Miracle-dz/UniFAR-FTUs huggingface dataset:
Macrolides Blunt Aldosterone Biosynthesis: A Proof-of-Concept Study in KCNJ5 Mutated Adenoma Cells Ex Vivo

Aldosterone-producing adenoma (APA), a major subtype of primary hyperaldosteronism, the main curable cause of human endocrine hypertension, involves somatic mutations in the potassium channel Kir3.4 (KCNJ5) in 30% to 70% of cases, typically the more florid phenotypes. Because KCNJ5 mutated channels were reported to be specifically sensitive to inhibition by macrolide antibiotics, which concentration dependently blunts aldosterone production in HAC15 transfected with the G151R and L168R mutated channel, we herein tested the effect of clarithromycin on aldosterone synthesis and secretion in a pure population of aldosterone-secreting cells obtained by immunoseparation (CD56+ cells) from APA tissues with/without the 2 most common KCNJ5 mutations. From a large cohort of patients with an unambiguous APA diagnosis, we recruited those who were wild type (n=3) or had G151R (n=2) and L168R (n=2) mutations. We found that clarithromycin concentration dependently lowered CYP11B2 gene expression (by 60%) and aldosterone secretion (by 70%; P<0.001 for both) in CD56+ cells isolated ex vivo from KCNJ5 mutated APAs, although it was ineffective in CD56+ cells from wild-type APAs. By proving the principle that the oversecretion of aldosterone can be specifically blunted in APA cells ex vivo with G151R and L168R mutations, these results provide compelling evidence of the possibility of specifically correcting aldosterone excess in patients with APA carrying the 2 most common KCNJ5 somatic mutations.
Extended Hubbard model for mesoscopic transport in donor arrays in silicon

Arrays of dopants in silicon are promising platforms for the quantum simulation of the Fermi-Hubbard model. We show that the simplest model with only on-site interaction is insufficient to describe the physics of an array of phosphorous donors in silicon due to the strong intersite interaction in the system. We also study the resonant tunneling transport in the array at low temperature as a mean of probing the features of the Hubbard physics, such as the Hubbard bands and the Mott gap. Two mechanisms of localization which suppresses transport in the array are investigated: The first arises from the electron-ion core attraction and is significant at low filling; the second is due to the sharp oscillation in the tunnel coupling caused by the intervalley interference of the donor electron's wave function. This disorder in the tunnel coupling leads to a steep exponential decay of conductance with channel length in one-dimensional arrays, but its effect is less prominent in two-dimensional ones. Hence, it is possible to observe resonant tunneling transport in a relatively large array in two dimensions.
Effect of basal and pulsatile LH release on FSH-stimulated follicle growth in ewes chronically treated with gonadotrophin-releasing hormone agonist.

Ewes chronically treated with gonadotrophin-releasing hormone (GnRH) agonist were used to investigate the importance of the peripheral concentration of LH in FSH-stimulated follicular development. Twenty-four Welsh Mountain ewes were treated with two agonist implants containing 3.3 mg buserelin. During week 6 of treatment all the ewes were given a 72-h continuous infusion of ovine FSH alone (3 micrograms/h) or FSH with large (7.5 micrograms)- or small (2.5 micrograms) amplitude pulses of ovine LH delivered at 4-hourly intervals. The importance of baseline LH throughout the FSH infusion was evaluated in six animals which were treated with a specific antiserum against bovine LH (LH-AS) 15-20 h before the start of FSH treatment. In the absence of LH-AS, infusion of FSH alone or with large or small pulses of LH stimulated the development of a normal number of small follicles (less than or equal to 2.5 mm in diameter) and large follicles (greater than 2.5 mm in diameter). These follicles had normal diameter and steroid secretion compared with control ewes on day 8 of the luteal phase. In contrast, the animals pretreated with LH-AS developed no follicles greater than 2.0 mm in diameter but the number of small follicles per ewe was significantly (P less than 0.05) increased. These results support the hypothesis that FSH in the absence of pulsatile LH release stimulates preovulatory follicular development in ewes treated with GnRH agonist. The follicular response to LH pulses of different amplitude is dependent on both the stage of development of the follicle and the peripheral concentration of FSH. (ABSTRACT TRUNCATED AT 250 WORDS)
The hygiene theory: fact or fiction?

Purpose of reviewThe “hygiene hypothesis” offers a potentially credible and parsimonious explanation for the increasing prevalence of allergy noted in many westernized populations. The authors review recent evidence both for and against this hypothesis. Recent findingsA strong body of epidemiologic evidence indicates that the original observations, namely of a birth order effect and increased risk of atopic disorders in those born into small, affluent households, are robust findings. Improved hygiene is believed to mediate its effect through decreased exposure to infectious agents in early life, and recent evidence has focused attention on the importance of the gastrointestinal microbial environment. In particular, infection with hepatitis A, Helicobacter pylori, and toxoplasma in those living in temperate climates, and geoheminths in those living in endemic areas, have been shown to be associated with reduced risk of atopic manifestations. It is postulated that these infections exert their effect through critically altering T-helper (Th)1/Th2 regulation, which is supported by the examination of the cytokine profiles of cord mononuclear cells when exposed to gastrointestinal flora and, furthermore, emerging evidence on the benefits of probiotics on symptoms of atopic dermatitis. Attempts to identify an inverse relation between Th1- and Th2-mediated disorders (as might be predicted by the Th1/Th2 paradigm) have, however, yielded conflicting results, raising the possibility that this model may be something of an oversimplification. SummaryThe hygiene hypothesis remains a credible but nonspecific explanation for observed variations over time, place and persons at risk for developing atopic allergic disorders. More prospective studies are needed to unravel which infectious agents exert a protective effect and the time period of importance for sensitization. The clinical implications of these advances in our understanding of the etiology of atopic allergic disorders are currently limited.
Two are Better than One: The Link between Management Systems and Business Performance

Little is known about the complementary performance benefits associated with facilities’ combined use of both quality management systems (QMS) and environmental management systems (EMS), and how these performance benefits might differ from those associated with facilities’ use of only one of these management systems (or neither). We suggest that complementarities arise because each management system fosters the development of internal capabilities that facilitates the adoption and routine operationalization of the other, while maintaining differentiated goals that enhance strategic value. We examine these relationships using a sample of 2,619 manufacturing facilities operating within six OECD countries, while controlling for self-selection issues. Our findings support the idea of complementarity in that facilities, that adopt both QMS and EMS, are associated with positive business performance more than facilities that adopt either QMS or an EMS on its own, or no management system.
Staphylococcus aureus is the most common identified cause of cellulitis: a systematic review

SUMMARY We utilized Medline to perform a systematic review of the literature to quantify the aetiology of cellulitis with intact skin. Of 808 patients with cellulitis, 127–129 (15·7–16·0%) patients had positive needle aspiration and/or punch biopsy cultures from intact skin. Of the patients with positive cultures, 65 (50·4–51·2%) had cultures positive for Staphylococcus aureus, 35 (27·1–27·6%) for group A streptococcus, and 35–37 (27·1–29·1%) for other pathogens. The most common aetiology of cellulitis with intact skin, when it can be determined, is S. aureus, outnumbering group A streptococcus by a ratio of nearly 2:1. Given the increasing incidence of community-associated methicillin-resistant S. aureus infections, our findings may have critical therapeutic implications.
The Frequency and Correlates of Spiritual Distress Among Patients With Advanced Cancer Admitted to an Acute Palliative Care Unit

Limited research is available on the frequency of spiritual distress and its relationship with physical and emotional distress. We reviewed patients admitted to our acute palliative care unit (APCU) and determined the association between patient characteristics, symptom severity using the Edmonton Symptom Assessment scale (ESAS), and spiritual distress as reported by a chaplain on initial visit. In all, 50 (44%) of 113 patients had spiritual distress. In univariate analysis, patients with spiritual distress were more likely to be younger (odds ratio [OR] = 0.96, P = .004), to have pain (OR = 1.2, P = .010) and depression (OR = 1.24, P = .018) compared to those without spiritual distress. Spiritual distress was associated with age (OR = 0.96, P = .012) and depression (OR = 1.27, P = .020) in multivariate analysis. Our findings support regular spiritual assessment as part of the interdisciplinary approach to optimize symptom control.
Is there a decline in verbal working memory over age? A study with the new standard computerized reading span test

In this study, the new standard computerized version of the reading span test was used to investigate the development of verbal working memory over age. A significant higher reading span and faster reaction times were expected for the young adults compared to the old adults, based on the processing resource theory (Just & Carpenter, 1992) and the theory of cognitive aging (Salthouse, 1994, 1996), and this hypothesis was confirmed. The new methodology made it possible to test whether there was an age-related increase in intrusion errors, which could be expected based on the inhibition theory of cognitive aging (Hasher & Zacks, 1988). The results showed that older adults made more intrusion errors than young adults thereby confirming the inhibition theory. Finally, the analysis of the memory-pattern showed a clear recency-effect for the young-, but not for the old adults. Interestingly, this has never been reported in literature before. Although more research is needed before any firm conclusions can be drawn, this decline in recency-effect shows that there are larger age-related effects in short term memory span than was expected on the basis of aging theories so far.
Performance Analysis of the Quick Idle State Protocol of CDMA 1xEV-DO Rev. B Systems

In this paper, we study the performance of Quick Idle State Protocol (QISP) introduced in CDMA 1xEV- DO Rev. B standard to enhance the battery life of Access Terminals (ATs) in the idle mode. We develop an analytical model to assess the performance of QISP and use it to compare QISP with Enhanced Idle State Protocol (EISP) of earlier standard. Specifically, we evaluate the average control channel monitoring time of ATs in the idle state as a function of AT page probability and the total number of pages in the control channel cycle. The results from the model indicate a considerable reduction in the awake time of access terminals with QISP within typical ranges of operating parameters. Finally, we offer some insights on the design of QISP within the flexibility offered by the 1xEV-DO Rev. B standard.
High serum coenzyme Q10, positively correlated with age, selenium and cholesterol, in Inuit of Greenland. A pilot study

Greenlanders (Eskimos) have low prevalence of ischaemic heart disease, partly explained by a lower extent of atherosclerosis and a low n‐6/n‐3 ratio of polyunsaturated fatty acids. As atherosclerosis is also a result of oxidative stress, the total antioxidative readiness could have a substantial impact. From a health survey we chose the subpopulation from the most remote area, where the traditional Greenlandic diet with high intake of sea mammals and fish predominates. The mean (SD) of S‐CoQ10 in males was 1.495 (0.529) nmol/ml and 1.421 (0.629) nmol/ml in females, significantly higher (p<0.001) compared to a Danish population. In a linear multiple regression model the S‐CoQ10 level is significantly positively associated with age and S‐selenium in males, and S‐total cholesterol in females. The high level of CoQ10 in Greenlanders probably reflects diet, since no bioaccumulation takes place, and it could probably be a substantial part of the antioxidative defense.
Autophagy activators suppress cystogenesis in an autosomal dominant polycystic kidney disease model

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in either PKD1 or PKD2. It is one of the most common heritable human diseases with eventual development of renal failure; however, effective treatment is lacking. While inhibition of mechanistic target of rapamycin (mTOR) effectively slows cyst expansions in animal models, results from clinical studies are controversial, prompting further mechanistic studies of mTOR-based therapy. Here, we aim to establish autophagy, a downstream pathway of mTOR, as a new therapeutic target for PKD. We generated zebrafish mutants for pkd1 and noted cystic kidney and mTOR activation in pkd1a mutants, suggesting a conserved ADPKD model. Further assessment of the mutants revealed impaired autophagic flux, which was conserved in kidney epithelial cells derived from both Pkd1-null mice and ADPKD patients. We found that inhibition of autophagy by knocking down the core autophagy protein Atg5 promotes cystogenesis, while activation of autophagy using a specific inducer Beclin-1 peptide ameliorates cysts in the pkd1a model. Treatment with compound autophagy activators, including mTOR-dependent rapamycin as well as mTOR-independent carbamazepine and minoxidil, markedly attenuated cyst formation and restored kidney function. Finally, we showed that combination treatment with low doses of rapamycin and carbamazepine was able to attenuate cyst formation as effectively as a single treatment with a high dose of rapamycin alone. In summary, our results suggested a modifying effect of autophagy on ADPKD, established autophagy activation as a novel therapy for ADPKD, and presented zebrafish as an efficient vertebrate model for developing PKD therapeutic strategies.
Design, synthesis and evaluation of 9-hydroxy-7H-furo[3,2-g]chromen-7-one derivatives as new potential vasodilatory agents

Two new 9-hydroxy-7H-furo[3,2-g]chromen-7-one derivatives were designed, synthesized and evaluated for their in vitro vasodilatory activity. The structures of two compounds were elucidated by infrared, 1H NMR, and mass spectral data. The invitro pharmacological evaluation indicated that both of them possessed well vasodilatory activity compared with imperatorin. The molecule docking also showed two target compounds docked well with L-calcium channel (PDB code: 3G43). The result suggested that they would be potential vasodilatory agents for hypertension.
Syndecan‐2 is a key regulator of transforming growth factor beta 2/smad2‐mediated adhesion in fibrosarcoma cells

Fibrosarcoma is a rare malignant tumor originating from fibroblasts. Transforming growth factor beta 2 (TGFβ2) has been established to regulate processes correlated to fibrosarcoma tumorigenesis. In this study, we investigated the possible participation of syndecan‐2 (SDC‐2), a cell membrane heparan sulfate (HS) proteoglycan on these TGFβ2 functions. Our results demonstrate that the inhibition of SDC‐2 expression by short interfering RNA (siSDC2) abolished TGFβ2‐dependent HT1080 cell adhesion (P ≤ 0.01). In parallel, the downregulation of SDC‐2 significantly inhibited TGFβ2‐induced Smad2 phosphorylation (P ≤ 0.01). The immunoflourescence signal of TGF receptor III as well as its protein expression was decreased in SDC‐2‐deficient cells. The enhancement of adhesion molecules integrin β1 (P ≤ 0.01) and focal adhesion kinase expression, induced by TGFβ2 treatment (P ≤ 0.001), was markedly inhibited in SDC‐2‐defficient cells (P ≤ 0.01). Conclusively, the obtained data suggest that SDC‐2 modulates TGFβ2 transcriptional regulation via Smad signaling to facilitate fibrosarcoma cell adhesion. © 2013 IUBMB Life, 65(2)134–143, 2013
Expression of AA4.1 marks lymphohematopoietic progenitors in early mouse development

The hematopoietic system of mice is established during the early to midgestational stage of development. However, the earliest lymphohematopoietic progenitors that appear during mouse development have been less well characterized compared with the hematopoietic stem cell compartment of fetal liver and bone marrow. We isolated the earliest lymphohematopoietic progenitors by using embryonic stem (ES) cell culture in vitro. Cells with the c-Kit+Lin− cell surface phenotype were present abundantly in ES cells cocultured with stromal cell lines. We further separated the cells into two distinct cell subsets based on AA4.1 expression. Although AA4.1+ and AA4.1− cells had equivalent potency to generate myeloid cell lineages, the lymphoid potential in ES-cell-derived cells was largely restricted to the cells expressing AA4.1. The same cell type was present abundantly in the early yolk sac and in fewer numbers (≈5% of that in the yolk sac) in the caudal half of the developing embryos. These data suggest that AA4.1 is a cell surface marker that can identify the earliest lymphohematopoietic progenitors in mouse development.
Haplogroup Classification of Korean Cattle Breeds Based on Sequence Variations of mtDNA Control Region

Many studies have reported the frequency and distribution of haplogroups among various cattle breeds for verification of their origins and genetic diversity. In this study, 318 complete sequences of the mtDNA control region from four Korean cattle breeds were used for haplogroup classification. 71 polymorphic sites and 66 haplotypes were found in these sequences. Consistent with the genetic patterns in previous reports, four haplogroups (T1, T2, T3, and T4) were identified in Korean cattle breeds. In addition, T1a, T3a, and T3b sub-haplogroups were classified. In the phylogenetic tree, each haplogroup formed an independent cluster. The frequencies of T3, T4, T1 (containing T1a), and T2 were 66%, 16%, 10%, and 8%, respectively. Especially, the T1 haplogroup contained only one haplotype and a sample. All four haplogroups were found in Chikso, Jeju black and Hanwoo. However, only the T3 and T4 haplogroups appeared in Heugu, and most Chikso populations showed a partial of four haplogroups. These results will be useful for stable conservation and efficient management of Korean cattle breeds.
Electronic nicotine delivery devices: ineffective nicotine delivery and craving suppression after acute administration

Electronic nicotine delivery devices (E-cigarettes) are marketed to deliver nicotine without tobacco toxicants and are sold in shopping malls and over the internet despite no published safety or efficacy data.1 2 These unregulated products consist of a battery, heater and cartridge containing a solution of nicotine, propylene glycol and other chemicals.3 Puffing activates the heater and the solution is vaporised and inhaled. Cartridges can be refilled using drops of solution sold in bottles labelled as containing over 500 mg nicotine, approximately 10 times the lethal dose. Some smokers emphasise the products' potential as a cessation aid,1 while some public health advocates highlight possible health risks and uncertain effects.1 4 Because there are no published studies examining the products' nicotine delivery or subjective and cardiovascular effect profile, this study examined how two brands of electronic nicotine delivery devices (E-cigarettes) influence plasma nicotine levels, heart rate and cigarette craving in cigarette smokers, and compared these effects to those produced by smokers' usual brand of cigarettes. Using previously described methods,5 smokers in this institutional review board-approved clinical laboratory study (n=16; all naive to electronic nicotine delivery devices (E-cigarettes): 5 women; 8 non-white; mean age=29.8 years, SD=10.7; mean cigarettes/day=18.5, SD=2.2) each provided informed consent and participated in 4 Latin-square ordered conditions (each separated by …
Optical character recognition of arabic printed text

Optical character recognition (OCR) systems improve human- machine interaction. They are widely used in many areas such as editing and storing previously printed or handwritten documents. Much of research has been done regarding the identification of Latin, Japanese and Chinese characters. However, very little investigation has been performed regarding Arabic recognition. Probably the reason is limitation of IT activities in Arabic speaking countries and the difficulty and complexity of Arabic characters identification compared to the others. More difficulties are introduced from the cursive nature of Arabic text. In this paper, a technique has been employed to segment printed Arabic text in order to separate the Arabic characters and then extracting powerful features for each to be recognized. In-order to recognize characters, those features are then compared with a pre-prepared database fields. Although the database was prepared from characters written in Time New Roman font, experimental results show the relatively high accuracy of the method developed when it is tested on several sizes of several fonts beside Time New Roman font.
Efficiency of two-phase designs for prevalence estimation.

BACKGROUND Unbiased estimation of the prevalence of diseases and other conditions is important but can be expensive, especially for conditions which do not necessarily lead to contact with health services. A two-phase population survey may seem an attractive option when there is a relatively cheap, although fallible, test for disease status available: the test is used in the first phase of the survey but in the second, only a subsample are classified by the relatively expensive, gold standard. Previously the cost efficiency of such studies compared with simple, one-phase random sample designs was investigated empirically and some questions remain unclear. METHODS A simple formula for the maximum reduction in cost or standard error that can be achieved by two-phase sampling compared with simple random sampling is derived mathematically. A formula for the minimum reduction is also given and the influence of prevalence on efficiency explained. RESULTS The main result shows that the sensitivity and specificity of the first stage test set an absolute limit on the efficiency of two-phase designs; in particular, two-phase sampling can never be justified on efficiency grounds alone if the test is not accurate enough.
Quantum-dot helium: Effects of deviations from a parabolic confinement potential.

The magneto-optical response to far-infrared radiation of quantum dots containing two electrons is studied theoretically. The symmetry-breaking effects of deviations from a strictly parabolic confinement potential are emphasized. We demonstrate the evidence of many-particle effects in systems where the generalized Kohn's theorem is no longer applicable. The calculated resonance spectrum reflects and explains all features observed in recent high-resolution measurements.