Miracle-dz/UniFAR-FTUs huggingface dataset:
Opposing Forces of A/T-Biased Mutations and G/C-Biased Gene Conversions Shape the Genome of the Nematode Pristionchus pacificus

Base substitution mutations are a major source of genetic novelty and mutation accumulation line (MAL) studies revealed a nearly universal AT bias in de novo mutation spectra. While a comparison of de novo mutation spectra with the actual nucleotide composition in the genome suggests the existence of general counterbalancing mechanisms, little is known about the evolutionary and historical details of these opposing forces. Here, we correlate MAL-derived mutation spectra with patterns observed from population resequencing. Variation observed in natural populations has already been subject to evolutionary forces. Distinction between rare and common alleles, the latter of which are close to fixation and of presumably older age, can provide insight into mutational processes and their influence on genome evolution. We provide a genome-wide analysis of de novo mutations in 22 MALs of the nematode Pristionchus pacificus and compare the spectra with natural variants observed in resequencing of 104 natural isolates. MALs show an AT bias of 5.3, one of the highest values observed to date. In contrast, the AT bias in natural variants is much lower. Specifically, rare derived alleles show an AT bias of 2.4, whereas common derived alleles close to fixation show no AT bias at all. These results indicate the existence of a strong opposing force and they suggest that the GC content of the P. pacificus genome is in equilibrium. We discuss GC-biased gene conversion as a potential mechanism acting against AT-biased mutations. This study provides insight into genome evolution by combining MAL studies with natural variation.
A New String-to-Dependency Machine Translation Algorithm with a Target Dependency Language Model

In this paper, we propose a novel string-todependency algorithm for statistical machine translation. With this new framework, we employ a target dependency language model during decoding to exploit long distance word relations, which are unavailable with a traditional n-gram language model. Our experiments show that the string-to-dependency decoder achieves 1.48 point improvement in BLEU and 2.53 point improvement in TER compared to a standard hierarchical string-tostring system on the NIST 04 Chinese-English evaluation set.
Benefit–risk assessment of pitavastatin for the treatment of hypercholesterolemia in older patients

With the practice-shifting changes made with the most recent guidelines for treating blood cholesterol, more older patients may be prescribed statin therapy. Therefore, it is imperative that practitioners have not only a working knowledge of information related to statins, but more specifically to their efficacy and safety in elderly populations. Pitavastatin is the most recent statin to receive regulatory approval. It is indicated for the treatment of primary hyperlipidemia or mixed dyslipidemia as an adjunctive therapy to diet. The overall body of evidence for the efficacy and safety of pitavastatin in elderly patients is small. The available data suggest that the ability of pitavastatin to lower low-density lipoprotein cholesterol in elderly patients is at least similar, and may be greater than that seen in comparatively younger cohorts. Taken together, the limited available data suggest that pitavastatin is effective at improving lipid parameters in elderly patients with a similar safety profile to other agents in the class. Until data become available distinguishing pitavastatin from the other available options, its ultimate role in the hyperlipidemia treatment armamentarium remains unclear.
A Theoretical Framework Contrasting the Resource-Based Perspective and the Knowledge-Based View

The purpose of this paper is to explore the relationship between the two most important perspectives of the firm, the RBV and the KBV, by examining the relative impact of firm-specific assets and knowledge capabilities on the firm’s competitive advantage. A composite model is proposed which elaborates upon both perspectives causal logic with respect to the conditions relevant for the firm success.
Molecular Characterization and Expression of a Heat Shock Protein Gene (HSP90) from the Carmine Spider Mite, Tetranychus cinnabarinus (Boisduval)

Abstract In this study, the cDNA of Tetranychus cinnabarinus (Boisduval) (Acarina: Tetranychidae) HSP90 (designated TcHSP90) was cloned using a combination of the homology cloning and rapid amplification of cDNA ends (RACE) approaches. The full-length cDNA of TcHSP90 is 2595 bp, including a 5′-untranslated region (UTR) of 177 bp, 3′-UTR of 249 bp, and an open reading frame (ORF) of 2169 bp. The ORF encodes a polypeptide of 722 amino acids with a predicted molecular weight of 83.45 kDa and a theoretical isoelectric point of 4.81. There is an mRNA polyadenylation signal of ATTAAA at the positions 2558–2564. In addition, the expression pattern of TcHSP90 mRNA relative to that of &bgr;-actin gene in the three stains of T. cinnabarinus (AbR, abamectin-resistant strain; HR, heat-resistant strain; SS, the susceptible strain) were examined by using fluorescent real time quantitative PCR after the impact of abamectin, high and low temperature, respectively. The results showed that under the normal condition, the mRNA level of TcHSP90 was 1.64 and 1.29-fold higher in the AbR and HR than in SS, respectively. After 8 h treatment with abamectin, the TcHSP90 mRNA levels of SS, AbR, and HR were 1.25, 1.87, and 2.05-fold higher than those of their untreated controls, respectively. The TcHSP90 mRNA levels of SS, AbR, and HR were also significantly increased after being induced at 40° C for 1 h, and they were 3.76, 3.42, and 3.79-fold higher than those of their untreated controls, respectively. The mRNA level of TcHSP90 was also significantly increased after being induced at 4° C for 1 h. These results suggest that TcHSP90 might be involved in the abamectin and extreme temperature resistance or tolerance.
A Peripheral Display Toolkit

Traditionally, computer interfaces have been confined to conventional displays and focused activities. However, as displays become embedded throughout our environment and daily lives, increasing numbers of them must operate on the periphery of our attention. Peripheral displays, ubiquitous computing devices that present information without demanding attention, are difficult to build, particularly because they must dynamically manage the cognitive load they place on users. We present a toolkit that aids the development of peripheral displays. We determined three key issues for the toolkit, based on a survey of existing peripheral displays and cognitive science literature: abstraction of data, selection of notification levels, and transitions between notification levels. Our contribution is the investigation of these key characteristics, combined with a toolkit that encapsulates them and supports the design of displays that focus on these issues. We describe our toolkit architecture, and present five sample peripheral displays demonstrating our toolkit’s capabilities.
Stochastic computing

The Stochastic Computer was developed as part of a program of research on the structure, realization and application of advanced automatic controllers in the form of Learning Machines. Although algorithms for search, identification, policy-formation and the integration of these activities, could be established and tested by simulation on conventional digital computers, there was no hardware available which would make construction of the complex computing structure required in a Learning Machine feasible. The main problem was to design an active storage element in which the stored value was stable over long periods, could be varied by small increments, and whose output could act as a 'weight' multiplying other variables. Since large numbers of these elements would be required in any practical system it was also necessary that they be small and of low cost. Conventional analog integrators and multipliers do not fulfill requirements of stability and low cost, and unconventional elements such as electro-chemical stores and transfluxors are unreliable or require sophisticated external circuitry to make them usable. Semiconductor integrated circuits have advantages in speed, stability, size and cost, and it was decided to design a computing element based on standard gates and flip-flops which would be amenable to large-scale integration.
Ambulatory blood pressure. An independent predictor of prognosis in essential hypertension.

To determine the prognostic significance of ambulatory blood pressure, we prospectively followed for up to 7.5 years (mean, 3.2) 1187 subjects with essential hypertension and 205 healthy normotensive control subjects who had baseline off-therapy 24-hour noninvasive ambulatory blood pressure monitoring. Prevalence of white coat hypertension, defined by an average daytime ambulatory blood pressure lower than 131/86 mm Hg in women and 136/87 mm Hg in men in clinically hypertensive subjects, was 19.2%. Cardiovascular morbidity, expressed as the number of combined fatal and nonfatal cardiovascular events per 100 patient-years, was 0.47 in the normotensive group, 0.49 in the white coat hypertension group, 1.79 in dippers with ambulatory hypertension, and 4.99 in nondippers with ambulatory hypertension. After adjustment for traditional risk markers for cardiovascular disease, morbidity did not differ between the normotensive and white coat hypertension groups (P = .83). Compared with the white coat hypertension group, cardiovascular morbidity increased in ambulatory hypertension in dippers (relative risk, 3.70; 95% confidence interval, 1.13 to 12.5), with a further increase of morbidity in nondippers (relative risk, 6.26; 95% confidence interval, 1.92 to 20.32). After adjustment for age, sex, diabetes, and echocardiographic left ventricular hypertrophy (relative risk versus subjects with normal left ventricular mass, 1.82; 95% confidence interval, 1.02 to 3.22), cardiovascular morbidity in ambulatory hypertension was higher (P = .0002) in nondippers than in dippers in women (relative risk, 6.79; 95% confidence interval, 2.45 to 18.82) but not in men (P = .91). Our findings suggest that ambulatory blood pressures stratifies cardiovascular risk in essential hypertension independent of clinic blood pressure and other traditional risk markers including echocardiographic left ventricular hypertrophy. (ABSTRACT TRUNCATED AT 250 WORDS)
Comprehensive understanding of TCP Incast problem

Since TCP Incast has been identified as a catastrophic problem in many typical data center applications, a lot of efforts have been made to analyze or solve it. The analysis work intends to model Incast problem from certain perspective, and the solutions try to solve the problem through designing enhanced mechanisms or algorithms. However, the proposed models are either closely coupled with particular protocol version or dependent on empirical observations, and the solutions cannot eliminate Incast problem entirely because the underlying issues are not identified completely. There is little work which attempts to close the gap between “analyzing” and “solving”, and present a comprehensive understanding. In this paper, we provide an in-depth understanding of how TCP Incast problem happens. We build up an interpretive model which emphasizes particularly on describing qualitatively how various factors, including system parameters and mechanism variables, affect network performances in Incast traffic pattern, but not on calculating the accurate throughput. With this model, we give plausible explanations why the various solutions for TCP Incast problem can help, but do not solve it entirely.
Early switch to oral antibiotics and early discharge guidelines in the management of community‐acquired pneumonia

Background and objective: The major cost of managing community‐acquired pneumonia (CAP) relates to the duration i.v. antibiotic use and length of hospital stay (LOS). Guidelines on early switch to oral antibiotics and early discharge from hospital may help to achieve a unified approach to managing CAP. The aim of this study was to assess the benefits and safety of these guidelines in an Australian respiratory medicine unit.
Cerebellar tDCS Effects on Conditioned Eyeblinks using Different Electrode Placements and Stimulation Protocols

There is good evidence that the human cerebellum is involved in the acquisition and timing of classically conditioned eyeblink responses (CRs). Animal studies suggest that the cerebellum is also important in CR extinction and savings. Cerebellar transcranial direct current stimulation (tDCS) was reported to modulate CR acquisition and timing in a polarity dependent manner. To extent previous findings three experiments were conducted using standard delay eyeblink conditioning. In a between-group design, effects of tDCS were assessed with stimulation over the right cerebellar hemisphere ipsilaterally to the unconditioned stimulus (US). An extracephalic reference electrode was used in Experiment 1 and a cephalic reference in Experiment 2. In both parts the influence on unconditioned eyeblink responses (UR) was investigated by starting stimulation in the second half of the pseudoconditioning phase lasting throughout the first half of paired trials. In a third experiment, effects of cerebellar tDCS during 40 extinction trials were assessed on extinction and reacquisition on the next day. In each experiment, 30 subjects received anodal, cathodal or sham stimulation in a double-blinded fashion. Using the extracephalic reference electrode, no significant effects on CR incidences comparing stimulation groups were observed. Using the cephalic reference anodal as well as cathodal cerebellar tDCS increased CR acquisition compared to sham only on a trend level. Analysis of timing parameters did not reveal significant effects on CR onset and peaktime latencies nor on UR timing. In the third experiment, cerebellar tDCS during extinction trials had no significant effect on extinction and savings on the next day. The present study did not reveal clear polarity dependent effects of cerebellar tDCS on CR acquisition and timing as previously described. Weaker effects may be explained by start of tDCS before the learning phase i.e., offline, individual thresholds and current flow based on individual anatomy may also play role. Likewise cerebellar tDCS during extinction did not modulate extinction or reacquisition. Further studies are needed in larger subject populations to determine parameters of stimulation and learning paradigms yielding robust cerebellar tDCS effects.
An Assessment of the Relationship between the Maxillary Sinus Floor and the Maxillary Posterior Teeth Root Tips Using Dental Cone-beam Computerized Tomography

Objectives: The aim of the present study was to assess the relationship between the maxillary sinus floor and the maxillary posterior teeth root tips using dental cone-beam CT. Methods: A total of 87 right and 89 left maxillary sinus regions from 92 patients were examined using dental cone-beam CT. Images were analyzed by a specialist in oral and maxillofacial radiology. Perpendicular lines were drawn on the cross-sectional images between the deepest point of the maxillary sinus floor and the root tips of the maxillary first and second premolars and first, second and third molars, and the distances were measured using built-in measurement tools. Means, standard deviations and minimum and maximum values were calculated for all right and left premolars and molars. T-tests were used to compare measurements between left and right sides and between female and male patients. Results: The distance between sinus floor and root tip was longest for the first premolar root tip and shortest for the second molar buccodistal root tip for both right and left sides. No statistically significant differences were found between the right and left side measurements or between female and male patients (P>.05). Conclusions: Knowledge of the anatomical relationship between the maxillary sinus floor and the maxillary posterior teeth root tips is important for the preoperative treatment planning of maxillary posterior teeth.
Enhanced cellular uptake of maleimide-modified liposomes via thiol-mediated transport

With a small amount of maleimide modification on the liposome surface, enhanced cellular uptake of liposomes and drug-delivery efficiency can be obtained both in vitro and in vivo. Herein, we describe the mechanisms underlying this enhanced cellular uptake. Suppression of the cellular uptake of maleimide-modified liposomes (M-GGLG, composed of 1,5-dihexadecyl N,N-diglutamyl-lysyl-L-glutamate [GGLG]/cholesterol/poly(ethylene glycol) – 1,2-distearoyl-sn-glycero-3-phosphoethanolamine [PEG5000-DSPE]/maleimide [M]-PEG5000-Glu2C18 at a molar ratio of 5:5:0.03:0.03) caused by temperature block and addition of serum was alleviated compared with that of liposomes without maleimide modification (GGLG liposomes, composed of GGLG/cholesterol/PEG5000-DSPE/PEG5000-Glu2C18 at a molar ratio of 5:5:0.03:0.03). When 0.01 nM N-ethylmaleimide was used to pre-block cellular thiols, the cellular uptake of M-GGLG liposomes was decreased to approximately 70% in HeLa, HCC1954, MDA-MB-468, and COS-7 cell lines. Moreover, inhibition of a thiol-related reductase such as protein disulfide isomerase resulted in a 15%–45% inhibition of the cellular uptake of M-GGLG liposomes, whereas GGLG liposomes were not influenced. Further, single and mixed inhibitors of clathrin-mediated endocytosis, caveolae-mediated endocytosis, and macropinocytosis did not efficiently inhibit the cellular uptake of M-GGLG liposomes. Using confocal microscopy, we verified that M-GGLG liposomes were localized partially in lysosomes after inhibition of the mentioned conventional endocytic pathways. Therefore, it was hypothesized that the mechanisms underlying the enhanced cellular uptake of liposomes by maleimide modification was thiol-mediated membrane trafficking, including endocytosis and energy-independent transport.
Xanthium strumarium L. Extracts Produce DNA Damage Mediated by Cytotoxicity in In Vitro Assays but Does Not Induce Micronucleus in Mice

Xanthium strumarium L. is a member of the Asteraceae commonly used in Cuba, mainly as diuretic. Some toxic properties of this plant have also been reported and, to date, very little is known about its genotoxic properties. The present work aims was to evaluate the potential cytotoxic and genotoxic risk of whole extract from Xanthium strumarium L. whole extract of aerial parts. No positive response was observed in a battery of four Salmonella typhimurium strains, when exposed to concentrations up to 5 mg/plate, with and without mammalian metabolic activation (liver microsomal S9 fraction from Wistar rats). In CHO cells, high concentrations (25–100 μg/mL) revealed significant reduction in cell viability. Results from sister chromatid exchanges, chromosome aberrations, and comet assay showed that X. strumarium extract is genotoxic at the highest concentration used, when clear cytotoxic effects were also observed. On the contrary, no increase in micronuclei frequency in bone marrow cells was observed when the extract was orally administered to mice (100, 500, and 2000 mg/Kg doses). The data presented here constitute the most complete study on the genotoxic potential of X. strumarium L. and show that the extract can induce in vitro DNA damage at cytotoxic concentrations.
Learning to “See” Less Than Nothing: Putting Perceptual Skills to Work for Learning Numerical Structure

How can children's natural perceptuo-motor skills be harnessed for teaching and learning mathematical structure? We address this question in the case of the integers. Existing research suggests that adult mental representations of integers recruit perceptuo-motor functionalities involving symmetry. Building on these findings, we designed a hands-on curriculum that emphasizes symmetry to teach integer concepts to fourth graders. Compared to two control conditions, children who went through the experimental curriculum showed evidence of incorporating symmetry into their mental representations of integers and performed higher on problems beyond the scope of instruction, including negative fractions and algebra-readiness problems. Gains did not come at the expense of basic integer computation skill. This study has direct practical implications, as current integers curricula generally omit symmetry. The research demonstrates an approach to designing instruction that involves identifying perceptuo-motor functionalities underlying numerical cognition and creating learning activities to recruit them.
Mass Follows Light

We use comparisons between the shapes of gravitational lens galaxies and models for their mass distributions to derive statistical constraints on the alignment of the mass distribution relative to the observed lens galaxy and on the strength of tidal shear perturbations. The mass distributions are aligned with the luminous galaxies, with a 10 degree upper limit on the rms dispersion in the angle between the major axes. Statistical constraints, such as our bound on the misalignment between mass and light, are an important new approach to reducing the uncertainties in individual lens models, particularly for lenses used to estimate the Hubble constant.
DNA Prime/Adenovirus Boost Malaria Vaccine Encoding P. falciparum CSP and AMA1 Induces Sterile Protection Associated with Cell-Mediated Immunity

Background Gene-based vaccination using prime/boost regimens protects animals and humans against malaria, inducing cell-mediated responses that in animal models target liver stage malaria parasites. We tested a DNA prime/adenovirus boost malaria vaccine in a Phase 1 clinical trial with controlled human malaria infection. Methodology/Principal Findings The vaccine regimen was three monthly doses of two DNA plasmids (DNA) followed four months later by a single boost with two non-replicating human serotype 5 adenovirus vectors (Ad). The constructs encoded genes expressing P. falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1). The regimen was safe and well-tolerated, with mostly mild adverse events that occurred at the site of injection. Only one AE (diarrhea), possibly related to immunization, was severe (Grade 3), preventing daily activities. Four weeks after the Ad boost, 15 study subjects were challenged with P. falciparum sporozoites by mosquito bite, and four (27%) were sterilely protected. Antibody responses by ELISA rose after Ad boost but were low (CSP geometric mean titer 210, range 44–817; AMA1 geometric mean micrograms/milliliter 11.9, range 1.5–102) and were not associated with protection. Ex vivo IFN-γ ELISpot responses after Ad boost were modest (CSP geometric mean spot forming cells/million peripheral blood mononuclear cells 86, range 13–408; AMA1 348, range 88–1270) and were highest in three protected subjects. ELISpot responses to AMA1 were significantly associated with protection (p = 0.019). Flow cytometry identified predominant IFN-γ mono-secreting CD8+ T cell responses in three protected subjects. No subjects with high pre-existing anti-Ad5 neutralizing antibodies were protected but the association was not statistically significant. Significance The DNA/Ad regimen provided the highest sterile immunity achieved against malaria following immunization with a gene-based subunit vaccine (27%). Protection was associated with cell-mediated immunity to AMA1, with CSP probably contributing. Substituting a low seroprevalence vector for Ad5 and supplementing CSP/AMA1 with additional antigens may improve protection. Trial Registration ClinicalTrials.govNCT00870987.