Miracle-dz/UniFAR-FTUs huggingface dataset:
Three novel mutations in CYBA among 22 Iranians with Chronic granulomatous disease

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by defect in one of the components of nicotinamide adenine dinucleotide phosphate (NADPH)‐oxidase enzyme. The enzyme is at least composed of membrane‐bound subunits gp91‐phox and p22‐phox (also named cytochrome b558), and cytosolic ones p40‐phox, p47‐phox and p67‐phox. A defect in the enzyme activity leads to impaired intracellular killing of phagocytic cells. The CYBA gene encoding p22‐phox is located on chromosome 16q24. In this study, new genetic changes of CYBA gene in 22 Iranian patients with autosomal recessive‐CGD (AR‐CGD) were identified. Twenty‐two patients with CGD were referred to Immunology, Asthma and Allergy Research Institute (IAARI) and enrolled in this study based on defect in NADPH oxidase activity, demographic data and clinical histories. All patients had p22‐phox deficiency based on Western blotting. Genomic DNA was extracted from peripheral blood mononuclear cells (PBMCs), and PCR followed by direct sequencing was performed to find p22‐phox mutations. Mutation analysis of CYBA revealed 12 different mutations, including three novel mutations: one was deletion of exon 1, and two were point mutations in exon 3 (c.136G>A (p.Gly46Ser)), and exon 6 (c.388C>T (p.Gln130X)). Three new mutations of CYBA gene in four of 22 Iranian patients with AR‐CGD were found. These three novel mutations can partly complete the database of Human Gene Mutation Database (HGMD) and other related ones. It can also be helpful for further prenatal diagnosis in the affected families. Given that currently bone marrow transplantation is considered to be the curative treatment for patients with CGD, finding mutations will also be useful for timely decision‐making in bone marrow transplantation.
Biology of tumor necrosis factor‐α– implications for psoriasis

Abstract: Numerous recent investigations have pointed to a key role of the proinflammatory, pleiotropic cytokine tumor necrosis factor‐α (TNF‐α) in host defense and inflammatory processes. TNF overexpression has been found in lesional skin and in the circulation of psoriatic patients, and it was suggested that TNF‐α is crucial in this and other immune diseases. Several approaches to inhibit TNF‐α activity have been developed. These include three different neutralizing antibodies to TNF‐α as well as three different soluble TNF‐α receptors with characteristic properties designed to bind the 17‐KDa soluble trimeric TNF‐α and the 26‐KDa membrane‐bound form of TNF‐α. Clinical trials have demonstrated significant antipsoriatic effects, and it is likely that blocking TNF‐α will become an important therapeutic option. The data available from these trials contribute to further understanding of the disease by demonstrating the major role of TNF‐α. An in‐depth understanding of the regulation of TNF gene expression, protein production, receptor expression, and signaling pathways may lead to further, potentially important novel therapeutic strategies and antipsoriatic active small molecules, suitable for oral application in the future. Here we review the current knowledge of TNF biology, the approaches to inhibit TNF activity, and their clinical and immunological effects in psoriasis. In addition, the host‐defense effects and chronic TNF‐blocking activity are discussed.
Agency, Socialization, and Support: A Critical Review of Doctoral Student Attrition.

Almost universally, residential doctoral programs have reported attrition rates of up to 50% for face-to-face programs and 50-70% for online doctoral programs. The purpose of this critical review was to explore current literature for doctoral attrition and persistence to explore reasons and attributes for improved persistence to completion. We analyzed a final sample of 79 studies for context with doctoral attrition and persistence and, following coding, pattern matching, and synthesis, four final constructs emerged: (a) chair agency and chair-candidate relationship; (b) candidate socialization and support systems; (c) candidate preparedness; and (d) financial considerations. These constructs indicated that internal factors from within the doctoral program have affected attrition and we encourage doctoral educational leadership to implement strategies to improve dissertation chair practices through professional development, increased candidate support and socialization opportunities, creation of clearer pathways from academic to dissertation research coursework, and improved financial opportunities and support for candidates. We recommend quantitative explanatory studies to further examine the four factors within the doctoral program to examine the effects on doctoral candidate completion.
The Changes in Phoria and Convergence to Divergence Peak Velocity Ratio Are Correlated

Purpose: Phoria is used in the diagnosis of binocular dysfunctions, such as convergence insufficiency. A common treatment for convergence insufficiency is vision therapy, yet it is controversial whether the phoria changes as a result of rehabilitation. Phoria can vary due to the duration and/or the type of prior visual tasks. The variability potentially observed within phoria measurements leads to difficulties in confidently assessing changes within longitudinal studies. Hence, we propose to measure phoria and vergence peak velocities on separate days to evaluate whether a more robust measurement can be attained. Methods: Eleven subjects with normal binocular vision participated in two identical experimental sessions. Four-degree convergence and divergence steps stimulated from targets at far, middle, and near initial vergence positions were recorded using a limbus tracking system. Near dissociated phoria was measured after a set of step stimuli. The vergence ratio was defined as the convergence peak velocity divided by the divergence peak velocity. Linear regression analyses calculated the correlation between the phoria and the vergence ratio, and the difference between phoria measurements and vergence ratio measurements, recorded on different days. Results: Near dissociated phoria measurements and vergence ratios were highly correlated for all three initial vergence positions (r > 0.85, p < 0.005). The change in phoria was significantly correlated to the change in vergence ratio (r > 0.94, p = 0.0001). The slope of the linear regression analysis between the phoria and the vergence ratio using individual subject data was repeatable between the sessions (r = 0.99, p < 0.00001) despite large changes in phoria observed in a few individuals. Conclusions: The change in phoria is significantly correlated to the change in vergence ratio. For longitudinal studies including the efficacy of vision therapies for patients with binocular dysfunctions, we suggest assessing both phoria and vergence velocities to reduce the variability potentially observed from different days.
Testing the Tracking Efficiency of Commodity Exchange Traded Funds (ETFs) across the Bearish and Bullish Market Regimes: Evidence from Indian Gold ETFs

ABSTRACT Commodity exchange traded funds (ETFs) help investors gain exposure to the underlying commodity in digital form. The present article attempts to examine the performance characteristics of 12 gold ETFs in India across the bear and bull markets. ETFs’ sensitivity to their underlying asset (gold prices) is observed to be lower during the bearish market regime, and, as such, the tracking error is found to be higher during the bearish market regime. Further, volume is reported to bear a significant positive impact on the tracking ability of ETFs whereas volatility and pricing deviation are found to negatively impact the tracking ability of ETFs.
Let Them Eat Cake: A Study of the Income Effects of Globalization on the Rich

There exists a substantial body of literature on the effects of Globalization on the poor populations of the world (Hall & Bass, 2010; Tran, 2010; Harrison & McMillan, 2006), but little exists on the effects of globalization on the rich. The model presented here serves to provide some insight into this other spectrum of the effects of globalization. The results indicate that, while economic and cultural globalization increase the income share held by the top twenty-percent of income earners, political globalization and restrictions to globalization decrease the income share held by this quintile.
The ameliorative effect of Cetraria islandica against diabetes-induced genetic and oxidative damage in human blood

Abstract Context: The aqueous extracts of Cetraria islandica (L.) Ach. (Parmeliaceae) is traditionally used in many countries against a number of conditions, including inflammatory conditions. Objective: The present study aimed to assess, for the first time, the effectiveness of C. islandica in cultured primary blood cells of Type 1 diabetes subjects. Materials and methods: Diabetic and control blood samples were treated with or without aqueous lichen extract (5 and 10 μg mL−1) for 48 h. The activity of antioxidant enzymes in erythrocytes and also malondialdehyde levels in plasma were determined to evaluate the oxidative status. DNA damages were analyzed by SCE, MN and comet assays in cultured human lymphocytes. Additionally, proliferation index (PI) was evaluated in peripheral blood lymphocytes. Results: There were significant increases in observed total DNA damage (comet assay) (240.2%) and SCE (168.8%), but not in MN frequencies of cultures with diabetes as compared (p > 0.05) to controls. Whereas, the significant reductions of total DNA damage (69.2 and 65.3%) and SCE frequencies (17.7 and 12.3%) were determined when the 5 and 10 mg mL−1 lichen extract was added to the cell culture medium, respectively. However, lichen extract did not completely inhibit the induction of SCEs in lymphocytes of patients with diabetes. C. islandica extract was also useful on PI rates. Discussion: In conclusion, the antioxidant role of C. islandica in alleviating diabetes-induced genomic instability and for increasing cell viability was firstly indicated in the present study.
Measurement of social capital as an indicator of community-based initiatives (CBI) in the Islamic Republic of Iran.

PURPOSE The purpose of this paper is to observe whether measurement of social capital is an effective tool or can be used as a standard tool for community-based initiatives (CBI) evaluation. It also points at the significance of social capital in the health related grass root initiatives. DESIGN/METHODOLOGY/APPROACH CBI is an integrated socio-economic development approach implemented by the organized communities, supported by inter-sectoral actions for improvement of quality of life and health of the people. Support by WHO's office of Eastern Mediterranean Region, Islamic Republic of Iran implement programmes like basic development needs, healthy cities, healthy villages and women in health and development, that are evaluated during 2005-2006. Social capital, that includes the networking, sharing norms and cooperation amongst communities, is measured as one of the indicators during the evaluation, by surveying 240 households in three CBI and three control villages, using the World Bank's, Social Development Department's Social Capital Assessment Tool for data collection. FINDINGS The evaluation results reveal that the social capital indicators like affiliation percentage; trust reciprocity; and collective action are better in CBI areas than their controls. CBI areas have a better access to public services, are more peaceful, people are more willing to help others and there is less segregation due to income and social status. ORIGINALITY/VALUE The evaluation findings support the use of social capital indicators for investigating the impact and affectivity of CBI for health and development, and underlines the need for their consideration during implementation processes and further investigation.
Physical State of HPV16 and Chromosomal Mapping of the Integrated Form in Cervical Carcinomas

Using a procedure based on restriction enzyme cleavage, self-ligation, and inverse polymerase chain reaction (rli PCR), the authors investigated 18 cervical intraepithelial neoplasia III (CIN III) cases and 37 invasive squamous carcinomas for integration of human papillomavirus type 16 (HPV16 ). All eighteen CIN III cases (severe dysplasia or high-grade squamous intraepithelial lesion) were found to harbor episomal HPV, but one of the samples contained mixed episomal and integrated forms. Seventeen of 37 invasive cervical carcinoma samples were identified previously as containing the completely integrated HPV16 genome by using PCR covering the entire E1/E2 gene, and this was confirmed by rli PCR in 16 cases. One case, however, showed a low level of episomal deoxyribonucleic acid in addition to the predominant integrated form. Of the remaining 20 carcinoma samples showing episomal forms in the previous analysis, 14 were found to contain integrated forms using rli PCR, and four contained multimeric episomal forms. Thus, in total, 31 of 37 of the carcinomas (84%) showed the integrated HPV16 genome. The rli PCR product from five carcinoma cases was cloned into a plasmid vector and used as a template for “primer walking” deoxyribonucleic acid sequencing to deduce human sequences flanking the integrated HPV genome. Based on this information, bacterial artificial chromosome (BAC) and P1-derived artificial chromosome (PAC) clones were obtained and used as probes in fluorescent in situ hybridization experiments on human metaphase chromosomes. The results of the fluorescent in situ hybridization experiments showed evidence for HPV16 integration in chromosome regions 1q25, 3q28, 6p25, 11p13, and 18q22. Sixteen carcinoma samples, containing episomal HPV16, were sequenced in the long control region. Evidence for changes in E2 binding or silencer YY1 sequences was found in only two samples.
Antigenic Properties of the Human Immunodeficiency Virus Envelope during Cell-Cell Fusion

ABSTRACT Human immunodeficiency virus (HIV) fusion and entry involves sequential interactions between the viral envelope protein, gp120, cell surface CD4, and a G-protein-coupled coreceptor. Each interaction creates an intermediate gp120 structure predicted to display distinct antigenic features, including key functional domains for viral entry. In this study, we examined the disposition of these features during the fusion of HeLa cells expressing either HIVHXB2 envelope (Env cells) or CXCR4 and CD4 (target cells). Cell-cell fusion, indicated by cytoplasmic dye transfer, was allowed to progress for various times and then arrested. The cells were then examined for reactivity with antibodies directed against receptor-induced epitopes on gp120. Analyses of cells arrested by cooling to 4°C revealed that antibodies against the CD4-induced coreceptor-binding domain, i.e., 17b, 48d, and CG10, faintly react with Env cells even in the absence of target cell or soluble CD4 (sCD4) interactions. Such reactivity increased after exposure to sCD4 but remained unchanged during fusion with target cells and was not intensified at the Env-target cell interface. Notably, the antibodies did not react with Env cells when treated with a covalent cross-linker either alone or during fusion with target cells. Immunoreactivity could not be promoted or otherwise altered on either temperature arrested or cross-linked cells by preventing coreceptor interactions or by using a 17b Fab. In comparison, two other gp120-CD4 complex-dependent antibodies against epitopes outside the coreceptor domain, 8F101 and A32, exhibited a different pattern of reactivity. These antibodies reacted with the Env-target cell interface only after 30 min of cocultivation, concurrent with the first visible transfer of cytoplasmic dye from Env to target cells. At later times, the staining surrounded entire syncytia. Such binding was entirely dependent on the formation of gp120-CD4-CXCR4 tricomplexes since staining was absent with SDF-treated or coreceptor-negative target cells. Overall, these studies show that access to the CD4-induced coreceptor-binding domain on gp120 is largely blocked at the fusing cell interface and is unlikely to represent a target for neutralizing antibodies. However, new epitopes are presented on intermediate gp120 structures formed as a result of coreceptor interactions. Such findings have important implications for HIV vaccine approaches based on conformational alterations in envelope structures.
Alteration of the N‐glycome of bovine milk glycoproteins during early lactation

Milk provides nutritional, immunological and developmental components for newborns. Whereas identification of such components has been performed by targeting proteins and free oligosaccharides, structural and functional analyses of the N‐glycome of milk glycoproteins are scarce. In this study, we investigated, for the first time, the alterations of the bovine milk N‐glycome during early lactation (1 day, 1, 2, 3 and 4 weeks postpartum), characterizing more than 80 N‐glycans. The glycomic profile of colostrum on day 1 after calving differed substantially from that in other periods during early lactation. The proteins in colostrum obtained 1 day postpartum were more highly sialylated than milk samples obtained at other time points, and the N‐glycolylneuraminic acid (Neu5Gc)/N‐acetylneuraminic acid (Neu5Ac) ratio was significantly higher on day 1, showing a gradual decline with time. In order to dissect the N‐glycome of colostrum, alterations of the N‐glycosylation profile of major bovine milk proteins during the early lactation stage were elucidated, revealing that the alteration is largely attributable to qualitative and quantitative N‐glycosylation changes of IgG, the major glycoprotein in colostrum. Furthermore, by preparing and analyzing IgGs in which the N‐glycan structure and subtypes were well characterized, we found that the interaction between IgG and FcRn was not affected by the structure of the N‐glycans attached to IgG. We also found that bovine FcRn binds IgG2 better than IgG1, strongly suggesting that the role of FcRn in the bovine mammary gland is to recycle IgG2 from the udder to blood, rather than to secrete IgG1 into colostrum.
Differential antagonisms of anticonvulsants to various components of maximal seizures induced by electroshock or pentylenetetrazol in mice.

Effects of antiepileptic drugs on various components (TF: tonic extension of forelimb, TH: tonic extension of hindlimb and CL: clonic convulsions or MCL: myoclonus) of maximal seizures induced by electroshock or pentylenetetrazol in mice were examined in order to classify these drugs. In addition, experiment was conducted similarly on the new anti-convulsant agent, 3-sulfamoylmethyl-1,2-benzisoxazole (AD-810), in order to assess this compound on the basis of the results with clinically useful antiepileptic drugs. From the results obtained in the present study, irrespective of the method, i.e. chemically or electrically induced seizures, anticonvulsant drugs tested can be classified into four main groups; 1) drugs (trimethadione, ethosuximide, nitrazepam, diazepam, erthotoin and metharbital) with an effect to antagonize all the whole seizure components. (TF, TH and CL or MCL) in an almost same antagonism, 2) drugs (phenacemide, dipropylacetate, pheneturide, acetylpheneturide and phenobarbital) which inhibit all forms of seizures at relatively dissociated doses for the prevention of each component of seizures, 3) drugs (diphenylhydantoin and carbamazepine) which selectively abolish both components (TF and TH) of tonic seizures, and 4) drugs (acetazolamide, sulthiame and primidone) exclusively blocking TH of tonic seizures. AD-810 demonstrated an antagonistic effect on tonic seizures but no on clonic ones with the same manner as seen with diphenylhydantoin and carbamazepine.
Multiphase LC oscillators

This paper proposes an extensive analysis of multiphase LC oscillators. N oscillators coupled in a ring topology can generate multiphase outputs. For their nature, these oscillators operate off-resonance and consequently their phase noise worsens at increasing coupling strength. Since the coupling transistors raise the total power consumption, the noise-power product degrades even more with respect to a stand-alone oscillator. On the other hand, at high coupling factors, component mismatches affect less the phase accuracy. Closed-form expressions for phase noise and phase accuracy are derived which are verified against circuit simulations.
The Euro Area: Does one currency fit all?

ABSTRACT The sovereign debt crisis since the late 2000s in the Euro Area revealed that, in reality, there are two monetary unions in Europe: the core and the periphery. The core-north countries have sounder fiscal balances and lower inflation rates, whereas the periphery-south ones are more prone to higher inflation and public deficits. The principal aim of this paper is to explore which countries handle the nominal exchange rate of the euro. By doing this we will effectively challenge the statement ‘. one size fits all’ upon which the euro project was built. We used the real exchange rates of the initial 12 Eurozone members as an empirical instrument. Our evidence is based on the bivariate regression analysis and the Asymmetric Component GARCH (AC-GARCH) model. We discovered that the countries of the Eurozone core influence more the euro nominal exchange rate than the periphery ones. In addition, the euro is more vulnerable to the volatility shocks of the German and the French real exchange rates.
Birth Data for Patients Who Later Develop Growth Hormone Deficiency: Preliminary Analysis of a National Register

ABSTRACT. This study analyses gestational age, mode of delivery and size at birth in children who later developed idiopathic or organic growth hormone deficiency (GHD). A data register of children on growth hormone (GH) treatment in Sweden was compared with the Swedish Medical Birth Register during a 14‐year period (1973‐1986) comprising 1.4 million newborn children. Size at birth was evaluated using a new Swedish reference standard based on data from around 500,000 newborn children. It was found that the children who later develop idiopathic GHD (IGHD) were born with a normal distribution of gestational age. They were more often born with breech delivery (7.1%versus 2.8%) or caesarean section (16.6%versus 10.4%) compared with normal children. The children's condition at birth was poorer than normal, as shown by the frequency of Apgar scores below 7 at 5 minutes (5.2%versus 1.2%). Finally, it was found that children who later develop IGHD (n = 220) had a median birth length of 0.87 SDS below the mean and a median birth weight of 0.60 SDS below the mean of the standard. In contrast, both the birth length and weight of the children who later develop organic GHD (OGHD) (n = 92) did not differ from that of the reference.