Miracle-dz/UniFAR-FTUs huggingface dataset:
Understanding large scale sequencing datasets through changes to protein folding.

The expansion of high-quality, low-cost sequencing has created an enormous opportunity to understand how genetic variants alter cellular behaviour in disease. The high diversity of mutations observed has however drawn a spotlight onto the need for predictive modelling of mutational effects on phenotype from variants of uncertain significance. This is particularly important in the clinic due to the potential value in guiding clinical diagnosis and patient treatment. Recent computational modelling has highlighted the importance of mutation induced protein misfolding as a common mechanism for loss of protein or domain function, aided by developments in methods that make large computational screens tractable. Here we review recent applications of this approach to different genes, and how they have enabled and supported subsequent studies. We further discuss developments in the approach and the role for the approach in light of increasingly high throughput experimental approaches.
A comparison of CMOS circuit techniques: differential cascode voltage switch logic versus conventional logic

Differential cascode voltage switch (DCVS) logic is a CMOS circuit technique that has potential advantages over conventional NAND/NOR logic in terms of circuit delay, layout density, power dissipation, and logic flexibility. A detailed comparison of DCVS logic and conventional logic is carried out by simulation, using SPICE, of the performance of full adders designed using the different circuit techniques. The parameters compared are: input gate capacitance, number of transistors required, propagation delay time, and average power dissipation. In the static case, DCVS appears to be superior to full CMOS in regards to input capacitance and device count but inferior in regards to power dissipation. The speeds of the two technologies are similar. In the dynamic case, DCVS can be faster than more conventional CMOS dynamic logic, but only at the expense of increased device count and power dissipation.
CloudAV: N-Version Antivirus in the Network Cloud

Antivirus software is one of the most widely used tools for detecting and stopping malicious and unwanted files. However, the long term effectiveness of traditional host-based antivirus is questionable. Antivirus software fails to detect many modern threats and its increasing complexity has resulted in vulnerabilities that are being exploited by malware. This paper advocates a new model for malware detection on end hosts based on providing antivirus as an in-cloud network service. This model enables identification of malicious and unwanted software by multiple, heterogeneous detection engines in parallel, a technique we term 'N-version protection'. This approach provides several important benefits including better detection of malicious software, enhanced forensics capabilities, retrospective detection, and improved deployability and management. To explore this idea we construct and deploy a production quality in-cloud antivirus system called CloudAV. CloudAV includes a lightweight, cross-platform host agent and a network service with ten antivirus engines and two behavioral detection engines. We evaluate the performance, scalability, and efficacy of the system using data from a real-world deployment lasting more than six months and a database of 7220 malware samples covering a one year period. Using this dataset we find that CloudAV provides 35% better detection coverage against recent threats compared to a single antivirus engine and a 98% detection rate across the full dataset. We show that the average length of time to detect new threats by an antivirus engine is 48 days and that retrospective detection can greatly minimize the impact of this delay. Finally, we relate two case studies demonstrating how the forensics capabilities of CloudAV were used by operators during the deployment.
Effectiveness of Traditional Chinese Acupuncture versus Sham Acupuncture: a Systematic Review

ABSTRACT Objective: to identify and synthesize the evidence from randomized clinical trials that tested the effectiveness of traditional Chinese acupuncture in relation to sham acupuncture for the treatment of hot flashes in menopausal women with breast cancer. Method: systematic review guided by the recommendations of the Cochrane Collaboration. Citations were searched in the following databases: MEDLINE via PubMed, Web of Science, CENTRAL, CINAHL, and LILACS. A combination of the following keywords was used: breast neoplasm, acupuncture, acupuncture therapy, acupuncture points, placebos, sham treatment, hot flashes, hot flushes, menopause, climacteric, and vasomotor symptoms. Results: a total of 272 studies were identified, five of which were selected and analyzed. Slight superiority of traditional acupuncture compared with sham acupuncture was observed; however, there were no strong statistical associations. Conclusions: the evidence gathered was not sufficient to affirm the effectiveness of traditional acupuncture compared with sham acupuncture.
Fuzzy rules extraction directly from numerical data for function approximation

In our previous work (1993) we developed a method for extracting fuzzy rules directly from numerical input-output data for pattern classification. In this paper we extend the method to function approximation. For function approximation, first, the universe of discourse of an output variable is divided into multiple intervals, and each interval is treated as a class. Then the same as for pattern classification, using the input data for each interval, fuzzy rules are recursively defined by activation hyperboxes which show the existence region of the data for the interval and inhibition hyperboxes which inhibit the existence region of data for that interval. The approximation accuracy of the fuzzy system derived by this method is empirically studied using an operation learning application of a water purification plant. Additionally, we compare the approximation performance of the fuzzy system with the function approximation approach based on neural networks. >
Surface Diffusion of Cellulases and Their Isolated Binding Domains on Cellulose*

The surface diffusion rate of bacterial cellulases from Cellulomonas fimi on cellulose was quantified using fluorescence recovery after photobleaching analysis. Studies were performed on an exo-β-1–4-glycanase (Cex), an endo-β-1–4-glucanase (CenA), and their respective isolated cellulose-binding domains (CBDs). Although these cellulose-binding domains bind irreversibly to microcrystalline cellulose, greater than 70% of bound molecules are mobile on the cellulose surface. Surface diffusion rates are dependent on surface coverage and range from a low of 2 × 10−11 to a maximum of 1.2 × 10−10 cm2/s. The fraction of mobile molecules increases only slightly with increasing fractional surface coverage density. Results demonstrate that the packing of C. fimicellulases and their isolated binding domains onto the cellulose surface is a dynamic process. This suggests that the exclusion of potential CBD binding sites on the cellulose due to steric effects of neighboring bound CBDs may not fully explain the apparent negative cooperativity exhibited in CBD adsorption isotherms. Comparison with the kinetics of cellulase hydrolysis of crystalline substrate suggests that surface diffusion rates do not limit cellulase activity.
Management of Neonates With Suspected or Proven Early-Onset Bacterial Sepsis

With improved obstetrical management and evidence-based use of intrapartum antimicrobial therapy, early-onset neonatal sepsis is becoming less frequent. However, early-onset sepsis remains one of the most common causes of neonatal morbidity and mortality in the preterm population. The identification of neonates at risk for early-onset sepsis is frequently based on a constellation of perinatal risk factors that are neither sensitive nor specific. Furthermore, diagnostic tests for neonatal sepsis have a poor positive predictive accuracy. As a result, clinicians often treat well-appearing infants for extended periods of time, even when bacterial cultures are negative. The optimal treatment of infants with suspected early-onset sepsis is broad-spectrum antimicrobial agents (ampicillin and an aminoglycoside). Once a pathogen is identified, antimicrobial therapy should be narrowed (unless synergism is needed). Recent data suggest an association between prolonged empirical treatment of preterm infants (≥5 days) with broad-spectrum antibiotics and higher risks of late onset sepsis, necrotizing enterocolitis, and mortality. To reduce these risks, antimicrobial therapy should be discontinued at 48 hours in clinical situations in which the probability of sepsis is low. The purpose of this clinical report is to provide a practical and, when possible, evidence-based approach to the management of infants with suspected or proven early-onset sepsis.
Object-based morphometry of the cerebral cortex

Most of the approaches dedicated to automatic morphometry rely on a point-by-point strategy based on warping each brain toward a reference coordinate system. In this paper, we describe an alternative object-based strategy dedicated to the cortex. This strategy relies on an artificial neuroanatomist performing automatic recognition of the main cortical sulci and parcellation of the cortical surface into gyral patches. A set of shape descriptors, which can be compared across subjects, is then attached to the sulcus and gyrus related objects segmented by this process. The framework is used to perform a study of 142 brains of the International Consortium for Brain Mapping (ICBM) database. This study reveals some correlates of handedness on the size of the sulci located in motor areas, which was not detected previously using standard voxel based morphometry.
Prolonged and Exclusive Breastfeeding Reduces the Risk of Infectious Diseases in Infancy

OBJECTIVE: To examine the associations of duration of exclusive breastfeeding with infections in the upper respiratory (URTI), lower respiratory (LRTI), and gastrointestinal tracts (GI) in infancy. METHODS: This study was embedded in the Generation R Study, a population-based prospective cohort study from fetal life onward in the Netherlands. Rates of breastfeeding during the first 6 months (never; partial for <4 months, not thereafter; partial for 4–6 months; exclusive for 4 months, not thereafter; exclusive for 4 months, partial thereafter; and exclusive for 6 months) and doctor-attended infections in the URTI, LRTI, and GI until the age of 12 months were assessed by questionnaires and available for 4164 subjects. RESULTS: Compared with never-breastfed infants, those who were breastfed exclusively until the age of 4 months and partially thereafter had lower risks of infections in the URTI, LRTI, and GI until the age of 6 months (adjusted odds ratio [aOR]: 0.65 [95% confidence interval (CI): 0.51–0.83]; aOR: 0.50 [CI: 0.32–0.79]; and aOR: 0.41 [CI: 0.26–0.64], respectively) and of LRTI infections between the ages of 7 and 12 months (aOR: 0.46 [CI: 0.31–0.69]). Similar tendencies were observed for infants who were exclusively breastfed for 6 months or longer. Partial breastfeeding, even for 6 months, did not result in significantly lower risks of these infections. CONCLUSIONS: Exclusive breastfeeding until the age of 4 months and partially thereafter was associated with a significant reduction of respiratory and gastrointestinal morbidity in infants. Our findings support health-policy strategies to promote exclusive breastfeeding for at least 4 months, but preferably 6 months, in industrialized countries.
Life Satisfaction and Relative Income: Perceptions and Evidence

Using a unique dataset we study both the actual and self-perceived relationship between subjective well-being and income comparisons against a wide range of potential comparison groups, enabling us to investigate a broader range of questions than in previous studies. In questions inserted into a 2008 module of the German-Socio Economic Panel Study we ask subjects to report (a) how their income compares to various groups, such a co-workers, friends, and neighbours, and (b) how important these income comparisons are to them. We find substantial gender differences, with income comparisons being much better predictors of subjective well-being in men than in women. Generic (same-gender) comparisons are the most important, followed by within profession comparisons. Once generic and within-profession comparisons are controlled for, income relative to neighbours has a negative coefficient, implying that living in a high-income neighbourhood increases happiness. The perceived importance of income comparisons is found to be uncorrelated with its actual relationship to subjective well-being, suggesting that people are unconscious of its real impact. Subjects who judge comparisons to be important are, however, significantly less happy than subjects who see income comparisons as unimportant. Finally, the marginal effect of relative income on subjective well-being does not depend on whether a subject is below or above the reference group income.
Entanglement Breaking Channels

This paper studies the class of stochastic maps, or channels, for which (I⊗Φ)(Γ) is always separable (even for entangled Γ). Such maps are called entanglement breaking, and can always be written in the form Φ(ρ)=∑kRkTrFkρ where each Rk is a density matrix and Fk>0. If, in addition, Φ is trace-preserving, the {Fk} must form a positive operator valued measure (POVM). Some special classes of these maps are considered and other characterizations given. Since the set of entanglement-breaking trace-preserving maps is convex, it can be characterized by its extreme points. The only extreme points of the set of completely positive trace preserving maps which are also entanglement breaking are those known as classical-quantum or CQ. However, for d≥3, the set of entanglement breaking maps has additional extreme points which are not extreme CQ maps.
Performance Evaluation of AMD RVI Hardware Assist

For the majority of common workloads, performance in a virtualized environment is close to that in a native environment. Virtualization does create some overheads, however. These come from the virtualization of the CPU, the MMU (Memory Management Unit), and the I/O devices. In some of their recent x86 processors AMD and Intel have begun to provide hardware extensions to help bridge this performance gap. In 2006, both vendors introduced their first-generation hardware support for x86 virtualization with AMD-VirtualizationTM (AMD-VTM) and Intel® VT-x technologies. Recently AMD introduced its second generation of hardware support that incorporates MMU virtualization, called Rapid Virtualization Indexing (RVI).
A Serendipitous Survey for Variability amongst the Mas- Sive Stellar Population of Westerlund 1 a Serendipitous Survey for Variability amongst the Massive Stellar Population of Westerlund 1 ⋆

A serendipitous survey for variability amongst the massive stellar population of Westerlund 1. Astronomy and Astrophysics, 514 A87. For guidance on citations see FAQs. Copyright and Moral Rights for the articles on this site are retained by the individual authors and/or other copyright owners. For more information on Open Research Online's data policy on reuse of materials please consult the policies page. ABSTRACT Aims. Massive stars are known to demonstrate significant spectroscopic and photometric variability over a wide range of timescales. However the physical mechanisms driving this behaviour remain poorly understood. Westerlund 1 presents an ideal laboratory for studying these processes in a rich, coeval population of post-main sequence stars and we present a pathfinding study aimed at charac-terising their variability. Methods. To do this we utilised the large body of spectroscopic and photometric data that has accumulated for Wd1 during the past decade of intensive studies, supplemented with the sparser historical observations extending back to the early 1960s. Results. Despite the heterogeneous nature of this dataset, we were able to identify both spectroscopic and photometric variability amongst every class of evolved massive star present within Wd 1. Spectroscopic variability attributable to both wind asphericity and photospheric pulsations was present amongst both the hot and cool hypergiants and the former, also with the Wolf Rayets. Given the limitations imposed by the data, we were unable to determine the physical origin of the wind structure inferred for the OB supergiants, noting that it was present in both single pulsating and binary stars. In contrast we suspect that the inhomogineities in the winds of the Wolf Rayets are driven by binary interactions and, conversely, by pulsations in at least one of the cool hypergiants. Photospheric pulsations were found for stars ranging from spectral types as early as O9 I through to the mid F Ia + yellow hypergiants-with a possible dependence on the luminosity class amongst the hot supergiants. The spectroscopically variable red supergiants (M2-5 Ia) are also potential pulsators but require further observations to confirm this hypothesis. Given these findings it was therefore rather surprising that, with the exception of W243, no evidence of the characteristic excursions of both luminous blue variables and yellow hypergiants was found. Nevertheless, future determination of the amplitude and periodicity of these pulsations as a function of temperature, lu-minosity and evolutionary state holds out the tantalising possibility of constraining the nature of the physical mechanisms driving …
Prevalence and correlates of diabetes in South asian indians in the United States: findings from the metabolic syndrome and atherosclerosis in South asians living in america study and the multi-ethnic study of atherosclerosis.

BACKGROUND Individuals from South Asia have high diabetes prevalence despite low body weight. We compared the prevalence of diabetes among South Asian Indians with other U.S. ethnic groups and explored correlates of diabetes. METHODS This was a cross-sectional study of 150 South Asian Indians (ages 45-79) in California, using similar methods to the Multi-Ethnic Study of Atherosclerosis (MESA). Type 2 diabetes was classified by fasting plasma glucose (FPG) >or=126 mg/dL, 2-h postchallenge glucose >or=200 mg/dL, or use of hypoglycemic medication. RESULTS A total of 29% of Asian Indians had diabetes, 37% had prediabetes, and 34% had normal glucose tolerance. After full adjustment for covariates, Indians still had significantly higher odds of diabetes compared to whites and Latinos, but not significantly different from African Americans and Chinese Americans in MESA: Indians [odds ratio (OR), 1.0], whites [OR, 0.29; 95% confidence interval (CI), 0.17-0.49], Latinos (OR, 0.59; CI, 0.34-1.00) African Americans (OR, 0.77; CI 0.45-1.32), Chinese Americans (OR, 0.78, CI, 0.45-1.32). Variables associated with prediabetes or diabetes among Indians included hypertension, fatty liver, visceral adiposity, microalbuminuria, carotid intima media thickness, and stronger traditional Indian beliefs. CONCLUSIONS Indian immigrants may be more likely to have diabetes than other U.S. ethnic groups, and cultural factors may play a role, suggesting that this is a promising area of research.
Temporal upregulation of prodynorphin mRNA in the primate striatum after cocaine self‐administration

Several human and rat studies suggest that the striatal dynorphin system is important for neuroadaptation following cocaine exposure. In the current study, prodynorphin (PDYN) mRNA expression was examined in monkeys at initial and chronic phases of cocaine self‐administration. Adult Rhesus monkeys were trained to self‐administer food (banana flavoured pellets) or cocaine (0.03 or 0.3 mg/kg per injection) on a fixed interval 3‐min schedule for 5 or 100 sessions. Each session ended after 30 reinforcers were delivered. The PDYN mRNA expression was analysed in the precommissural striatum using in situ hybridization histochemistry. We found a specific activation of PDYN mRNA expression in the limbic‐innervated patch/striosome compartment of the dorsal caudate and dorsal putamen during the initial (i.e. 5 day) phase of the high dose cocaine self‐administration. After 100 days of the high dose exposure, the patch/striosome compartment remained activated, but an increase in PDYN mRNA levels was also evident in the sensorimotor‐connected matrix compartment of the caudate. Neither self‐administration phase resulted in significant changes in the corresponding striatal regions of the low dose cocaine‐exposed primates. Moreover, cocaine self‐administration failed to alter the PDYN mRNA expression in high‐ or low‐expressing PDYN cell populations in the nucleus accumbens during any condition studied. These results demonstrate the vulnerability of the dorsal striatum (in particular the caudate) to neuroadaptations following long‐term high dose cocaine self‐administration. In addition, the temporal nature of the changes in PDYN gene expression within the striatal compartments could reflect a change in drug responsivity that occurs during the transition to drug dependence.
The Association of Alternate VEGF Ligands with Resistance to Anti-VEGF Therapy in Metastatic Colorectal Cancer

Background Circulating angiogenic factors are altered in patients with mCRC receiving bevacizumab. Evaluation of alterations in levels of VEGF ligands may provide insights into possible resistance mechanisms. Methods PlGF, VEGF-A, VEGF-C, and VEGF-D were measured from two cohorts of patients. Sequential plasma samples were obtained from a discovery cohort of 42 patients treated with chemotherapy and bevacizumab. A validation cohort included plasma samples from a cross-sectional of 403 patients prior to chemotherapy, or after progression on a regimen with or without bevacizumab. Results In the discovery cohort, VEGF-C was increased prior to progression and at progression (+49% and +95%, respectively, p<0.01), consistent with previously reported elevations in PlGF. Levels of VEGF-D were increased (+23%) at progression (p=0.05). In the validation cohort, samples obtained from patients after progression on a regimen with bevacizumab had higher levels of PlGF and VEGF-D (+43% and +6%, p=0.02, p=0.01, respectively) compared to untreated patients, but failed to validate the increase in VEGF-C seen in the first cohort. Patients who progressed on chemotherapy with bevacizumab had significantly elevated levels of PlGF (+88%) but not VEGF-C and VEGF-D compared to patients treated with chemotherapy alone. Elevations of PlGF and VEGF-D appeared transient and returned to baseline with a half-life of 6 weeks. Conclusions Increases in PlGF and VEGF-D were observed after progression on chemotherapy with bevacizumab. These changes appear to be reversible after discontinuing therapy. These ligands are associated with resistance to bevacizumab-containing chemotherapy in mCRC, but causation remains to be established.
Impact of Geometrical Structures on the Output of Neuronal Models: A Theoretical and Numerical Analysis

What is the difference between the efferent spike train of a neuron with a large soma versus that of a neuron with a small soma? We propose an analytical method called the decoupling approach to tackle the problem. Two limiting casesthe soma is much smaller than the dendrite or vica versaare theoretically investigated. For both the two-compartment integrate-and-fire model and Pinsky-Rinzel model, we show, both theoretically and numerically, that the smaller the soma is, the faster and the more irregularly the neuron fires. We further conclude, in terms of numerical simulations, that cells falling in between the two limiting cases form a continuum with respect to their firing properties (mean firing time and coefficient of variation of inter-spike intervals).