Miracle-dz/UniFAR-FTUs huggingface dataset:
Soluble domains of telomerase reverse transcriptase identified by high‐throughput screening

Telomerase is a ribonucleoprotein complex responsible for extending the ends of eukaryotic chromosomes. Structural and biophysical studies of this enzyme have been limited by the inability to produce large amounts of recombinant protein. Here we perform a high‐throughput screen to map regions of the Tetrahymena thermophila TERT (Telomerase Reverse Transcriptase) protein that are overexpressed in a soluble form in Escherichia coli using a GFP‐fusion system. Many of the soluble protein domains identified do not coincide with domains inferred from multiple sequence alignment, so screening for fluorescent colonies provided information not otherwise readily obtained. The method revealed an essential, independently folded N‐terminal domain that was expressed and purified with high yield and found to be suitable for structural analysis. These results provide a tool for future structural and biophysical studies of TERT.
CFTR mutations in Turkish and North African cystic fibrosis patients in Europe: implications for screening.

AIMS To obtain more insight into the variability of the CFTR mutations found in immigrant cystic fibrosis (CF) patients who are living in Europe now, and to estimate the test sensitivity of different frequently used methods of DNA analysis to detect CF carriers or patients among these Turkish or North African immigrants. METHODS A survey among 373 European CF centers asking which CFTR mutations had been found in Turkish and North African CF patients. RESULTS 31 and 26 different mutations were reported in Turkish and North African patients, identifying 64.2% (113/176) and 87.4% (118/135) alleles, respectively (p < 0.001). The mean sensitivity (detection rate) of three most common CFTR mutation panels to detect these mutations differed between Turkish and North African people, 44.9% (79/176) versus 69.6% (94/135) (p < 0.001), and can be increased to 57.4% (101/176) and 79.3% (107/135) (p < 0.001), respectively, by expanding these panels with 13 mutations which have been found on two or more alleles. CONCLUSION 35.8% and 12.6%, respectively, of CF alleles in Turkish and North African patients living in Europe now had not been identified. Among these populations, the test sensitivity of common CFTR mutation panels is insufficient for use in screening programs in Europe, even after expansion with frequent Turkish and North African mutations. This raises questions about whether and how to implement CF carrier and neonatal screening in a multiethnic society.
NT-proBNP levels in premenopausal women with polycystic ovarian syndrome and/or obesity

According to some studies, polycystic ovarian syndrome (PCOS) patients have an increased risk for diabetes mellitus and often show an adverse cardiovascular risk profile. NT-proBNP was shown to have a high predictive value regarding cardiovascular events, especially in those without overt cardiovascular disease. The aim of this study was to investigate the levels of NT-proBNP in 70 women with PCOS and/or obesity in relation to other classical cardiovascular risk factors. There was no statistical difference between NT-proBNP levels between obese, lean PCOS and obese PCOS patients; between patients with or without metabolic syndrome; or between patients with different cardiovascular risk, according to The Androgen Excess and PCOS Society consensus. NT-proBNP does not show significant correlation to age, weight, BMI, WHR, WSR, systolic or diastolic blood pressure and results from oral glucose tolerance test (OGTT), except for immunoreactive insulin (IRI) at 120 min. NT-proBNP correlates weakly with HDL, but not with other indices of lipid metabolism.
Explaining the Spatial Variation in Homeownership Rates: Results for German Regions

Lerbs O. W. and Oberst C. A. Explaining the spatial variation in homeownership rates: results for German regions, Regional Studies. This paper employs cross-sectional data on ninety-six German regions to investigate the interregional variability of homeownership rates. Among the explanatory variables, the analysis includes important regional housing market indicators as well as regional socio-demographic composition, urbanization and labour market performance. An estimation strategy is chosen which accounts for different forms of spatial dependence between the regional units. It is found that regional differences in the relative price of owning versus renting and the affordability of owner-occupied housing play a key role in explaining why homeownership rates vary so substantially across the country. The results indicate significant neighbourhood effects for several variables.
Why Does Threonine, and Not Serine, Function as the Active Site Nucleophile in Proteasomes?*

Proteasomes belong to the N-terminal nucleophile group of amidases and function through a novel proteolytic mechanism, in which the hydroxyl group of the N-terminal threonines is the catalytic nucleophile. However, it is unclear why threonine has been conserved in all proteasomal active sites, because its replacement by a serine in proteasomes from the archaeon Thermoplasma acidophilum (T1S mutant) does not alter the rates of hydrolysis of Suc-LLVY-amc (Seemüller, E., Lupas, A., Stock, D., Lowe, J., Huber, R., and Baumeister, W. (1995) Science 268, 579–582) and other standard peptide amide substrates. However, we found that true peptide bonds in decapeptide libraries were cleaved by the T1S mutant 10-fold slower than by wild type (wt) proteasomes. In degrading proteins, the T1S proteasome was 3.5- to 6-fold slower than the wt, and this difference increased when proteolysis was stimulated using the proteasome-activating nucleotidase (PAN) ATPase complex. With mutant proteasomes, peptide bond cleavage appeared to be rate-limiting in protein breakdown, unlike with wt. Surprisingly, a peptide ester was hydrolyzed by both particles much faster than the corresponding amide, and the T1S mutant cleaved it faster than the wt. Moreover, the T1S mutant was inactivated by the ester inhibitorclasto-lactacystin-β-lactone severalfold faster than the wt, but reacted with nonester irreversible inhibitors at similar rates. T1A and T1C mutants were completely inactive in all these assays. Thus, proteasomes lack additional active sites, and the N-terminal threonine evolved because it allows more efficient protein breakdown than serine.
Case reports of malformations associated with maternal diabetes: history and critique

Several malformations and malformation complexes have been alleged to be associated with maternal type 1 diabetes mellitus: in particular, sacral dysplasia, caudal regression/sirenomelia, femoral dysplasia, and holoprosencephaly. For some of the malformations the claim rests on case material, and for others on theoretical considerations. The history and evolution of these ideas are presented.
Molecular interactions of BBX24 and BBX25 with HYH, HY5 HOMOLOG, to modulate Arabidopsis seedling development

BBX24 and BBX25 are two important transcriptional regulators, which regulate seedling photomorphogenesis in Arabidopsis. Very recently, we have shown that BBX24 and BBX25 negatively regulate the expression of BBX22, reducing the function of HY5, by physically interacting with its bZIP domain.1 Furthermore, HY5 HOMOLOG, HYH, has been reported to heterodimerize with HY5 and enhances its photomorphogenic function in seedling de-etiolation by serving as coactivator.8 Here, we further report that BBX24 and BBX25 physically interact with HYH. The physical interactions of BBX24 and BBX25 with HYH could lead to depletion of HYH molecules from the active pool and, thus indirectly, reduce the function of HY5 in promoting photomorphogenesis. Hence, our results suggest another mode of regulation by which BBX24 and BBX25 exert their negative effects on HY5 indirectly through HYH for the fine-tuning of seedling photomorphogenesis.
Self-potential observations during hydraulic fracturing

Self-Potential Observations During Hydraulic Fracturing Jeffrey R. Moore Steven D. Glaser University of California, Berkeley Lawrence Berkeley National Laboratory Department of Civil and Environmental Engineering 760 Davis Hall Berkeley, CA USA E-mail: moore@ce.berkeley. edu Abstract The self-potential (SP) response during hydraulic fracturing of intact Sierra granite was investigated in the laboratory. Excellent correlation of pressure drop and SP suggests that the SP response is created primarily by electrokinetic coupling. For low pressures, the variation of SP with pressure drop is linear, indicating a constant coupling coefficient (Cc) of -200 mV/MPa. However for pressure drops >2 MPa, the magnitude of the Cc increases by 80% in an exponential trend. This increasing Cc is related to increasing permeability at high pore pressures caused by dilatancy of micro-cracks, and is explained by a decrease in the hydraulic tortuosity. Resistivity measurements reveal a decrease of 2% prior to hydraulic fracturing and a decrease of ~35% after fracturing. An asymmetric spatial SP response created by injectate diffusion into dilatant zones is observed prior to hydraulic fracturing, and in most cases this SP variation revealed the impending crack geometry seconds before failure. At rupture, injectate rushes into the new fracture area where the zeta potential is different than in the rock porosity, and an anomalous SP spike is observed. After fracturing, the spatial SP distribution reveals the direction of fracture propagation. Finally, during tensile cracking in a point load device with no water flow, a SP spike is observed that is caused by contact electrification. However, the time constant of this event is much less than that for transients observed during hydraulic fracturing, suggesting that SP created solely from material fracture does not contribute to the SP response during hydraulic fracturing. 1. Introduction Hydraulic fracturing creates a network of tensile fractures in low-permeability reservoir rock by introducing high fluid pressures at depth in a borehole. Permeability Moore and Glaser, in press JGR, B – 2006JB004373
Chronic necrotizing pulmonary aspergillosis: approach to management.

OBJECTIVE To describe our experience with 6 patients and to review the current literature to update the approach to the diagnosis and treatment of chronic necrotizing pulmonary aspergillosis. DESIGN Patient reports and MEDLINE review of English-language literature published after 1980. RESULTS Chronic necrotizing pulmonary aspergillosis (CNPA) is a subacute infection most commonly seen in patients with altered local defense from preexisting pulmonary disease or in patients with risk factors that alter systemic immune status. Delays in diagnosis are common. Although initial reports advocated intravenous amphotericin B, itraconazole has emerged as a better initial therapy because of its documented efficacy and minimal toxicity. The dose and duration of therapy should be based on clinical response. In patients who do not respond to medical therapy, pulmonary resection can be considered, but postoperative morbidity is high. Recurrent or relapsing infections occur; chronic maintenance therapy with itraconazole can be considered in patients with residual parenchymal scarring. A wide range of mortality rates has been reported for CNPA. Outcome is most likely influenced by severity of comorbid conditions, extent of underlying pulmonary disease, delays in diagnosis, and initiation of effective therapy.
Socioeconomic, demographic and environmental determinants of infant mortality in Nepal

Summary The Nepal Fertility and Family Planning Survey of 1986 demonstrated that demographic variables, previous birth interval and survival of preceding child, still predominated as determinants of infant mortality, particularly in rural areas of Nepal. However, in urban Nepal, where the level of socioeconomic development is higher, an environmental variable, along with previous birth interval and survival of preceding child emerges as important in determining infant mortality. Separate policy measures for child survival prospects in rural and urban Nepal are suggested.
Local Improvement Results for Anderson Acceleration with Inaccurate Function Evaluations

We analyze the convergence of Anderson acceleration when the fixed point map is corrupted with errors. We consider uniformly bounded errors and stochastic errors with infinite tails. We prove local improvement results which describe the performance of the iteration up to the point where the accuracy of the function evaluation causes the iteration to stagnate. We illustrate the results with examples from neutronics.
Limited ability to extend the digits of the human hand independently with extensor digitorum

While the human hand has an extraordinary capacity to manipulate objects, movement of its digits is usually not completely independent. These limits have been documented for extrinsic flexor muscles, although hand skills also require selectivity for extension movements. Hence, we measured the degree of independent control of the major extrinsic extensor (extensor digitorum, ED). Subjects grasped a cylinder, with the thumb perpendicular to the fingers. Load cells were connected to the proximal phalanges of the fingers and the thumb's distal phalanx. Intramuscular recordings using needle electrodes were made from the individual digital compartments of ED. Subjects were instructed to extend each digit isometrically in a voluntary ramp contraction to 50% maximal force. In total, the behaviour of 283 single motor units was analysed. More than half of the units associated with one ‘test’ finger were recruited inadvertently when another digit contracted to 50% maximum, with most units being recruited by extension of the adjacent digits. Usually, test motor units were recruited at higher forces by extension of fingers further from the test finger. Unexpectedly, extension of the thumb recruited many motor units acting on the little finger. Across tasks, at recruitment of the test motor units, the force produced by the test finger often differed between the voluntary and inadvertent contractions. Overall, the independent control of the output of ED is limited; this may reflect ‘spill‐over’ of motor commands to other digital extensor compartments. This level of control of the extrinsic extensor muscles is more independent than the control of the deep extrinsic flexor muscle but less independent than that of the superficial extrinsic flexor muscle.
Selective hypersensitivity to diclofenac

NSAIDs can produce idiosyncratic reactions by different pathogenic mechanisms. Intolerance reactions are elicited by different NSAIDs depending on the potency of the cyclooxygenase (COX) inhibition. Other reactions suggest an IgEmediated mechanism. These generally occur in a short time after drug administration, and they are mediated by a unique drug or group of drugs with similar chemical structure. The NSAIDs most often involved in these kinds of reactions are pyrazolones and ASA. Some cases of selective hypersensitivity to other NSAIDs such as di ̄unisal (1) and diclofenac (2) have been described. Finally, NSAIDs also elicit delayed-hypersensitivity reactions, as in contact dermatitis, erythema multiforme, and Stevens-Johnson syndrome. We present 12 patients diagnosed with selective hypersensitivity to diclofenac, with good tolerance of other NSAIDs con®rmed by oral challenge. Twelve nonatopic patients, including six men, 24±71 years old (mean 49.5), were referred to our allergy unit because of Patients with hypersensitivity to diclofenac often tolerate other NSAIDs. epithelia in the mother, but only for cat epithelia in the daughter. Cyclamen cultivars, which belong to the Primulaceae (primrose) family, are popular indoor ornamental plants. Their natural ancestors are short (a few centimeters high), shadowand humidity-loving plants native to Alpine forests. The brightly colored ̄owers are pollinated by insects. Therefore, sensitization to these heavy pollens does not occur under normal conditions. However, the speci®c occupational conditions described in this report led to intense exposure and in that way sensitized two out of the three members of this family. Presumably, their slightly atopic constitution made them more susceptible to this sensitization. No doubt, in many smallscale occupational settings, high-level exposure occurs to substances of both vegetable and animal origin. This entails the risk of sensitization. It is crucial to inform such workers of this serious risk. Only in that way is it possible to implement the necessary preventive measures.
Prevalence and causes of vision loss in North Africa and the Middle East: 1990–2010

Background To describe the prevalence and causes of visual impairment and blindness in North Africa and the Middle East (NAME) in 1990 and 2010. Methods Based on a systematic review of medical literature, we examined prevalence and causes of moderate and severe vision impairment (MSVI; presenting visual acuity <6/18, ≥3/60) and blindness (presenting visual acuity <3/60). Results In NAME, the age-standardised prevalence of blindness decreased from 2.1% to 1.1% and MSVI from 7.1% to 4.5%. In 2010, 3.119 million people were blind, and 13.700 million had MSVI. Women were generally more often affected than men. Main causes of blindness were cataract, uncorrected refractive error, macular degeneration and glaucoma. Main causes of MSVI were cataract and uncorrected refractive errors. Proportions of blindness and MSVI from trachoma significantly decreased. Conclusions Although the absolute numbers of people with blindness and MSVI increased from 1990 to 2010, the overall age-standardised prevalence of blindness and MSVI among all ages and among those aged 50 years and older decreased significantly (p<0.05). Cataract and uncorrected refractive error were the major causes of blindness and MSVI.
Activation of TRPM7 Channels by Phospholipase C-coupled Receptor Agonists*

TRPM7 is a ubiquitously expressed nonspecific cation channel that has been implicated in cellular Mg2+ homeostasis. We have recently shown that moderate overexpression of TRPM7 in neuroblastoma N1E-115 cells elevates cytosolic Ca2+ levels and enhances cell-matrix adhesion. Furthermore, activation of TRPM7 by phospholipase C (PLC)-coupled receptor agonists caused a further increase in intracellular Ca2+ levels and augmented cell adhesion and spreading in a Ca2+-dependent manner (1). Regulation of the TRPM7 channel is not well understood, although it has been reported that PIP2 hydrolysis closes the channel. Here we have examined the regulation of TRPM7 by PLC-coupled receptor agonists such as bradykinin, lysophosphatidic acid, and thrombin. Using FRET assays for second messengers, we have shown that the TRPM7-dependent Ca2+ increase closely correlates with activation of PLC. Under non-invasive “perforated patch clamp” conditions, we have found similar activation of TRPM7 by PLC-coupled receptor agonists. Although we could confirm that, under whole-cell conditions, the TRPM7 currents were significantly inhibited following PLC activation, this PLC-dependent inhibition was only observed when [Mg2+]i was reduced below physiological levels. Thus, under physiological ionic conditions, TRPM7 currents were activated rather than inhibited by PLC-activating receptor agonists.
Effect of breastfeeding on growth in Yemeni infants.

OBJECTIVE To estimate the prevalence of effective breastfeeding (EBF) practice and its association with weight of young infants, mother's education, employment status, and parity. METHODS The study is a cross-sectional, conducted in Dula Health Center in Sana'a city, the capital of Yemen during the year 2003. Six hundred and twenty-one mothers and their exclusively breastfed apparently healthy infants attended to the health center for immunization were enrolled in the study. Effective breastfeeding was evaluated according to the World Health Organization integrated management of childhood illnesses literature. Weight was measured using Seca scale. We conducted interview to investigate the age of the child, parity, employment status, and education of the mother. RESULTS The mean age of infants was 49.7+/-16.8 days. The prevalence of EBF was 16.9% (n=105). Good positioning was observed in 26.7% (n=166), followed by good suckling in 23.7% (n=147) and finally by good attachment in 20.3% (n=126). The mean weight of EBF infants was 3.9+/-0.5 kg, whereas that of the ineffectively breastfed group was 3.5+/-0.5 kg (p<0.0001). The 2 groups were compared with gender and age matched. The mean weight of well-attached infants was 3.8+/-0.55 kg and for those with good suckling was 3.8 +/- 0.55 kg and for those with good positioning was 3.7+/-0.59 kg. No association was found between EBF with mother's education and employment status while parity was positively related to EBF rate. CONCLUSION Prevalence of EBF is low. Infants with EBF are heavier than the ineffectively breast-fed infants.
Oxygen reactions in a non-aqueous Li+ electrolyte.

Oxygen (O2) reduction is one of the most studied reactions in chemistry.1 Widely investigated in aqueous media, O2 reduction in non-aqueous solvents, such as CH3CN, has been studied for several decades.2–7 Today, O2 reduction in non-aqueous Li+ electrolytes is receiving considerable attention because it is the reaction on which operation of the Li–air (O2) battery depends.8–29 The Li–O2 battery is generating a great deal of interest because theoretically its high energy density could transform energy storage.8, 9 As a result, it is crucial to understand the O2 reaction mechanisms in non-aqueous Li+ electrolytes. Important progress has been made using electrochemical measurements including recently by Laoire et al.29 No less than five different mechanisms for O2 reduction in Li+ electrolytes have been proposed over the last 40 years based on electrochemical measurements alone.25–29 The value of using spectroelectrochemical methods is that they can identify directly the species involved in the reaction. Here we present in situ spectroscopic data that provide direct evidence that LiO2 is indeed an intermediate on O2 reduction, which then disproportionates to the final product Li2O2. Spectroscopic studies of Li2O2 oxidation demonstrate that LiO2 is not an intermediate on oxidation, that is, oxidation does not follow the reverse pathway to reduction.
Experience of mindfulness in people with bipolar disorder: A qualitative study

Abstract The aim of the study was to explore experiences of practising mindfulness and how this related to living with, and managing, bipolar disorder. Qualitative methodology was used to explore the experiences of 12 people with bipolar disorder who had been practising mindfulness for at least 18 weeks. Semi-structured interviews exploring how mindfulness practice related to living with bipolar disorder were recorded verbatim, transcribed and analysed using thematic analysis. Seven themes emerged: Focusing on what is present; clearer awareness of mood state/change; acceptance; mindfulness practice in different mood states; reducing/stabilizing negative affect; relating differently to negative thoughts; reducing impact of mood state. All participants reported subjective benefits and challenges of mindfulness practice, and gave insights into processes of change.