Miracle-dz/UniFAR-FTUs huggingface dataset:
Global analysis of double-strand break processing reveals in vivo properties of the helicase-nuclease complex AddAB

In bacteria, double-strand break (DSB) repair via homologous recombination is thought to be initiated through the bi-directional degradation and resection of DNA ends by a helicase-nuclease complex such as AddAB. The activity of AddAB has been well-studied in vitro, with translocation speeds between 400–2000 bp/s on linear DNA suggesting that a large section of DNA around a break site is processed for repair. However, the translocation rate and activity of AddAB in vivo is not known, and how AddAB is regulated to prevent excessive DNA degradation around a break site is unclear. To examine the functions and mechanistic regulation of AddAB inside bacterial cells, we developed a next-generation sequencing-based approach to assay DNA processing after a site-specific DSB was introduced on the chromosome of Caulobacter crescentus. Using this assay we determined the in vivo rates of DSB processing by AddAB and found that putative chi sites attenuate processing in a RecA-dependent manner. This RecA-mediated regulation of AddAB prevents the excessive loss of DNA around a break site, limiting the effects of DSB processing on transcription. In sum, our results, taken together with prior studies, support a mechanism for regulating AddAB that couples two key events of DSB repair–the attenuation of DNA-end processing and the initiation of homology search by RecA–thereby helping to ensure that genomic integrity is maintained during DSB repair.
Students as partners as the future of student engagement

Introduction In this opinion piece I offer a vision for student engagement as students as partners a mind-set predicated on students and academics (faculty in North America) collaborating in meaningful partnerships that becomes a cultural norm within universities. In the context of 21st century universities that seek to graduate students with complex skillsets that extend far beyond knowledge acquisition, such a cultureshift is particularly relevant. The importance of developing language in fostering this transition from student engagement to students as partners is discussed. Students as partners offer a view of student engagement that is a joint endeavour to shape and influence university teaching and learning. The language of students as partners deliberately emphasises the relational and social elements of mutual learning. Engaging students and academics (faculty in North America) in collaborative partnerships is process-orientated, reflecting the dynamic and on-going nature of learning that should characterise higher education. This is the vision of student engagement in higher education for which I argue.
HEALTH-LED GROWTH SINCE 1800

This paper argues that the marked reduction in the burden of parasitic and infectious diseases (PID) together with improved nutrition over the past two centuries in today's advanced countries has resulted in markedly improved physiological capital and cognitive skills and, consequently, in productivity advances. Using a unique annual dataset covering the period 1800–2011 for 21 OECD (Organisation for Economic Co-operation and Development) countries, it is found that health improvements can account for approximately a third of the productivity advances in the OECD countries since 1865, and that these improvements have been influential for enhancement in education, savings, innovations, life expectancy, and democracy.
Minimum 6-year Followup of Highly Cross-linked Polyethylene in THA

To reduce wear rates and particulate debris, highly cross-linked polyethylene has been in use in total hip arthroplasty for 8 years. We designed this followup study to primarily determine the total penetration rate of the femoral head and the steady-state wear rate of cross-linked polyethylene in patients undergoing primary total hip arthroplasty. We retrospectively reviewed data from 182 patients (200 hips) with a minimum 6-year followup (mean, 6.9 years; range, 6-8 years) and an average age of 60.2 years at surgery. The average Harris hip score, University of California-Los Angeles activity score, and WOMAC score were 91.1, 6.3, and 11.3, respectively. Radiographic evaluation showed no evidence of loosening or osteolytic lesions around the cup or stem. No revisions were performed for polyethylene wear or liner fracture. The average steady-state wear rate was −0.002 ± 0.01 mm per year and −0.026 ± 0.13 mm per year for 28-mm and 32-mm head sizes, respectively. We observed no correlation between the total wear rate and femoral head size, brand of polyethylene, age, gender, primary diagnosis, mode of fixation, surgical approach, University of California-Los Angeles activity score, Harris hip score, or WOMAC. Highly cross-linked polyethylene liners are associated with excellent midterm clinical, radiographic, and wear results in this group of patients.Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
Establishment of an indicator cell system for hepatitis C virus

Although a cell culture system for HCV JFH‐1 strain has been developed, no robust cell culture system for serum‐derived HCV is available. In this study, we have established systems capable of monitoring infection with JFH‐1 virus based on specific reporter gene expression through proteolysis of chimeric transcription factors by HCV NS3/4A protease. We utilized a transcriptional factor Gal4‐TBP that synergistically enhances transcription of the GAL4UAS and HIV‐1 LTR tandem promoter with the Tat protein. We constructed chimeric Tat and Gal4‐TBP transcription factors containing the HCV NS3/4A cleavage sequence of a mitochondria‐resident IPS‐1, but not those of the HCV polyprotein, and manipulated them to localize in the ER. Upon infection with JFH‐1 virus, the transcription factors were efficiently cleaved by HCV protease, migrated into the nucleus and activated the reporter gene under the tandem promoter. Upon infection with JFH‐1 virus, the Huh7OK1/TG‐Luc cell line carrying the transcription factors and a luciferase gene under the promoter expressed luciferase in a dose‐dependent manner in close correlation with HCV RNA replication. Huh7OK1/TG‐LNGFR cells carrying the transcription factors and a cDNA of human low affinity nerve growth factor receptor under the promoter were selectively concentrated by immunomagnetic cell sorting upon infection with JFH‐1 virus. These results indicate that the chimeric constructs bearing the ER‐resident IPS‐1 sequence are specifically recognized and efficiently cleaved by HCV protease and are harnessed for detection of HCV replication and for recovery of HCV‐infected cells. This strategy may be applicable for the establishment of cell culture systems for the isolation of serum‐derived HCV.
The role of antigen presenting cells at distinct anatomic sites: they accelerate and they slow down allergies

It has been repeatedly demonstrated that allergic reactions are driven by the continuous flow of antigen uptake and presentation processes, which are perpetuated mainly by dendritic cells (DC). The ability of allergens to cause allergic inflammation is contingent upon the presence of an immunological milieu and microenvironment that either privileges Th2 responses or prohibits these reactions by the induction of contraregulatory anti‐inflammatory activities of the immune system. In the light of recent developments it appears that DC have to manage two opposing tasks: on the one hand they can favor pro‐inflammatory reactions and actively induce a T‐cell response, yet on the other hand they serve an important function as ‘silencers’ in the immune system by sending out anti‐inflammatory, tolerance inducing signals. This unique capacity of DC has opened several exciting possibilities for a role of DC in both – accelerating and slowing down allergic reactions. It is therefore a challenge to understand in which way DC subtypes located at distinct anatomic sites with frequent allergen exposure, such as the skin, the nasal mucosa, the respiratory tree or the mucosa of the intestinal tract can have an impact on mechanisms involved in tolerance induction or effective immunity.
The Choice between Public versus Private Debt and Political Uncertainty

In this paper, we study the effect of political uncertainty on the choice of debt source. Specifically, we examine whether national elections, which aggravates information asymmetry leads to a high degree of reliance on bank debt. Our results show that firms substitute away from public debt toward bank debt during election years. This finding is robust to a battery of sensitivity tests. We also find that the positive relationship between national elections and bank debt ratio is more pronounced in opaque firms and financially constrained firms, respectively. Furthermore, we find that the positive association between national elections and the degree of reliance on bank debt is more profound in firms from countries with stronger (weaker) shareholder rights (labor protection and creditor rights). Finally, we document that firms tend to use more bank debt when elections are closely contested and in countries with stronger constraints on the government.
Celecoxib for the prevention of colorectal adenomatous polyps.

BACKGROUND Overexpression of cyclooxygenase 2 (COX-2) has been associated with colorectal adenomatous polyps and cancer, prompting researchers to propose its inhibition as a chemopreventive intervention. METHODS The Prevention of Colorectal Sporadic Adenomatous Polyps trial was a randomized, placebo-controlled, double-blind study of the COX-2 inhibitor celecoxib given daily in a single 400-mg dose. At 107 centers in 32 countries, we randomly assigned 1561 subjects who had had adenomas removed before enrollment to receive celecoxib (933 subjects) or placebo (628 subjects) daily, after stratification according to the use or nonuse of low-dose aspirin. The primary outcome was detection of adenomas at either year 1 or year 3 by colonoscopy and was compared among the groups with the use of the Mantel-Cox test. RESULTS Colonoscopies were performed at year 1 on 88.7 percent of the subjects who had undergone randomization and at year 3 on 79.2 percent. Of the 557 subjects in the placebo group and the 840 subjects in the celecoxib group who were included in the efficacy analysis, 264 and 270, respectively, were found to have at least one adenoma at year 1, at year 3, or both. The cumulative rate of adenomas detected through year 3 was 33.6 percent in the celecoxib group and 49.3 percent in the placebo group (relative risk, 0.64; 95 percent confidence interval, 0.56 to 0.75; P<0.001). The cumulative rate of advanced adenomas detected through year 3 was 5.3 percent in the celecoxib group and 10.4 percent in the placebo group (relative risk, 0.49; 95 percent confidence interval, 0.33 to 0.73; P<0.001). Adjudicated serious cardiovascular events occurred in 2.5 percent of subjects in the celecoxib group and 1.9 percent of those in the placebo group (relative risk, 1.30; 95 percent confidence interval, 0.65 to 2.62). CONCLUSIONS The use of 400 mg of celecoxib once daily significantly reduced the occurrence of colorectal adenomas within three years after polypectomy. (ClinicalTrials.gov number, NCT00141193 [ClinicalTrials.gov].).
Winning the competition for supplier resources: The role of preferential resource allocation from suppliers

Purpose This paper examines the competition between buying firms for the supplier’s competitive resources. The purpose of this paper is to examine how indirect capabilities – the ability to access external resources – can help in obtaining preferential resource allocation from suppliers. Design/methodology/approach Partial least squares structural equation modeling is used to analyze data of 163 buying firms that assess preferential resource allocation from suppliers. Findings Two indirect capabilities (a buying firm’s selection capability and relational capability) positively influence the firm’s competitive advantage. These relations are significantly mediated by preferential resource allocation of suppliers. The impact of preferential resource allocation appeared stronger for manufacturing firms than for service firms. Research limitations/implications This study’s data set represents the buyer’s assessment of suppliers’ resource allocation. Future research should aim for dyadic data for further validation. In addition, due to sample size limitations, this study’s data does not allow sector segmentation. A larger study that provides insights into segmentation is suggested for future research. Practical implications The results inform managers about the relevance of the competition for supplier resources with rival firms that share suppliers, and the influence of this competition on firm competitiveness. Managers should not only focus on the supplier itself, but also on the capabilities of the supply chain management (SCM) function to recognize and integrate the supplier resources. Originality/value This study adds to the extended resource-based view literature by integrating the notion of supplier resource competition. In addition, the study shows the importance of indirect capabilities for obtaining preferential resource allocation from suppliers. Finally, the authors show the importance of separating between service and manufacturing when examining SCM practices.
Innate Sex Bias of Staphylococcus aureus Skin Infection Is Driven by α-Hemolysin

Numerous studies have reported sex bias in infectious diseases, with bias direction dependent on pathogen and site of infection. Staphylococcus aureus is the most common cause of skin and soft tissue infections (SSTIs), yet sex bias in susceptibility to S. aureus SSTI has not been described. A search of electronic health records revealed an odds ratio of 2.4 for S. aureus SSTI in males versus females. To investigate the physiological basis of this bias, we compared outcomes between male and female mice in a model of S. aureus dermonecrosis. Consistent with the epidemiological data, female mice were better protected against SSTI, with reduced dermonecrosis followed later by increased bacterial clearance. Protection in females was disrupted by ovariectomy and restored by short-term estrogen administration. Importantly, this sex bias was mediated by a sex-specific response to the S. aureus–secreted virulence factor α-hemolysin (Hla). Infection with wild-type S. aureus suppressed inflammatory cytokine production in the skin of female, but not male, mice when compared with infection with an isogenic hla deletion mutant. This differential response was conserved following injection with Hla alone, demonstrating a direct response to Hla independent of bacterial burden. Additionally, neutrophils, essential for clearing S. aureus, demonstrated sex-specific S. aureus bactericidal capacity ex vivo. This work suggests that sex-specific skin innate responsiveness to Hla and neutrophil bactericidal capacity play important roles in limiting S. aureus SSTI in females. Understanding the molecular mechanisms controlling this sex bias may reveal novel targets to promote host innate defense against S. aureus skin infection.
Problems and Solutions in Laboratory Testing for Hemophilia

A diagnosis of hemophilia A or hemophilia B begins with clinical assessment of the patient and is facilitated by laboratory testing. The influence of the latter on a diagnosis of hemophilia A or hemophilia B is clear-a diagnosis cannot be made without laboratory confirmation of a deficiency of factor FVIII (FVIII) or factor IX (FIX), respectively. Moreover, the degree of hemophilia severity is specifically characterized by laboratory test results. In turn, patient management, including choice and application of therapies, is influenced by the diagnosis, as well as by identification of respective disease severity. An incorrect diagnosis may lead to inappropriate management and unnecessary therapy, and thus to adverse outcomes. Moreover, identification of factor inhibitors in hemophilia will lead to additional and differential treatments, and incorrect identification of inhibitors or inhibitor levels may also lead to inappropriate management. Problems in hemophilia diagnosis or inhibitor detection can occur at any stage in the clinical diagnosis/laboratory interface, from the "pre-preanalytical" to "preanalytical" to "analytical" to "postanalytical" to "post-postanalytical. " This report outlines the various problems in laboratory testing for hemophilia and provides various strategies or solutions to overcome these challenges. Although some outlined solutions are specific to the potential errors related to hemophilia, others are general in nature and can be applied to other areas of laboratory hemostasis. Key to improvement in this area is adoption of best practice by all involved, including clinicians, phlebotomists, and laboratories. Also key is the recognition that such errors may occur, and thus that clinicians should assess laboratory test results in the context of their patient's clinical history and follow-up any potential errors, thus avoid misdiagnoses, by requesting repeat testing on a fresh sample.
Relationship between Selected Physical Characteristics and Functional Capacity in the Anterior Cruciate Ligament-Insufficient Athlete.

Traditionally, clinicians have utilized various physical characteristics as criteria to assess the functional status of anterior cruciate ligament (ACL)-insufficient athletes without validating the efficacy of such assessments. The primary purposes of this study were to determine the relationship between traditionally used physical characteristics and functional capacity of individuals with an ACL insufficiency and to compare functional results of two groups of ACL-insufficient athletes. Forty-one subjects were tested for strength and power on an isokinetic device, anthropometric characteristics, and function using three functional performance tests (FPT). Results revealed that conventional physical characteristics correlated poorly (r = .01 to r = .42) with the functional tests. Additionally, athletes who were able to return to preinjury levels of activity performed significantly (p < 0.05) better on the FPT than those who were unable to return to preinjury activities. Based on the results of this study, use of such traditional physical characteristics for predicting function in the ACL-insufficient athlete may be inappropriate, and the functional performance tests designed for this study appear to be the most valuable assessment of the athlete's functional capacity. J Orthop Sports Phys Ther 1992;16(4):174-181.
Highly Efficient Neural Conversion of Human Pluripotent Stem Cells in Adherent and Animal‐Free Conditions

Neural differentiation of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) can produce a valuable and robust source of human neural cell subtypes, holding great promise for the study of neurogenesis and development, and for treating neurological diseases. However, current hESCs and hiPSCs neural differentiation protocols require either animal factors or embryoid body formation, which decreases efficiency and yield, and strongly limits medical applications. Here we develop a simple, animal‐free protocol for neural conversion of both hESCs and hiPSCs in adherent culture conditions. A simple medium formula including insulin induces the direct conversion of >98% of hESCs and hiPSCs into expandable, transplantable, and functional neural progenitors with neural rosette characteristics. Further differentiation of neural progenitors into dopaminergic and spinal motoneurons as well as astrocytes and oligodendrocytes indicates that these neural progenitors retain responsiveness to instructive cues revealing the robust applicability of the protocol in the treatment of different neurodegenerative diseases. The fact that this protocol includes animal‐free medium and human extracellular matrix components avoiding embryoid bodies makes this protocol suitable for the use in clinic. Stem Cells Translational Medicine 2017;6:1217–1226
EEG Databases for Emotion Recognition

Emotion recognition from Electroencephalogram (EEG) rapidly gains interest from research community. Two affective EEG databases are presented in this paper. Two experiments are conducted to set up the databases. Audio and visual stimuli are used to evoke emotions during the experiments. The stimuli are selected from IADS and IAPS databases.14 subjects participated in each experiment. Emotiv EEG device is used for the data recording. The EEG data are rated by the participants with arousal, valence, and dominance levels. The correlation between powers of different EEG bands and the affective ratings is studied. The results agree with the literature findings and analyses of benchmark DEAP database that proves the reliability of the two databases. Similar brain patterns of emotions are obtained between the established databases and the benchmark database. A SVM-based emotion recognition algorithm is proposed and applied to both databases and the benchmark database. Use of a Fractal Dimension feature in combination with statistical and Higher Order Crossings (HOC) features gives us results with the best accuracy. Up to 8 emotions can be recognized. The accuracy is consistent between the established databases and the benchmark database.
Access to palliative care services in hospital: a matter of being in the right hospital. Hospital charts study in a Canadian city

Access to palliative care (PC) is a major need worldwide. Using hospital charts of all patients who died over one year (April 2008–March 2009) in two mid-sized hospitals of a large Canadian city, similar in size and function and operated by the same administrative group, this study examined which patients who could benefit from PC services actually received these services and which ones did not, and compared their care characteristics. A significantly lower proportion (29%) of patients dying in hospital 2 (without a PC unit and reliant on a visiting PC team) was referred to PC services as compared to in hospital 1 (with a PC unit; 68%). This lower referral likelihood was found for all patient groups, even among cancer patients, and remained after controlling for patient mix. Referral was strongly associated with having cancer and younger age. Referral to PC thus seems to depend, at least in part, on the coincidence of being admitted to the right hospital. This finding suggests that establishing PC units or a team of committed PC providers in every hospital could increase referral rates and equity of access to PC services. The relatively lower access for older and non-cancer patients and technology use in hospital PC services require further attention.
The Dynamic Effects of Endogenous Technological Advancement on Carbon Emissions in China

This research utilises an improved dynamic panel model to investigate the environmental effect of different technological resources in the big three regions of China, i.e. the eastern, western and central regions, from 1990 to 2014. The results show that research and development (R&D) capital stock contributes the most to the reduction of carbon emissions, whether at the national or provincial level, but physical capital stock results in an evident increment of carbon emissions in the three regions, especially in eastern China. Human capital stock, on the other hand, causes some mitigation in eastern and central China, except for western China. The spillover of international technology stock from foreign direct investment has less effect on carbon emission abatement than does import trade, though there are distinct regional differences.