Miracle-dz/UniFAR-FTUs huggingface dataset:
Altered b -Cell Prohormone Processing and Secretion in Type 1 Diabetes

Analysis of data from clinical cohorts, and more recently from human pancreatic tissue, indicates that reduced prohormone processing is an early and persistent ﬁ nding in type 1 diabetes. In this article, we review the current state of knowledge regarding altera-tions in islet prohormone expression and processing in type 1 diabetes and consider the clinical impact of these ﬁ ndings. Lingering questions, including pathologic etiologies and consequences of altered prohormone expression and secretion in type 1 diabetes, and the natural history of circulating prohormone production in health and disease, are considered. Finally, key next steps required to move forward in this area are outlined, including longitudinal testing of relevant clinical populations, studies that probe the genetics of altered prohormone processing, the need for combined functional and histologic testing of human pancreatic tissues, continued interrogation of the intersection between prohormone processing and autoimmunity, and optimal approaches for analysis. Successful resolution of these questions may offer the potential to use altered prohormone processing as a biomarker to inform therapeutic strategies aimed at personalized intervention during the natural history of type 1 diabetes and as a pathogenic anchor for identi ﬁ cation of potential dis-ease-speci ﬁ c endotypes. The is cleaved further by PC1/3 to form insulin and C-peptide. Ex vivo studies as well as analysis of circulating forms of proinsulin in humans, revealing higher levels of the des-31,32 proinsulin intermediate in comparison with des-64,65 proinsulin, support a model where initial cleavage by PC1/3 is strongly favored. preproinsulin, the creating 67-residue end cleaved is cleaved at its N-terminal end C-terminus of IAPP is amidated a -ami- dating monooxygenase Alternative processing of proIAPP in is Recent analyses have suggested that may be more critical than for -cell proinsulin processing, although impacts on human proIAPP tested
A Comparison of Inference Methods in High-Dimensional Linear Regression

Building confidence/credible intervals for the high-dimensional (p >> n) linear models have been the subject of exploration for many years. In this paper, we explore three specific setups. First, we look at the Bayesian paradigm for the LASSO model. A double-exponential prior has been applied to the regression coefficient and from that, a posterior distribution is derived to get the necessary quantiles to calculate the credible intervals for the regression coefficients. Second, we explore the de-sparsified LASSO estimates, and using its asymptotic normality, we calculate the confidence intervals for the model coefficients. Finally, we incorporate an adaptive LASSO model. To calculate the confidence intervals, we have used the residual and perturbation bootstrap methods and obtained the necessary quantiles. All three methods have been put through a simulation study to compare the interval coverage of the true coefficient values. The width of the intervals is also compared. We make n, the sample size fixed, and explore the cases where we put a set of correlated covariates as true values. The considered number of covariates, p includes 200, 500, and 1000. We also compare the time it takes to complete 10 runs of each setup on a personal computer. We assume two kinds of correlation structures for data. We call the first one AR-1 and the second one is known as compound symmetry. For AR-1 cases, when p >> n, the Bayesian LASSO provides better coverage for true non-zero coefficient, especially if the correlation is close to 0.9 and 0.5. For compound symmetry cases, the desparsified LASSO seems to provide closer to the nominal coverage regardless of the value of correlation coefficient, ρ. However, the coverage is around 0.90 for p = 1000. This better coverage comes with the cost of getting wider intervals for highly corre-
Complex by the Src-FAK Kinase a Phosphatase Phosphorylation of Protein Tyrosine Autophosphorylation and Directs the Adhesion Kinase (FAK) Grb2 Promotes Integrin-Induced Focal

Grb2 promotes integrin-induced focal adhesion kinase (FAK) autophosphorylation and directs the phosphorylation of protein tyrosine phosphatase α by the Src-FAK kinase complex. The integrin-activated Src-focal adhesion kinase (FAK) kinase complex phosphorylates PTP (cid:2) at Tyr789, initiating PTP (cid:2) -medi-ated signaling that promotes cell migration. Recruitment of the BCAR3-Cas complex by PTP (cid:2) -phospho-Tyr789 at focal adhesions is one mechanism of PTP (cid:2) signaling. The adaptor protein Grb2 is also recruited by PTP (cid:2) -phospho-Tyr789, although the role of the PTP (cid:2) -Grb2 complex in integrin signaling is unknown. We show that silencing Grb2 expression in ﬁbroblasts abol-ishes PTP (cid:2) -Tyr789 phosphorylation and that this is due to two unexpected actions of Grb2. First, Grb2 promotes integrin-in-duced autophosphorylation of FAK-Tyr397. This is impaired in Grb2-depleted cells and prohibits FAK activation and formation of the Src-FAK complex. Grb2-depleted cells contain less paxillin, and paxillin overexpression rescues FAK-Tyr397 phosphorylation, suggesting that the FAK-activating action of Grb2 involves paxillin. A second distinct role for Grb2 in PTP (cid:2) -Tyr789 phosphorylation involves Grb2-mediated coupling of Src-FAK and PTP (cid:2) . This requires two phosphosites, FAK-Tyr925 and PTP (cid:2) Tyr789, for Grb2-Src homology 2 (SH2) binding. We propose that a Grb2 dimer links FAK and PTP (cid:2) , and this positions active Src-FAK in proximity with other, perhaps integrin-clustered, molecules of PTP (cid:2) to enable maximal PTP (cid:2) -Tyr789 phosphorylation. These ﬁndings identify Grb2 as a new FAK activator and reveal its essential role in coordinating PTP (cid:2) tyrosine phosphorylation to enable downstream integrin signaling and migration.
In Vivo and In Vitro Characterization of Primary Human Liver Macrophages and Their Inﬂammatory State

: Liver macrophages (LMs) play a central role in acute and chronic liver pathologies. Investigation of these processes in humans as well as the development of diagnostic tools and new therapeutic strategies require in vitro models that closely resemble the in vivo situation. In our study, we sought to gain further insight into the role of LMs in different liver pathologies and into their characteristics after isolation from liver tissue. For this purpose, LMs were characterized in human liver tissue sections using immunohistochemistry and bioinformatic image analysis. Isolated cells were characterized in suspension using FACS analyses and in culture using immunoﬂuorescence staining and laser scanning microscopy as well as functional assays. The majority of our investigated liver tissues were characterized by anti-inﬂammatory LMs which showed a homogeneous distribution and increased cell numbers in correlation with chronic liver injuries. In contrast, pro-inﬂammatory LMs appeared as temporary and locally restricted reactions. Detailed characterization of isolated macrophages revealed a complex disease dependent pattern of LMs consisting of pro- and anti-inﬂammatory macrophages of different origins, regulatory macrophages and monocytes. Our study showed that in most cases the macrophage pattern can be transferred in adherent cultures. The observed exceptions were restricted to LMs with pro-inﬂammatory characteristics.
Stock Prices Prediction Using Machine Learning and Deep Learning Techniques

- Predicting how the stock market will perform is one of the most difficult things to do. There are so many factors involved in the prediction – physical factors vs. psychological, rational, and irrational behaviour, etc. All these aspects combine to make share prices volatile and very difficult to predict with a high degree of accuracy. Can we use machine learning as a game changer in this domain? Using features like the latest announcements about an organization, their quarterly revenue results, etc., machine learning techniques have the potential to unearth patterns and insights we did not see before, and these can be used to make unerringly accurate predictions.
Formulation and Evaluation of Controlled Release Tablet of Lamotrigine

Controlled drug delivery can be defined as delivery of the drug at a predetermined rate and/or to a location according to the needs of the body and disease states for a definite time period. Controlled release drug administration means not only the prolongation of the duration of drug delivery, similar to the objective in sustained release and prolonged release, but the term also implies the predictability and reproducibility of drug release kinetics. Oral controlled release drug delivery system is one that provides continuous oral delivery of drugs at predictable and reproducible kinetics for a pre-determined period throughout the course of GI transit.
15 Germany ’ s Labour Market Policies How the Sick Man of Europe Performed a Second Economic Miracle

Not even two decades ago Germany was widely derided as ‘the sick man of the Euro’ (The Economist 1999). A ‘slow-motion country’ (Franz and Immerfall 2003), stagnant, and ridden by political paralysis in reforming its permanent problem (Trampusch 2003), the rigid labour market. Times have changed, and Germany has since been praised as an ‘economic superstar’ (Dustmann et al. 2014), a ‘jobs miracle’ (Krugman 2009), and a ‘labour market miracle’ (Burda and Hunt 2011). It has come to be held up as a ‘strong referencemodel for other countries’ and for ‘effective, evidence-based policymaking’ (Rinne and Zimmermann 2013: 18, 19). How has this big change of fortune and reputation been achieved? This chapter tells the story of how the turnaround was the product of a combination of structural reforms from 2002 onwards and short-term measures in face of the global recession starting in 2008. Both sets of measures reinforced one another, as they both followed an approach of ‘putting work first’ (i.e. maximizing employment). The prioritization of employment implied a paradigm shift in Germany, which had a long-standing reputation as a passive welfare state. The step change towards active and rapid integration into work as a policy priority was triggered by the so-called Hartz reforms, implemented between 2002 and 2005. Job search assistance and monitoring gained importance, whereas ineffective job creation schemes were abolished or reduced. These activation-focused reforms successfully tackled structural unemployment and increased the overall employment rate. They strengthened Germany’s economic resilience during the 2008 economic crisis, though crucial in mitigating the impact of the recession on Germany’s labour market were the short-time work allowance, a time-limited state subsidy, and instruments of working-time flexibility at the firm level to adjust working hours to match a decline in demand, as well as two closely spaced stimulus packages in 2008 and 2009. The German success story is one of good reform crafting, political leadership, and astute macro-economic crisis management benefiting from the fortuitous OUP CORRECTED PROOF – FINAL, 25/7/2019, SPi
Profit Maximization via Virtual Resources Allocation in Cloud-Computing

: With increasing demand for high performance computing and data storage, distributed computing systems have attracted a lot of attention. To have a cost efficient usage of computing resources, resource scalability and on demand services are required through virtualization and distributed computing. Service charges and business costs both should known by the service provider for the profit maximization. These are determined by the multi server system configuration and the applications. Optimizations of computing and networking resources need to be jointly performed. The problem of optimal multi server configuration for profit maximization in cloud computing takes such factors as the service provider’s margin and profit, the quality of service(QoS), the cost of renting, the cost of energy consumption, the workload of an application, the service level agreement(SLA), the configuration of multi server system, the amount of service. Optimization problem can be formulated and solved analytically by using M/M/m queuing model in multi server system configuration. As a framework to virtual resource mapping , a mixed integer programming(MIP) problem is formulated which relates to cost efficiency of resource mapping procedure. The link mapping can be achieved by multi commodity flow allocation problem.
CHARACTERISTICS OF QUANTUM DOTS LASER SUBJECTED TO CONVENTIONAL AND FILTERED OPTICAL FEEDBACK

The quantum dots laser under the influence of conventional and filtered feedback is analyzed in the framework of the extended Lang-Kobayashi rate equations. The feedbacks comes from two separate branches: conventional and filtered optical feedback. We introduce a filtered feedback to control the unstable behavior of laser induced by conventional optical feedback. The stationary states, so called external filtered modes, of quantum dot laser under the influence of double feedback are obtained analytically. The locations of these modes are plotted in the plane of different parameters. Finally, it is shown that under appropriate conditions the laser system generate different behavior as continuous wave, periodic and chaotic behavior. In the case of equal feedback strengths in both channels it is shown that for a small feedback strength the phase portrait is a stable focus. With increase of the both feedback strengths the phase portrait became a limit cycle, and finally goes to a strange attractor.
EFFECT OF GRADED LEVELS OF LYSINE ON LATE BEHAVIOR OF LAYING HENS IN NORTHERN GUINEA SAVANNA.

An experiment was conducted with 120 beak trimmed 46 weeks old layers (Shika Brown Strain) to investigate the effect of varying lysine levels on late behaviour of the hens in deep litter system. Laying Hens were randomly allocated to 5 experimental diets containing varying lysine levels (0, 0.1, 0.2, 0.3 and 0.4%) each replicated 3 times. Behavioural observations were obtained using focal continuous sampling and instantaneous scan sampling methods, timed for 15 minute before feeding the hens and after feeding, respectively. The result indicated that both normal and stereotype behaviours increased significantly with increasing lysine level in the diet (58.01+2.91%; p < 0.01) and (18.60+1.32%; p<0.001) respectively. It was therefore concluded that including 0.4% level of lysine in the diet of laying hens during the late laying period may affect the behaviour of the hens either positively or negatively during the dry season period in northern guinea savannah. Farmers in Nigeria could therefore control undesirable behaviours such as egg destruction and feather pecking through nutritional and other management factors for optimum flock performance.
The Research of Critical Success Factors for Performance-oriented Electronic Support Systems - Resource-Based View

—Intensive competition has driven enterprise to look for more effective methods to increase performance. The Electronic Performance Support System (EPSS) has been proposed to provide instant performance whenever and wherever needed. However, due to its difference to traditional e-learning mindset, the adoption and design of EPSS is still at the early stage. This research aims to find the critical success factors of EPSS adoption through Resource-Based View (RBV). Six companies that adopted EPSS were interviewed and the success factors were identified. The results show that organizational needs, knowledge management and renewal, training materials and top management support are among the most cited factors for success. Finally, specific recommendations for companies in different adoption phases are given for better success rate.
Warming E ﬀ ort and Energy Budget Di ﬀ erence of Various Human Land Use Intensity: Case Study of Beijing, China

: Human land use intensity a ﬀ ects the surface energy balance by changing the biogeophysical parameters. This study used Moderate Resolution Imaging Spectroradiometer remote sensing data and surface energy balance algorithms to quantify changes in surface energy budgets corresponding to changes in land use in Beijing from 2000 to 2015. Land use was reclassiﬁed by considering land use intensity. The di ﬀ erence in the latent heat ﬂux (LE) and net radiation (R n ) (LE − R n ) expressed the warming or cooling e ﬀ ect. The results showed that: (i) The increasing trend of net longwave radiation in Beijing o ﬀ set the decreasing trend of net shortwave radiation. The R n changed slightly, while the LE and LE − R n showed a signiﬁcant increase of 0.55 and 0.56 W / (m 2 · year), respectively. The ﬁndings indicated that considering only radiative forcing, or even R n , was not enough to measure the impacts of land use change on the energy budget. (ii) The order of R n , LE, and LE − R n values from high to low were natural and seminatural areas, cropland, mixed pixel areas, urban expansion areas, and old urban areas. Compared with natural and seminatural areas, the changing LE − R n trend in the other four land use types decreased with the increase in human impact intensity, indicating that human activities weakened the positive change trend of LE − R n and increased the warming e ﬀ ect. (iii) Although the temporal trend of LE increased in Beijing from 2000 to 2015, the e ﬀ ect of R n on LE − R n was greater than that of LE, especially in the four land use types a ﬀ ected by human activities. The results for surface temperature in various land use types conﬁrmed this point. This study highlights the energy budget di ﬀ erences of various land use types a ﬀ ected by human activities. It makes an important contribution to understanding the urban heat island e ﬀ ect from a biogeophysical perspective.
Validity and reliability of the Noor EvidenceBased Medicine Questionnaire: A cross-sectional study

Background Evidence-based medicine (EBM) is a widely accepted scientific advancement in clinical set-tings that helps achieve better, safer, and more cost-effective healthcare. However, pres-ently, validated instruments to evaluate healthcare professionals’ attitude and practices toward implementing EBM are not widely available. Therefore, the present study aimed to determine the validity and reliability of a newly developed knowledge, attitude, and practice (KAP) questionnaire on EBM for use among healthcare professionals. The Noor Evidence-Based Medicine Questionnaire was tested among physicians in a government hospital between July and August 2018. Exploratory factor analysis and internal consistency reliability-based Cronbach’s alpha statistic were conducted. The questionnaire was distributed among 94 physicians, and 90 responded (response rate of 95.7%). The initial number of items in the KAP domains of the Noor Evidence-Based Medicine Questionnaire were 15, 17, and 13, respectively; however, two items in the practice domain with communalities < 0.25 and factor loadings < 0.4 were removed. The factor structure accounted for 52.33%, 66.29%, and 55.39% of data variance in the KAP domains, respectively. Cronbach’s alpha values were 0.81, 0.81, and 0.84 for KAP domains, respec-tively, indicating high reliability. This can be used to evaluate the knowledge, attitudes, and behaviour of healthcare professionals toward EBM. Future testing of this questionnaire among other medical will expand the of this
PHOTODYNAMIC THERAPY APPLIED IN NON-SURGICAL TREATMENT OF PERIODONTITIS KLINIČKI I MIKROBIOLOŠKI EFEKTI PRIMENE FOTODINAMSKE TERAPIJE U NEHIRURŠKOJ TERAPIJI PARODONTOPATIJE

3 Background/Aim. Treatment of periodontitis undergoes several treatment phases. Nonsurgical periodontal treatment (NSPT) represents basic treatment stage and it is applied to all the patients undergoing periodontal treatment. Adjunctive antimicrobial photodynamic therapy (aPDT) is one of several contemporary and relatively new possibilities with a role to inactivate microorganisms responsible for the occurrence and progression of a disease. The aim of this study was to comparatively analyse clinical and microbiological effects of the NSPT alone as well as combined with aPDT. Methods. Split-mouth method design was used in a prospective randomized controlled trial. The following clinical parameters have been registered and monitored: plaque index (PI), bleeding on probing, probing depth (PD) and clinical attachment level (CAL). The presence of microorganisms Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Treponema denticola has been detected by the polymerase chain reaction (PCR) method. Samples have been tested before the therapy, as well as three months after the therapy. Therapeutic modalities of NSPT and NSPT with adjunct aPDT have been examined. Results. All of the analysed clinical parameters have proved statistically significant improvement after the application of both treatment modalities (p<0,001). Microbiological analyses have shown that total number of microorganisms is statistically significantly lower after the application of both methods (p<0,001). Following the treatment, there was a statistically significantly reduced number of microorganisms Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Treponema denticola (p<0,001). NSPT combined with aPDT led to a statistically significant improvement of both clinical parameters and microbiological status in relation to causal therapy applied on its own. Conclusion. The research has shown improvement of all clinical indicators after the application of both treatment modalities. Total number of microorganisms has been reduced as well as the number of specific microorganisms. Combining aPDT with NSPT led to a reduction in the number of microorganisms compared to NSPT alone.
A New Wireless Power-Transfer Circuit for Retinal Prosthesis

This paper presents a novel resonant power converter for transcutaneous power transmission in retinal prosthesis applications. In retinal prosthetic applications, the frequency and power of the transmitted signal must be limited to a specific range such that the living tissue is not harmed. The design goal is to transmit power with maximum efficiency, and minimum sensitivity to the nonideal power transfer link. The proposed wireless power-transfer circuit offers significant advantages over conventional ones, which usually use Class E converters. The proposed approach has very low sensitivity to coupling factor/load variations in the inductive link and demonstrates very fast dynamic response. In addition, the proposed approach does not require a dc–dc converter to control the output power. Soft switching is achieved for the proposed circuitry despite the variations in the coupling coefficient. Thus, superior efficiency can be obtained using the proposed approach. Theoretical analysis and various simulations validate the superior performance of the proposed approach. In addition, a 1-MHz experimental prototype has been prepared to verify the feasibility of the proposed wireless power-transfer circuit.