Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutations in myotilin cause myofibrillar myopathy

Background and Objective: The term myofibrillar myopathy (MFM) is a noncommittal term for a pathologic pattern of myofibrillar dissolution associated with accumulation of myofibrillar degradation products and ectopic expression of multiple proteins. Ultrastructural studies implicate the Z-disk as the site of the initial pathologic change, and mutations in two Z-disk-related proteins, desmin and αB-crystallin, have been identified in a minority of patients with MFM. The authors’ objective was to determine whether mutations in myotilin, a key Z-disk component and the disease protein in limb-girdle muscular dystrophy (LGMD) 1A, are another cause of MFM. Methods: The authors used histochemical, immunocytochemical, ultrastructural, and mutation analysis. Results: The authors detected four missense mutations in 6 of 57 patients with MFM in the serine-rich exon 2 of MYOT, where the two previously identified LGMD1A mutations are located. Three mutations were novel, and one had been previously identified in LGMD1A. Each patient had evidence for neuropathy, and at least three kinships had associated cardiomyopathy. Distal weakness greater than proximal weakness was present in three patients. Except for minor differences, the morphologic features were similar to those in other patients with MFM. Conclusions: 1) Mutations in myotilin cause MFM; 2) exon 2 of MYOT is a hotspot for mutations; 3) peripheral neuropathy, cardiomyopathy, and distal weakness greater than proximal weakness are part of the spectrum of myotilinopathy; 4) not all cases of myotilinopathy have a limb-girdle phenotype; and 5) the molecular basis of the majority of MFM cases remains to be discovered.
Hedgehog Pathway Antagonist 5E1 Binds Hedgehog at the Pseudo-active Site

Proper hedgehog (Hh) signaling is crucial for embryogenesis and tissue regeneration. Dysregulation of this pathway is associated with several types of cancer. The monoclonal antibody 5E1 is a Hh pathway inhibitor that has been extensively used to elucidate vertebrate Hh biology due to its ability to block binding of the three mammalian Hh homologs to the receptor, Patched1 (Ptc1). Here, we engineered a murine:human chimeric 5E1 (ch5E1) with similar Hh-binding properties to the original murine antibody. Using biochemical, biophysical, and x-ray crystallographic studies, we show that, like the regulatory receptors Cdon and Hedgehog-interacting protein (Hhip), ch5E1 binding to Sonic hedgehog (Shh) is enhanced by calcium ions. In the presence of calcium and zinc ions, the ch5E1 binding affinity increases 10–20-fold to tighter than 1 nm primarily because of a decrease in the dissociation rate. The co-crystal structure of Shh bound to the Fab fragment of ch5E1 reveals that 5E1 binds at the pseudo-active site groove of Shh with an epitope that largely overlaps with the binding site of its natural receptor antagonist Hhip. Unlike Hhip, the side chains of 5E1 do not directly coordinate the Zn2+ cation in the pseudo-active site, despite the modest zinc-dependent increase in 5E1 affinity for Shh. Furthermore, to our knowledge, the ch5E1 Fab-Shh complex represents the first structure of an inhibitor antibody bound to a metalloprotease fold.
Direct adaptive regulation of unknown nonlinear dynamical systems via dynamic neural networks

A direct nonlinear adaptive state regulator, for unknown dynamical systems that are modeled by dynamic neural networks is discussed. In the ideal case of complete model matching, convergence of the state to zero plus boundedness of all signals in the closed loop is ensured. Moreover, the behavior of the closed loop system is analyzed for cases in which the true plant differs from the dynamic neural network model in the sence that it is of higher order, or due to the presence of a modeling error term. In both cases, modifications of the original control and update laws are provided, so that at least uniform ultimate boundedness is guaranteed, even though in some cases the stability results obtained for the ideal case are retained.
Analysis of High Frequency QRS Potential During Exercise Testing in Patients with Coronary Artery Disease and in Healthy Subjects

High resolution ECG waveforms from leads V3, V4, V5, and V6 were analyzed in two groups of male subjects before, during, and following treadmill exercise testing. Group A included 32 coronary artery disease (CAD) patients, with arteriographically proven > 75% obstruction of at least two main coronary arteries, and group B included 30 healthy subjects, without history or symptoms of CAD. Signal averaging and filtering techniques ware used in order to enhance the signal‐to‐noise ratio of the recorded ECG. The averaged QRS waveforms were filtered between 150 and 250 Hz. QRS complexes of the four leads were combined to form a “precordial average complex” (PAC). The PAC signals were examined for each subject at different stages of the exercise test and two parameters were computed: the root mean square (RMS) voltage; and the peak amplitude. The values of RMS and peak amplitudes measured at each stage of the exercise test were normalized to the values at rest. Normalized RMS (NRMS) values at peak exercise, immediately after peak exercise, and during the recovery phase were found to be higher for the healthy subjects than for the CAD group (1.17 ± 0.31 vs 0.94 ± 0.26, P < 0.008 at peak exercise, 1.13 ± 0.24 vs 0.84 ± 0.19, P < 0.001 after peak exercise, 1.08 ± 0.22 vs 0.94 ± 0.17, P < 0.007 during recovery). Cut‐off NRMS value of one had a sensitivity of 81.3% and a specificity of 70.0% in differentiating CAD patients from healthy subjects in the examined groups. Normalized peak amplitude (NAMP) values exhibited similar behavior, with higher values for the healthy subjects than for the CAD group (1.23 ± 0.48 vs 0.94 ± 0.36, P < 0.03 at peak exercise, 1.20 ± 0.34 vs 0.83 ± 0.28, P < 0.001 after peak exercise, 1.10 ± 0.29 vs 0.94 ± 0.23, P < 0.02 during recovery). Specificity of 73.3% and sensitivity of 71.8% were found using a postpeak NAMP cut‐off value of 1. In conclusion, the present study shows that using high frequency ECG may contribute to identifying patients with CAD. Further studies in larger groups of patients are required to better define the true predictive value of the method described for the diagnosis of CAD.
Targeting oncogenic PLCE1 by miR-145 impairs tumor proliferation and metastasis of esophageal squamous cell carcinoma

Phospholipase C epsilon 1 (PLCE1) is a susceptibility gene in esophageal squamous cell carcinoma (ESCC). Nevertheless, the role of PLCE1 in ESCC tumorigenesis has not been elucidated. In this study, we determined the function of PLCE1 and its regulatory microRNA (miRNA) in ESCC. PLCE1 protein was excessively expressed in ESCC and precancerous lesions compared with that in normal tissues. High PLCE1 expression levels in ESCC were significantly linked with poor overall survival. Knockdown of PLCE1 promoted the apoptosis, cytokine-induced apoptosis, and sensitivity of cancer cells to chemotherapeutic drugs but abrogated the proliferation and EMT phenotype of ESCC in vitro. Notably, miR-145 was newly identified as a potent repressor of PLCE1 expression by directly targeting the 3′UTR of PLCE1. MiR-145 also inhibited cell proliferation, migration, and metastasis, as well as controlled the cytoskeleton dynamics of esophageal cancer. Moreover, miR-145 was expressed at low levels in a large cohort of patients with ESCC and was inversely correlated with PLCE1 protein expression in cancer cells and tissues. These findings demonstrate that PLCE1 functions as tumor promoter in ESCC and can be suppressed by miR-145 through inhibition of PLCE1 translation. Hence, delivery of PLCE1-targeting miR-145 is a potential therapeutic approach for esophageal cancer.
The Dynamics of Social Exclusion in Europe

Jedanaesto poglavlje Povezanost između stambene politike, socijalne politike i politike urbanizacije napisala je C. Hamburger. Stambena je politika u nordijskim zemljama tradicionalno usko povezana s određenim socijalnim ciljevima koje se trebalo postići u suradnji sa socijalnom politikom. U novije se vrijeme stambena politika više okreće problemima imigracijskih skupina i posebnih društvenih skupina, među kojima u novije vrijeme važno mjesto imaju stari ljudi. Politika urbanizacije uvijek je vodila računa o problemima segregacije i u novije se vrijeme značajna sredstva ulažu u podizanje standarda u zapuštenim, prigradskim, suburbanim naseljima.
The Value Relevance of Earnings and the Prediction of Future Cash Flows

In this paper we test the validity of the prediction test of future cash flows as a substitute for the test of value relevance of earnings. We theoretically show that the R 2 of the cash flows prediction regression is contaminated by (1) the relative presence of noise in future cash flows (2) the relative presence of noise in the covariance between future cash flows and current earnings. We test if either of the above two factors contribute to the result of Kim and Kross (2005) that the ability of earnings to predict one-year-ahead cash flows has increased over the recent decades, in contrast to the evidence of decreasing value relevance of earnings presented by others. We find empirical evidence that both factors contributed to their result. From the significant presence of noise in cash flows (97%) and also in the covariance (87%), we conclude that the cashflows prediction test is a poor substitute for the test of value relevance of earnings, and perhaps of other accounting numbers as well.
Input–output and process LCAs in the building sector: are the results compatible with each other?

ABSTRACT Buildings are a major contributor to climate change. Use phase has traditionally been the focus area, but the importance of construction-phase has increased with the emergence of energy-efficient buildings. Life-cycle assessment (LCA) is arguably the best method to assess and analyze the emissions caused by buildings. However, within LCA there are two very different approaches – process LCA and input–output (IO) LCA – which lead to different results. When looking at the scale of published LCA results, it is evident that IO LCAs are placed at the top end, and process LCAs at the bottom end. It is thus questionable whether LCA can provide data that can be used for decision-making and policy formation. This study takes a step toward filling this gap by presenting a comparison of process and IO LCA results of the pre-use phase of a residential concrete element building in Finland. Exactly the same scope is utilized in order to maximize comparability. The results depict how the two main LCA methods produce significantly different results. The implications of acknowledging this are discussed. The results fall in midway between the extremes published using the two methods but still deviate from each other by a multiplier of almost 2.
Factors affecting performance/success of small-scale rural non-farm enterprises in Lesotho

Purpose This paper aims to study the different factors that determine the performance or success of small-scale, non-farm enterprises in Lesotho. Evidence shows that small-scale enterprises in developing countries are confronted with different challenges and problems that make them less viable. As a result, the capacity of small-scale, non-farm enterprises in employment creation, income generation and providing the means of livelihood to the poor people is not significant. In Lesotho, many people who are retrenched from the South African mines are absorbed in small-scale, non-farm enterprises to make a living. However, small-scale enterprises are faced with different challenges. The research findings suggest that factors leading to success/performance of rural non-farm enterprises in Lesotho include gender of the entrepreneur, age of the entrepreneur, ability of the entrepreneur to establish wider social networks, large population/market, availability of communication networks and infrastructure, participation of enterprises in the international market and costs of doing business and competition. In this regard, the paper makes policy recommendations that can be used to improve performance/success of small-scale, non-farm enterprises. Design/methodology/approach This research uses both qualitative and quantitative research methods to analyse data. Findings The main finding of the research is that foreign competition hinders the success of non-farm enterprises in Lesotho. The research findings further reveal that enterprises owned by women make the highest turnover compared to those owned by men. Practical implications This study brings in different factors that can ensure or hinder success/performance of small-scale, rural non-enterprises. Originality/value The research paper is of value in that it is the first study in Lesotho that considers different factors that determine business success in relation to employment creation, turnover and profitability.
Gendered Solutions to the Care Gap Issue in Iceland

Abstract Iceland has for some years enjoyed an international reputation as one of the most gender-equal societies in the world. It has also received a fair amount of international attention for an innovative approach to making parental leave compatible with gender equality by dividing the period into three equally long parts with non-transferable periods reserved for both parents. Still, there is a fairly long period that needs bridging from when parental leave ends and public day-care for children begins. During this intervening period parents have to find their own solution for childcare. We interviewed Icelandic parents about their use of parental leave and the bridging of the care gap period and argue that this gap is a major hindrance in the realization of the gender equality goals of the law on parental leave. We also note that unequal division of parental leave is generally not considered to violate the ideal of gender equality.
Outcome from mild traumatic brain injury

Purpose of review The focus of this review is outcome from mild traumatic brain injury. Recent literature relating to pathophysiology, neuropsychological outcome, and the persistent postconcussion syndrome will be integrated into the existing literature. Recent findings The MTBI literature is enormous, complex, methodologically flawed, and controversial. There have been dozens of studies relating to pathophysiology, neuropsychological outcome, and the postconcussion syndrome during the past year. Two major reviews have been published. Some of the most interesting prospective research has been done with athletes. Summary The cognitive and neurobehavioral sequelae are self-limiting and reasonably predictable. Mild traumatic brain injuries are characterized by immediate physiological changes conceptualized as a multilayered neurometabolic cascade in which affected cells typically recover, although under certain circumstances a small number might degenerate and die. The primary pathophysiologies include ionic shifts, abnormal energy metabolism, diminished cerebral blood flow, and impaired neurotransmission. During the first week after injury the brain undergoes a dynamic restorative process. Athletes typically return to pre-injury functioning (assessed using symptom ratings or brief neuropsychological measures) within 2–14 days. Trauma patients usually take longer to return to their pre-injury functioning. In these patients recovery can be incomplete and can be complicated by preexisting psychiatric or substance abuse problems, poor general health, concurrent orthopedic injuries, or comorbid problems (e.g. chronic pain, depression, substance abuse, life stress, unemployment, and protracted litigation).
An Experimental Study of Heat Adaptation of Bioabsorbable Craniofacial Meshes and Plates

Intraoperative heating of bioabsorbable plates and mesh panels to above the glass transition temperature is commonly performed to assist their adaptation to bone. Some studies suggest that once heat-adapted, such implants under certain conditions tend to partially revert to their preadapted shape, termed a "memory effect. " We investigated this phenomenon by using heat-adapted 82:18 poly-L-lactic acid:polyglycolic acid copolymer mesh panel and plate specimens with a glass transition temperature of 57°C. The specimens retained limited malleability even at temperatures as low as 45°C, substantially below the nominal glass transition temperature, as measured by shape relaxation experiments. At 40°C to 42°C, however, shape relaxation was not observed. A three-dimensional synthetic bone construct was also fixated using 90°C heat-adapted plates, then incubated in a 37°C buffer bath for 4 weeks, with periodic measurement of the shape of the construct. No changes in shape were recorded over this interval, suggesting that heat-adapted bioabsorbable implants forming a three-dimensional fixation network with multiple bone fragments cannot independently shape relax with the overall interconnectedness of the network ensuring its stability over time.
Evaluation of new GenoType MTBDRplus for detection of resistance in cultures and direct specimens of Mycobacterium tuberculosis.

SETTINGS Molecular methods frequently used in laboratories can now give us useful information about low growth bacteria. OBJECTIVE To evaluate the new GenoType MTBDRplus assay for its ability to detect mutations in the 81-bp hotspot region of the rpoB gene, mutations in codon 315 of the katG gene and alterations in the inhA promoter region. DESIGN Prospective resistance to rifampicin (RMP) and isoniazid (INH) study using Mycobacterium tuberculosis positive specimens and cultures comparing the results of GenoType MTBDRplus with those obtained phenotypically with the Bactec MGIT (Mycobacterial Growth Indicator Tube) 960. RESULTS In 59 specimens (18 smear microscopy samples and 41 solid and liquid medium cultures), mutations were detected in all of 36 M. tuberculosis strains phenotypically resistant to RMP (100%), and in 35 of 37 strains phenotypically resistant to INH (94.59%). The new assay prompted a 21.6% increase in the direct detection of INH resistance in the strains studied, due to the incorporation of inhA promoter region probes in the test. CONCLUSIONS The GenoType MTBDRplus assay is a valid method for detecting the most common mutations in strains resistant to RMP and INH. However, further phenotypic testing is required, as the assay failed to detect 100% of INH and RMP resistance.
IMPACT OF CENTRAL BANK COMMUNICATIONS ON STOCK PRICES IN NIGERIA

BEING A THESIS SUBMITTED TO THE POST GRADUATE SCHOOL, AHMADU BELLO UNIVERSITY, ZARIA, IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE AWARD OF MASTER DEGREE OF SCIENCE IN ECONOMICS NOVEMBER 2012
Immunohistochemical characterization of calf pneumonia produced by the combined endobronchial administration of bovine herpesvirus 1 and Pasteurella haemolytica.

Ten calves ("group 4") were inoculated endobronchially with Pasteurella haemolytica 4 days after inoculation with bovine herpesvirus 1 (BHV-1). Four calves (group 3) were similarly inoculated with P. haemolytica alone, and three (group 2) with BHV-1 alone. All group 4 animals showed severe respiratory signs and had bilateral lobar pneumonia; one died 6 days after inoculation with P. haemolytica. Two types of pneumonic lesion were observed. One was characterized by interlobular and interstitial lymphatic thrombosis, fibrinous pleuritis and coagulative necrosis, and the other by necrotizing bronchiolitis with intranuclear inclusion bodies. The former type of lesion was associated with the presence of P. haemolytica antigen and the latter with the presence of BHV-1 antigen. The weight of infection of BHV-1 and P. haemolytica in bronchoalveolar (BAL) fluid was clearly reflected in the immunohistochemical demonstration of the corresponding antigens in BAL fluid cells. Group 4 calves differed from the calves of groups 1-3 in showing 10-1530 times more endotoxin in BAL fluid. These findings suggested that BHV-1 infection partly destroyed the clearance mechanisms of the respiratory tract epithelium and exacerbated the subsequent P. haemolytica infection.
Review and evaluation of innovative technologies for measuring diet in nutritional epidemiology.

INTRODUCTION The use of innovative technologies is deemed to improve dietary assessment in various research settings. However, their relative merits in nutritional epidemiological studies, which require accurate quantitative estimates of the usual intake at individual level, still need to be evaluated. OBJECTIVE To report on the inventory of available innovative technologies for dietary assessment and to critically evaluate their strengths and weaknesses as compared with the conventional methodologies (i.e. Food Frequency Questionnaires, food records, 24-hour dietary recalls) used in epidemiological studies. METHODS A list of currently available technologies was identified from English-language journals, using PubMed and Web of Science. The search criteria were principally based on the date of publication (between 1995 and 2011) and pre-defined search keywords. RESULTS Six main groups of innovative technologies were identified ('Personal Digital Assistant-', 'Mobile-phone-', 'Interactive computer-', 'Web-', 'Camera- and tape-recorder-' and 'Scan- and sensor-based' technologies). Compared with the conventional food records, Personal Digital Assistant and mobile phone devices seem to improve the recording through the possibility for 'real-time' recording at eating events, but their validity to estimate individual dietary intakes was low to moderate. In 24-hour dietary recalls, there is still limited knowledge regarding the accuracy of fully automated approaches; and methodological problems, such as the inaccuracy in self-reported portion sizes might be more critical than in interview-based applications. In contrast, measurement errors in innovative web-based and in conventional paper-based Food Frequency Questionnaires are most likely similar, suggesting that the underlying methodology is unchanged by the technology. CONCLUSIONS Most of the new technologies in dietary assessment were seen to have overlapping methodological features with the conventional methods predominantly used for nutritional epidemiology. Their main potential to enhance dietary assessment is through more cost- and time-effective, less laborious ways of data collection and higher subject acceptance, though their integration in epidemiological studies would need additional considerations, such as the study objectives, the target population and the financial resources available. However, even in innovative technologies, the inherent individual bias related to self-reported dietary intake will not be resolved. More research is therefore crucial to investigate the validity of innovative dietary assessment technologies.
Evaluation of a selective screening for colorectal carcinoma

Although the efficacy of mass screening for colorectal carcinoma (CRC) with a fecal occult blood test has been demonstrated in several randomized trials, a mass screening approach used in countries with intermediate or low incidence of CRC might be costly. Screening high risk people may be an alternative approach, to aid in the prevention of death from CRC. However, the efficacy of CRC screening for high risk people in such countries is uncertain.