased, whereas the release point became more fixed. These findings imply that throwing perform- ance is impaired when the coordination is disrupted as a result of inflexible movement executed by conscious control.
Optimum displacement for compound image generation in medical ultrasound

Incoherent averaging of measurements made at different look directions can be used to reduce speckle noise in medical ultrasound images. An analytic expression for the correlation between two measurements made at different spatial positions is derived. Using this expression, the optimum aperture displacement for efficient incoherent averaging (i.e. compounding) is computed and found to equal approximately one-half the aperture length. <<ETX>>
Density measure for line-drawing simplification

We present an approach for clutter control in NPR line drawing where measures of view and drawing complexity drive the simplification or omission of lines. We define two types of density information: the a-priori density and the causal density, and use them to control which parts of a drawing need simplification. The a-priori density is a measure of the visual complexity of the potential drawing and is computed on the complete arrangement of lines from the view. This measure affords a systematic approach for characterizing the structure of cluttered regions in terms of geometry, scale, and directionality. The causal density measures the spatial complexity of the current state of the drawing as strokes are added, allowing for clutter control through line omission or stylization. We show how these density measures permit a variety of pictorial simplification styles where complexity is reduced either uniformly, or in a spatially-varying manner through indication.