Miracle-dz/UniFAR-FTUs huggingface dataset:
Experimental Investigation on the Fracture Behaviour of Natural Stones Exposed to Monotonic and Cyclic Loading

The present paper is devoted to an experimental study on the fracture behaviour of natural stones, commonly used as elements for building cladding, under both monotonic and cyclic loading, with particular emphasis to white Carrara marble. The effect of progressive damage produced by in-service thermal fluctuations can be investigated through the application of appropriate cyclic mechanical loads. In the experimental tests conducted, some static mechanical properties of marble are characterized by means of three-point bending tests on edge-cracked prismatic specimens for the determination of Young's modulus, tensile strength and fracture energy. Moreover, cyclic three-point bending tests are conducted to determine the propagation rate of nominally Mode-I fatigue cracks. Finally, the fatigue behaviour of the marble is studied through a cohesive crack model, in which the direct tensile strength of the material is determined by a Brazilian test, and the behaviour is calibrated by means of a suitable FE model. The effect of crack path on the fracture resistance of marble is discussed.
Anchor-Free Correlated Topic Modeling: Identifiability and Algorithm

In topic modeling, many algorithms that guarantee identifiability of the topics have been developed under the premise that there exist anchor words -- i.e., words that only appear (with positive probability) in one topic. Follow-up work has resorted to three or higher-order statistics of the data corpus to relax the anchor word assumption. Reliable estimates of higher-order statistics are hard to obtain, however, and the identification of topics under those models hinges on uncorrelatedness of the topics, which can be unrealistic. This paper revisits topic modeling based on second-order moments, and proposes an anchor-free topic mining framework. The proposed approach guarantees the identification of the topics under a much milder condition compared to the anchor-word assumption, thereby exhibiting much better robustness in practice. The associated algorithm only involves one eigen-decomposition and a few small linear programs. This makes it easy to implement and scale up to very large problem instances. Experiments using the TDT2 and Reuters-21578 corpus demonstrate that the proposed anchor-free approach exhibits very favorable performance (measured using coherence, similarity count, and clustering accuracy metrics) compared to the prior art.
Nonalcoholic steatohepatitis versus steatosis: Adipose tissue insulin resistance and dysfunctional response to fat ingestion predict liver injury and altered glucose and lipoprotein metabolism

Nonalcoholic fatty liver disease (NAFLD) ranges from simple steatosis (SS) to nonalcoholic steatohepatitis (NASH). Though liver‐related risk seems confined to NASH, it is currently unclear whether NASH has a higher risk of cardiovascular disease (CVD) and diabetes than SS as a result of the coexistence of obesity and other cardiometabolic confounders. Adipose tissue is an emerging modulator of liver disease in NAFLD and of cardiometabolic disease in the general population. We evaluated in SS and NASH (1) glucose homeostasis and cardiovascular risk profile and (2) the effect of adipose tissue dysfunction, assessed in fasting conditions and postprandially, on liver injury, glucose and lipoprotein metabolism, and markers of early atherosclerosis. Forty nonobese, nondiabetic, normolipidemic biopsy‐proven NAFLD patients (20 with SS and 20 with NASH) and 40 healthy subjects, matched for overall/abdominal adiposity and metabolic syndrome, underwent an oral fat load test, with measurement of plasma triglyceride‐rich lipoproteins, oxidized low‐density lipoproteins, adipokines, and cytokeratin‐18 fragments, and an oral glucose tolerance test with minimal model analysis to yield glucose homeostasis parameters. Circulating endothelial adhesion molecules were measured, and adipose tissue insulin resistance (adipose IR) index and visceral adiposity index were calculated. Despite similar fasting values, compared to SS, NASH showed a more atherogenic postprandial lipoprotein profile, an altered adipokine response (i.e., higher resistin increase and an adiponectin fall), and hepatocyte apoptosis activation after fat ingestion. Adipose IR index, endothelial adhesion molecules, and hepatic insulin resistance progressively increased across NAFLD stages. NASH, but not SS, showed an impaired pancreatic β‐cell function. On multiple regression analysis, adipose IR index and postprandial adiponectin independently predicted liver histology and altered cardiometabolic parameters. Conclusion: Adipose tissue dysfunction, including a maladaptive adipokine response to fat ingestion, modulates liver injury and cardiometabolic risk in NAFLD. (HEPATOLOGY 2012;56:933–942)
Use, Disuse, and Misuse of Automated Refactorings (Extended Version)

Though refactoring tools have been available for more than a decade, research has shown that programmers underutilize such tools. However, little is known about why programmers do not take advantage of these tools. We have conducted a field study on programmers in their natural settings working on their code. As a result, we collected a set of interaction data from about 1268 hours of programming using our minimally intrusive data collectors. Our quantitative data show that programmers prefer lightweight methods of invoking refactorings, usually perform small changes using the refactoring tool, proceed with an automated refactoring even when it may change the behavior of the program, and rarely preview the automated refactorings. We also interviewed nine of our participants to provide deeper insight about the patterns that we observed in the behavioral data. We found that programmers use predictable automated refactorings even if they have rare bugs or change the behavior of the program. This paper reports some of the factors that affect the use of automated refactorings such as invocation method, awareness, naming, trust, and predictability and the major mismatches between programmers’ expectations and automated refactorings. The results of this work contribute to producing more effective tools for refactoring complex software. Keywords-Software engineering; Software maintenance; Programming environments; Human factors; User interfaces; Human computer interaction;
ADAPTIVE RADIATIONS, ECOLOGICAL SPECIALIZATION, AND THE EVOLUTIONARY INTEGRATION OF COMPLEX MORPHOLOGICAL STRUCTURES

The evolutionary integration of complex morphological structures is a macroevolutionary pattern in which morphogenetic components evolve in a coordinated fashion, which can result from the interplay among processes of developmental, genetic integration, and different types of selection. We tested hypotheses of ecological versus developmental factors underlying patterns of within‐species and evolutionary integration in the mandible of phyllostomid bats, during the most impressive ecological and morphological radiation among mammals. Shape variation of mandibular morphogenetic components was associated with diet, and the transition of integration patterns from developmental to within‐species to evolutionary was examined. Within‐species (as a proxy to genetic) integration in different lineages resembled developmental integration regardless of diet specialization, however, evolutionary integration patterns reflected selection in different mandibular components. For dietary specializations requiring extensive functional changes in mastication patterns or biting, such as frugivores and sanguivores, the evolutionary integration pattern was not associated with expected within‐species or developmental integration. On the other hand, specializations with lower mastication demands or without major functional reorganization (such as nectarivores and carnivores), presented evolutionary integration patterns similar to the expected developmental pattern. These results show that evolutionary integration patterns are largely a result of independent selection on specific components regardless of developmental modules.
Clinical practice. Stage IV chronic kidney disease.

A 54-year-old woman with type 2 diabetes presents for care. Her creatinine level has increased from 1.1 mg per deciliter (97 μmol per liter) 4 years ago to 3.1 mg per deciliter (274 μmol per liter) at the most recent measurement (estimated glomerular filtration rate, 26 ml per minute per 1.73 m2 of body-surface area). Her urinary protein excretion is 2.8 g per 24 hours. Her blood pressure is 155/90 mm Hg, and the glycated hemoglobin level is 7.6 mg per deciliter. Her current medications include an oral hypoglycemic agent, an angiotensin-converting–enzyme inhibitor, a statin, and a thiazide diuretic. How should her case be managed?
Horizontal Accuracy Monitoring System for Precision Machinery

Horizontal accuracy refers to a crucial factor affecting machining precision. Poor horizontal accuracy of the machine can lead to uneven vertical loading on the feet, causing deformation of the machine bed due to gravity. This resultant error affects the motion straightness and angular accuracy of the equipment, leading to subpar machining flatness. Adjusting the horizontal accuracy of the equipment is achieved by adjusting the heights of the leveling bolts. Currently, most research focused on offline systems for assessing horizontal accuracy with fewer efforts on real-time monitoring mechanisms. Thus, based on precision equipment and a case study of base leveling assembly, we proposed a real-time horizontal accuracy monitoring system. The system included smart feet with force-sensing capabilities and a computer application. The system was used to observe variations in vertical loads on the feet and calculate the horizontal state of the target plane. It offered an interface for users to check real-time foot load values. The relationship between vertical loads and the test platform’s tilting angle was constructed by an artificial intelligence model. The user interface displayed the current load, calculated horizontal state, and the standard load under the equipment’s horizontal state. Initially, CAD software was used as an assist while reference loads for each foot on the equipment. Then, through experimentation, standard loads of each foot at a horizontal state were determined. These standard load data were the basis for setting horizontal accuracy thresholds. Reference loads as theoretical values were used to verify the reasonableness of the standard loads. In this study, the standard loads for the base leveling assembly process of a precision device were determined using intelligent feet. The real-time loads and device status during this process were displayed on the user interface, aiding assemblers in level alignment. Finally, an online monitoring mechanism was implemented by setting allowable values based on the standard loads. The accuracy of classification for single-axis tilting angle interval in the range of 1 to 1.5 mm/m reached 70%.
The development of high-content screening (HCS) technology and its importance to drug discovery

ABSTRACT Introduction: High-content screening (HCS) was introduced about twenty years ago as a promising analytical approach to facilitate some critical aspects of drug discovery. Its application has spread progressively within the pharmaceutical industry and academia to the point that it today represents a fundamental tool in supporting drug discovery and development. Areas covered: Here, the authors review some of significant progress in the HCS field in terms of biological models and assay readouts. They highlight the importance of high-content screening in drug discovery, as testified by its numerous applications in a variety of therapeutic areas: oncology, infective diseases, cardiovascular and neurodegenerative diseases. They also dissect the role of HCS technology in different phases of the drug discovery pipeline: target identification, primary compound screening, secondary assays, mechanism of action studies and in vitro toxicology. Expert opinion: Recent advances in cellular assay technologies, such as the introduction of three-dimensional (3D) cultures, induced pluripotent stem cells (iPSCs) and genome editing technologies (e.g., CRISPR/Cas9), have tremendously expanded the potential of high-content assays to contribute to the drug discovery process. Increasingly predictive cellular models and readouts, together with the development of more sophisticated and affordable HCS readers, will further consolidate the role of HCS technology in drug discovery.
Inhibition of Calcineurin or IMP Dehydrogenase Exerts Moderate to Potent Antiviral Activity against Norovirus Replication

ABSTRACT Norovirus is a major cause of acute gastroenteritis worldwide and has emerged as an important issue of chronic infection in transplantation patients. Since no approved antiviral is available, we evaluated the effects of different immunosuppressants and ribavirin on norovirus and explored their mechanisms of action by using a human norovirus (HuNV) replicon-harboring model and a surrogate murine norovirus (MNV) infectious model. The roles of the corresponding drug targets were investigated by gain- or loss-of-function approaches. We found that the calcineurin inhibitors cyclosporine (CsA) and tacrolimus (FK506) moderately inhibited HuNV replication. Gene silencing of their cellular targets, cyclophilin A, FKBP12, and calcineurin, significantly inhibited HuNV replication. A low concentration, therapeutically speaking, of mycophenolic acid (MPA), an uncompetitive IMP dehydrogenase (IMPDH) inhibitor, potently and rapidly inhibited norovirus replication and ultimately cleared HuNV replicons without inducible resistance following long-term drug exposure. Knockdown of the MPA cellular targets IMPDH1 and IMPDH2 suppressed HuNV replication. Consistent with the nucleotide-synthesizing function of IMPDH, exogenous guanosine counteracted the antinorovirus effects of MPA. Furthermore, the competitive IMPDH inhibitor ribavirin efficiently inhibited norovirus and resulted in an additive effect when combined with immunosuppressants. The results from this study demonstrate that calcineurin phosphatase activity and IMPDH guanine synthase activity are crucial in sustaining norovirus infection; thus, they can be therapeutically targeted. Our results suggest that MPA shall be preferentially considered immunosuppressive medication for transplantation patients at risk of norovirus infection, whereas ribavirin represents as a potential antiviral for both immunocompromised and immunocompetent patients with norovirus gastroenteritis.
A Way Forward for Cancer Chemoprevention: Think Local

As cells progress through carcinogenesis, the associated exponential expansion of genetic and molecular aberrations and resultant heterogeneity make therapeutic success increasingly unattainable. Therapeutic intervention at early stages of carcinogenesis that occurs within the primary organ and in the face of a lower burden of molecular aberrations, constitutes a basic tenet of cancer chemoprevention, and provides a situation that favors a greater degree of therapeutic efficacy compared with that of advanced cancer. A longstanding barrier to chemoprevention relates to the requirement for essentially no systemic toxicity, and the fact that when large numbers of people are treated, the emergence of systemic toxicity is almost universal. A rational means to address this in fact relates to a second basic tenet of the chemopreventive strategy: the focus of therapeutic intervention is to disrupt a process that is in essence localized to a single organ. Based upon this consideration, a strategy which is based upon local delivery of therapeutics to an at-risk organ will achieve therapeutic efficacy while avoiding systemic delivery and its associated toxicity. This article will review the rationale for undertaking such an approach, describe successful clinical achievements based on this strategy, describe ongoing efforts to expand the impact of this approach, and together will highlight the high impact that this approach has already had on the field as well as its extremely high potential for future impact. Cancer Prev Res; 10(1); 14–35. ©2016 AACR.
Moderators, mediators and nonspecific predictors of outcome after cognitive rehabilitation of executive functions in a randomised controlled trial

ABSTRACT Moderators, mediators and nonspecific predictors of treatment after cognitive rehabilitation of executive functions in a randomised controlled trial Objective: To explore moderators, mediators and nonspecific predictors of executive functioning after cognitive rehabilitation in a randomised controlled trial, comparing Goal Management Training (GMT) with an active psycho-educative control-intervention, in patients with chronic acquired brain injury. Methods: Seventy patients with executive dysfunction were randomly allocated to GMT (n = 33) or control (n = 37). Outcome measures were established by factor-analysis and included cognitive executive complaints, emotional dysregulation and psychological distress. Results: Higher age and IQ emerged as nonspecific predictors. Verbal memory and planning ability at baseline moderated cognitive executive complaints, while planning ability at six-month follow-up mediated all three outcome measures. Inhibitory cognitive control emerged as a unique GMT specific mediator. A general pattern regardless of intervention was identified; higher levels of self-reported cognitive—and executive–symptoms of emotional dysregulation and psychological distress at six-month follow-up mediated less improvement across outcome factors. Conclusions: The majority of treatment effects were nonspecific to intervention, probably underscoring the variables’ general contribution to outcome of cognitive rehabilitation interventions. Interventions targeting specific cognitive domains, such as attention or working memory, need to take into account the patients’ overall cognitive and emotional self-perceived functioning. Future studies should investigate the identified predictors further, and also consider other predictor candidates.
Diabetic retinopathy: An update

Diabetes mellitus is a major cause of avoidable blindness in both the developing and the developed countries. Significant technological advances have taken place to improve the diagnostic accuracy of diabetic retinopathy. In the last three decades, the treatment strategies have been revised to include, besides laser photocoagulation, early surgical interventions and pharmacotherapies.
The impact of microgravity-based proteomics research

Proteomics is performed in microgravity research in order to determine protein alterations occurring qualitatively and quantitatively, when single cells or whole organisms are exposed to real or simulated microgravity. To this purpose, antibody-dependent (Western blotting, flow cytometry, Luminex® technology) and antibody-independent (mass spectrometry, gene array) techniques are applied. The anticipated findings will help to understand microgravity-specific behavior, which has been observed in bacteria, as well as in plant, animal and human cells. To date, the analyses revealed that cell cultures are more sensitive to microgravity than cells embedded in organisms and that proteins changing under microgravity are highly interactive. Furthermore, one has to distinguish between primary gravity-induced and subsequent interaction-dependent changes of proteins, as well as between direct microgravity-related effects and indirect stress responses. Progress in this field will impact on tissue engineering and medicine and will uncover possibilities of counteracting alterations of protein expression at lowered gravity.
Biomarkers in sepsis

Purpose of review This review discusses the current developments in biomarkers for sepsis. Recent findings With quantum leaps in technology, an array of biomarkers will become available within the next decade as point-of-care tools that will likely revolutionize the management of sepsis. These markers will facilitate early and accurate diagnosis, faster recognition of impending organ dysfunction, optimal selection and titration of appropriate therapies, and more reliable prognostication of risk and outcome. These diagnostics will also enable an improved characterization of the biological phenotype underlying sepsis and thus a better appreciation of the condition. Summary The potential for novel biomarkers in sepsis will need to be properly realized with considerable funding, academic–industry collaborations, appropriate investigations and validation in heterogenous populations, but these developments do hold the capacity to transform patient care and outcomes.
Ethane-1,1,2-trisphosphonic acid hemihydrate.

Ethane-1,1,2-trisphosphonic acid crystallizes as a hemihydrate, C(2)H(9)O(9)P(3). 0.5H(2)O, in which the water O atom lies on an inversion centre in the space group P2(1)/c. The acid component, which contains a short but noncentred O-H.O hydrogen bond, adopts a gauche conformation. The acid components are linked by an extensive series of O-H.O hydrogen bonds to form layers, which are linked into pairs by the water molecules.
BMICA-independent component analysis based on B-spline mutual information estimator

The information theoretic concept of mutual information provides a general framework to evaluate dependencies between variables. Its estimation however using B-Spline has not been used before in creating an approach for Independent Component Analysis. In this paper we present a B-Spline estimator for mutual information to find the independent components in mixed signals. Tested using electroencephalography (EEG) signals the resulting BMICA (B-Spline Mutual Information Independent Component Analysis) exhibits better performance than the standard Independent Component Analysis algorithms of FastICA, JADE, SOBI and EFICA in similar simulations. BMICA was found to be also more reliable than the 'renown' FastICA.
Distribution of the cytoskeletal protein, Nestin, in acute leukemia

Abstract Nestin is a neuroepithelial stem cell marker that is expressed in some types of tumor cells. Recent reports suggest that Nestin may be closely related to malignant cell proliferation and migration. Acute leukemia (AL) is characterized by a lack of differentiation, which results in uncontrolled proliferation in the bone marrow and accumulation of immature cells. The expression and function of Nestin in AL is unclear. We investigated Nestin immunohistochemical patterns of 87 patients that included 47 cases of acute myeloid leukemia (AML) and 40 cases of acute lymphoblastic leukemia (ALL), and 20 patients in complete remission (CR) from AML or ALL. We also investigated the clinico-pathological features of 87 cases of AL and their CR and overall survival (OS). Nestin was expressed in leukemic blasts and mature granulocytic cells in most cases (39/47) of AML. Conversely, Nestin was expressed in mature granulocytic cells in fewer cases (6/40) of ALL, but not in blasts. Nestin expression appeared in leukemic blasts of AML, but not ALL. Nestin expression in AML blast cells was not associated with CR or OS. We provide evidence that Nestin is expressed in AL and might be a useful immunohistochemical marker for identifying AML and ALL.