Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of a real-time reverse transcription PCR assay for detection of a novel nidovirus associated with a neurological disease of the Australian brushtail possum (Trichosurus vulpecula)

AIMS: To develop a quantitative reverse transcription PCR (RT-qPCR) assay for detection of the putative wobbly possum disease (WPD) virus and to apply this test to investigate the viral load in archival tissues from past WPD transmission studies. METHODS: The real-time assay was developed as a two-step RT-qPCR in a SYBR green format and validated using serial dilutions of a linearised plasmid containing target DNA. The copy number values were normalised to the amount of RNA in each reverse transcription reaction and presented as viral copies/pg RNA. The viral load was determined in archival samples from animals that had received inoculations of infectious WPD tissue suspensions. Thirty samples originating from 22 possums, comprising five samples from three healthy possums and 25 samples from 19 possums that had received inoculations of infectious WPD tissue suspensions were tested. RESULTS: The assay was linear (R2 > 0.99) within the tested range from 1 to 107 target copies/µL, with an efficiency of >90%. The intra-assay variability CV values ranged from 0.8 to 4.5% for different standards, with the inter-assay variability CV values ranging from 0.4 to 2.5%, indicating good precision and reproducibility of the assay. The novel nidovirus was detected in all 25 samples from WPD-affected possums. Tissues from three control possums and from one experimentally infected rabbit were negative for WPD RNA. The viral load in WPD-positive tissues differed between individual possums and between tissue types, ranging from 2.2 to 359,980 copies/pg RNA. The highest viral load was detected in liver, followed by brain, spleen, kidney and urine. There was a more than four log difference in the viral load between pools of tissues originating from two outbreaks of WPD in different geographical regions. CONCLUSIONS: Detection of viral RNA in a variety of tissues from WPD affected possums, including brain, is consistent with the multi-organ distribution of histopathological lesions observed in WPD. Our data suggest that liver may constitute the sample of choice for diagnostic testing. Differences in the viral load in tissues from possums inoculated with infectious WPD tissue suspensions from Rotorua or Invermay origin suggest that WPD viruses with different biological properties may exist. CLINICAL RELEVANCE: We have developed a RT-qPCR assay for detection of the putative WPD virus. The test showed good sensitivity and reproducibility over the wide dynamic range of template concentrations. It provides a tool for future diagnostic and research purposes.
Mathematical Modeling of Two-dimensional Unsteady Flow in Growing Tumor

We investigate the problem of unsteady fluid flow in growing solid tumors. We develop a mathematical model for a growing tumor whose boundary is taken as a sphere, and the unsteady fluid flow within the tumor is assumed to be two dimensional with respect to the radial distance and the latitudinal angle in spherical coordinates. The expressions for the time, radial and latitudinal variations of the flow velocity, pressure, and the two investigated drug concentrations within the tumor were determined analytically. We calculated these quantities in the tumor as well as in a corresponding normal tissue. We find, in particular, that blood pressure in the tumor would be higher than that in the normal tissue, and there could be blood flow circulation in the tumor. For a given spatial location in the tumor, the amount of drug delivered to the growing tumor decreases first with time, but then the rate of decrease reduces with further increase in time. The Therapeutic Index, which is a measure of the efficiency of drug delivery in the tumor in the biomedical science, is determined for different values of the parameters and discussed in the absence or presence of the drugs' interactions which may exist in the presence of the two drugs in the tumor. The main results of our model agree with the available experiments.
Balancing minimum spanning and shortest path trees

Efficient algorithms are known for computing a minimum spann.ing tree, or a shortest path. tree (with a fixed vertex as the root). The weight of a shortest path tree can be much more than the weight of a minimum spa,nning tree. Conversely, the distance bet,ween the root, and any vertex in a minimum spanning tree may be much more than the distance bet#ween the two vertices in the graph. Consider the problem of balancing between the two kinds of trees: Does every graph contain a tree that is “light” (at most a constant times heavier than the minimum spanning t,ree), such that the distance from the root to any vertex in t,he tree is no more than a constant times the true distance? This paper answers the question in the affirmative. It is shown that there is a continuous tradeoff between the two parameters. For every y > 0, there is a tree in the graph whose total weight is at most 1 + $? times the weight of a minimum spanning tree, such that the di&nce in the tree between the root, and any vertex is at, most 1 + &y times the true distance. Efficient sequential and parallel algorithms achieving these factors are provided. The algorithms are shown to be optimal in two ways. First, it is shown that no algorithm can achieve better factors in all graphs, because there a.re graphs that do not have better trees. Second, it is shown that even on a per-graph basis, finding trees that achieve better factors is NP-hard.
Modulation of exon skipping by high‐affinity hnRNP A1‐binding sites and by intron elements that repress splice site utilization

The RNA‐binding protein hnRNP A1 is a splicing regulator produced by exclusion of alternative exon 7B from the A1 pre‐mRNA. Each intron flanking exon 7B contains a high‐affinity A1‐binding site. The A1‐binding elements promote exon skipping in vivo, activate distal 5′ splice site selection in vitro and improve the responsiveness of pre‐mRNAs to increases in the concentration of A1. Whereas the glycine‐rich C‐terminal domain of A1 is not required for binding, it is essential to activate the distal 5′ splice site. Because A1 complexes can interact simultaneously with two A1‐binding sites, we propose that an interaction between bound A1 proteins facilitates the pairing of distant splice sites. Based on the distribution of putative A1‐binding sites in various pre‐mRNAs, an A1‐mediated change in pre‐mRNA conformation may help define the borders of mammalian introns. We also identify an intron element which represses the 3′ splice site of exon 7B. The activity of this element is mediated by a factor distinct from A1. Our results suggest that exon 7B skipping results from the concerted action of several intron elements that modulate splice site recognition and pairing.
Depression is a Risk Factor for Poor Glycemic Control and Retinopathy in African-Americans With Type 1 Diabetes

Objective: To examine longitudinal data about depression in relationship to glycemic control and as a risk factor for diabetic retinopathy (DR). Depression is a common psychiatric disorder among diabetic persons and has been shown in cross-sectional studies to be associated with the vascular complications of diabetes. Methods: A total of 483 African-American patients with Type 1 diabetes had a baseline examination and 6-year follow-up examination. Evaluations at both visits included administering the Beck Depression Inventory (BDI), a detailed ophthalmologic examination, retinal photographs, and measurement of glycosylated hemoglobin as an index of glycemic control. Six-year progression of DR between baseline and follow-up visits was evaluated from the change in retinopathy severity using the Early Treatment of Diabetic Retinopathy Study grading scale. Results: Patients with high BDI scores at both baseline and 6-year follow-up visits had significantly higher baseline glycosylated hemoglobin values (p = .01), and were more likely to show progression of DR (odds ratio (OR) = 2.44; 95% confidence interval (CI): 1.01–5.88; p = . 049) and progression to proliferative diabetic retinopathy (PDR) (OR = 3.19; 95% CI: 1.30–7.87; p = .01) than patients with low BDI scores at both visits. This was independent of baseline medical risk factors for DR. Conclusion: Six-year longitudinal data indicate that depression is significantly associated with both poor glycemic control and higher 6-year progression to PDR in African-Americans with Type 1 diabetes. AER = albumin excretion rate; BDI = Beck Depression Inventory; CI = confidence interval; DR = diabetic retinopathy; HbA1C = hemoglobin A1C; HPA = hypothalamo-pituitary-adrenal; OR = odds ratio; PDR = proliferative diabetic retinopathy.
`A life on hold': adolescents' experiences of stem cell transplantation in a long-term perspective

Stem cell transplantation is one of the treatment methods for cancer in children and adolescents which has resulted in a positive outcome. Unfortunately this method of treatment brings with it a number of late effects such as short stature, cognitive effects and infertility. However, a majority of children and adolescents experience a good quality of life. By examining their medical records this study has gained a deeper understanding of the situation for the minority of young people who describe themselves as suffering severe mental distress which they relate to their illness and treatment. The population comprised seven adolescents who sought psychotherapeutic support several years after treatment. They describe how they are affected by the feeling of being different, the loss of contact with friends and their dependence on parents. The study points to the need for long-term psychosocial support for children and adolescents who have undergone stem cell transplantation.
Identification of Peptide and Protein Ligands for the Caveolin-scaffolding Domain

Caveolin, a 21-24-kDa integral membrane protein, is a principal component of caveolae membranes. We have suggested that caveolin functions as a scaffolding protein to organize and concentrate certain caveolin-interacting proteins within caveolae membranes. In this regard, caveolin co-purifies with a variety of lipid-modified signaling molecules, including G-proteins, Src-like kinases, Ha-Ras, and eNOS. Using several independent approaches, it has been shown that a 20-amino acid membrane proximal region of the cytosolic amino-terminal domain of caveolin is sufficient to mediate these interactions. For example, this domain interacts with G-protein α subunits and Src-like kinases and can functionally suppress their activity. This caveolinderived protein domain has been termed the caveolin-scaffolding domain. However, it remains unknown how the caveolin-scaffolding domain recognizes these molecules. Here, we have used the caveolin-scaffolding domain as a receptor to select random peptide ligands from phage display libraries. These caveolin-selected peptide ligands are rich in aromatic amino acids and have a characteristic spacing in many cases. A known caveolin-interacting protein, Gi2α, was used as a ligand to further investigate the nature of this interaction. Gi2α and other G-protein α subunits contain a single region that generally resembles the sequences derived from phage display. We show that this short peptide sequence derived from Gi2α interacts directly with the caveolin-scaffolding domain and competitively inhibits the interaction of the caveolin-scaffolding domain with the appropriate region of Gi2α. This interaction is strictly dependent on the presence of aromatic residues within the peptide ligand, as replacement of these residues with alanine or glycine prevents their interaction with the caveolin-scaffolding domain. In addition, we have used this interaction to define which residues within the caveolin-scaffolding domain are critical for recognizing these peptide and protein ligands. Also, we find that the scaffolding domains of caveolins 1 and 3 both recognize the same peptide ligands, whereas the corresponding domain within caveolin-2 fails to recognize these ligands under the same conditions. These results serve to further demonstrate the specificity of this interaction. The implications of our current findings are discussed regarding other caveolin- and caveolae-associated proteins.
Pharmacotherapy of paediatric epilepsy

Childhood epilepsy is a common condition, with an annual incidence of ∼ 40 of 100,000 in the first decade of life. Although childhood epilepsy is more likely to remit than epilepsy in adults, the developmental and social impact of epilepsy during childhood may extend beyond the childhood years, affecting the individual’s potential in cognitive, emotional and socio-economic arenas. The goal of medical management of childhood epilepsy is seizure freedom, with minimal or no adverse effects. Achievement of this goal is crucial in the effort to minimise the long-term disabilities associated with childhood epilepsy. Pharmacotherapy is a cornerstone of management of childhood epilepsy. This review addresses some of the challenges in treatment of epilepsy, which are unique to childhood, and reviews the newer anticonvulsants available and what is known about their role in childhood epilepsy.
Complications of Pregnancy and Fetal Development

Although the outcome of pregnancy for women with diabetes meilitus has improved in recent years, the infant of the diabetic mother has an increased risk of major clinical problems, particularly in the early neonatal period. These include birth injury due to macrosomia, neonatal hypoglycemia, respiratory distress syndrome, and serious congenital anomalies. Because of the great difficulties encountered during attempts to investigate these problems in clinical research protocols, there is a continuing need to establish appropriate animal models of the diabetic pregnancy. Studies carried out over the past decade, primarily with chemically-induced diabetes have suggested techniques which might be useful. In general, the choice of the animal to be studied will depend on the hypotheses being addressed. For instance, small animals such as rabbits and rats made diabetic with streptozotocin have been successfully used for investigation of fetal lung development. Furthermore, the rat model has been helpful for evaluation of fetal anomalies associated with maldevelopment of the spine and central nervous system. Larger animals, such as the nonhuman primate, are more appropriate for studying placental function and amniotic fluid composition in diabetic pregnancies. The task group on pregnancy and fetal development recommends that animal models of diabetes meilitus be used for a more extensive hormonal and metabolic characterization of diabetic mothers during pregnancy, for investigation of placental physiology with respect to the transfer of substrates from mother to fetus, for systematic and comprehensive study of mechanisms controlling fetal lung development, and for delineation of the pathophysiology of neonatal hypoglycemia. it is further recommended that animal models of spontaneous diabetes such as the BB/W rat be used in future studies dealing with pregnancy and fetal development. Because females with spontaneous diabetes show reduced conception rates, there is a pressing need to enhance the fertility of these animals in order to intensify studies on fetal development.
"Spooky Action at a Distance" in the Cardinalized Probability Hypothesis Density Filter

The cardinalized probability hypothesis density (CPHD) filter is a recursive Bayesian algorithm for estimating multiple target states with varying target number in clutter. In the present work, it is shown that a missed detection in one part of the field of view has a significant effect on the probability hypothesis density (PHD) arbitrarily far apart from the missed detection. In the case of zero false alarm rate, this effect is particularly pronounced and can be calculated by solving the CPHD filter equations analytically. While the CPHD filter update of the total cardinality distribution is exact, the local target number estimate close to the missed detection is artificially strongly reduced. A first ad-hoc approach towards a "locally" CPHD filter for reducing this deficiency is presented and discussed.
Concomitant MDS with isolated 5q deletion and MGUS: case report and review of molecular aspects

Patients with monoclonal gammopathy of undetermined significance (MGUS) have a higher risk for the development of concomitant primary cancers such as multiple myeloma (MM) and myelodysplastic syndrome (MDS). We report the case of patient initially suffering from MGUS of the IgG lambda subtype for more than 10 yr, which evolved to MM and MDS with deletion (5q) with severe pancytopenia. Due to pancytopenia, he received dose‐reduced treatment with lenalidomide and dexamethasone. He achieved an ongoing transfusion independency after about 1 month of treatment. Bone marrow taken 14 months after start of treatment showed a complete cytogenetic response of the del(5q) clone and a plasma cell infiltration below 5%. In contrast to the development of MM in MGUS patients, the subsequent occurrence of MDS after diagnosis of MGUS is infrequent. Moreover, the biological association of MDS with MGUS is not sufficiently understood, but the non‐treatment‐related occurrence supports the pathogenetic role of pre‐existing alterations of stem cells. Here, we summarize data on concomitant MDS and MGUS/MM with particular emphasis on molecular aspects.
jMonAtt: Integrity Monitoring and Attestation of JVM-Based Applications in Cloud Computing

Cloud computing has expanded rapidly as a promising technology in the recent years and has drastically altered the majority of opinions about computing mode and application deployment. While the cloud has been proved to improve efficiency and earn benefit for a great number of various services providers, yet a good few enterprises still hesitate to move to the cloud because of security threats. In this paper, we present jMonAtt architecture to provide robust trustworthy guarantees for high-level cloud applications through the enforcement of the trustworthiness evaluation and dynamic attestation with the assistance of HotSpot virtual machine. Moreover, it has less impact on the execution of an attested target when our architecture is deployed in the cloud application system.
B73-Mo17 Near-Isogenic Lines Demonstrate Dispersed Structural Variation in Maize1[W][OA]

Recombinant inbred lines developed from the maize (Zea mays ssp. mays) inbreds B73 and Mo17 have been widely used to discover quantitative trait loci controlling a wide variety of phenotypic traits and as a resource to produce high-resolution genetic maps. These two parents were used to produce a set of near-isogenic lines (NILs) with small regions of introgression into both backgrounds. A novel array-based genotyping platform was used to score genotypes of over 7,000 loci in 100 NILs with B73 as the recurrent parent and 50 NILs with Mo17 as the recurrent parent. This population contains introgressions that cover the majority of the maize genome. The set of NILs displayed an excess of residual heterozygosity relative to the amount expected based on their pedigrees, and this excess residual heterozygosity is enriched in the low-recombination regions near the centromeres. The genotyping platform provided the ability to survey copy number variants that exist in more copies in Mo17 than in B73. The majority of these Mo17-specific duplications are located in unlinked positions throughout the genome. The utility of this population for the discovery and validation of quantitative trait loci was assessed through analysis of plant height variation.
Fluctuations of Corneal Sensitivity in Dry Eye Syndromes—A Longitudinal Pilot Study

Purpose: The aim of this study was to observe corneal sensitivity (CoS) longitudinally in patients with dry eye and to evaluate the correlation between CoS, severity, and the etiology of dry eye syndrome (DES). Methods: In this prospective study, 46 patients with DES were examined on 4 occasions within 3 months. CoS was measured by the Cochet–Bonnet esthesiometer. Tear films were evaluated for lipid layer thickness, breakup time, fluorescein and lissamine green staining, and Schirmer test. Patients were classified into etiologic subgroups: hormonal, immunologic, toxic, neural, and environmental. For statistical statistics, Mann–Whitney and Kruskal–Wallis tests were used. Results: Serial data curves of CoS demonstrated pronounced variability of values. CoS and SICCA scores were negatively correlated (r = −0.454, P = 0.007). The Schirmer test and CoS were positively correlated (r = 0.363, P = 0.013). The environmental group had the highest CoS values (5.5). There was no significant difference in CoS neither between nerve-induced and nonnerve-induced DES groups (P = 0.858) nor within the subgroups (P = 0.118). During 3 months, CoS increased in all patients (4.8–5.1). The DES severity was negatively correlated with CoS, indicating a reduction of neural function in severe DES. Conclusions: Our results showed diminished CoS in severe dry eye although there was a high variability of CoS. This supports the hypothesis of different states of compensation as the disease continues and an association of CoS with different causes of dry eye. However, no statistical differences were found between etiological subgroups.
Importance of Image Guidance in Glenohumeral Joint Injections: Comparing Rates of Needle Accuracy Based on Approach and Physician Level of Training

ObjectiveThis study compared the accuracy of blind glenohumeral joint (GHJ) injections between physical medicine and rehabilitation interventional fellows (inexperienced provider) and a sports medicine board–certified physical medicine and rehabilitation attending physician (experienced provider) using either an anterior or posterior approach. MethodsA retrospective analysis of 162 consecutive patients comprising 165 GHJ injections was performed. All GHJ injections were initially placed via anatomic landmark guidance by either an experienced or an inexperienced provider. Contrast medium using live fluoroscopy was injected to determine if intra-articular placement had been obtained. ResultsThe overall accuracy of a blind GHJ injection, regardless of the provider level of experience, was 45.5%. The inexperienced provider was accurate 37.6% of the time, and the experienced provider was accurate 64.6% of the time. The difference in provider accuracy based on level of experience was shown to be statistically significant at P less than 0.05. There was no statistically significant difference between the anterior and posterior approaches regardless of physician level of experience. ConclusionsThe results of this study suggest that image guidance is an important utility for accurate navigation into the GHJ space regardless of the level of training. Neither the anterior nor the posterior approach proved to be significantly more accurate.
The role of trust in supply chain governance

Purpose – The purpose of this paper is to provide and illustrate a framework for the role of governance mechanisms in information sharing among supply chain members. The importance of trust in governing interorganizational relationships is emphasized.Design/methodology/approach – Trust, bargaining power, and contract are three key constructs supporting the governance of information sharing and material flow coordination in supply chains. A conceptual framework showing how these governance mechanisms affect coordination and ultimately, supply chain performance is presented. Four types of trust – calculative, competence, integrity, and predictability – are thought to play an important role in determining the efficacy of information sharing. Three research questions are posed on the relationships among trust, bargaining power, contracts, and information sharing in supply chain coordination. These governance issues are shown to be key factors in the supply chain business model, as illustrated in a case study .