Miracle-dz/UniFAR-FTUs huggingface dataset:
Cognitive, behavior and academic functioning in adolescent and young adult survivors of childhood acute lymphoblastic leukemia: A report from the Childhood Cancer Survivor Study

Background— Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for neurocognitive deficits that impact adolescence and young adulthood development, and influence educational attainment and future independence. Methods— Cognitive and behavior symptoms were assessed via a standardized parent questionnaire for 1560 adolescent survivors of ALL diagnosed between 1970 and 1999. Significant symptoms (≥ 90 th percentile) and learning problems were compared between survivors and a sibling cohort. Multivariable regression models were used to examine associations with demographic/treatment characteristics. In a subset of survivors with longitudinal data (n=925), associations between adolescent symptoms/problems and adult educational attainment were examined. intensity therapy was associated with greater risk for attention problems at the end of therapy and two years post treatment. (23) Significant correlations among survivors treated with CRT and chemotherapy (IT/IV-MTX) confounds our ability to analyze the independent contribution of chemotherapy only treatment on outcomes in the current analysis. Our data also suggest that the onset of neurologic conditions following diagnosis increased risk for adolescent cognitive, behavior, and learning problems. Prior CCSS studies have identified that CRT is a particularly strong risk factor for first and recurrent strokes in survivors. (24, 25) Vascular damage imposed by CRT has been associated with stroke in childhood cancer survivors. (26) Survivors of childhood ALL with reported stroke at baseline represented a small percentage of our cohort; nonetheless, the strength of this predictor with regard to adolescent outcomes suggests that these survivors should be monitored closely.
THE DEVELOPMENT OF ADAPTIVE DRIVING MODIFICATIONS FOR THE DISABLED VEHICLE: A REVIEW

Restriction and inability to drive a vehicle are known to be the biggest factors limiting mobility, in particular for the person with disabilities. This review identifies the development of adaptive driving modifications and its use for the disabled driver in a comprehensive approach. By far, assistive aids variations have managed to improve the disabled person activity for daily living limitation. Some of the assistive aids reported manage to address the issues on mobility for the person with disability from its use. Even so, it was discovered that some of the modification used resulted with the risk of injuring the user. The discovery from this review is hoped able to help in justifying the necessities in using assistive aids, allowing the person with disabilities to drive independently. Nevertheless, important summaries and the conclusions will be presented based on the gathered data. Keywords: Modification Development, Adaptive Driving, Disabled Vehicle, Usability, Effects
Plasma Homocysteine and Carotid Intima-Media Thickness in Type 1 Diabetes: A Prospective Study

OBJECTIVE— Plasma homocysteine (tHcy) has been positively associated with carotid intima-media thickness (IMT) in non-diabetic populations and in a few cross-sectional studies of diabetic patients. We investigated cross-sectional and prospective associations of a single measure of tHcy with common and internal carotid IMT over a 6-year period in type 1 diabetes. RESEARCH DESIGN AND METHODS— tHcy levels were measured once, in plasma obtained in 1997-1999 from patients (n=599) in the Epidemiology of Diabetes Interventions and Complications (EDIC) study, the observational follow-up of the Diabetes Control and Complications Trial (DCCT). Common and internal carotid IMT were determined twice, in EDIC “Year 6” (1998-2000) and “Year 12” (2004-2006), using B-mode ultra-sonography. RESULTS— After adjustment, plasma tHcy [median (interquartile range): 6.2 (5.1, 7.5) μmol/L] was significantly correlated with age, diastolic blood pressure, renal dysfunction, and smoking (all p<0.05). In an unadjusted model only, increasing quartiles of tHcy correlated with common and internal carotid IMT, again at both EDIC time-points (p<0.01). However, multivariate logistic regression revealed no significant associations between increasing quartiles of tHcy and the 6-year change in common and internal carotid IMT (highest vs. lowest quintile) when adjusted for conventional risk factors. CONCLUSIONS— In a type 1 diabetes cohort from the EDIC study, plasma tHcy measured in samples drawn in 1997-1999 was associated with measures of common and internal carotid IMT measured both one and seven years later, but not with IMT progression between the two time-points. The data do not support routine measurement of tHcy in people with Type 1 diabetes.
The Impacts of Environmental, Social, and Governance Factors on Firm Performance: Panel Study of Malaysian Companies

Purpose - The ESG factor, which consists of environmental, social, and governance factors, represents the non-financial performance of a company. United Nations Principles for Responsible Investment (UN-PRI) invites investors to consider ESG issues when evaluating the performance of any company. Moreover, nowadays the contribution of corporations towards sustainable development is a major concern of investors, creditors, government, and other environmental agencies. Therefore, the purpose of this paper is to examine the impact of ESG factors on the performance of Malaysian public limited companies in terms of profitability, firm value, and cost of capital.Design/methodology/approach – A total of 54 companies are selected from Bloomberg’s ESG database that has complete ESG and financial data from 2010 to 2013. This study conducted panel data regressions such as the pooled OLS, fixed effect, and random effect.Findings - Based on the regression results, there is no significant relationship between individual and combined factors of ESG and firm profitability (i.e., ROE) as well as firm value (i.e., Tobin’s Q). Moreover, individually, none of the factors of ESG is significant with the cost of capital (WACC), but the combined score of ESG positively and significantly influences the cost of capital (WACC) of a company.Practical implications - As this is a new study on Malaysia, the findings of this study will be useful to investors, SRI analysts, policy makers, and other related agencies.Originality/value – To the best of the authors’ knowledge, this study is among the first empirical study to examine the impact of ESG factors on the performance of Malaysian public limited companies in terms of profitability, firm value, and cost of capital.
BJRD16468 1..9

1KATRIJN L MMICHIELSEN, MSc, 2IGNACE VERGOTE, MD, PhD, 1RAPHAËLA DRESEN, MD, PhD, 1KATYAOP DE BEECK, MD, 1RAGNA VANSLEMBROUCK, MD, 2,3FRÉDÉRIC AMANT, MD, PhD, 2KARIN LEUNEN, MD, PhD, 1PHILIPPE MOERMAN, MD, PhD, 4STEFFEN FIEUWS, PhD, 1FREDERIK DE KEYZER, MSc and 1VINCENT VANDECAVEYE, MD, PhD Department of Imaging and Pathology, University Hospitals Leuven, Leuven, Belgium Department of Obstetrics and Gynaecology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium Belgium and Center Gynaecological Oncology Amsterdam (CGOA), Antoni van Leeuwenhoek, Amsterdam, Netherlands Department of Public Health and Primary Care, University Hospitals Leuven, Leuven, Belgium
Increasing the conformational entropy of the Ω -loop lid domain in PEPCK impairs catalysis and decreases catalytic fidelity

Many studies have shown that the dynamic motions of individual protein segments can play an important role in enzyme function. Recent structural studies on the gluconeogenic enzyme PEPCK demonstrate that PEPCK contains a 10-residue Ω -loop domain that acts as an active site lid. Based upon these structural studies we have previously proposed a model for the mechanism of PEPCK catalysis in which the conformation of this mobile lid-domain is energetically coupled to ligand binding resulting in the closed conformation of the lid, necessary for correct substrate positioning, becoming more energetically favorable as ligands associate with the enzyme. Here we test this model by the introduction of a point mutation (A467G) into the center of the Ω -loop lid that is designed to increase the entropic penalty for lid closure. Structural and kinetic characterization of this mutant enzyme demonstrates that the mutation has decreased the favorability of the enzyme adapting the closed lid conformation. As a consequence of this shift in the equilibrium defining the conformation of the active site lid, the enzyme’s ability to stabilize the reaction intermediate is reduced resulting in catalytic defect. This stabilization is initially surprising, as the lid domain makes no direct contacts with the enolate intermediate formed during the reaction. Furthermore, during the conversion of OAA to PEP, the destabilization of the lid closed conformation results in the reaction becoming decoupled as the enolate intermediate is protonated rather than phosphorylated resulting in the formation of pyruvate. Taken together, the structural and kinetic characterization of A467G-PEPCK support our model of the role of the active site lid in catalytic function and demonstrate that the shift in the lowest energy conformation between open and closed lid states is a function of the free energy available to the enzyme through ligand binding and the entropic penalty for ordering of the ten-residue Ω -loop lid domain.
An empirical assessment of the operational performance through internal benchmarking: a case of a global logistics firm

Abstract This article solves an operational performance measurement problem of a global logistics firm through an internal benchmarking tool. The intended impact is to enable logistics firms to form a deeper understanding of their own internal processes and metrics. The methodology of this in-depth action research involves a sequential approach with a series of interviews, questionnaire-based surveys, operations data collated through observations and process mapping yielding real-world data. A series of statistical tests are conducted to analyse the collated data. Strategic priorities of the firm are integrated with the firm’s operational performance to ascertain the effective performance by considering both the tangible and intangible measures. The outcomes inform both practitioners and academics how the firm could improve its freight forwarding business’s profitability by ensuring that its operations meet the prioritised criteria. The ‘best practice’ derived from internal benchmarking forms an intermediate step towards external benchmarking. The outcomes facilitate investigating the current business strategy, the standard operating procedures and the scope of improving those.
Triage options for HPV-positive women in cervical cancer screening

Human papillomavirus (HPV) infection is a necessary cause of cervical cancer, the first step in a carcinogenic process that can take decades (1). Thus, a negative result from a sensitive HPV test provides sufficient reassurance that cervical cancer will not develop over a long period of time and allows extending screening intervals for at least 3–5 years. These findings have led to the incorporation of HPV testing into screening programs in several countries. However, it is less clear how to manage women who test HPV-positive since most HPV infections will resolve after months to a few years. It is important to identify women with a prevalent precancer who need treatment while avoiding unnecessary referral of women who have only transient infections. HPV-positive women. HPV16 and HPV18 predict a much higher risk of precancer compared to other carcinogenic HPV types over a long period of time (4). HPV16/18 genotyping is objective, and is directly provided as part of some HPV assays. In contrast, p16 is a marker of HPV oncogene activity that works independent of carcinogenic type and indicates early stages of transformation (5). The p16 assay requires preparation of a cytologic slide and microscopic evaluation for p16 staining.
High-throughput fluorescence microscopy using multi-frame motion deblurring

: We demonstrate multi-frame motion deblurring for gigapixel wide-ﬁeld ﬂuorescence microscopy using fast slide scanning with coded illumination. Our method illuminates the sample with multiple pulses within each exposure, in order to introduce structured motion blur. By deconvolving this known motion sequence from the set of acquired measurements, we recover the object with up to 10 × higher SNR than when illuminated with a single pulse (strobed illumination), while performing acquisition at 5 × higher frame-rate than a comparable stop-and-stare method. Our coded illumination sequence is optimized to maximize the reconstruction SNR. We also derive a framework for determining when coded illumination is SNR-optimal in terms of system parameters such as source illuminance, noise, and motion stage speciﬁcations. This helps system designers to choose the ideal technique for high-throughput microscopy of very large samples.
Novel mechanism for hyper-reflexia and spasticity

We established that hyper-reflexia is delayed after spinal transection in the adult rat, and that passive exercise could normalize low frequency-dependent depression of the H-reflex. We were also able to show that such passive exercise will normalize hyper-reflexia in patients with spinal cord injury (SCI). Recent results demonstrate that spinal transection results in changes in the neuronal gap junction protein connexin 36 below the level of the lesion. Moreover, a drug known to increase electrical coupling was found to normalize hyper-reflexia in the absence of passive exercise, suggesting that changes in electrical coupling may be involved in hyper-reflexia. We also present results showing that a measure of spasticity, the stretch reflex, is rendered abnormal by transection and normalized by the same drug. These data suggest that electrical coupling may be dysregulated in SCI, leading to some of the symptoms observed. A novel therapy for hyperreflexia and spasticity may require modulation of electrical coupling.
Mitochondrial Oxidative Stress in Temporal Lobe Epilepsy

Mitochondrial oxidative stress and dysfunction are contributing factors to various neurological disorders. Recently, there has been increasing evidence supporting the association between mitochondrial oxidative stress and epilepsy. Although certain inherited epilepsies are associated with mitochondrial dysfunction, little is known about its role in acquired epilepsies such as temporal lobe epilepsy. Mitochondrial oxidative stress and dysfunction are emerging as key factors that not only result from seizures, but may also contribute to epileptogenesis. The occurrence of epilepsy increases with age, and mitochondrial oxidative stress is a leading mechanism of aging and age-related degenerative disease, suggesting a further involvement of mitochondrial dysfunction in seizure generation. Mitochondria have critical cellular functions that effect neuronal excitability including production of adenosine triphosphate (ATP), fatty acid oxidation, control of apoptosis and necrosis, regulation of amino acid cycling, neurotransmitter biosynthesis, and regulation of cytosolic Ca 2+ homeostasis. Mitochondria are the primary site of reactive oxygen species (ROS) production making them uniquely vulnerable to oxidative stress and damage which can further affect cellular macromolecule function, the ability of the electron transport chain to produce ATP, antioxidant defenses, mitochondrial DNA stability, and synaptic glutamate homeostasis. Oxidative damage to one or more of these cellular targets may affect neuronal excitability and increase seizure susceptibility. The specific targeting of mitochondrial oxidative stress, dysfunction, and bioenergetics with pharmacological and non-pharmacological treatments may be a novel avenue for attenuating epileptogenesis and seizure initiation.
QTL Mapping of Acute Functional Tolerance in the LXS Recombinant Inbred Strains

, Abstract Background— We previously reported that acute functional tolerance (AFT) to the hypnotic effects of alcohol was significantly correlated to drinking in the dark (DID) in the LXS RI panel, but only in mice that had been pretreated with alcohol. Here we have conducted QTL mapping for AFT. DNA sequencing of the progenitor ILS and ISS strains and microarray analyses were also conducted to identify candidate genes and functional correlates. Methods— LXS mice were given either saline or alcohol (5 g/kg) on day one and then tested for loss of righting reflex (LORR) AFT on day two. QTLs were mapped using standard procedures. Two microarray analyses from brain were conducted: 1) naïve LXS mice and 2) an alcohol treatment time course in the ILS and ISS. The full genomes of the ILS and ISS were sequenced to a depth of ~30×. Results— A significant QTL for AFT in the alcohol pretreatment group mapped to distal chromosome 4; numerous suggestive QTLs were also mapped. Preference drinking and DID have previously been mapped to the chromosome 4 locus. The credible interval of the significant chromosome 4 QTL spanned 23 Mb and included 716 annotated genes of which 150 had at least one non-synonymous SNP or small indel that differed between the ILS and ISS; expression of 48 of the genes was cis -regulated. Enrichment analysis indicated broad functional categories underlying AFT including proteolysis, transcription regulation, chromatin modification, protein kinase activity, apoptosis, and others.
Behavioral and functional evidence of mGlu2/3 and mGlu5 metabotropic glutamate receptor dysregulation in cocaine-escalated rats: Factor in the transition to dependence

Background— Rats with extended daily cocaine access show escalating cocaine self-administration and behavioral signs of dependence. Regulation of glutamatergic transmission by metabotropic glutamate receptors (mGluR) has emerged as a mechanism in the addictive actions of drugs of abuse. We examined here whether neuroadaptive dysregulation of mGluR function is a factor in escalating cocaine self-administration. Methods— Rats with 1 h daily cocaine access (short access, ShA) vs . 6 h access (long access, LgA) were tested for differences in the effects of the mGluR2/3 agonist LY379268 and the mGluR5 antagonist MTEP on cocaine-reinforced progressive-ratio (PR) responding and differences in expression levels and functional activity of mGluR2/3 and mGluR5. Results— The LgA groups showed higher PR breakpoints than ShA groups. LY379268 (0-3 mg/ kg, s.c.) dose-dependently lowered breakpoints in the LgA group but reduced breakpoints only at 3 mg/kg in the ShA group. Consistent with this behavioral effect, functional mGluR2/3 activity was significantly elevated following LgA cocaine exposure. MTEP (0-3 mg/kg, i.p.) reduced breakpoints in the ShA group only. LgA cocaine exposure was associated with decreased mGluR5 expression, accompanied by reduced functional mGluR5 activity in the nucleus accumbens. A downward trend developed in mGluR5 protein expression in the medial prefrontal cortex and hippocampus. Conclusion— Functional upregulation of mGluR2/3 and downregulation of mGluR5 are likely factors in the transition to cocaine dependence. The differential behavioral effects of LY379268 and MTEP in rats with a history of long access to cocaine have implications for the treatment target potential of mGluR2/3 and mGluR5.
Collaborative Research Project Networks

Many businesses seeking enhanced innovation have corporate research teams that engage in collaborative research projects (CRPs), with external entities such as universities, public organizations, or customers. Anecdotal evidence, however, suggests mixed outcomes of CRPs in terms of corporate research impact, which implies successful transfer of novel knowledge generated within CRPs to company-internal business networks to develop radically innovative products. We use the multiple regression quadratic assignment procedure (MRQAP) and meta-analysis to analyze six CRP networks. Our findings indicate that the network’s relational characteristics (tie strength) and structural characteristics (network range) are important determinants of knowledge transfer at the fuzzy front end of innovation.
A study on the effect of main process parameters of rotary ultrasonic machining for drilling BK7 glass

BK7 glass is an important engineering material with extensive applications in high-quality and precision transmissive optical components. However, BK7 glass is considered to be a difficult-to-cut material due to its high brittleness and nonconductivity. This article presents the use of rotary ultrasonic machining process for drilling holes in BK7 glass. No previous reports have been found in the literature to experimentally investigate the response of the BK7 glass to rotary ultrasonic drilling. The experimental investigations take into account the effect of the key rotary ultrasonic machining input parameters including the ultrasonic power, spindle speed and feed rate on the output responses of cutting force, exit chipping, surface roughness, hole cylindricity and overcut errors, and surface integrity. The results show that the input parameters within the current ranges can significantly affect the quality of the drilled holes. Moreover, the selected level of any input parameter has the ability to significantly affect the influence of the other input parameters on the output responses. Through proper selection of input parameters, holes could be drilled in BK7 glass with less fractured topography, low surface roughness (1.32 µm), low exit chipping size (0.85), and very low cylindricity (3 µm) and overcut (73.6 µm) errors.
Murine T Cells By Drake M. LaFace,* MikaelVestberg,*YoungYang,*

A series of human CD8 transgenic (hCD8 Tg) mice with differential expression in the thymus and periphery were produced to investigate CD8 coreceptor regulation of repertoire selection and T cell responses. Expression of hCD8 markedly enhanced responses to both HLA class I molecules and hybrid A2/K b molecules providing functional evidence for a second interaction site, outside of the ct3 domain, which is essential for optimal coreceptor function. Peripheral T cell expression o fhCD8 was sufficient to augment responsiveness to HLA class I, as hCD8 Tg mice which lacked thymic expression responded as well as mice expressing hCD8 in the thymus and periphery. Both murine CD8 + and CD4 + T cells expressing hCD8 transgenes exhibited markedly enhanced responses to foreign HLA class I, revealing the ability of T cell receptor repertoires selected on either murine class I or class II to recognize human class I major histocompatibility complex (MHC). In contrast to recognition of foreign class I, thymic expression of hCD8 transgenes was absolutely required to enhance recognition of antigenic peptide restricted by self-HLA class I. Thus, our studies revealed disparate requirements for CD8 coreceptor expression in the thymus for selection of a T cell repertoire responsive to foreign MHC and to antigenic peptides bound to self-MHC, providing a novel demonstration of positive selection that is dependent on human CD8.