Miracle-dz/UniFAR-FTUs huggingface dataset:
Capsid Serotype and Timing of Injection Determines AAV Transduction in the Neonatal Mice Brain

Adeno-associated virus (AAV) mediated gene expression is a powerful tool for gene therapy and preclinical studies. A comprehensive analysis of CNS cell type tropism, expression levels and biodistribution of different capsid serotypes has not yet been undertaken in neonatal rodents. Our previous studies show that intracerebroventricular injection with AAV2/1 on neonatal day P0 results in widespread CNS expression but the biodistribution is limited if injected beyond neonatal day P1. To extend these observations we explored the effect of timing of injection on tropism and biodistribution of six commonly used pseudotyped AAVs delivered in the cerebral ventricles of neonatal mice. We demonstrate that AAV2/8 and 2/9 resulted in the most widespread biodistribution in the brain. Most serotypes showed varying biodistribution depending on the day of injection. Injection on neonatal day P0 resulted in mostly neuronal transduction, whereas administration in later periods of development (24–84 hours postnatal) resulted in more non-neuronal transduction. AAV2/5 showed widespread transduction of astrocytes irrespective of the time of injection. None of the serotypes tested showed any microglial transduction. This study demonstrates that both capsid serotype and timing of injection influence the regional and cell-type distribution of AAV in neonatal rodents, and emphasizes the utility of pseudotyped AAV vectors for translational gene therapy paradigms.
Population Consequences of Environmental Sex Reversal

Abstract: When sex determination in a species is predominantly genetic but environmentally reversible, exposure to (anthropogenic) changes in the environment can lead to shifts in a population's sex ratio. Such scenarios may be common in many fishes and amphibians, yet their ramifications remain largely unexplored. We used a simple model to study the (short‐term) population consequences of environmental sex reversal (ESR). We examined the effects on sex ratios, sex chromosome frequencies, and population growth and persistence after exposure to environmental forces with feminizing or masculinizing tendencies. When environmental feminization was strong, X chromosomes were driven to extinction. Analogously, extinction of normally male‐linked genetic factors (e.g., Y chromosomes) was caused by continuous environmental masculinization. Although moderate feminization was beneficial for population growth in the absence of large viability effects, our results suggest that the consequences of ESR are generally negative in terms of population size and the persistence of sex chromosomes. Extreme sex ratios resulting from high rates of ESR also reduced effective population sizes considerably. This may limit any evolutionary response to the deleterious effects of ESR. Our findings suggest that ESR changes population growth and sex ratios in some counter‐intuitive ways and can change the predominant factor in sex determination from genetic to fully environmental, often within only a few tens of generations. Populations that lose genetic sex determination may quickly go extinct if the environmental forces that cause sex reversal cease.
The twin threshold model: risk-intermediate foraging by rufous hummingbirds, Selasphorus rufus


I developed two versions of the twin threshold model (TTM) to assess risk-sensitive foraging decisions by rufous hummingbirds. The model incorporates energy thresholds for both starvation and reproduction and assesses how three reward distributions with a common mean but different levels of variance interact with these critical thresholds to determine fitness. Fitness, a combination of survival and reproduction, is influenced by both the amount of variance in the distributions and the relative position of the common mean between the thresholds. The model predicts that risk-intermediate foraging is often the optimal policy, and that risk aversion is favoured as the common mean of the distributions approaches the starvation threshold, whereas risk preference is favoured as the common mean approaches the reproduction threshold. Tests with free-living hummingbirds supported these predictions. Hummingbirds were presented with three distributions of nectar rewards that had a common mean but Nil, Moderate or High levels of variance. Birds preferred intermediate levels of variance (Moderate) when presented with all three rewards simultaneously, and became more risk-averse as the mean of the distributions was decreased but more risk-prone as the mean was increased. Birds preferred Nil when it was paired with Moderate or with High, but preferred Moderate in the presence of Nil and High together. This reversal of preference is a violation of regularity, conventionally interpreted as irrational choice behaviour. I provide an alternative version of the TTM demonstrating that violations of regularity can occur when relative instead of absolute evaluation mechanisms are used.
A review of extra-articular prosthetic stabilization of the cranial cruciate ligament-deficient stifle

Summary Extra-articular prosthetic stabilization techniques have been used as a method of stabilization of the cranial cruciate ligament (CrCL)-deficient stifle for decades. During extra-articular prosthetic stabilization, the prosthesis is anchored to the femur and tibia, and tensioned in the attempt to resolve femorotibial instability. The position of the anchor points of the prosthesis is crucial for restoring a normal range of joint motion and mitigating alterations in prosthesis tension during motion. Recently developed techniques offer several innovations with potential advantages such as bone-to-bone fixation, prosthetic materials with better mechanical properties, and improved isometry of the anchor points. Whether these innovations provide clinically superior results to the traditional techniques such as lateral circumfabellar-tibial suture techniques has yet to be determined.
Non-stationary Clustering Bayesian Networks for glaucoma

Glaucoma is a major cause of blindness and its mechanisms are not fully understood. The progression of the disease can be slowed by early diagnosis, but this is a difficult task because available data is typically noisy and has high variability. Several artificial intelligence approaches have been used in this context, although they generally don’t exploit the temporal nature of the data. Here we propose an algorithm for modeling and clustering time series based on Non-stationary Dynamic Bayesian Network models. Our method is tested both on a simulated and a glaucoma dataset, obtaining promising performances and enabling meaningful insight in the field.
An overview on the Influence of Pozzolanic Materials on Properties of Concrete

Concrete is the most normally used material for construction. The worldwide production of cement has significantly increased since 1990.Production of cement results in a lot of environmental toxic waste as it involves the emission of CO2 gas. Complementary cementitious materials are finely ground solid materials that are used to replace a portion of the cement in a concrete mixture. These complementary materials may be naturally occurring, manufactured or natural waste. Various types of pozzolanic materials that improve cement properties have been used in cement industry for a long time. This paper reviews the use of pozzolanic material in concrete. A detailed literature review is carried.
GRB 060605: multi-wavelength analysis of the first GRB observed using integral field spectroscopy

The long and relatively faint gamma-ray burst GRB 060605 detected by Swift/BAT lasted about 20 sec. Its afterglow could be observed with Swift/XRT for nearly 1 day, while Swift/UVOT could detect the afterglow during the first 6 hours after the event. Here, we report on integral field spectroscopy of its afterglow performed with PMAS /PPak mounted at the Calar Alto 3.5 m telescope. In addition, we report on a detailed analysis of XRT and UVOT data and on the results of deep late-time VLT observations that reveal the GRB host galaxy. We find t hat the burst occurred at a redshift of z=3.773, possibly associated with a faint, RC = 26.4± 0.3 host. Based on the optical and X-ray data, we deduce information on the SED of the afterglow, the position of the cooling frequency in the SED, the nature of the circumburst environment, its collimation factor, and its energetics. We find that the GRB fi reball was expanding into a constant-density medium and that the explosion was collimated with a narrow half-opening angle of about 2.4 degrees. The initial Lorentz factor of the fireball was about 250; however, its beaming-corrected energy release in the gamma-ray band was comparably low. The optical, X-ray afterglow, on the other hand, was rather luminous. Finally, we find that the data are consistent withi n the error bars with an achromatic evolution of the afterglo w during the suspected jet break time at about 0.27 days after the burst.
Efficacy of Emotion Regulation for Patients Suffering from Chronic Obstructive Pulmonary Disease

Background: To study the influence values of self-management program intervention on efficacy of emotion regulation for patients suffering from chronic obstructive pulmonary disease (COPD). Methods: Eighty-six diagnosed chronic COPD patients in stable phase in Linzi District People’s Hospital, Zibo Shandong Province, PR China from June 2014 to June 2015 were selected in succession. They were divided into control group and observation group randomly with 43 cases in each group. In control group, conventional out-of-hospital continued nursing mode was used while strengthened self-management program guidance was used in observation group (including seven modules that included disease knowledge, breathing exercises, emotion management, home oxygen therapy, medicine intake technique, healthy life behaviors, and action plans in deterioration stage) to compare their differences of results. Results: For follow-up visits of 6 months, self-management behaviors of patients in two groups had increased, including physical fitness training, cognitive symptom management practice and medical care scores, and the increase range in observation group was more obvious and differences were of statistical significance (P < 0.05); self-efficacy of emotion regulation in two groups is increasing, including positive affect, despondency/distress, anger/irritation and total scores, furthermore, the increase range in observation group is more obvious and differences are of statistical significance (P < 0.05). Conclusion: Self-management program intervention can improve self-management behaviors of COPD patients and it is significant in terms of improving efficacy of emotion regulation and prognosis.
ROADS, PERSONAL MOBILITY & POVERTY: THE CHALLENGE

Drawing on research into rural mobility carried out in Ghana and Malawi and other field experience from Zambia, Kenya and Ghana, data is presented that demonstrates that there is very wide range of use of motor vehicle transport for personal movement. For example, the motorised mobility rate in Kwabre in Ghana was found to be 35 trips per person per year while it was found to be less about one tenth of a trip per person per year in five Districts in Malawi (ie a 350 fold range). The evidence suggests that at current service and fare levels the poorest people can only make use of motor vehicle transport for the long distance transport of crops. In contrast better off rural populations will make extensive use of transport services for a wide variety of social and economic purposes. A tentative income based model of mobility is presented. It is recognised that road investments can be an expensive intervention relative to the incomes of those affected and there may be no guarantee that the poorest members of the community will benefit other than through the direct effects of transport cost savings on the economics of crop marketing. Complementary measures are required in order to increase the personal mobility of the very poor. In order to take a more holistic approach to the alleviation of poverty through transport measures, it is suggested that direct interventions should be made to encourage the provision of transport services at low fare levels for the most disadvantaged rural communities. A possible Private-Public Partnership solution is suggested. (A)
CHARGE syndrome: the phenotypic spectrum of mutations in the CHD7 gene

Background: CHARGE syndrome is a non-random clustering of congenital anomalies including coloboma, heart defects, choanal atresia, retarded growth and development, genital hypoplasia, ear anomalies, and deafness. A consistent feature in CHARGE syndrome is semicircular canal hypoplasia resulting in vestibular areflexia. Other commonly associated congenital anomalies are facial nerve palsy, cleft lip/palate, and tracheo-oesophageal fistula. Specific behavioural problems, including autistic-like behaviour, have been described. The CHD7 gene on chromosome 8q12.1 was recently discovered as a major gene involved in the aetiology of this syndrome. Methods: The coding regions of CHD7 were screened for mutations in 107 index patients with clinical features suggestive of CHARGE syndrome. Clinical data of the mutation positive patients were sampled to study the phenotypic spectrum of mutations in the CHD7 gene. Results: Mutations were identified in 69 patients. Here we describe the clinical features of 47 of these patients, including two sib pairs. Most mutations were unique and were scattered throughout the gene. All patients but one fulfilled the current diagnostic criteria for CHARGE syndrome. No genotype-phenotype correlations were apparent in this cohort, which is best demonstrated by the differences in clinical presentation in sib pairs with identical mutations. Somatic mosaicism was detected in the unaffected mother of a sib pair, supporting the existence of germline mosaicism. Conclusions:CHD7 mutations account for the majority of the cases with CHARGE syndrome, with a broad clinical variability and without an obvious genotype-phenotype correlation. In one case evidence for germline mosaicism was provided.
The Collaborative Software Process

Anecdotal and qualitative evidence from industry indicates that two programmers working side-by-side at one computer, collaborating on the same design, algorithm, code, or test, perform substantially better than the two working alone. Statistical evidence has shown that programmers perform better when following a defined, repeatable process such as the Personal Software Process (PSP). Bringing these two ideas together, the Collaborative Software Process (CSP) has been developed as the first author’s doctoral dissertation. The CSP is a defined, repeatable process for two programmers working collaboratively. The CSP is an extension of the PSP, and it relies upon the foundation of the PSP. This paper discusses empirical evidence that demonstrates that software developers working collaboratively using the CSP produce products with higher quality more quickly than those working individually using the PSP. An experiment was run in 1999 with approximately 40 senior Computer Science students at the University of Utah. All students learned both the CSP and the PSP. Two-thirds of the students worked in two-person collaborative teams using the CSP to develop their programming assignments. The other students worked independently using the PSP to develop the same assignments. The productivity, cycle time, and quality of the two groups have been compared. Empirical results point in favor of the collaborative teams using the CSP.
Randomized placebo-controlled dose-ranging and pharmacodynamics study of roxadustat (FG-4592) to treat anemia in nondialysis-dependent chronic kidney disease (NDD-CKD) patients

Background Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis. This Phase 2a study tested efficacy (Hb response) and safety of roxadustat in anemic nondialysis-dependent chronic kidney disease (NDD-CKD) subjects. Methods NDD-CKD subjects with hemoglobin (Hb) ≤11.0 g/dL were sequentially enrolled into four dose cohorts and randomized to roxadustat or placebo two times weekly (BIW) or three times weekly (TIW) for 4 weeks, in an approximate roxadustat:placebo ratio of 3:1. Efficacy was assessed by (i) mean Hb change (ΔHb) from baseline (BL) and (ii) proportion of Hb responders (ΔHb ≥ 1.0 g/dL). Pharmacodynamic evaluation was performed in a subset of subjects. Safety was evaluated by adverse event frequency/severity. Results Of 116 subjects receiving treatment, 104 completed 4 weeks of dosing and 96 were evaluable for efficacy. BL characteristics for roxadustat and placebo groups were comparable. In roxadustat-treated subjects, Hb levels increased from BL in a dose-related manner in the 0.7, 1.0, 1.5 and 2.0 mg/kg groups. Maximum ΔHb within the first 6 weeks was significantly higher in the 1.5 and 2.0 mg/kg groups than in the placebo subjects. Hb responder rates were dose dependent and ranged from 30% in the 0.7 mg/kg BIW group to 100% in the 2.0 mg/kg BIW and TIW groups versus 13% in placebo. Conclusions Roxadustat transiently and moderately increased endogenous erythropoietin and reduced hepcidin. Adverse events were similar in the roxadustat and placebo groups. Roxadustat produced dose-dependent increases in blood Hb among anemic NDD-CKD patients in a placebo-controlled trial. Clinical Trials Registration Clintrials.gov #NCT00761657.
THE ROLE OF NONAFFILIATED OUTSIDE DIRECTORS IN MONITORING THE FIRM AND THE EFFECT ON SHAREHOLDER WEALTH

The paper addresses the issue of the importance of independent, outside directors in monitoring the affairs of the firm. There is much debate about whether nonaffiliated directors are more supportive of the shareholderinterest hypothesis or the management entrenchment hypothesis. In this study of 1,026 announcements of the appointment of independent outside directors between 1990-1994, the author finds statistically significant cumulative abnormal returns during the two-day window of the announcement. However, the pattern of returns is nonmonotonic in nature in regard to the outside directors already in place. After a critical mass of outside directors is assembled, the addition of another director is likely to produce little or nothing in the way of positive abnormal returns.
Automatic test case generation for UML activity diagrams

The test case generation from design specifications is an important work in testing phase. In this paper, we use UML activity diagrams as design specifications, and present an automatic test case generation approach. The approach first randomly generates abundant test cases for a JAVA program under testing. Then, by running the program with the generated test cases, we can get the corresponding program execution traces. Last, by comparing these traces with the given activity diagram according to the specific coverage criteria, we can get a reduced test case set which meets the test adequacy criteria. The approachcan also be used to check the consistency between the program execution traces and the behavior of UML activity diagrams.
Aspergillosis and the role of mucins in cystic fibrosis

The prevalence of aspergillosis in CF patients has until recently been underestimated, but increasing evidence suggests that it may play an important role in the progression of CF lung disease. In healthy airways, Aspergillus fumigatus can be efficiently removed from the lung by mechanisms such as mucociliary clearance and cough. However, these mechanisms are defective in CF, allowing pathogens such as A. fumigatus to germinate and establish chronic infections within the airways. The precise means by which A. fumigatus contributes to CF lung disease remain largely unclear. As the first point of contact within the lung, and an important component of the innate immune system, it is likely that the mucus barrier plays an important role in this process. Study of the functional interplay between this vital protective barrier, and in particular its principal structural components, the polymeric gel‐forming mucins, and CF pathogens such as A. fumigatus, is at an early stage. A. fumigatus protease activity has been shown to upregulate mucus production by inducing mucin mRNA and protein expression, and A. fumigatus proteases and glycosidases are able to degrade mucins. This may allow A. fumigatus to alter mucus barrier properties to promote fungal colonization of the airways and/or utilize mucins as a nutrient source. Moreover, conidial surface lectin binding to mucin glycans is a key aspect of clearance of Aspergillus from the lung in health but may be an important aspect of colonization, where mucociliary clearance is compromised, as in the CF lung. Here we discuss the nature of the mucus barrier and its mucin components in CF, and how they may be implicated in A. fumigatus infection. Pediatr Pulmonol 2017;52:548–555. © 2016 The Authors. Pediatric Pulmonology. Published by Wiley Periodicals, Inc.
A Scalable Self-organizing Map Algorithm for Textual Classification: A Neural Network Approach to Thesaurus Generation

The rapid proliferation of textual and multimedia online databases, digital libraries, Internet servers, and intranet services has turned researchers' and practitioners' dream of creating an information-rich society into a nightmare of info-gluts. Many researchers believe that turning an info-glut into a useful digital library requires automated techniques for organizing and categorizing large-scale information. This paper presents research in which we sought to develop a scaleable textual classification and categorization system based on the Kohonen's self-organizing feature map (SOM) algorithm. In our paper, we show how self-organization can be used for automatic thesaurus generation. Our proposed data structure and algorithm took advantage of the sparsity of coordinates in the document input vectors and reduced the SOM computational complexity by several order of magnitude. The proposed Scaleable SOM (SSOM) algorithm makes large-scale textual categorization tasks a possibility. Algorithmic intuition and the mathematical foundation of our research are presented in detail. We also describe three benchmarking experiments to examine the algorithm's performance at various scales: classification of electronic meeting comments, Internet homepages, and the Compendex collection.