Miracle-dz/UniFAR-FTUs huggingface dataset:
Linkage strategies for genetically complex traits. III. The effect of marker polymorphism on analysis of affected relative pairs.

The results from the second paper of this series are reexamined for markers that are not completely polymorphic. A maximum lod score (MLS) criterion is defined for affected relative pairs. The expected MLS (EMLS) is calculated as a function of the marker polymorphic information content (PIC) for various values of lambda R (relative risk ratio) and different relative types by using simulations. An m-allele model with equal allele frequencies is employed. The EMLS is calculated for two sampling strategies: scheme 1, which uses pairs only, and scheme 2, which also includes additional informative relatives. For scheme 2, the percent of the maximum achievable EMLS (i.e., for a marker with a PIC of 1.0) is approximately equal to the marker PIC value for all relative types. For scheme 1, the EMLS is greatly diminished unless PIC is high, especially for distant relatives. For example, scheme 1 is not cost-effective for sibs unless PIC greater than . 7; for second- and third-degree relatives, PIC must be greater than . 85. Therefore, in general, it will be worthwhile to type additional relatives in linkage studies using affected pairs. The comparative value of sibs versus distant relatives depends on lambda R, recombination theta, and PIC. For large lambda R and PIC values, distant relatives are preferred. Alternatively, for smaller lambda R and PIC values, sibs are best.
Validation according to OIE criteria of a monoclonal, recombinant p26–based, serologic competitive enzyme-linked immunosorbent assay as screening method in surveillance programs for the detection of Equine infectious anemia virus antibodies

The Italian National Reference Center for equine infectious anemia (CRAIE; Rome, Italy) developed and validated a monoclonal, recombinant p26–based competitive enzyme-linked immunosorbent assay (cELISA) for the detection of EIA virus antibodies employing the 2010 criteria of the World Organization for Animal Health (OIE). The following parameters were evaluated: cutoff values, repeatability, reproducibility, concordance, analytical sensitivity (Se), absolute analytical specificity (Sp), and diagnostic Se and Sp. Positive and negative predictive values were also defined in relation to the estimated prevalence. When the cELISA was used as a screening test for 96,468 samples in the Italian EIA surveillance program, 17% more EIA cases were detected than by the agar gel immunodiffusion test, and the apparent diagnostic Sp estimated from these samples was 99.8%, which was more than the diagnostic Sp (80.2%) estimated from validation. The high Se and Sp of the cELISA confirm its fit for purpose as a screening test.
Fast and accurate side‐chain topology and energy refinement (FASTER) as a new method for protein structure optimization

We have developed an original method for global optimization of protein side‐chain conformations, called the Fast and Accurate Side‐Chain Topology and Energy Refinement (FASTER) method. The method operates by systematically overcoming local minima of increasing order. Comparison of the FASTER results with those of the dead‐end elimination (DEE) algorithm showed that both methods produce nearly identical results, but the FASTER algorithm is 100–1000 times faster than the DEE method and scales in a stable and favorable way as a function of protein size. We also show that low‐order local minima may be almost as accurate as the global minimum when evaluated against experimentally determined structures. In addition, the new algorithm provides significant information about the conformational flexibility of individual side‐chains. We observed that strictly rigid side‐chains are concentrated mainly in the core of the protein, whereas highly flexible side‐chains are found almost exclusively among solvent‐oriented residues. Proteins 2002;48:31–43. © 2002 Wiley‐Liss, Inc.
Promotion and Wages in Mid-Career: Gender, Unionism, and Sector

This paper considers the role of gender in the promotion process and the impact of promotion on wages and wage growth, using data from the National Longitudinal Survey of Youth (NLSY79). Its focus is upon mid-career promotion and wages, thereby complementing extant studies of the NLSY79 that relate to differences between men and women at an earlier stage in their careers. The paper is further differentiated from these studies and the wider promotions literature in considering the role of unionism and the public sector. It is reported that mid-career females are more likely than males to be promoted in the private sector (and no less likely in the public sector); that wages are increasing in promotion, and the effect is generally higher for females; and that female wage growth from contemporaneous promotion is almost as high as that for males in the private sector and much higher in the public sector. These rather positive results for females represent in most cases an improvement over the early-career findings but in mid-career the mediating influence of unionism is more negative, and not just for females.
Treatment of malignant gliomas with TGF-β2 antisense oligonucleotides

Antisense oligodeoxynucleotides (AS-ODNs) have been widely used to determine gene function, validate drug targets and as novel therapeutics for human diseases. In this review, we describe the development of AS-ODNs, including their modifications, pharmacokinetics and toxicity in animal models and humans, and their preclinical and clinical development in the therapy of human high-grade gliomas. The most advanced AS-ODN for the therapy of high-grade gliomas is a phosphorothioate-modified AS-ODN, AP 12009 (trabedersen), which targets mRNA encoding TGF-β2. AP 12009 is administered intratumorally using convection-enhanced delivery. A series of Phase I and II clinical trials have evaluated the toxicity profile and optimal dose of the substance. A randomized, controlled international Phase III study was initiated in March 2009 and will compare trabedersen 10 µM versus conventional alkylating chemotherapy in patients with recurrent or refractory anaplastic astrocytoma after standard radio- and chemotherapy.
Children mix direct and indirect speech: evidence from pronoun comprehension

ABSTRACT This study investigates children's acquisition of the distinction between direct speech (Elephant said, “I get the football”) and indirect speech (Elephant said that he gets the football), by measuring children's interpretation of first, second, and third person pronouns. Based on evidence from various linguistic sources, we hypothesize that the direct–indirect distinction is acquired relatively late. We also predict more mistakes for third person pronouns compared to first and second person pronouns. We tested 136 Dutch-speaking children between four and twelve in a referent selection task and found that children interpret pronouns in direct speech predominantly as in indirect speech, supporting our hypothesis about a late acquisition of the direct–indirect distinction. In addition, we found differences between I, you, and he that deviate from a simple first and second vs. third person split. We discuss our results in the light of cross-linguistic findings of direct–indirect mixing.
“The First Day He Kicked Shoes at Me, the Last Day He Brought Me a Picture of Himself”: Investigating the Practicum Experiences of Pre-service Teachers

The purpose of this study was to describe the ways in which the experiences gained during practica influence the developing self-efficacy of Canadian pre-service teachers for teaching in inclusive classrooms. Questionnaires were issued to participants in teacher education programs at 11 universities across Canada, and the data were subjected to content analysis. Several themes that emerged from the participant responses were found to be influential in pre-service teachers’ feelings of efficacy, with behaviour management having the greatest influence, regardless of whether participants felt successful or challenged. Academic outcomes, relationships with students, and other school adults as resources were also identified as themes influencing pre-service teachers’ feelings of success and challenge in practica. The data revealed attitudes and beliefs about inclusion and the impact these may have on teacher efficacy. Several elements can positively influence teacher efficacy including the ability to identify and utilize instructional and personnel resources, the ability to form supportive professional relationships with other school adults, and the ability to recognize achievement as it pertains to the individual rather than prescribed norms. As beliefs about self-efficacy are informed by enactive mastery experiences, vicarious experiences, physiological factors, and verbal persuasion, teacher preparation programs can foster teacher efficacy by encouraging the development of positive attitudes and equipping teachers with the skills they need.
Molecular Cloning and Characterization of Marmoset Aldehyde Oxidase

Common marmosets (Callithrix jacchus), New World monkeys, are a promising primate model for preclinical drug metabolism studies because of the similarities of cytochrome P450 (P450) enzyme function to those of humans. Despite an increasing number of drug candidates catalyzed by non-P450 enzymes, drug metabolizing enzymes other than P450s have been hardly identified or characterized in marmosets. In this study, we identified aldehyde oxidase (AOX) 1 gene by marmoset genome analysis. AOX1 cDNA was cloned from marmoset livers by reverse transcription-polymerase chain reaction. Deduced amino acid sequences of AOX1 cDNA showed high sequence identities (92–93%) with primate AOX1s. Phylogenetic analysis showed that marmoset AOX1 was closely clustered with primate AOX1s, unlike nonprimate animal model AOX1s of pig, rabbit, rat, and mouse used in drug metabolism. The tissue expression analyses by real-time reverse-transcription polymerase chain reaction and immunoblotting showed that marmoset AOX1 mRNA and protein were abundantly expressed in livers, similar to cynomolgus monkeys and humans. Marmoset AOX1 heterologously expressed in Escherichia coli catalyzed the oxidation of carbazeran and phthalazine, typical AOX1 substrates, similar to cynomolgus monkey and human AOX1s. Human and marmoset AOX1 effectively catalyzed phthalazine oxidation when assessed with Michaelis-Menten kinetics, but cynomolgus monkey AOX1 catalyzed this reaction with cooperative kinetics with high capacity. These results indicated that tissue distribution and enzymatic function of AOX1 enzyme is similar between marmosets and humans, suggesting that marmosets are a suitable primate model for AOX-dependent drug metabolism in preclinical studies.
A Cost-Efficient NVM-Based Journaling Scheme for File Systems

Modern file systems employ journaling techniques to guarantee data consistency in case of unexpected system crashes or power failures. However, journaling file systems usually suffer from performance decrease due to the extra journal writes. Moreover, the emerging non-volatile memory technologies (NVMs) have the potential capability to improve the performance of journaling file systems by being deployed as the journaling storage devices. However, traditional journaling techniques, which are designed for hard disks, fail to perform efficiently in NVMs. In order to address this problem, we propose an NVM-based journaling scheme, called NJS. The basic idea behind NJS is to reduce the journaling overhead of traditional file systems while fully exploiting the byte-accessibility characteristic, and alleviating the relatively slow write and endurance limitation of NVM. Our NJS consists of three major contributions: (i) In order to minimize the amount of journal writes, NJS only needs to write the metadata of file systems and over-write data to NVM as write-ahead logging, thus alleviating the relatively slow write and endurance limitation of NVM. (ii) We propose a novel journaling update scheme in which the journaling data blocks can be updated in the byte-granularity based on the difference of the old and new versions of journal blocks, thus fully exploiting the unique byte-accessibility characteristic of NVM. (iii) NJS includes a garbage collection mechanism that absorbs the redundant journal updates, and actively delays the checkpointing to the file system. Evaluation results show the efficiency and efficacy of NJS. For example, compared with original Ext4 with a ramdisk-based journaling device, the throughput improvement of Ext4 with our NJS is up to 137.1%.
Genomic removal of a therapeutic mini-dystrophin gene from adult mice elicits a Duchenne muscular dystrophy-like phenotype.

Duchenne muscular dystrophy (DMD) is caused by dystrophin deficiency. A fundamental question in DMD pathogenesis and dystrophin gene therapy is whether muscle health depends on continuous dystrophin expression throughout the life. Published data suggest that transient dystrophin expression in early life might offer permanent protection. To study the consequences of adulthood dystrophin loss, we generated two strains of floxed mini-dystrophin transgenic mice on the dystrophin-null background. Muscle diseases were prevented in skeletal muscle of the YL238 strain and the heart of the SJ13 strain by selective expression of a therapeutic mini-dystrophin gene in skeletal muscle and heart, respectively. The mini-dystrophin gene was removed from the tibialis anterior (TA) muscle of 8-month-old YL238 mice and the heart of 7-month-old SJ13 mice using an adeno-associated virus serotype-9 Cre recombinase vector (AAV.CBA.Cre). At 12 and 15 months after AAV.CBA. Cre injection, mini-dystrophin expression was reduced by ∼87% in the TA muscle of YL238 mice and ∼64% in the heart of SJ13 mice. Mini-dystrophin reduction caused muscle atrophy, degeneration and force loss in the TA muscle of YL238 mice and significantly compromised left ventricular hemodynamics in SJ13 mice. Our results suggest that persistent dystrophin expression is essential for continuous muscle and heart protection.
The functional role of human right hippocampal/parahippocampal theta rhythm in environmental encoding during virtual spatial navigation

Low frequency theta band oscillations (4–8 Hz) are thought to provide a timing mechanism for hippocampal place cell firing and to mediate the formation of spatial memory. In rodents, hippocampal theta has been shown to play an important role in encoding a new environment during spatial navigation, but a similar functional role of hippocampal theta in humans has not been firmly established. To investigate this question, we recorded healthy participants’ brain responses with a 160‐channel whole‐head MEG system as they performed two training sets of a virtual Morris water maze task. Environment layouts (except for platform locations) of the two sets were kept constant to measure theta activity during spatial learning in new and familiar environments. In line with previous findings, left hippocampal/parahippocampal theta showed more activation navigating to a hidden platform relative to random swimming. Consistent with our hypothesis, right hippocampal/parahippocampal theta was stronger during the first training set compared to the second one. Notably, theta in this region during the first training set correlated with spatial navigation performance across individuals in both training sets. These results strongly argue for the functional importance of right hippocampal theta in initial encoding of configural properties of an environment during spatial navigation. Our findings provide important evidence that right hippocampal/parahippocampal theta activity is associated with environmental encoding in the human brain. Hum Brain Mapp 38:1347–1361, 2017. © 2016 Wiley Periodicals, Inc.
Evaluation of pelvic contractility in ureteropelvic junction obstruction: an experimental study.

BACKGROUND/PURPOSE Ureteropelvic junction (UPJ) obstruction causes adaptive and/or compensatory alterations in renal pelvic contractility. As these alterations directly affect the outcome after renal damage, definition of these alterations is of the utmost importance from a clinical point of view. Thus, an experimental study was designed to determine the alterations of renal pelvic contractility in response to partial and complete UPJ obstruction. METHODS Fifteen adult female New Zealand white rabbits were randomly assigned into three groups (each containing 5 rabbits) according to the degree of unilateral UPJ obstruction. Group I: sham operation was performed and served as the control group; group II: partial UPJ obstruction was made; group III: complete UPJ obstruction was made. The animals in groups I and II were sacrificed after three weeks and the rabbits in group III were sacrificed after two weeks. Muscle strips from the renal pelvis were prepared. Spontaneous mechanical activity and contractile responses to phenylephrine (PE), serotonin (5-HT), and KCl were recorded isometrically and compared in all groups. RESULTS Both the frequency and amplitude of spontaneous mechanical contractions were significantly (p < 0.05) increased in partial (group II) and complete UPJ obstruction (group III) groups. PE and 5-HT-induced tonic contractions, which were more prominent in the complete and partial obstruction groups when compared with the control group (p < 0.05). PE and 5-HT also increased the frequency of spontaneous contractions in both partial and complete obstruction groups. KCl induced long lasting tonic contractions in the control muscles. The duration of contraction to reach the maximum amplitude was shortened in the obstruction groups and the amplitudes of the contractions were significantly augmented when compared to control preparations. CONCLUSION UPJ obstruction alters the contractile properties of renal pelvis smooth muscle. Increased frequency of spontaneous mechanical activity suggests that pacemaker cells of the renal pelvis change their activities in response to UPJ obstruction. Increase in tonic contraction amplitudes in response to PE and 5-HT suggests an increased sensitivity of smooth muscle cells to these agents. Potentiation of the contractile response to KCl suggests that adaptive changes take place at the level of excitation-contraction coupling in the smooth muscle of the renal pelvis following UPJ obstruction.
Outcomes of resection of giant hepatocellular carcinoma in a tertiary institution: does size matter?

BACKGROUND The surgical management of giant hepatocellular carcinoma (G-HCC), or HCC of ≥10 cm in diameter, remains controversial. The aim of this study was to compare the outcomes of surgical resection of, respectively, G-HCC and small HCC (S-HCC), or HCC measuring <10 cm. METHODS A retrospective review of all patients (n = 86) diagnosed with HCC and submitted to resection in a tertiary hospital during the period from January 2007 to June 2012 was conducted. Overall survival (OS), recurrence rates and perioperative mortality at 30 days were compared between patients with, respectively, G-HCC and S-HCC. Prognostic factors for OS were analysed. RESULTS The sample included 23 patients with G-HCC (26.7%) and 63 with S-HCC (73.3%) based on histological tumour size. Patient demographics and comorbidities were comparable. Median OS was 39.0 months in patients with G-HCC and 65.0 months in patients with S-HCC (P = 0.213). Although size did not affect OS in this cohort, the presence of satellite lesions [hazard ratio (HR) 3.70, P = 0.012] and perioperative blood transfusion (HR 2.85, P = 0.015) were negative predictors for OS. CONCLUSIONS Surgical resection of G-HCC provides OS comparable with that after resection of S-HCC.
Adaptive period estimation of a class of periodic random processes

The problem of period uncertainty when evaluating spectrum estimates for wide sense cyclostationary processes is addressed in this paper. In particular, the extended Kalman filter (EKF) and a parallel bank of Kalman filters are investigated as different methods for adaptive estimation of a time-varying period. An example is given concerning an AR(1) process and a number of time-varying periods are adaptively tracked for different periodic functions. Convergence characteristics are also assessed. Finally, a combined detection-estimation approach is also investigated.
Genetic fingerprinting and identification of differentially expressed genes in isolates of Leishmania donovani from Indian patients of post-kala-azar dermal leishmaniasis

SUMMARY Post-kala-azar dermal leishmaniasis (PKDL) is an unusual dermatosis that develops as a sequel in 5–15% of cured cases of kala-azar (KA) after months or years of treatment in India. Molecular differences are reported to exist between the KA and PKDL isolates which may underlie the diversity in clinical manifestations of the disease. Here, arbitrary primed-PCR (AP-PCR) has been used for genetic fingerprinting of parasite isolates from dermal lesions of PKDL patients (n=14) and compared with bone-marrow derived parasites from KA patients (n=3). All isolates showed an identical AP-PCR pattern with 4 arbitrary primers. Further, AP-PCR was exploited to identify the stage regulated genes of the parasite. Six polymorphic fragments were identified in PKDL in comparison with KA isolates, and were subjected to Northern blot analysis. Five polymorphic fragments represented transcribed sequences; 4 out of 5 drew differential expression in pro- and amastigote stages, although the expression was comparable between PKDL and KA isolates. The study led to the identification of genes, which exhibit stage-regulated expression in Leishmania donovani derived from PKDL or KA patients, including a putative phosphodiesterase, DEAD box RNA helicase, iron superoxide dismutase b (fesodb) and a hypothetical protein. Demonstration of transcripts of DEAD box RNA helicase in PKDL and KA diseased tissues implicates its role in disease pathogenesis.
Virtual Spherical Gaussian Lights for Real‐time Glossy Indirect Illumination

Virtual point lights (VPLs) are well established for real‐time global illumination. However, this method suffers from spiky artifacts and flickering caused by singularities of VPLs, highly glossy materials, high‐frequency textures, and discontinuous geometries. To avoid these artifacts, this paper introduces a virtual spherical Gaussian light (VSGL) which roughly represents a set of VPLs. For a VSGL, the total radiant intensity and positional distribution of VPLs are approximated using spherical Gaussians and a Gaussian distribution, respectively. Since this approximation can be computed using summations of VPL parameters, VSGLs can be dynamically generated using mipmapped reflective shadow maps. Our VSGL generation is simple and independent from any scene geometries. In addition, reflected radiance for a VSGL is calculated using an analytic formula. Hence, we are able to render one‐bounce glossy interreflections at real‐time frame rates with smaller artifacts.
Compact TM01 to TE11 mode converter designed with matching sections

A method for designing compact TM01 to TE11 mode converter using dielectric slabs with matched sections is proposed in this letter. The dielectric slabs are fixed in a circular waveguide sectored by thin metallic plate partition. The designs incorporate the quarter wavelength dielectric matching section utilizing two methods i.e. inserting a different dielectric material and horizontal corrugation of existing dielectric material to minimize the length of circular waveguide mode converter. The mode converter is designed to operate at the center frequency of 3 GHz with maximum conversion efficiency of 98.4% and a bandwidth of nearly 12% for both types of matching sections. For practical realization of the concept, Teflon and FR4 are used as dielectric materials. The proposed mode converter is linear, symmetric and easy to fabricate and moreover, a length of 1.7 λ provides the advantage of being light weight and compact.