Miracle-dz/UniFAR-FTUs huggingface dataset:
Disruption of Protein Processing in the Endoplasmic Reticulum of DYT1 Knock-in Mice Implicates Novel Pathways in Dystonia Pathogenesis

Dystonia type 1 (DYT1) is a dominantly inherited neurological disease caused by mutations in TOR1A, the gene encoding the endoplasmic reticulum (ER)-resident protein torsinA. Previous work mostly completed in cell-based systems suggests that mutant torsinA alters protein processing in the secretory pathway. We hypothesized that inducing ER stress in the mammalian brain in vivo would trigger or exacerbate mutant torsinA-induced dysfunction. To test this hypothesis, we crossed DYT1 knock-in with p58(IPK)-null mice. The ER co-chaperone p58(IPK) interacts with BiP and assists in protein maturation by helping to fold ER cargo. Its deletion increases the cellular sensitivity to ER stress. We found a lower generation of DYT1 knock-in/p58 knock-out mice than expected from this cross, suggesting a developmental interaction that influences viability. However, surviving animals did not exhibit abnormal motor function. Analysis of brain tissue uncovered dysregulation of eiF2α and Akt/mTOR translational control pathways in the DYT1 brain, a finding confirmed in a second rodent model and in human brain. Finally, an unbiased proteomic analysis identified relevant changes in the neuronal protein landscape suggesting abnormal ER protein metabolism and calcium dysregulation. Functional studies confirmed the interaction between the DYT1 genotype and neuronal calcium dynamics. Overall, these findings advance our knowledge on dystonia, linking translational control pathways and calcium physiology to dystonia pathogenesis and identifying potential new pharmacological targets. SIGNIFICANCE STATEMENT Dystonia type 1 (DYT1) is one of the different forms of inherited dystonia, a neurological disorder characterized by involuntary, disabling movements. DYT1 is caused by mutations in the gene that encodes the endoplasmic reticulum (ER)-resident protein torsinA. How mutant torsinA causes neuronal dysfunction remains unknown. Here, we show the behavioral and molecular consequences of stressing the ER in DYT1 mice by increasing the amount of misfolded proteins. This resulted in the generation of a reduced number of animals, evidence of abnormal ER protein processing and dysregulation of translational control pathways. The work described here proposes a shared mechanism for different forms of dystonia, links for the first time known biological pathways to dystonia pathogenesis, and uncovers potential pharmacological targets for its treatment.
The effect of university–industry collaboration on the scientific impact of publications: the Canadian case, 1980–2005

Previous research on university-industry collaboration in Canada, using mean impact factors as a proxy, concluded that the scientific impact of such research is not inferior to that of university research. Using field-normalized impact factors and citation counts, this paper re-examines the Canadian case. It shows that, when impact factors are field-normalized, university-industry papers are published, on average, in journals with lower impact factors than papers originating from universities only. However, field-normalized citation values reveal the opposite: the average scientific impact of university-industry papers is significantly above that of both university-only papers and industry-only papers. Collaboration with industries is, thus, far from detrimental to the scientific impact of university research and even increases it significantly.
ROLE OF BUSINESS ANALYTICS IN MANAGEMENT EDUCATION

Management education has witnessed significant reforms due to the impacts of globalization, new learning technologies, and unparalleled economic uncertainty. The increasing use of Analytics in B schools to educate its importance is inevitable. The opportunities utilization for business analytics in b schools is indispensable. The Programs offered by current institutions and the market needs reveal the gap which is infact insidious. The study will bring forth the bountiful courses related to business analytics which may fill the gap in the management education offering in institutions across the world.
Revisiting the growth effects of government bonds in the emerging capital market.

We revisited the effects of government bonds for the growth on the Nigerian capital market. Utilising time-series data obtained from the Nigeria Stock Exchange (NSE) annual reports for the period from 2010 to 2017, this study through the Generalised Method of Moments (GMM) regression estimator found that the value and the number of listed government bonds’ positively and significantly affect capital market growth in Nigeria. Furthermore, low capitalisation of government bonds negatively affects the growth of the market. The null hypothesis of the Hansen J-statistics is accepted; hence this implies that the IVs used in the GMM model is valid. We concluded that government bonds have positive and significant effects on the growth of the Nigerian capital market, thus government bonds have made the NSE All-Share Index grow over the period under investigation. Following the findings from the study, it was recommended, inter alia, that there should be more issuance of government bonds to the public and further to enhance the efficiency of the capital markets, both primary and secondary, while the funds raised from the capital market through government issuance should be channelled towards Nigeria’s productive sectors to promote an all-inclusive growth in the Nigerian economy.
Management of chronic sinusitis in cystic fibrosis

Chronic rhinosinusitis is extremely common in patients with cystic fibrosis. It causes numerous problems in these patients and can put them at risk for life‐threatening illness. Potential problems include nasal obstruction, congestion, sinus pain and pressure, infection (usually with Pseudomonas organisms), hyposmia or anosmia, and the seeding of bacteria into the lower respiratory tract. Cystic fibrosis patients with chronically infected sinuses are at increased risk for pneumonia following lung transplantation. A prophylactic protocol has been developed for the management of chronic sinusitis in patients with cystic fibrosis. These patients are fully evaluated at the Nasal Dysfunction Clinic of the University of California, San Diego (UCSD), Medical Center. Based on the results of the evaluation, they are treated with endoscopic sinus surgery, partial middle turbinectomy, septoplasty, and a large middle meatal maxillary antrostomy. Surgery is followed by a rigorous regimen of pulsatile hypotonic saline nasal irrigation to wash away tenacious cystic secretions. Tobramycin (Nebcin®) is given once daily in the nasal irrigant to inhibit the growth of Pseudomonas organisms. At the USCD Nasal Dysfunction Clinic, this prepulmonary transplantation protocol is now used in all cystic fibrosis patients with chronic sinusitis.
Robust discrimination designs

Summary. We study the construction of experimental designs, the purpose of which is to aid in the discrimination between two possibly non‐linear regression models, each of which might be only approximately specified. A rough description of our approach is that we impose neighbourhood structures on each regression response and determine the members of these neighbourhoods which are least favourable in the sense of minimizing the Kullback–Leibler divergence. Designs are obtained which maximize this minimum divergence. Both static and sequential approaches are studied. We then consider sequential designs whose purpose is initially to discriminate, but which move their emphasis towards efficient estimation or prediction as one model becomes favoured over the other.
Providing Safe Drinking Water to 1.1 Billion Unserved People

Despite substantial advances in the past 100 years in public health, technology and medicine, 20% of the world population, mostly comprised of the poor population segments in developing countries (DCs), still does not have access to safe drinking water. To reach the United Nations (UN) Millennium Goal of halving the proportion of people without access to safe water by 2015, the global community will need to provide an additional one billion urban residents and 600 million rural residents with safe water within the next twelve years. This paper examines current water treatment measures and implementation methods for delivery of safe drinking water, and offers suggestions for making progress towards the goal of providing a timely and equitable solution for safe water provision. For water treatment, based on the serious limitations of boiling water and chlorination, we suggest an approach based on filtration coupled with ultraviolet (UV) disinfection, combined with public education. Additionally, owing to the capacity limitations for non-governmental organizations (NGOs) to take on this task primarily on their own, we suggest a strategy based on financially sustainable models that include the private sector as well as NGOs.
Polymers in Mucoadhesive Drug-Delivery Systems: A Brief Note

Bioadhesion can be defined as the process by which a natural or a synthetic polymer can adhere to a biological substrate. When the biological substrate is a mucosal layer then the phenomena is known as mucoadhesion. The substrate possessing bioadhesive property can help in devising a delivery system capable of delivering a bioactive agent for a prolonged period of time at a specific delivery site. The current review provides a good insight on mucoadhesive polymers, the phenomenon of mucoadhesion and the factors which have the ability to affect the mucoadhesive properties of a polymer.
Episode-centred analysis of drinking to intoxication in university students.

AIMS To demonstrate the use of an internet-based retrospective diary to measure intoxication and to describe the epidemiology of intoxication in a university community. METHODS A probability sample of 1564 New Zealand university students completed an Internet-based survey (82% response), including a retrospective diary in which the volume consumed on each of the preceding seven days and the duration of each episode were recorded, along with the respondent's gender, weight, and their typical quantity/frequency of consumption, as a measure of tolerance. These parameters were used to compute an estimated blood alcohol concentration (EBAC) for each episode. RESULTS Using an EBAC of 0.08 g/100 ml as a criterion for intoxication produced lower estimates of incidence than binge drinking guidelines (>40 g for women, >60 g for men), or subjective reports. EBACs of 0.08 g per cent were exceeded at least weekly by 37% of women and 39% of men. Teenage females had higher EBACs than teenage males, despite lower consumption. Intoxication was positively associated with lower age, European or Maori ethnicity relative to Asian, Pacific, or other ethnicities, and with residential halls relative to other living arrangements. Faculty of study was inconsistently related to intoxication. DISCUSSION Frequent drinking to intoxication is normative behaviour in this population group. Of particular concern are intoxication levels in females aged 16-21 years and in males throughout their 20s. The web-based retrospective diary is a useful means of measuring intoxication by self-report. Where time permits it can be enhanced by specification of drinking locations and beverage-specific questions.
Predictors of chronic obstructive pulmonary disease exacerbations

Purpose of review A frequent-exacerbation phenotype of chronic obstructive pulmonary disease (COPD) exists that is independent of disease severity. Establishment of methods to predict ‘frequent exacerbators’ is critical. The purpose of this review is to critically assess the recent literature regarding predicting COPD exacerbations, and to provide recommendations for future research. Recent findings Although there are many studies in which inflammatory biomarkers have been used in an attempt to predict future exacerbations, it is likely that these biomarkers represent a consequence rather than the cause. Genetic predictors are involved in causal pathways. Thus, genetics should be investigated in order to understand the exacerbation mechanism and to develop new therapeutic approaches. Some single nucleotide-type genetic polymorphisms are associated with exacerbations, and the individuals with genotypes protective against infection are less susceptible to exacerbations. In contrast, we reported that loss of Siglec-14, a lectin likely involved in host defense, was associated with a reduced COPD exacerbation risk. Summary We should take into consideration that a protein involved in host defense such as Siglec-14, that could also trigger exaggerated response, might also generate unwanted local and systemic inflammation, which could be detrimental to a host and could generate COPD with a frequent-exacerbation phenotype, its progression, and its comorbidities.
Outcome after Bariatric Surgery in Two Adolescents with Hypothalamic Obesity Following Treatment of Craniopharyngioma

Treatment of craniopharyngioma (CP) in childhood can lead to severe, debilitating obesity with devastating medical and psychological outcomes. Despite sustained nutritional and exercise-oriented interventions, no efficacious medical option is available for hypothalamic obesity. We describe two adolescents who developed morbid obesity and significant comorbidities following diagnosis and treatment of CP, in whom bariatric surgery was achieved, illustrating a novel approach for symptomatic hypothalamic obesity, as well as positive and negative outcomes.
Internal organization of membranes at end bulbs of held in the anteroventral cochlear nucleus

The end bulb of Held in the rostral ventral cochlear nucleus of the chinchilla and guinea pig was studied with the freeze‐fracture technique. The end bulb has multiple, small active zones which are uniformly distributed within the calyceal portion of this terminal. Single or small groups of active zones are surrounded by enlarged channels of extracellular space often containing processes of astrocytes. Small plasmalemmal deformations occur at these active zones. The number of these deformations is thought to be indicative of exocytotic transmitter release because they are more frequent in animals fixed in a noisy environment compared to animals fixed in a quiet environment. Thus, our study provides a basis for the quantitative study of changes in transmitter secretion at a central nervous system synapse driven by a controllable natural stimulus.
Yeast Checkpoint Genes in DNA Damage Processing: Implications for Repair and Arrest

Yeast checkpoint control genes were found to affect processing of DNA damage as well as cell cycle arrest. An assay that measures DNA damage processing in vivo showed that the checkpoint genes RAD17, RAD24, and MEC3 activated an exonuclease that degrades DNA. The degradation is probably a direct consequence of checkpoint protein function, because RAD17 encodes a putative 3′-5′ DNA exonuclease. Another checkpoint gene, RAD9, had a different role: It inhibited the degradation by RAD17, RAD24, and MEC3. A model of how processing of DNA damage may be linked to both DNA repair and cell cycle arrest is proposed.
Evaluation and surgical treatment of acoustic neuroma.

Abstract In 46 consecutive patients treated surgically for acoustic neuroma and followed for a minimum of two years, there was no operative mortality; 90 per cent returned to their previous level of activity, and all were able to care for themselves. Total removal of tumor was possible in 70 per cent, and radical subtotal removal in another 10 per cent. Facial-nerve function was preserved in 80 per cent, even in some patients with a large tumor. Any patient with progressive, unexplained hearing loss should have audiometric vestibular evaluation. If tumor is suspected, x-ray studies are indicated, including tomography and neuroradiologic contrast studies, with positive-contrast encephalography if clinical signs are limited to the eighth nerve, and pneumoencephalography when signs indicate a large lesion. When diagnostic studies suggest a small tumor (less than 2.0 cm in diameter), total removal can usually be accomplished by a translabyrinthine operation unless there is fifth-nerve involvement. Large tumor.
Hyperthyroid-induced cardiomyopathy in an adolescent.

to sleep flat on her back without problems. According to her mother, she had a long history of tachycardia. Her mother said that one year earlier while undergoing a routine physical examination, the girl had a heart rate of >130 beats/min. The patient’s family history was negative for congenital heart disease, cardiomyopathy, or sudden unexplained death. The girl’s maternal aunt had
Coimmunopurification of Phosphorylated Bacterial- and Plant-Type Phosphoenolpyruvate Carboxylases with the Plastidial Pyruvate Dehydrogenase Complex from Developing Castor Oil Seeds12[W][OA]

The phosphoenolpyruvate carboxylase (PEPC) interactome of developing castor oil seed (COS; Ricinus communis) endosperm was assessed using coimmunopurification (co-IP) followed by proteomic analysis. Earlier studies suggested that immunologically unrelated 107-kD plant-type PEPCs (p107/PTPC) and 118-kD bacterial-type PEPCs (p118/BTPC) are subunits of an unusual 910-kD hetero-octameric class 2 PEPC complex of developing COS. The current results confirm that a tight physical interaction occurs between p118 and p107 because p118 quantitatively coimmunopurified with p107 following elution of COS extracts through an anti-p107-IgG immunoaffinity column. No PEPC activity or immunoreactive PEPC polypeptides were detected in the corresponding flow-through fractions. Although BTPCs lack the N-terminal phosphorylation motif characteristic of PTPCs, Pro-Q Diamond phosphoprotein staining, immunoblotting with phospho-serine (Ser)/threonine Akt substrate IgG, and phosphate-affinity PAGE established that coimmunopurified p118 was multiphosphorylated at unique Ser and/or threonine residues. Tandem mass spectrometric analysis of an endoproteinase Lys-C p118 peptide digest demonstrated that Ser-425 is subject to in vivo proline-directed phosphorylation. The co-IP of p118 with p107 did not appear to be influenced by their phosphorylation status. Because p118 phosphorylation was unchanged 48 h following elimination of photosynthate supply due to COS depodding, the signaling mechanisms responsible for photosynthate-dependent p107 phosphorylation differ from those controlling p118's in vivo phosphorylation. A 110-kD PTPC coimmunopurified with p118 and p107 when depodded COS was used. The plastidial pyruvate dehydrogenase complex (PDCpl) was identified as a novel PEPC interactor. Thus, a putative metabolon involving PEPC and PDCpl could function to channel carbon from phosphoenolpyruvate to acetyl-coenzyme A and/or to recycle CO2 from PDCpl to PEPC.
Antecedents and Outcomes of E-Procurement Adoption: An Integrative Model

Organizations increasingly emphasize the use of information technology in the procurement process. An integrative model of e-procurement adoption that captures its antecedents, two types of e-procurement use, and their respective effects on relationship development and perceived efficiency gains are proposed and empirically tested using the data collected from senior managers in four technology-intensive industries. Our findings indicate that the use of coordination e-procurement applications has both direct and indirect effects on perceived efficiency gains, while transactional application use can directly lead to efficiency gains. In addition, the use of e-procurement applications is strongly influenced by organizational learning ability and normative pressures. The findings provide a new perspective for managers in their future implementation of e-procurement applications.
Lymphocytic gastritis and gastric permeability in patients with celiac disease.

BACKGROUND & AIMS Lymphocytic gastritis is associated with celiac disease. Gastric permeability can now be assessed by a sucrose test, and intestinal permeability measured by a lactulose/mannitol test is increased in untreated celiac patients. The aim of this study was to prospectively compare gastric and intestinal permeability with histological changes of the stomach and small bowel in patients with celiac disease. METHODS Gastric and intestinal permeability were measured by oral or duodenal (during endoscopy) administration of a triple sugar solution containing 20 g sucrose, 10 g lactulose, and 5 g mannitol in 100 mL water in 43 adult patients with celiac disease (28 without diet) and in 30 healthy controls. Endoscopical biopsy specimens were taken from the antrum and distal duodenum and investigated for intraepithelial lymphocyte counts. RESULTS Urinary sucrose excretion decreased after duodenal administration (n = 8) as opposed to oral administration and thus measured gastric permeability in celiac disease. Gastric permeability was elevated in 60% of the celiac patients and correlated with antral intraepithelial lymphocyte counts. Intestinal permeability (measured by a lactulose/mannitol test) was also elevated in 69% of the celiac patients and correlated with duodenal intraepithelial counts. CONCLUSIONS There is a high prevalence of lymphocytic gastritis in untreated celiac disease associated with elevated gastric permeability. Celiac disease seems to be a general disorder of the gastrointestinal tract associated with disturbed permeability.
Surface antigen produced by herpes simplex virus (HSV).

Surface antigen of cells infected with herpes simplex virus (HSV) was studied by mixed agglutination technique. The surface antigen was stable to heat at 56°C, formalin, periodate and 2-4-dinitrophenol, but was not detected after treatment with acetone or ethanol. Surface antigen preceded infectious virus and required protein synthesis. DNA synthesis was not required since cytosine arabinoside did not inhibit production of surface antigen. HSV surface antigen was not shared by other members of the herpesvirus group. Detection of surface antigen by mixed agglutination was distinguished from surface conditions responsible for adherence of sensitized sheep erythrocytes.
Plasma C-Reactive Protein and Lipoprotein Levels, and Progression of Coronary Artery Disease after Myocardial Infarction Treated with Thrombolysis

Background: There is a paucity of studies using quantitative coronary angiography (QCA) to determine progression of coronary artery disease (CAD) after an acute coronary event. Furthermore, despite a great interest in effects of inflammation and ‘early’ lipid lowering therapy, no data have been published on the role of plasma C-reactive protein (CRP) and lipoprotein levels in CAD progression after myocardial infarction. Methods: Seventy-two patients with myocardial infarction treated with thrombolysis, but not with statins, were investigated with QCA during admission and after 6 months. Plasma CRP concentrations were measured by a high sensitive method 2 days after the acute event, and plasma high-sensitive CRP and lipoprotein levels were determined 3 months after myocardial infarction. Results: Overall, there was no significant progression of CAD, but when stenoses were grouped into those reducing the lumen diameter greater or less than 50%, progression was seen in stenoses originally <50%, whereas regression was seen in stenoses >50%. No consistent associations were seen between plasma CRP, lipoprotein lipid or lipoprotein(a) levels and CAD. Conclusions: Progression of stenoses <50% might be of clinical importance since these stenoses are more prone to rupture. Furthermore, the lack of associations between change in minimum lumen diameter and plasma CRP and lipoprotein concentrations suggests that positive effects on CAD progression of early treatment with anti-inflammatory or lipid-lowering drug therapy may not be expected in this subset of patients.