Miracle-dz/UniFAR-FTUs huggingface dataset:
Eteplirsen treatment for Duchenne muscular dystrophy

Objective To describe the quantification of novel dystrophin production in patients with Duchenne muscular dystrophy (DMD) after long-term treatment with eteplirsen. Methods Clinical study 202 was an observational, open-label extension of the randomized, controlled study 201 assessing the safety and efficacy of eteplirsen in patients with DMD with a confirmed mutation in the DMD gene amenable to correction by skipping of exon 51. Patients received once-weekly IV doses of eteplirsen 30 or 50 mg/kg. Upper extremity muscle biopsy samples were collected at combined study week 180, blinded, and assessed for dystrophin-related content by Western blot, Bioquant software measurement of dystrophin-associated immunofluorescence intensity, and percent dystrophin-positive fibers (PDPF). Results were contrasted with matched untreated biopsies from patients with DMD. Reverse transcription PCR followed by Sanger sequencing of newly formed slice junctions was used to confirm the mechanism of action of eteplirsen. Results Reverse transcription PCR analysis and sequencing of the newly formed splice junction confirmed that 100% of treated patients displayed the expected skipped exon 51 sequence. In treated patients vs untreated controls, Western blot analysis of dystrophin content demonstrated an 11.6-fold increase (p = 0.007), and PDPF analysis demonstrated a 7.4-fold increase (p < 0.001). The PDPF findings were confirmed in a re-examination of the sample (15.5-fold increase, p < 0.001). Dystrophin immunofluorescence intensity was 2.4-fold greater in treated patients than in untreated controls (p < 0.001). Conclusion Taken together, the 4 assays, each based on unique evaluation mechanisms, provided evidence of eteplirsen muscle cell penetration, exon skipping, and induction of novel dystrophin expression. Classification of evidence This study provides Class II evidence of the muscle cell penetration, exon skipping, and induction of novel dystrophin expression by eteplirsen, as confirmed by 4 assays.
Reconfigurable NanoFETs: Performance Projections for Multiple-Top-Gate Architectures

In nanowire or nanotube field-effect transistors (nanoFETs) electrostatic doping can be induced by electrical fields originating from multiple independent gates. Therefore, nanoFETs are predestined to explore reconfigurability. Solving the coupled nonlinear Poisson and drift-diffusion differential equations for the three-dimensional electrostatic potential and the one-dimensional channel charge, respectively, we predict the performance of four different reconfigurable (R) nanoFET geometries. The investigated architectures compass FETs with one (1G), two (2G), and three top-gate (3G) terminals with a moderate channel length of half a micrometer. Therefore, the theoretically investigated R-nanoFETs can be manufactured at low costs, allowing to test the performance projections claimed in this paper. The 2G R-nanoFET proved to be the most versatile architecture when no application specific optimization is attempted. However, all considered geometries offer interesting properties. Shortening the program gate with the drain simplifies the local routing and only slightly diminish the performance. A smaller footprint 1G R-nanoFET delivers comparable intrinsic gains at the cost of increased static power dissipation. Finally, a 3G R-nanoFET enables additional dynamic configuration options and faster on/off switching due to a control gate positioned at an increased distance to other metallic contacts.
Resource allocation in rate-limited OFDMA Systems: A hybrid heuristic approach

This paper presents a novel resource allocation procedure for OFDMA downlinks, which stems from an hybridization of the Harmony Search and the Differential Evolution heuristic algorithms. In this setup it is known that optimum subcarrier and power allocation is achieved through 1) assigning each subcarrier to the user with highest channel gain at the given frequency, and 2) a Water-Filling procedure over the set of considered channel gains. This work addresses the scenario where stringent rate constraints are imposed for each user at the transmitter, scenario where the previous optimum resource allocation procedure no longer holds. The proposed iterative technique hinges on the aforementioned combinatorial heuristics, jointly with an iterative greedy subcarrier shifting procedure that accounts for the fulfillment of the established rate restrictions. Preliminary simulation results are provided for the extended vehicular ITU channel model, which shed light on the performance of the proposed allocation procedure.
Association Between Gestational Hypertension and Risk of Cardiovascular Disease Among 617 589 Norwegian Women

Background Preeclampsia and gestational hypertension (GH) are the most common hypertensive pregnancy disorders. Preeclampsia has been linked to increased risk of cardiovascular disease (CVD), but a similar association for GH has not been established. We aimed to determine the association between GH and subsequent CVD, and explore the additional role of small‐for‐gestational‐age infants, preterm delivery, and parity. Methods and Results Data from the Medical Birth Registry of Norway were linked to the Cardiovascular Disease in Norway project and the Norwegian Cause of Death Registry. Hazard ratios and 95% confidence intervals were computed using Cox proportional hazard regression, comparing women with and without GH during their first and/or second pregnancy. We included all women with a first delivery from 1980 through 2009 (n=617 589) and followed them for a median of 14.3 (quartile 1–quartile 3: 6.9–21.5) years. Women with GH in the first pregnancy had 1.8‐fold (95% confidence interval, 1.7–2.0) higher risk of subsequent CVD compared with women without any hypertensive pregnancy disorder. When GH occurred in combination with small‐for‐gestational‐age infants and/or preterm delivery, the hazard ratio was 2.6 (95% confidence interval, 2.3–3.0). When women with GH were compared with women with preeclampsia, the risk of CVD was comparable when the pregnancy complications occurred in either the first or second pregnancy but was significantly higher for preeclampsia without complications when the disorder occurred in both pregnancies. Conclusions GH was associated with increased risk of subsequent CVD, and the highest risk was observed when GH was combined with small‐for‐gestational‐age infants and/or preterm delivery.
Auditor Ratification: Can't Get No (Dis)Satisfaction

SYNOPSIS: The auditor ratification vote provides shareholders with an opportunity to voice their opinions about the company's choice of auditor, but, historically, less than 2 percent of shareholders express dissent in their vote. Motivated by regulatory attention on the importance of shareholder involvement and the institutional power of proxy advisors on voting outcomes, I examine the proxy advisor's role in the auditor ratification vote. I find that proxy advisors have a statistically significant influence over shareholder voting outcomes when they recommend against auditor ratification, but the Against recommendation is rare, and the qualitative significance is less clear. Proxy advisor Against recommendations are based on concerns about auditor independence and poor audit quality, but there appears to be variation in the extent to which proxy advisors issue Against recommendations for each of these criteria. I discuss the implications of the findings, which should be of interest to regulators, invest.
Experimental research of high field pinning centers in 2% C doped MgB2 wires at 20 K and 25 K

High field pinning centers in MgB2 doped with 2 at. % carbon under a low and a high hot isostatic pressures have been investigated by transport measurements. The field dependence of the transport critical current density was analyzed within the different pinning mechanisms: surface pinning, point pinning, and pinning due to spatial variation in the Ginzburg-Landau parameter (Δκ pinning). Research indicates that a pressure of 1 GPa allows similar pinning centers to Δκ pinning centers to be obtained. This pinning is very important, because it makes it possible to increase the critical current density in high magnetic fields at 20 K and 25 K. Our results indicate that the δTc and δl pinning mechanisms, which are due to a spatial variation in the critical temperature (Tc) and the mean free path, l, respectively, create dislocations. The high density of dislocations with inhomogeneous distribution in the structure of the superconducting material creates the δl pinning mechanism. The low density of dislocations.
SRSF 3 promotes pluripotency through Nanog mRNA export and coordination of the 1 pluripotency gene expression program 2 3

7 Department of Anatomy and Developmental Biology, Monash University, Australia; 8 Biomedicine Discovery Institute, Development and Stem Cells Program, Monash University, 9 Australia; Bioinformatics Platform, Monash University, Australia; School of Biological 10 Sciences, Monash University, Australia, The Francis Crick Institute, UK; Australian 11 Regenerative Medicine Institute, Monash University, Australia; Department of Biochemistry 12 and Molecular Biology, Monash University, Australia; Current address: Australian 13 Regenerative Medicine Institute, Monash University, Australia. 14
Long range Coulomb interaction in the ground state of bilayer graphene

We report on our studies of interacting electrons in bilayer graphene in a magnetic field. We demonstrate that the long range Coulomb interactions between electrons in this material are highly important. We show that in the unbiased bilayer (where both layers are at the same electrostatic potential), the interactions can cause mixing of Landau levels in moderate magnetic fields. For the biased bilayer (when the two layers are at different potentials), we demonstrate that the interactions are responsible for a change in the total spin of the ground state for half-filled Landau levels in the valence band.
Design, Simulation and Analysis of Multiple L-Slot Microstrip Patch Antenna

In this paper a multiple L-slot microstrip patch antenna is proposed that can be used to satisfy WLAN and WiMAX application. The proposed antenna is designed to operate with resonant frequency at 3.1 GHz for WiMAX application and by using multiple L-slot the resonance frequency is further reduced that can make possible to use it for WLAN applications also. The co-axial feeding technique is employed to feed the proposed antenna. Multiple L-slot is used on the patch to analyze the performance. The bandwidth enhancement is focused at higher operating frequencies. The simulation results such as Radiation pattern, VSWR, Gain, and Return loss are simulated using Ansoft HFSS. The simulation results of Multiple L-slot micro-strip patch antenna was obtained and the performance improvement is analyzed and presented. Keywords— Microstrip antenna; resonant frequency; , Lslot; co-axial feed; WLAN; WiMAX.
Global imbalances and destabilizing speculation

Global imbalances have become a major source of systemic risk to the global economy. They can have adverse repercussions in the short and long term on both surplus and deficit economies due to the potentially disruptive effect of a sudden adjustment. They can be amplified by short term speculation that prevents the real exchange rate to perform its adjusting role. The paper examines past and recent patterns of destabilizing short term speculative flows that have led to financial fragility and real costs for a number of various economies. Domestic policies aimed at preventing speculation and overvaluation such as nonmonetary anti-inflationary policies as well as temporary measures to constrain speculative flows should be coupled with globally coordinated policies to reduce global imbalances. Among the latter intermediate exchange rate regimes or regional cooperative schemes should be favoured. An international monetary system should provide a code of conduct, multilateral oversight and negotiations, and a multilateral body that could identify the size of the deviation enforce the necessary measures to correct the imbalances.
Prognostic evaluation of the elastic properties of the ascending aorta in dilated cardiomyopathy

Nowadays there is an increased interest in the role of aortic stiffness in the pathophysiology of heart failure (HF), as it is a major determinant of left ventricular (LV) performance. We aimed at assessing the predictive value of the aortic stiffness parameters, measured by echocardiography, in patients affected by nonischaemic dilated cardiomyopathy (DCM) regarding three end‐points: death, HF rehospitalization, combined death or HF rehospitalization in a long‐term follow‐up.
Effective Treatment of a Refractory Hairy Cell Leukemia Variant with Splenic Pre-Irradiation and Alemtuzumab

A 72-year-old Japanese man presented with 43.1 × 109/l hairy cells and apparent splenomegaly. The leukemia cells had unevenly distributed microvilli and round nuclei with dense chromatin and one or two clear nucleoli, lacked CD25 expression and were negative for tartrate-resistant acid phosphatase. The case was diagnosed as hairy cell leukemia variant (HCLv) and proved refractory to various chemotherapies, including cladribine, pentostatin, interferon-α, CHOP and rituximab. Because of the CD52 expression, we treated the patient with alemtuzumab. Pretreatment with 22.5 Gy to the spleen reduced the spleen size from 12 to 4 cm below the left costal margin, and the number of circulating leukemic cells decreased from 229.0 to 63.6 × 109/l. Subsequent administration of 24.0 mg of alemtuzumab eliminated leukemic cells in the peripheral blood on day 12, and the spleen was not palpable after the administration of 54.0 mg of alemtuzumab. In vitro treatment with alemtuzumab confirmed the cytotoxic effect against the patient’s leukemic cells in the presence of complement. This is the first report showing clinical effectiveness of splenic irradiation and alemtuzumab against refractory HCLv.
Diabetes and Cardiovascular Diseases ( VIII ) Coronary Artery Surgery in Diabetic Patients

Rev Esp Cardiol 2002;55(12):1311-22 1311 Currently, 15% to 30% of the patients that undergo coronary artery surgery are diabetics. As a group, they have less favorable anatomic and clinical characteristics than the general population. Specifically, diabetics have more extensive coronary disease, more vessels involved, and more diffuse stenosis, so they need a higher number of distal anastomoses to achieve complete revascularization. In spite of these drawbacks, they can undergo coronary artery bypass procedures with an operative mortality similar to that of non-diabetic patients. However, some postoperative complications are significantly more prevalent among diabetics, mainly renal failure, neurological accidents, sternal dehiscence, and infection. In early studies of the late results of surgical revascularization, mainly based on venous grafts, late survival and clinical improvement were less satisfactory in diabetics than in non-diabetics. However, in recent experiences, in which the internal mammary artery has been used extensively, the clinical outcome of diabetics has been similar to that of non-diabetics, confirming this procedure as the preferred one in revascularizing the coronary arteries of diabetics with multivessel disease. Off-pump surgery and extensive use of arterial grafts are becoming established strategies for reducing operative risk and improving longterm clinical results. However, continuous, strict medical management of hyperglycemia and other known coronary risk factors, especially lipid levels, is essential.
A machine learning approach to quantifying noise in medical images

As advances in medical imaging technology are resulting in significant growth of biomedical image data, new techniques are needed to automate the process of identifying images of low quality. Automation is needed because it is very time consuming for a domain expert such as a medical practitioner or a biologist to manually separate good images from bad ones. While there are plenty of de-noising algorithms in the literature, their focus is on designing filters which are necessary but not sufficient for determining how useful an image is to a domain expert. Thus a computational tool is needed to assign a score to each image based on its perceived quality. In this paper, we introduce a machine learning-based score and call it the Quality of Image (QoI) score. The QoI score is computed by combining the confidence values of two popular classification techniques—support vector machines (SVMs) and Naïve Bayes classifiers. We test our technique on clinical image data obtained from cancerous tissue samples. We used 747 tissue samples that are stained by four different markers (abbreviated as CK15, pck26, E_cad and Vimentin) leading to a total of 2,988 images. The results show that images can be classified as good (high QoI), bad (low QoI) or ugly (intermediate QoI) based on their QoI scores. Our automated labeling is in agreement with the domain experts with a bi-modal classification accuracy of 94%, on average. Furthermore, ugly images can be recovered and forwarded for further post-processing.
Increasing the value recovery from short-rotation coppice harvesting.

Farmers are reluctant to establish short-rotation coppice because too many uncertainties remain about its economic feasibility. Up to now, most progress has been accomplished by increasing plantation yields through genetic improvement and by reducing management costs through mechanization. In contrast, the potential increase of value recovery has received much less attention. We therefore compared whole-tree chipping with integrated harvesting to test whether more profit could be made by producing pulpwood logs and wood chips, rather than wood chips only. The two systems were compared side-by-side with identical machinery on the same field. Chip production cost was higher for integrated harvesting (15 € Mg-1), because the system was less productive (9 Mg h-1), as compared with whole-tree chipping (9 € Mg-1 and 25 Mg h-1). Pulpwood log production only occurred with the integrated harvesting system, at a cost of 8 € Mg-1. Integrated harvesting incurred higher production costs, but also accrued better value recovery. Under current market conditions, the two systems offered similar profits, in the vicinity of 5000 € ha-1. However, integrated harvesting offered higher flexibility, with a potentially better resilience to market fluctuations.
Statistical mechanics of cellular automata

Cellular automata are used as simple mathematical models to investigate self-organization in statistical mechanics. A detailed analysis is given of ''elementary'' cellular automata consisting of a sequence of sites with values 0 or 1 on a line, with each site evolving deterministically in discrete time steps according to p definite rules involving the values of its nearest neighbors. With simple initial configurations, the cellular automata either tend to homogeneous states, or generate self-similar patterns with fractal dimensions approx. =1.59 or approx. =1.69. With ''random'' initial configurations, the irreversible character of the cellular automaton evolution leads to several self-organization phenomena. Statistical properties of the structures generated are found to lie in two universality classes, independent of the details of the initial state or the cellular automaton rules. More complicated cellular automata are briefly considered, and connections with dynamical systems theory and the formal theory of computation are discussed.
Everolimus in the treatment of neuroendocrine tumors: efficacy, side-effects, resistance, and factors affecting its place in the treatment sequence

ABSTRACT Introduction: Since the initial approval of everolimus in 2011, there have been a number of important changes in therapeutic/diagnostic modalities as well as classification/staging systems of neuroendocrine tumors (NETs), which can significantly impact the use of everolimus in patients with advanced NETs. Areas covered: The efficacy of everolimus monotherapy and combination therapy demonstrated in clinical studies involving patients with advanced NETs are reviewed. Several factors affecting everolimus use are described including: the development and routine use of NET classification/staging systems; widespread use of molecular imaging modalities; side effects; drug resistance; and the availability of other treatment options. Furthermore, the current position of everolimus in the treatment approach is discussed, taking into account the recommendations from the recent guidelines. Expert opinion: Although everolimus demonstrated its high efficacy and tolerability in the RADIANT trials and other clinical studies, there still remain a number of controversies related to everolimus treatment in the management of NETs. The synergistic anti-growth effect of other agents in combination with everolimus or its effect on overall survival have not been established. The appropriate order of the use of everolimus in the treatment of advanced NETs still remains unclear, which needs to be defined in further studies and will be addressed in the new guidelines.
Molecular Basis of the Brain Renin Angiotensin System in Cardiovascular and Neurologic Disorders: Uncovering a Key Role for the Astroglial Angiotensin Type 1 Receptor AT1R

The central renin angiotensin system (RAS) is one of the most widely investigated cardiovascular systems in the brain. It is implicated in a myriad of cardiovascular diseases. However, studies from the last decade have identified its involvement in several neurologic abnormalities. Understanding the molecular functionality of the various RAS components can thus provide considerable insight into the phenotypic differences and mechanistic drivers of not just cardiovascular but also neurologic disorders. Since activation of one of its primary receptors, the angiotensin type 1 receptor (AT1R), results in an augmentation of oxidative stress and inflammatory cytokines, it becomes essential to investigate not just neuronal RAS but glial RAS as well. Glial cells are key homeostatic regulators in the brain and are critical players in the resolution of overt oxidative stress and neuroinflammation. Designing better and effective therapeutic strategies that target the brain RAS could well hinge on understanding the molecular basis of both neuronal and glial RAS. This review provides a comprehensive overview of the major studies that have investigated the mechanisms and regulation of the brain RAS, and it also provides insight into the potential role of glial AT1Rs in the pathophysiology of cardiovascular and neurologic disorders.