Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Determinants of Microvascular Complications in Type 1 Diabetes

Diabetes mellitus is one of the most prevalent chronic diseases of modern societies and a major health problem in nearly all countries. Its prevalence has risen sharply worldwide during the past few decades (Amos et al., 1997; Shaw et al., 2010). Moreover, predictions show that diabetes prevalence will continue to rise, reaching epidemic proportions by 2030: 7.7% of world population, representing 439 million adults worldwide (Shaw et al., 2010). This increase is largely due to the epidemic of obesity and consequent type 2 diabetes (T2DM). However, the incidence of type 1 diabetes (T1DM) is also rising all over the world (DiaMond Project Group, 2006; Maahs et al., 2010). Recent data for Europe (Patterson et al., 2009) predict the doubling of new cases of T1DM between 2005 and 2020 in children younger than 5 years and an increase of 70% in children younger than 15 years, old. Despite major progresses in T1DM treatment during the past decades, mortality in T1DM patients continues to be much higher than in general population, with wide variations in mortality rates between countries. In Europe, these variations are not explained by the country T1DM incidence rate or its gross domestic product, but are greatly influenced by the presence of its chronic complications, especially diabetic renal disease (Groop et al., 2009; Patterson et al., 2007). In fact, much of the health burden related to T1DM is created by its chronic vascular complications, involving both large (macrovascular) and small (microvascular) blood vessels. Many genetic, metabolic and hemodynamic factors are involved in the genesis of diabetic vascular complications. However, major epidemiological and interventional studies showed that chronic hyperglycemia is the main contributor to diabetic tissue damage (DCCT Research Group, 1993). If the degree of metabolic control remains the main risk factor for the development of diabetic chronic complications, an important contribution can be attributed to genetic risk factors, some of them common for all microvascular complications (diabetic retinopathy, neuropathy, and renal disease) and some specific for each of them (Cimponeriu et al., 2010). Additional factors are represented by some accelerators such as hypertension and dyslipidemia. In the following pages, we present briefly the pathogenesis type 1 diabetes and its chronic microvascular complications. The main information of the genetic background in T1DM with particular focus on gene variants having strong impact on endothelial dysfunction as the key factor in the development of microvascular disorders are also summarized.
The tail is wagging the dog

The rules and regulations regarding the classification process through which athletes must be vetted to determine eligibility for Paralympic competition have been transformed drastically over the last two decades. A complex classification system initially developed by the International Organizations of Sport for the Disabled (IOSD) has been the distinctive feature of the Paralympic movement over this period. Key consideration must be given to the equitable nature of any classification system imposed by the International Paralympic Committee (IPC) in order to comply with the ideology of Paralympism. Paralympism is manifest in the dictum of the Paralympic movement: `empower, inspire and achieve'. Using ethnographic data obtained by the author while a Paralympic athlete and journalist, this article explores recent debates within the sport of athletics surrounding classification. This is achieved by highlighting the process of classification and how, as a result of this process, some bodies are celebrated and others are not within a sporting culture established as a ghetto for imperfection.
The structure and properties of gluten: an elastic protein from wheat grain.

The wheat gluten proteins correspond to the major storage proteins that are deposited in the starchy endosperm cells of the developing grain. These form a continuous proteinaceous matrix in the cells of the mature dry grain and are brought together to form a continuous viscoelastic network when flour is mixed with water to form dough. These viscoelastic properties underpin the utilization of wheat to give bread and other processed foods. One group of gluten proteins, the HMM subunits of glutenin, is particularly important in conferring high levels of elasticity (i.e. dough strength). These proteins are present in HMM polymers that are stabilized by disulphide bonds and are considered to form the 'elastic backbone' of gluten. However, the glutamine-rich repetitive sequences that comprise the central parts of the HMM subunits also form extensive arrays of interchain hydrogen bonds that may contribute to the elastic properties via a 'loop and train' mechanism. Genetic engineering can be used to manipulate the amount and composition of the HMM subunits, leading to either increased dough strength or to more drastic changes in gluten structure and properties.
Mobile learning in resource-constrained environments: A case study of medical education

Background: The achievement of the millennium development goals may be facilitated by the use of information and communication technology in medical and health education. Aims: This study intended to explore the use and impact of educational technology in medical education in resource-constrained environments. Methods: A multiple case study was conducted in two Nepalese teaching hospitals. The data were analysed using activity theory as an analytical basis. Results: There was little evidence for formal e-learning, but the findings indicate that students and residents adopted mobile technologies, such as mobile phones and small laptops, as cultural tools for surprisingly rich ‘informal’ learning in a very short time. These tools allowed learners to enhance (a) situated learning, by immediately connecting virtual information sources to their situated experiences; (b) cross-contextual learning by documenting situated experiences in the form of images and videos ─ and re-using the material for later reflection and discussion and (c) engagement with educational content in social network communities. Conclusion: By placing the students and residents at the centre of the new learning activities, this development has begun to affect the overall educational system. Leveraging these tools is closely linked to the development of broad media literacy, including awareness of ethical and privacy issues.
Estado de la biodiversidad terrestre de la Región Autónoma Atlántico Sur (RAAS), Nicaragua

La Region AutoLnoma Atlantico Sur (RAAS) de Nicaragua aparece con frecuencia en la literatura academica a raiz de su alta diversidad cultural y biologica, y por su reconocimiento como uno de los ultimos lugares remotos del mundo. No obstante, la biodiversidad terrestre de la region carece de representacion en las publicaciones cientificas, las cuales se limitan a perspectivas generales no basadas en datos cientificos, estudios de la etnobotanica e investigaciones sobre la deforestacion o regeneracion del bosque. Este articulo presenta un informe de los resultados preliminares de una investigacion sobre la diversidad de los mamiferos y aves terrestres, basada en el uso de camaras con sensores de movimiento. Asimismo, se refiere tanto la literatura historica como la literatura contemporanea de la zona para explorar las implicaciones potenciales. La evidencia sugiere que la recopilacion de datos basicos sobre la biodiversidad regional debe ser una prioridad en la etapa actual, durante la cual varias fuerzas locales y globales van conectando y cambiando la Costa Caribe; convirtieendola en un lugar no tan remoto, y si sostenible y amigable a la fauna silvestre como aparece en la mayoria de la literatura.
The Howiesons Poort of South Africa: what we know, what we think we know, what we need to know

This contribution aims to provide a concise review of Howiesons Poort research conducted over the past eight decades since the industry was first identified. A review is considered useful in the light of current interest in the industry and what it means in terms of technological and cognitive evolution. It is also true that far-reaching behavioural hypotheses have been built around the Howiesons Poort, some with very little supporting evidence. Recent developments in stone tool analysis, environmental reconstruction and dating methodology are providing us with new tools to measure the time depth and limits of the Howiesons Poort. Such methods may also provide detailed empirical data to build onto or re-assess hypotheses regarding human behaviour associated with this stone tool industry.
Risk and protective factors for cognitive impairment in persons aged 85 years and older

Objective: To determine risk and protective factors for mild cognitive impairment (MCI) among persons 85 years and older. Methods: Participants in the population-based prospective Mayo Clinic Study of Aging were comprehensively evaluated at baseline and at 15 monthly intervals to determine incident MCI. At baseline, lifestyle factors in midlife and late life were assessed by self-reported questionnaire; vascular and comorbid conditions were abstracted from participants' medical records. Results: Of 256 participants who were cognitively normal at enrollment (median age 87.3 years, 62% women), 121 developed MCI at a median 4.1 years of follow-up. Predictors of MCI were APOE ε4 allele (hazard ratio [HR] 1.89; p = 0.008), current depressive symptoms (HR 1.78; p = 0.02), midlife onset of hypertension (HR 2.43; p = 0.005), increasing number of vascular diseases (HR 1.13; p = 0.02), and chronic conditions from the Charlson Comorbidity Index (HR 1.08; p = 0.006). Models were adjusted for sex and education, with age as the time variable. The risk of MCI was reduced for participants who reported engagement in artistic (HR 0.27; p = 0.03), craft (HR 0.55; p = 0.02), and social (HR 0.45; p = 0.005) activities in both midlife and late life, and in the use of a computer in late life (HR 0.47; p = 0.008). Conclusions: Chronic disease burden increases risk of MCI, whereas certain lifestyle factors reduce risk in persons 85 years and older. This implies that preventive strategies for MCI may need to begin in midlife and should persist throughout late life.
A hierarchical multi-agent dynamical system architecture for resilient control systems

Resilient control systems refers to the ones that maintain state awareness and an accepted level of operational normalcy in response to disturbances, including threats of an unexpected and malicious nature. In this paper, we propose a notional research philosophy and resulting framework based on a three-layer architecture of hierarchical multi-agent dynamic systems (HMADS). While a number of different alternatives have been proposed for distributed control system design, few provide the level of integration necessary to support claims of superior performance over traditional designs. We discuss multiple notional attributes associated with HMADS, namely, their functionalities, hardware independence and intelligence. We provide a framework for design of HMADS, and use power systems as a notional example as an illustration of the HMADS design philosophy.
Tako-Tsubo and reverse Tako-Tsubo cardiomyopathy: temporal evolution of the same disease?

A 58-year-old female presented with severe chest pain following news of bereavement. ECG suggested myocardial ischaemia, and troponin-I (2.19 µg/mL) was raised. Left ventricular (LV) echocardiogram ( Panel 1 ) showed apico-midventricular akinesia and basal hyperkinesia. Forty-eight hours later, coronary arteries were normal ( Panel 2a and b ) and LV angiogram ( Panel 3a and b ) showed mid-ventricular ballooning and …
Defective Dopamine Generation From Dihydroxyphenylalanine in Stable Essential Hypertensive Patients

We studied the metabolic pathways of dihydroxyphenylalanine (DOPA) and dopamine as well as the cardiovascular and renal responses to a single administration of DOPA (500 mg orally) in stable essential hypertension. We found that after DOPA, stable hypertensive patients compared with controls showed more blood pressure decrease without reflex tachycardia, had lower creatinine clearance but a higher fractional excretion of sodium, and had lower plasma renin activity at the height of DOPA action. Hypertensive patients also showed increased plasma DOPA, the ratio of plasma DOPA to dopamine, and the sum of plasma DOPA and 3-O-methyl-DOPA, as well as increased urinary 3-O-methyl-DOPA and the plasma and urine dopamine metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid. Finally, despite an augmented post-DOPA glomerular load of DOPA, the predominant source of urinary dopamine, the excretion rates of dopamine and its metabolites remained comparable in hypertensive patients to those in control subjects. These data suggest that, in stable hypertensive patients, exogenous DOPA is to a lesser degree decarboxylated to dopamine, which is more rapidly metabolized intraneuronally. Contrasting with this finding are the hyperdopaminergic features, such as hypernatriuresis with renin suppression and excessive blood pressure decline in the absence of reflex tachycardia. They may be due to an upregulation of renal, vascular, and brain dopaminergic receptors secondary to a preexisting dopaminergic deficiency in stable essential hypertension.
Transthyretin and cystatin C are catabolized in proximal tubular epithelial cells and the proteins are not useful as markers for renal cell carcinomas

Ten human kidney specimens and thirty‐two renal cell carcinomas were investigated for the presence of transthyretin mRNA and cystatin C mRNA using Northern blot analysis. Five of ten kidney specimens and 15 of 32 renal carcinomas were also immunohistochemically investigated for the presence of the corresponding proteins. Transthyretin mRNA could not be detected in any of the normal or neoplastic tissue preparations, whereas low amounts of cystatin C mRNA were found in nine of ten normal kidneys and in 24 of 32 renal cell carcinomas. Immunoreactive transthyretin and cystatin C were present in proximal tubular epithelial cells of all kidney specimens, whereas neither of the proteins was detected in the tumour cells of the renal carcinomas. Immunoreactive cystatin C was, however, demonstrated in scattered monocyte/macrophage‐like cells. We conclude that the presence of immunoreactive transthyretin and cystatin C in proximal tubular cells of the kidney is most likely due to reabsorption of the proteins from the primary urine. The small amounts of cystatin C mRNA in some of the normal and neoplastic renal preparations are probably due to cystatin C synthesis in macrophages. Transthyretin has been recommended as an immunohistochemical marker for renal cell carcinomas. Our results, however, clearly indicate that neither transthyretin nor cystatin C constitutes a useful marker for such neoplasms.
Refined exponential stability for stochastic Markovian jump systems with nonlinearity and time-varying delays

This paper is concerned with exponential stability for stochastic Markovian jump systems with nonlinearity and time-varying delay. By combining Lyapunov-Krasovskii functional method and Jensen inequality technique, a delay-dependent and delay-rate-dependent exponential stability criterion for stochastic Markovian jump systems with nonlinearity and time-varying delay is investigated. The proposed approach removes some free-weighting matrices required in [Int. J. Robust Nonlinear control, 2010, 20(1): 16-26], which reduces computational complexity. It is mathematically shown that the approach proposed here may be less conservative than the one mentioned above. Two numerical examples are provided to illustrate the applicability and the benefits of the proposed approach.
Best bilinear shell element: flat, twisted or curved?

This thesis concerns the accuracy of finite element models for shell structures. The focus is on low-order approximations of layer and vibration modes in shell deformations with particular reference to problems with concentrated loads. It is shown that parametric error amplification, or numerical locking, arises in these cases when bilinear elements are used and the formulation is based on the so-called degenerated solid approach. Furthermore, an alternative way for designing bilinear shell elements is discussed. The procedure is based on a refined shallow shell model which allows for an effective coupling between the membrane and bending strain in the energy expression. AMS subject classifications: 74S05, 74K25
Locating controlling regions of neural networks using constrained evolutionary computation

Detection of controlling regions/driver nodes of the cortical networks helps the networks dynamics reach a desired state. Controllability of the complex networks can be accomplished through minimizing two quantities related to the eigenvalues of the extended adjacency matrix. The identification problem of the driver nodes can be solved as a Constrained Optimization Problem which unifies these two quantities into one framework. The cat cortical network is taken as an example of a directed weighted complex network. In this paper, the Constrained Dynamic Differential Evolution (CDDE) algorithm is generalized to produce the Generalized Constrained Dynamic Differential Evolution (GCDDE) algorithm. The GCDDE uses the exploitation probability Pe to determine whether the crossover rate CR takes random large values from the range [0.5, 1] to produce different levels of exploration ability or takes random small values from the range [0, 0.5] to produce different levels of exploitation ability. Through the value of Pe, GCCDE can attain the tradeoff between exploration and exploitation with multiformity. Then, the algorithms GCDDE and CDDE are applied to determine the controlling regions of the cortical networks. The results illustrate that GCDDE outperforms four state-of-the-art Constrained Optimization Evolutionary Algorithms and also approaches of the control theory and graph theory. Using GCDDE, the identification problem of driver nodes is investigated in a macroscopic manner. It is found that the controlling regions have a high in-degree and a low out-degree. It is important to mention that when the number of driver nodes increases, the GCDDE can find feasible optimal solutions that make the cat cortical network more controllable.
2-(1-Adamantyl)-4-bromoanisole at 123 K

In the title compound [systematic name: 2-(1-adamantyl)-4-bromo-1-methoxybenzene], C17H21BrO, two weak intramolecular C—H⋯O hydrogen bonds influence the molecular conformation. The crystal packing exhibits C—H⋯π interactions, with a relatively short intermolecular C⋯Cg contact of 3.568 (5) Å, where Cg is the centroid of the benzene ring. The crystal studied exhibited inversion twinning.
Effects of Melittin on Endothelium‐Dependent Relaxation and Cyclic GMP Levels in Rat Aorta

The present study investigates the mechanism of endothelium-dependent relaxation of vascular smooth muscle. Melittin, a polypeptide found in honeybee venom and a known activator of phospholipase A2, induced transient, endothelium-dependent relaxations of rat thoracic aortae contracted with norepinephrine. Higher concentrations of melittin induced relaxations followed by contractions. Prior incubation of melittin with trypsin abolished the changes in relaxation and contraction due to melittin. Melittin (10 μg/ml)-induced relaxations were associated with transiently elevated levels of cyclic GMP with a peak increase of 30-fold, which occurred 30 seconds after melittin exposure. Melittin (10 μg/ml) elevated cyclic AMP levels less than twofold and this effect was variable. A lower concentration of melittin (1 μg/ml) elevated cyclic GMP levels approximately twofold, while exposure to 1 μg/ml melittin in the presence of the cyclic GMP phosphodiesterase inhibitor, M&B 22948 (1 mM), increased cyclic GMP levels fivefold. Removal of the endothelium prevented the increased levels of cyclic GMP and cyclic AMP due to melittin. Exposure to the guanylate cyclase inhibitor, methylene blue, prevented the increased levels of cyclic GMP. Methylene blue, nordihydroguaiaretic acid, and the phospholipase A2inhibitor, parabromophenacyl bromide, inhibited melittin-induced relaxations, while the cydo-oxygenase inhibitor, indomethacin, was without effect. Arachidonic acid increased cyclic AMP levels but had no effect on cyclic GMP levels in the presence or absence of indomethacin. Relaxations to melittin, and to the endothelium-dependent vasodilators acetylcholine, trypsin, histamine, and the Ca2+ ionophore A23187, and/or the associated increased cyclic GMP levels, were reduced following exposure to melittin. Prior exposure to polyarginine (10 μg/ml), which induced endothelium-dependent relaxations that were prevented by methylene blue, also inhibited relaxations to the endothelium-dependent vasodilators. In contrast, relaxations to sodium nitro-prusside were potentiated in tissues previously exposed to melittin. Removal of the endothelium by rubbing the intimal surface also potentiated relaxations to sodium nitroprusside. Scanning electron micrographs of the intimal surface demonstrated that melittin and polyarginine greatly damaged the endothelial cells. The present results suggest that polycation containing peptides induce endothelium-dependent relaxation through elevation of cyclic GMP levels within the smooth muscle. Furthermore, these peptides may desensitize tissues to endothelium-dependent vasodilation by causing damage to the endotheUal cells.
Structural relationship between a bacterial developmental protein and eukaryotic PP2C protein phosphatases

Bacillus subtilis SpoIIE is a Ser protein phosphatase whose action on the phosphoprotein SpoIIAA triggers the cell type‐specific activation of a sporulation transcription factor. Here we report that SpoIIE displays sequence similarity to the PP2C family of eukaryotic Ser/Thr protein phosphatases, and that residues common to these proteins are required for the function of both SpoIIE and TPD1, a yeast PP2C. These findings suggest that SpoIIE and the PP2C protein phosphatases are structurally related, and reveal a striking formal similarity between the SpoIIAA regulatory circuit and that of mammalian mitochondrial pyruvate dehydrogenase. This similarity may reflect an evolutionarily conserved mechanism of biological regulation based on the interplay of His protein kinase‐like Ser kinases and PP2C‐like protein phosphatases.
Making self-help more helpful: a randomized controlled trial of the impact of augmenting self-help materials with implementation intentions on promoting the effective self-management of anxiety symptoms.

OBJECTIVE The effectiveness of self-help materials may be constrained by failures to undertake recommended exercises or to deploy the techniques that one has learned at the critical moment. The present randomized controlled trial investigated whether augmenting self-help materials with if-then plans (or implementation intentions) could overcome these problems and enhance the self-management of anxiety symptoms. METHOD At baseline, participants who reported anxiety symptoms completed the Hospital Anxiety and Depression Scale (HADS) and the state version of the State-Trait Anxiety Inventory (STAI). Participants were then randomized via a computer program to standard self-help (n = 86), augmented self-help (n = 90), or no-intervention (n = 86) conditions. Eight weeks later, 95% (n = 249) of the participants completed the HADS and STAI again. RESULTS Findings showed a significant reduction in anxiety in the augmented self-help condition compared with both the standard self-help and no-intervention conditions (caseness rates on the HADS at follow-up were 21%, 49%, and 44%, respectively). Mediation analyses indicated that the benefits of augmented self-help materials were explained by improved detection of anxiety-related triggers and greater experienced benefits of the self-help techniques. CONCLUSIONS These findings suggest that implementation intentions offer a valuable supplement to self-help materials that can enhance their impact on outcomes.