Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanisms of allelic and clinical heterogeneity of lamin A/C phenotypes

Mutations in the lamin A/C (LMNA) gene cause a broad range of clinical syndromes that show tissue-restricted abnormalities of post mitotic tissues, such as muscle, nerve, heart, and adipose tissue. Mutations in other nuclear envelope proteins cause clinically overlapping disorders. The majority of mutations are dominant single amino acid changes (toxic protein produced by the single mutant gene), and patients are heterozygous with both normal and abnormal proteins. Experimental support has been provided for different models of cellular pathogenesis in nuclear envelope diseases, including changes in heterochromatin formation at the nuclear membrane (epigenomics), changes in the timing of steps during terminal differentiation of cells, and structural abnormalities of the nuclear membrane. These models are not mutually exclusive and may be important in different cells at different times of development. Recent experiments using fusion proteins of normal and mutant lamin A/C proteins fused to a bacterial adenine methyltransferase (DamID) provided compelling evidence of mutation-specific perturbation of epigenomic imprinting during terminal differentiation. These gain-of-function properties include lineage-specific ineffective genomic silencing during exit from the cell cycle (heterochromatinization), as well as promiscuous initiation of silencing at incorrect places in the genome. To date, these findings have been limited to a few muscular dystrophy and lipodystrophy LMNA mutations but seem shared with a distinct nuclear envelope disease, emerin-deficient muscular dystrophy. The dominant-negative structural model and gain-of-function epigenomic models for distinct LMNA mutations are not mutually exclusive, and it is likely that both models contribute to aspects of the many complex clinical phenotypes observed.
Immunotherapeutic efficacy of recombinant Mycobacterium smegmatis expressing Ag85B–ESAT6 fusion protein against persistent tuberculosis infection in mice

The application of immunotherapy in combination with chemotherapy is considered an effective treatment strategy against persistent Mycobacterium tuberculosis (Mtb) infection. In this study, we constructed a novel recombinant Mycobacterium smegmatis (rMS) strain that expresses Ag85B and ESAT6 fusion protein (AE–rMS). Immunization of C57BL/6 mice with AE–rMS generated mainly Th1-type immune responses by strongly stimulating IFN-γ- and IL-2-producing splenocytes and increasing antigen-specific cytotoxic T lymphocyte (CTL) activity. To test the immunotherapeutic efficacy of AE–rMS, a persistent tuberculosis infection (PTBI) model was established via tail-vein injection of C57BL/6 mice with 1 × 104 colony forming units (CFU) of Mtb strain H37Rv in combination with concurrent chemotherapy drugs isoniazid (INH) and pyrazinamide (PZA). PTBI mice immunized with AE–rMS showed high levels of IFN-γ secreted by splenocytes and decreased bacteria loads in lung. Treatment with only the anti-tuberculosis (anti-TB) drugs RFP and INH (RI), decreased bacteria loads to low levels, with the Th1-type immune response further attenuated. Moreover, AE–rMS, when combined with RI treatment, further reduced the bacteria load as well as the pathological tissue damage in lung. Together, these results demonstrated the essential roles of AE–rMS-induced Th1-type responses, providing an effective treatment strategy by combining AE–rMS and RI for persistent TB.
Nest size is predicted by female identity and the local environment in the blue tit (Cyanistes caeruleus), but is not related to the nest size of the genetic or foster mother

The potential for animals to respond to changing climates has sparked interest in intraspecific variation in avian nest structure since this may influence nest microclimate and protect eggs and offspring from inclement weather. However, there have been relatively few large-scale attempts to examine variation in nests or the determinates of individual variation in nest structure within populations. Using a set of mostly pre-registered analyses, we studied potential predictors of variation in the size of a large sample (803) of blue tit (Cyanistes caeruleus) nests across three breeding seasons at Wytham Woods, UK. While our pre-registered analyses found that individual females built very similar nests across years, there was no evidence in follow-up (post hoc) analyses that their nest size correlated to that of their genetic mother or, in a cross-fostering experiment, to the nest where they were reared. In further pre-registered analyses, spatial environmental variability explained nest size variability at relatively broad spatial scales, and especially strongly at the scale of individual nest boxes. Our study indicates that nest structure is a characteristic of individuals, but is not strongly heritable, indicating that it will not respond rapidly to selection. Explaining the within-individual and within-location repeatability we observed requires further study.
A narrative review on offshore wind power transmission using low frequency AC system

Offshore wind power generation, transmission and integration around the world are becoming higher, and it provides technical and economic challenges for future practitioners and industries to make an alternative transmission system to an existing system in reduction of cost. In most of countries, e.g. The German government planned to install 25000MW of offshore wind farms by 2030. The greater part of offshore wind farms are integrated with High Voltage AC (HVAC) transmission to the onshore grid. Offshore wind farms are integrated with High Voltage DC (HVDC) transmission for long distances (>50km) to the grid because of capacitive cable current in HVAC. The major challenge in HVDC transmission is the installation, operation and maintenance (O&M) of the Voltage Sourced Converter (VSC) HVDC substation in the offshore climate. Currently, in case offshore wind farm the research have been fastened to reduce the complexity with increasing reliability and minimizing cost. This paper gives a comprehensive review of integration of offshore wind farm via Low Frequency AC or Fractional Frequency AC (LFAC or FFAC) transmission. LFAC transmission is adopted from HVAC and it is operated at one third of nominal frequency (16.67 Hz). As compared to HVDC the main advantage of LFAC is an absence of the offshore converter station, hence system complexity and cost reduced. In design considerations, especially the offshore transformer is one of the challenges. This paper presents a comprehensive review on components and its design considerations of offshore novel LFAC transmission. The offshore wind turbine considerations, collector network and different types of onshore frequency converters explained in detail.
Combining techniques from different NN-based language models for machine translation

This paper presents two improvements of language models based on Restricted Boltzmann Machine (RBM) for large machine translation tasks. In contrast to other continuous space approach, RBM based models can easily be integrated into the decoder and are able to directly learn a hidden representation of the n-gram. Previous work on RBM-based language models do not use a shared word representation and therefore, they might suffer of a lack of generalization for larger contexts. Moreover, since the training step is very time consuming, they are only used for quite small copora. In this work we add a shared word representation for the RBM-based language model by factorizing the weight matrix. In addition, we propose an efficient and tailored sampling algorithm that allows us to drastically speed up the training process. Experiments are carried out on two German to English translation tasks and the results show that the training time could be reduced by a factor of 10 without any drop in performance. Furthermore, the RBM-based model can also be trained on large size corpora.
RepulsionPak: Deformation-Driven Element Packing with Repulsion Forces

We present a method to fill a container shape with deformable instances of geometric elements selected from a library, creating a 2D artistic composition called an element packing. Each element is represented as a mass-spring system, allowing them to deform to achieve a better fit with their neighbours and the container. We start with an initial random placement of small elements and gradually transform them using repulsion forces that trade off between the evenness of the packing and the deformations of the individual elements. Our method produces compositions in which the negative space between elements is approximately uniform in width, similar to real-world examples created by artists. We validate our approach by performing a quantitative study using spatial statistics.
Differences in photosensibility in epilepsies of childhood and adolescence compared to adulthood.

Auteur(s) : Dorothee Kasteleijn-Nolst Trenite1, Colin Ferrie2 1Department of Medical Genetics, University Medical Centre Utrecht (UMCU), Locatie Wilhelmina Kinderziekenhuis, Utrecht, Netherlands 2Department of Paediatric Neurology, Leeds General Infirmary, Leeds, United Kingdom The study by Y. Lu et al. (2008) reported here is a retrospective analysis of an original cohort of more than 1000 children who attended the Neuropediatric Department of Kiel University Hospital in Germany over a period [. ]
OpSets: Sequential Specifications for Replicated Datatypes (Extended Version)

We introduce OpSets, an executable framework for specifying and reasoning about the semantics of replicated datatypes that provide eventual consistency in a distributed system, and for mechanically verifying algorithms that implement these datatypes. Our approach is simple but expressive, allowing us to succinctly specify a variety of abstract datatypes, including maps, sets, lists, text, graphs, trees, and registers. Our datatypes are also composable, enabling the construction of complex data structures. To demonstrate the utility of OpSets for analysing replication algorithms, we highlight an important correctness property for collaborative text editing that has traditionally been overlooked; algorithms that do not satisfy this property can exhibit awkward interleaving of text. We use OpSets to specify this correctness property and prove that although one existing replication algorithm satisfies this property, several other published algorithms do not. We also show how OpSets can be used to develop new replicated datatypes: we provide a simple specification of an atomic move operation for trees, an operation that had previously been thought to be impossible to implement without locking. We use the Isabelle/HOL proof assistant to formalise the OpSets approach and produce mechanised proofs of correctness of the main claims in this paper, thereby eliminating the ambiguity of previous informal approaches, and ruling out reasoning errors that could occur in handwritten proofs.
Globalisation, Development and Transition

This unique book provides a comprehensive survey of the major economic issues that have helped shape the modern world. It includes discussions of the latest research findings in the international economic development literature and scrutinises some of the most important debates in contemporary economics. Brian Snowdon examines the many controversies relating to long-run growth and development, problems of transitions from socialism to capitalism, international competitiveness and the impacts of globalisation.
Homozygosity for the Protein S Heerlen Allele Is Associated with Type I PS Deficiency in a Thrombophilic Pedigree with Multiple Risk Factors

Summary The multifactorial character of thrombotic disease is shown in a Spanish pedigree in which the propositus, with recurrent deep vein thrombosis, inherited the factor V R/Q506 mutation, the prothrombin 20210G/A variant and type III Protein S deficiency. Among 14 relatives carrying one or two of these three risk factors, thrombosis is present in a heterozygote for R/Q506 and in another for 20210G/A, who also had slightly positive antiphospholipid antibodies. Type I PS deficiency was also found in a young asymptomatic woman. PROS1 analysis showed coexistence of type III and type I PS deficiency to be associated with heterozygosity and homozygosity, respectively, for the P460 or PS Heerlen allele of the S/P460 variant. Analysis of PS values in this and other pedigrees segregating this variant revealed that not only free but also mean total PS levels are slightly but significantly lower in the SP460 heterozygotes than in the SS460 homozygotes. These findings strongly suggest a role of the P460 variant in the expression of the PS deficient phenotype.
Drivers and rates of stock assessments in the United States

Fisheries management is most effective when based on scientific estimates of sustainable fishing rates. While some simple approaches allow estimation of harvest limits, more data-intensive stock assessments are generally required to evaluate the stock’s biomass and fishing rates relative to sustainable levels. Here we evaluate how stock characteristics relate to the rate of new assessments in the United States. Using a statistical model based on time-to-event analysis and 569 coastal marine fish and invertebrate stocks landed in commercial fisheries, we quantify the impact of region, habitat, life-history, and economic factors on the annual probability of being assessed. Although the majority of landings come from assessed stocks in all regions, less than half of the regionally-landed species currently have been assessed. As expected, our time-to-event model identified landed tonnage and ex-vessel price as the dominant factors determining increased rates of new assessments. However, we also found that after controlling for landings and price, there has been a consistent bias towards assessing larger-bodied species. A number of vulnerable groups such as rockfishes (Scorpaeniformes) and groundsharks (Carcharhiniformes) have a relatively high annual probability of being assessed after controlling for their relatively small tonnage and low price. Due to relatively low landed tonnage and price of species that are currently unassessed, our model suggests that the number of assessed stocks will increase more slowly in future decades.
Path protection in optical flexible networks with distance-adaptive modulation formats

Thanks to a flexible frequency grid, Elastic Optical Networks (EONs) will support a more efficient usage of the spectrum resources. On the other hand, this efficiency may lead to even more disruptive effects of a failure on the number of involved connections with respect to traditional networks. In this paper, we study the problem of providing path protection to the lightpaths against a single fiber failure event in the optical layer. Our optimization task is to minimize the spectrum requirements for the protection in the network. We develop a scalable exact mathematical model using column generation for both shared and dedicated path protection schemes. The model takes into account practical constraints such as the modulation format, regenerators, and shared risk link groups. We demonstrate the effectiveness of our model through extensive simulation on two real-world topologies of different sizes. Finally, we compare the two protection schemes under different scenario assumptions, studying the impact of factors such as number of regenerators and demands on their performances.
Impulse propagation through the cardiac junctional regions of the axolotl and the turtle.

In isolated preparations from the axolotl and turtle hearts thepropagation of impulses through different cardiac tissues was studied. Intracellular records were taken from the various types of fibers. Notchedaction potentials were recorded in two junctional regions: the atrioventricularring (A-V. R.) and the ventricle-bulbus cordis (V-B. C.). The action potential recorded in either the A-V. R. or the V-B. C.regions has a notch in its depolarization phase. The temporal occurrenceof the notch was determined by the activation of the correspondingneighboring tissues. The two components given by the notch can beseparated out by using different experimental variables.The A-V. R. and the V-B. C. junctional regions are constitutedby groups of horizontal fibers. When these are severed from the otheradjacent cardiac tissues, it can be seen that the junctional fibers presentspontaneous activity and that the action potential recorded from themis characterized by a slow rate of rise, absence of a notch, and a slowdiastolic depolarization.In these junctional regions it was found that the conduction velocitywas lower than that of any of the other cardiac tissues (Table 1). Thesejunctional regions are preferential sites for delays and blockages inpropagation.The morphological studies revealed that the cells of the A-V intermediateregion are characterized by:(a) small cross sectional diameter ofcytoplasmic extensions;(b) isolated and scanty myofibrils;(c) abundantglycogen deposits; and (d) sparsity of junctional contacts.The electrophysiological and ultrastructural characteristics reportedhere, point towards the conclusion that in the axolotl and turtle hearts themechanisms that underlie the delays in propagation in the junctional regions are similar to those of the mammalian in spite of the absenceof specialized conductive tissues in the lower species.
Function of mitochondrial pyruvate carriers in hepatocellular carcinoma patients

Mitochondrial pyruvate carriers (MPC) have been identified as a critical component of energy metabolism in the cancer cells of multiple malignant tumor types. The aim of the present study was to investigate the association between the expression of MPC1 and MPC2 and the prognosis of patients with hepatocellular carcinoma (HCC). A total of 85 formalin-fixed paraffin-embedded HCC tissues were assessed using immunohistochemistry. A further 20 fresh pathological specimens, including cancer and adjacent normal liver tissues from patients who had undergone a hepatectomy, were analyzed using western blotting and reverse transcription-quantitative polymerase chain reaction. The relative expression of MPC1 and MPC2 was quantified using Image-Pro Plus software, and the association between MPC expression and clinical outcomes was analyzed by Student's t-test. MPC1 and MPC2 protein expression was significantly downregulated in HCC, but no association was identified between the expression of MPC1 or MPC2 and the clinicopathological characteristics of the patients. MPC1 mRNA levels were decreased in each cancer sample, while a mixture of increased and decreased MPC2 mRNA levels observed in the HCC samples. Multivariate regression analysis indicated that the protein level and the microvascular invasion of MPC1 were positively associated with the recurrence of HCC (P=0.000 and P=0.017, respectively). MPC1 may therefore serve as an attractive biomarker for the identification of patients with HCC at a high risk of recurrence following curative resection.
Market and Industry Factors in Stock Price Behavior

The analysis of the interdependence of an ensemble of security prices changes carries with it implications for such seemingly diverse financial topics as (1) methods of portfolio selection, (2) the design of index numbers, and (3) the theory of cost of capital. The concluding section of this work will attempt to relate these subjects to the principal statistical results in addition to suggesting further research that can capitalize on the present finding.
Soy consumption and prostate cancer risk in men: a revisit of a meta-analysis.

BACKGROUND Epidemiologic studies have shown that the consumption of soy foods may be associated with a reduction in cancer risk in humans. OBJECTIVE The purpose of this study was to conduct a meta-analysis on the association between soy consumption and prostate cancer risk in men. DESIGN We systematically reviewed studies obtained through a thorough Medline literature search and identified 15 epidemiologic publications on soy consumption and 9 on isoflavones in association with prostate cancer risk. We extracted the most adjusted relative risks (RRs) and odds ratios (ORs) of the highest and the lowest reported categories of intake from each study and conducted this analysis using a random-effects model in which studies with smaller SEEs are given greater weight in the summary measure. RESULTS Our analysis of studies on soy intake yielded a combined RR/OR of 0.74 (95% CI: 0.63, 0.89; P = 0.01). When separately analyzed, studies on nonfermented soy foods yielded a combined RR/OR of 0.70 (95% CI: 0.56, 0.88; P = 0.01) and those on fermented soy foods yielded a combined RR/OR of 1.02 (95% CI: 0.73, 1.42; P = 0.92). The analysis of studies on isoflavones yielded a combined RR/OR of 0.88 (95% CI: 0.76, 1.02; P = 0.09). Further separate analyses showed a combined RR/OR of 0.52 (95% CI: 0.34, 0.81; P = 0.01) from studies with Asian populations and 0.99 (95% CI: 0.85, 1.16; P = 0.91) from studies with Western populations. CONCLUSIONS The results of this analysis suggest that consumption of soy foods is associated with a reduction in prostate cancer risk in men. This protection may be associated with the type and quantity of soy foods consumed.
Association between a pro plant‐based dietary score and cancer risk in the prospective NutriNet‐santé cohort

Diverse plant products (e.g. fruits, vegetables, legumes) are associated with decreased cancer risk at several locations while red and processed meat were found to increase cancer risk. A pro plant‐based dietary score reflecting the relative contribution of consumed plant vs animal products was developed, and was associated with lower overall mortality, type 2 diabetes and cardiovascular disease risk, among omnivorous adults. For the first time, we investigated the prospective associations between this pro plant‐based dietary score and cancer risk. This study included 42,544 men and women of the French NutriNet‐Santé prospective cohort (2009‐2016) aged ≥45 years who completed at least three 24‐hr‐dietary records during the first year of follow‐up. The risk of developing cancer was compared across sex‐specific tertiles of pro plant‐based dietary score by multivariable Cox models. In total, 1,591 first primary incident cancer cases were diagnosed during follow‐up, among which 487 breast, 243 prostate, 198 digestive and 68 lung cancers. A higher pro plant‐based dietary score was associated with decreased risks of overall (HRt3vs.t1=0.85; 95% CI 0.76, 0.97; Ptrend =0.02), digestive (HRt3vs.t1=0.68; 95% CI 0.47; 0.99; Ptrend = 0.04) and lung (HRt3vs.t1=0.47; 95% CI 0.25, 0.90; Ptrend =0.02) cancer, though no substantial associations were found for breast or prostate cancers. This large cohort study supports a beneficial role of higher intakes of plant‐based products along with lower intakes of animal products, within a balanced omnivorous diet, regarding primary cancer prevention. These results are consistent with mechanistic evidence from experimental studies.