Miracle-dz/UniFAR-FTUs huggingface dataset:
Tail Analysis Without Parametric Models: A Worst-Case Perspective

A common bottleneck in evaluating extremal performance measures is that, because of their very nature, tail data are often very limited. The conventional approach selects the best probability distribution from tail data using parametric fitting, but the validity of the parametric choice can be difficult to verify. This paper describes an alternative based on the computation of worst-case bounds under the geometric premise of tail convexity, a feature shared by all common parametric tail distributions. We characterize the optimality structure of the resulting optimization problem, and demonstrate that the worst-case convex tail behavior is in a sense either extremely light tailed or extremely heavy tailed. We develop low-dimensional nonlinear programs that distinguish between the two cases and compute the worst-case bound. We numerically illustrate how the proposed approach can give more reliable performances than conventional parametric methods. The online appendix is available at https://doi.org/10.1287/.
Novel targets and future strategies for acute cardioprotection: Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart

Ischaemic heart disease and the heart failure that often results, remain the leading causes of death and disability in Europe and worldwide. As such, in order to prevent heart failure and improve clinical outcomes in patients presenting with an acute ST-segment elevation myocardial infarction and patients undergoing coronary artery bypass graft surgery, novel therapies are required to protect the heart against the detrimental effects of acute ischaemia/reperfusion injury. During the last three decades, a wide variety of ischaemic conditioning strategies and pharmacological treatments have been tested in the clinic - however, their translation from experimental to clinical studies for improving patient outcomes has been both challenging and disappointing. Therefore, in this Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart, we critically analyse the current state of ischaemic conditioning in both the experimental and clinical settings, provide recommendations for improving its translation into the clinical setting, and highlight novel therapeutic targets and new treatment strategies for reducing acute myocardial ischaemia/reperfusion injury.
FOXJ2 controls meiosis during spermatogenesis in male mice

Spermatogenesis is a highly complex cell differentiation process necessary for production of haploid spermatozoa. Central to this unique process is spermatocyte meiosis. FOXJ2 (Forkhead box J2), a FOX transcription factor, is specifically expressed in meiotic spermatocytes in adult mouse testes, so we used a germ cell specific conditional knockout model (Foxj2flox/flox, Mvh‐Cre) to explore its role in spermatogenesis. Loss of FOXJ2 in the male germ line led to meiotic arrest and complete infertility. Although, DNA double‐strand breaks (DSBs) were initiated, Foxj2‐deficient spermatocytes failed to form chromosomal synapses and perform DSB repair. Furthermore, Foxj2‐deficient spermatocytes contained significantly less mRNA encoding DSB repair‐associated factors (Rad18, Rad51, Brca1, Brca2, and Tex15) and meiotic arrest‐related proteins (Fzr1, Hsp70‐2, Spata22, Eif4g3, and Zpac); in contrast, no change was observed in the expression of spermatogonia markers (Gfra1, Zbtb16, and c‐Kit) and germ cell markers (Dazl, Mvh, and Tra98). Taken together, FOXJ2 appears to promote meiotic progression in male mice by a mechanism that needs further investigation. Mol. Reprod. Dev. 83: 684–691, 2016 © 2016 Wiley Periodicals, Inc.
Observer-based control for networked systems with event-triggering predictive scheme

This paper studies the observer-based event-triggered predictive control problem for networked control systems (NCSs). First, we propose a discrete event-triggered transmission scheme for the observer by introducing a quadratic event-triggering function. Then, based on the above scheme, a novel class of event-triggered predictive control algorithms on the controller node are designed for compensating for the communication delays actively and achieving the desired control performance while using less network resources. The closed-loop systems with the proposed observer-based event-triggered predictive control scheme for the analysis are established correspondingly. The design problems of the controller and the event-triggering parameter are discussed by using the linear matrix inequality (LMI) approach and the switching Lyapunov functional method. Finally, a practical example is employed to demonstrate the compensation effect for the communication delays with the proposed scheme in this paper.
Budgeting Time for Dynamic Vehicle Routing with Stochastic Customer Requests

Parcel services route vehicles to pick up parcels in the service area. Pickup requests occur dynamically during the day and are unknown before their actual request. Because of working hour restrictions, service vehicles only have a limited time to serve dynamic requests. As a result, not all requests can be confirmed. To achieve an overall high number of confirmed requests, dispatchers have to budget their time effectively by anticipating future requests. To determine the value of a decision, i.e., the expected number of future confirmations given a point of time and remaining free time budget, we present an anticipatory time budgeting heuristic (ATB) drawing on methods of approximate dynamic programming. ATB frequently simulates a problem’s realization to subsequently approximate the values for every vector of point of time and free time budget to achieve an approximation of an optimal decision policy. Since the number of vectors is vast, we introduce the dynamic lookup table (DLT), a general approach ad.
FOXC1 identifies basal-like breast cancer in a hereditary breast cancer cohort

Breast cancers arising in the setting of the hereditary breast cancer genes BRCA1 and BRCA2 are most commonly classified as basal-like breast cancer (BLBC) or luminal breast cancer, respectively. BLBC is an aggressive subtype of breast cancer associated with liver and lung metastases and poorer prognosis than other subtypes and for which chemotherapy is the only systemic therapy. Multiple immunohistochemical markers are used to identify the basal-like subtype, including the absence of estrogen receptor alpha, progesterone receptor, and human epidermal growth factor receptor 2. Forkhead box C1 (FOXC1) has been identified as a specific marker expressed in BLBC in general breast cancer cohorts. We examined an institutional cohort of breast cancer patients with germline BRCA1 (n=46) and BRCA2 (n=35) mutations and found that FOXC1 expression on immunohistochemical staining is associated with BRCA1 vs BRCA2 mutations [30/46 vs. 6/35]. In BRCA1 mutant tumors, FOXC1 was expressed in 28/31 BLBC tumors and 2/13 non-BLBC tumors, In BRCA2 mutant tumors, FOXC1 was expressed in 5/5 BLBC tumors and 1/30 non-BLBC tumors. In cell culture models of BRCA1-mutant breast cancer, FOXC1 is associated with increased proliferation and may serve as a marker for sensitivity to PARP-inhibitor therapy with olaparib.
A New Shape Descriptor Based on Tensor Scale

Tensor scale is a morphometric parameter that unifies the representation of local structure thickness, orientation, and anisotropy, which can be used in several computer vision and image processing tasks. In this paper, we exploit this concept for binary images and propose a shape descriptor that encodes region and contour properties in a very efficient way. Experimental results are provided, showing the effectiveness of the proposed descriptor, when compared to other relevant shape descriptors, with regard to their use in content-based image retrieval systems.
Free Energy, Enthalpy and Entropy from Implicit Solvent End-Point Simulations

Free energy is the key quantity to describe the thermodynamics of biological systems. In this perspective we consider the calculation of free energy, enthalpy and entropy from end-point molecular dynamics simulations. Since the enthalpy may be calculated as the ensemble average over equilibrated simulation snapshots the difficulties related to free energy calculation are ultimately related to the calculation of the entropy of the system and in particular of the solvent entropy. In the last two decades implicit solvent models have been used to circumvent the problem and to take into account solvent entropy implicitly in the solvation terms. More recently outstanding advancement in both implicit solvent models and in entropy calculations are making the goal of free energy estimation from end-point simulations more feasible than ever before. We review briefly the basic theory and discuss the advancements in light of practical applications.
Cell Therapy Clinical Trials for Stress Urinary Incontinence: Current Status and Perspectives

Stress urinary incontinence (SUI) affects 200 million people worldwide. Standard therapies often provide symptomatic relief, but without targeting the underlying etiology, and show tremendous patient-to-patient variability, limited success and complications associated with the procedures. We review in this article the latest clinical trials performed to treat SUI using cell-based therapies. These therapies, despite typically including only a small number of patients and short term evaluation of results, have proven to be feasible and safe. However, there is not yet a consensus for the best cell source to be used to treat SUI and not all patients may be suitable for these therapies. Therefore, more clinical trials should be promoted recruiting large number of patients and evaluating long term results.
Maternal depression impacts child psychopathology across the first decade of life: Oxytocin and synchrony as markers of resilience.

BACKGROUND While maternal depression is known to carry long-term negative consequences for offspring, very few studies followed children longitudinally to address markers of resilience in the context of maternal depression. We focused on oxytocin (OT) and mother-child synchrony - the biological and behavioral arms of the neurobiology of affiliation - as correlates of resilience among children of depressed mothers. METHOD A community birth-cohort was recruited on the second postbirth day and repeatedly assessed for maternal depression across the first year. At 6 and 10 years, mothers and children underwent psychiatric diagnosis, mother-child interactions were coded for maternal sensitivity, child social engagement, and mother-child synchrony, children's OT assayed, and externalizing and internalizing problems reported. RESULTS Exposure to maternal depression markedly increased child propensity to develop Axis-I disorder at 6 and 10 years. Child OT showed main effects for both maternal depression and child psychiatric disorder at 6 and 10 years, with maternal or child psychopathology attenuating OT response. In contrast, maternal depression decreased synchrony at 6 years but by 10 years synchrony showed only child disorder effect, highlighting the shift from direct to indirect effects as children grow older. Path analysis linking maternal depression to child externalizing and internalizing problems at 10 years controlling for 6-year variables indicated that depression linked with decreased maternal sensitivity and child OT, which predicted reduced child engagement and synchrony, leading to higher externalizing and internalizing problems. OT and synchrony mediated the effects of maternal depression on child behavior problems and an alternative model without these resilience components provided less adequate fit. CONCLUSIONS Maternal depression continues to play a role in children's development beyond infancy. The mediating effects of OT and synchronous, mutually regulated interactions underscore the role of plasticity in resilience. Results emphasize the need to follow children of depressed mothers across middle childhood and construct interventions that bolster age-appropriate synchrony.
Artificial intelligence as structural estimation: Deep Blue, Bonanza, and AlphaGo

This article clarifies the connections between certain algorithms to develop artificial intelligence (AI) and the econometrics of dynamic structural models, with concrete examples of three 'game AIs'. Chess-playing Deep Blue is a calibrated value function, whereas shogi-playing Bonanza is an estimated value function via Rust’s nested fixed-point (NFXP) method. AlphaGo’s 'supervised-learning policy network' is a deep-neural-network implementation of the conditional-choice-probability (CCP) estimation reminiscent of Hotz and Miller's first step; the construction of its 'reinforcement-learning value network' is analogous to their conditional choice simulation (CCS). I then explain the similarities and differences between AI-related methods and structural estimation more generally, and suggest areas of potential cross-fertilization.
Computational Performance and Statistical Accuracy of *BEAST and Comparisons with Other Methods

Under the multispecies coalescent model of molecular evolution, gene trees have independent evolutionary histories within a shared species tree. In comparison, supermatrix concatenation methods assume that gene trees share a single common genealogical history, thereby equating gene coalescence with species divergence. The multispecies coalescent is supported by previous studies which found that its predicted distributions fit empirical data, and that concatenation is not a consistent estimator of the species tree. *BEAST, a fully Bayesian implementation of the multispecies coalescent, is popular but computationally intensive, so the increasing size of phylogenetic data sets is both a computational challenge and an opportunity for better systematics. Using simulation studies, we characterize the scaling behavior of *BEAST, and enable quantitative prediction of the impact increasing the number of loci has on both computational performance and statistical accuracy. Follow-up simulations over a wide range of parameters show that the statistical performance of *BEAST relative to concatenation improves both as branch length is reduced and as the number of loci is increased. Finally, using simulations based on estimated parameters from two phylogenomic data sets, we compare the performance of a range of species tree and concatenation methods to show that using *BEAST with tens of loci can be preferable to using concatenation with thousands of loci. Our results provide insight into the practicalities of Bayesian species tree estimation, the number of loci required to obtain a given level of accuracy and the situations in which supermatrix or summary methods will be outperformed by the fully Bayesian multispecies coalescent.
Visualization of Culprit Perforators in Anterolateral Pontine Infarction: High-Resolution Magnetic Resonance Imaging Study

Background: The stroke mechanism for anterolateral pontine infarction (ALPI) is poorly understood. We aimed to investigate the perforator arteries relevant to ALPI using high-resolution MRI (HR-MRI). Methods: Of 62 patients with ALPI who were admitted to the Asan Medical Center, 13 patients agreed to participate in this study. We used HR-MRI with a 3-Tesla scanner and assessed the perforating branches directly connected with the infarcted area. Results: Perforating arteries penetrating ALPI were identified in all 13 patients. Perforators arising from the basilar artery (BA) were involved in the stroke mechanism in 9 patients, the superior cerebellar artery (SCA) perforator in 1 patient, and the anterior inferior cerebellar artery perforator in 1 patient. In 2 patients, both BA and SCA perforators were involved. Conclusions: Using 3-Tesla HR-MRI may allow visualization of the perforating branches presumably related to ALPI. Identification of the relevant cerebral perforating arteries may help us to understand the stroke mechanism in patients with posterior circulation territory infarction.
Technology-Facilitated Sexual Violence: A Literature Review of Empirical Research

Technology-facilitated sexual violence (TFSV) refers to a range of behaviors where digital technologies are used to facilitate both virtual and face-to-face sexually based harms. Such behaviors include online sexual harassment, gender- and sexuality-based harassment, cyberstalking, image-based sexual exploitation, and the use of a carriage service to coerce a victim into an unwanted sexual act. This article reviews the current state of knowledge on these different dimensions, drawing on existing empirical studies. While there is a growing body of research into technology-facilitated harms perpetrated against children and adolescents, there is a dearth of qualitative and quantitative research on TFSV against adults. Moreover, few of the existing studies provide reliable data on the nature, scope, and impacts of TFSV. Preliminary studies, however, indicate that some harms, much like sexual violence more broadly, may be predominantly gender-, sexuality-, and age-based, with young women being overrepresented as victims in some categories. This review collects the empirical evidence to date regarding the prevalence and gender-based nature of TFSV against adults and discusses the implications for policy and programs, as well as suggestions for future research.
Age‐dependent electrocardiographic changes in Pgc‐1β deficient murine hearts

Increasing evidence implicates chronic energetic dysfunction in human cardiac arrhythmias. Mitochondrial impairment through Pgc‐1β knockout is known to produce a murine arrhythmic phenotype. However, the cumulative effect of this with advancing age and its electrocardiographic basis have not been previously studied. Young (12‐16 weeks) and aged (>52 weeks), wild type (WT) (n = 5 and 8) and Pgc‐1β−/− (n = 9 and 6), mice were anaesthetised and used for electrocardiographic (ECG) recordings. Time intervals separating successive ECG deflections were analysed for differences between groups before and after β1‐adrenergic (intraperitoneal dobutamine 3 mg/kg) challenge. Heart rates before dobutamine challenge were indistinguishable between groups. The Pgc‐1β−/− genotype however displayed compromised nodal function in response to adrenergic challenge. This manifested as an impaired heart rate response suggesting a functional defect at the level of the sino‐atrial node, and a negative dromotropic response suggesting an atrioventricular conduction defect. Incidences of the latter were most pronounced in the aged Pgc‐1β−/− mice. Moreover, Pgc‐1β−/− mice displayed electrocardiographic features consistent with the existence of a pro‐arrhythmic substrate. Firstly, ventricular activation was prolonged in these mice consistent with slowed action potential conduction and is reported here for the first time. Additionally, Pgc‐1β−/− mice had shorter repolarisation intervals. These were likely attributable to altered K+ conductance properties, ultimately resulting in a shortened QTc interval, which is also known to be associated with increased arrhythmic risk. ECG analysis thus yielded electrophysiological findings bearing on potential arrhythmogenicity in intact Pgc‐1β−/− systems in widespread cardiac regions.
Membrane‐Tethered Metalloproteinase Expressed by Vascular Smooth Muscle Cells Limits the Progression of Proliferative Atherosclerotic Lesions

Background The MMP (matrix metalloproteinase) family plays diverse and critical roles in directing vascular wall remodeling in atherosclerosis. Unlike secreted‐type MMPs, a member of the membrane‐type MMP family, MT1‐MMP (membrane‐type 1 MMP; MMP14), mediates pericellular extracellular matrix degradation that is indispensable for maintaining physiological extracellular matrix homeostasis. However, given the premature mortality exhibited by MT1‐MMP–null mice, the potential role of the proteinase in atherogenesis remains elusive. We sought to determine the effects of both MT1‐MMP heterozygosity and tissue‐specific gene targeting on atherogenesis in APOE (apolipoprotein E)–null mice. Methods and Results MT1‐MMP heterozygosity in the APOE‐null background (Mmp14 +/− Apoe −/−) significantly promoted atherogenesis relative to Mmp14 +/+ Apoe −/− mice. Furthermore, the tissue‐specific deletion of MT1‐MMP from vascular smooth muscle cells (VSMCs) in SM22α‐Cre(+)Mmp14 F/F Apoe −/− (VSMC‐knockout) mice likewise increased the severity of atherosclerotic lesions. Although VSMC‐knockout mice also developed progressive atherosclerotic aneurysms in their iliac arteries, macrophage‐ and adipose‐specific MT1‐MMP–knockout mice did not display this sensitized phenotype. In VSMC‐knockout mice, atherosclerotic lesions were populated by hyperproliferating VSMCs (smooth muscle actin– and Ki67–double‐positive cells) that were characterized by a proinflammatory gene expression profile. Finally, MT1‐MMP–null VSMCs cultured in a 3‐dimensional spheroid model system designed to mimic in vivo–like cell–cell and cell–extracellular matrix interactions, likewise displayed markedly increased proliferative potential. Conclusions MT1‐MMP expressed by VSMCs plays a key role in limiting the progression of atherosclerosis in APOE‐null mice by regulating proliferative responses and inhibiting the deterioration of VSMC function in atherogenic vascular walls.
Automated cell-type classification in intact tissues by single-cell molecular profiling

A major challenge in biology is identifying distinct cell classes and mapping their interactions in vivo. Tissue-dissociative technologies enable deep single cell molecular profiling but do not provide spatial information. We developed a proximity ligation in situ hybridization technology (PLISH) with exceptional signal strength, specificity, and sensitivity in tissue. Multiplexed data sets can be acquired using barcoded probes and rapid label-image-erase cycles, with automated calculation of single cell profiles, enabling clustering and anatomical re-mapping of cells. We apply PLISH to expression profile ~2900 cells in intact mouse lung, which identifies and localizes known cell types, including rare ones. Unsupervised classification of the cells indicates differential expression of ‘housekeeping’ genes between cell types, and re-mapping of two sub-classes of Club cells highlights their segregated spatial domains in terminal airways. By enabling single cell profiling of various RNA species in situ, PLISH can impact many areas of basic and medical research.
Poster: Benchmarking Microservice Systems for Software Engineering Research

Despite the prevalence and importance of microservices in industry, there exists limited research on microservices, partly due to lacking a benchmark system that reflects the characteristics of industrial microservice systems. To fill this gap, we conduct a review of literature and open source systems to identify the gap between existing benchmark systems and industrial microservice systems. Based on the results of the gap analysis, we then develop and release a medium-size benchmark system of microservice architecture.