A Monadic Semantics for Core Curry

We give a deterministic, big-step operational semantics for the essential core of the Curry language, including higher-order functions, call-by-need evaluation, non-determinism, narrowing, and residuation. The semantics is structured in modular monadic style, and is presented in the form of an executable interpreter written in Haskell. It uses monadic formulations of state, non-determinism, and resumption-based concurrency.     

Probabilistic Approach to Predict Cracking in Lightly Reinforced Microconcrete Panels

The ultimate strength of structures made of brittle materials—such as microconcrete—strongly depends on microstructural defects, the structure size, and the loading pattern. Probabilistic approaches allow one to take account of such dependencies. By using a Weibull model, cracking of ferrocement panels is analyzed. Provided the behavior of the reinforcement remains elastic, it is shown that the Weibull parameters identified on unreinforced microconcrete samples tested in flexure may be used to predict multiple cracking in ferrocement panels tested in tension. A key aspect of the analysis is related to the understanding and modeling of the stress heterogeneity effect on the local failure probability of unreinforced as well as reinforced microconcrete by the use of a so-called Weibull stress.     

Neurotrophic control of ovarian development

Substantial evidence now exists indicating that the neurotrophins, a family of growth factors required for the survival, development, and differentiation of various neuronal populations of the nervous system, are also important for the development of nonneuronal tissues. Such a function was first suggested by studies showing the presence of high-affinity neurotrophin receptors in a variety of nonneuronal tissues including those of the cardiovascular, endocrine, immune, and reproductive systems. Within the latter, the gonads appear to be a preferential site of neurotrophin action as suggested by the presence in the mammalian ovary of at least four of the five known neurotrophins and all of the neurotrophin receptors thus far identified. While the various functions that the neurotrophins may have in the ovary are still being elucidated, it is now clear that in addition to recruiting the ovarian innervation, they play a direct role in the regulation of two different maturational periods that are critical for the acquisition of female reproductive function: early follicular development and ovulation. Neurotrophins facilitate the development of newly formed follicles by promoting the initial differentiation and the subsequent growth of primordial follicles. These actions appear to be related to the ability of neurotrophins to sustain the proliferation of both mesenchymal and granulosa cells, and to induce the synthesis of follicle stimulating hormone (FSH) receptors. At the time of the first ovulation, neurotrophins contribute to the ovulatory cascade by increasing prostaglandin E(2) release, reducing gap junction communication, and inducing cell proliferation within the thecal compartment of preovulatory follicles.     

Friction and wear behaviour of Thordon XL and LgSn80 in sliding against plasma-sprayed Cr2O3 coatings

This paper studies the friction and wear behaviour of two important bearing materials, Thordon XL and LgSn80, in dry and lubricated sliding vs. plasma-sprayed Cr₂O₃ coatings. As a reference, AISI 1043 steel is also studied under the same conditions. SEM, EDS and surface topography were employed to study the wear mechanisms. The results indicate that the Thordon XL/Cr₂O₃ coating pair gives the lowest dry friction coefficient (0.16) under a normal load of 45.3 N (pressure 0.453 MPa) at a velocity of 1 m/s. The dry friction coefficient of Thordon XL/Cr₂O₃ coating increases to 0.38 under a normal load of 88.5 N (pressure 0.885 MPa). The dry friction coefficients of the LgSn80/Cr₂O₃ coating are in the range of 0.31–0.46. Secondly, both dry wear rate under low normal load (45.3 N) and lubricated wear rate under a load of 680 N for Thordon XL are lower than those of LgSn80 in sliding against plasma-sprayed Cr₂O₃ coatings at a speed of 1 m/s. However, under a normal load of 88.5 N the dry wear rate of Thordon XL is much higher than that of LgSn80. Thirdly, a high viscosity lubricant (SAE 140) leads to lower wear for Thordon XL and LgSn80 than a low viscosity lubricant (SAE 30). Finally, the dominating wear mechanism for Thordon XL is shear fracture when against the plasma-sprayed Cr₂O₃ ceramic coating. For LgSn80 against plasma-sprayed Cr₂O₃ ceramic coating, abrasive wear is the governing failure mechanism.     

A parallel micro evolutionary algorithm for heterogeneous computing and grid scheduling

This work presents a novel parallel micro evolutionary algorithm for scheduling tasks in distributed heterogeneous computing and grid environments. The scheduling problem in heterogeneous environments is NP-hard, so a significant effort has been made in order to develop an efficient method to provide good schedules in reduced execution times. The parallel micro evolutionary algorithm is implemented using MALLBA, a general-purpose library for combinatorial optimization. Efficient numerical results are reported in the experimental analysis performed on both well-known problem instances and large instances that model medium-sized grid environments. The comparative study of traditional methods and evolutionary algorithms shows that the parallel micro evolutionary algorithm achieves a high problem solving efficacy, outperforming previous results already reported in the related literature, and also showing a good scalability behavior when facing high dimension problem instances.     

Comparison of metaheuristics for the k‐labeled spanning forest problem

In this paper, we study the k‐labeled spanning forest (kLSF) problem in which an undirected graph whose edges are labeled and an integer‐positive value are given; the aim is to find a spanning forest of the input graph with the minimum number of connected components and the upper bound on the number of labels. The problem is related to the minimum labeling spanning tree problem and has several applications in the real world. In this paper, we compare several metaheuristics to solve this NP‐hard problem. In particular, the proposed intelligent variable neighborhood search (VNS) shows excellent performance, obtaining high‐quality solutions in short computational running time. This approach integrates VNS with other complementary approaches from machine learning, statistics, and experimental algorithmics, in order to produce high‐quality performance and completely automate the resulting optimization strategy.     

Somatostatin,Cortistatin and Their Receptors Exert Antitumor Actions in Androgen-Independent Prostate Cancer Cells: Critical Role of Endogenous Cortistatin

Somatostatin (SST), cortistatin (CORT), and their receptors (SSTR1-5/sst5TMD4-TMD5) comprise a multifactorial hormonal system involved in the regulation of numerous pathophysiological processes. Certain components of this system are dysregulated and play critical roles in the development/progression of different endocrine-related cancers. However, the presence and therapeutic role of this regulatory system in prostate cancer (PCa) remain poorly explored. Accordingly, we performed functional (proliferation/migration/colonies-formation) and mechanistic (Western-blot/qPCR/microfluidic-based qPCR-array) assays in response to SST and CORT treatments and CORT-silencing (using specific siRNA) in different PCa cell models [androgen-dependent (AD): LNCaP; androgen-independent (AI)/castration-resistant PCa (CRPC): 22Rv1 and PC-3], and/or in the normal-like prostate cell-line RWPE-1. Moreover, the expression of SST/CORT system components was analyzed in PCa samples from two different patient cohorts [internal (n = 69); external (Grasso, n = 88)]. SST and CORT treatment inhibited key functional/aggressiveness parameters only in AI-PCa cells. Mechanistically, antitumor capacity of SST/CORT was associated with the modulation of oncogenic signaling pathways (AKT/JNK), and with the significant down-regulation of critical genes involved in proliferation/migration and PCa-aggressiveness (e.g., MKI67/MMP9/EGF). Interestingly, CORT was highly expressed, while SST was not detected, in all prostate cell-lines analyzed. Consistently, endogenous CORT was overexpressed in PCa samples (compared with benign-prostatic-hyperplasia) and correlated with key clinical (i.e., metastasis) and molecular (i.e., SSTR2/SSTR5 expression) parameters. Remarkably, CORT-silencing drastically enhanced proliferation rate and blunted the antitumor activity of SST-analogues (octreotide/pasireotide) in AI-PCa cells. Altogether, we provide evidence that SST/CORT system and SST-analogues could represent a potential therapeutic option for PCa, especially for CRPC, and that endogenous CORT could act as an autocrine/paracrine regulator of PCa progression.     

DeepHP: A New Gastric Mucosa Histopathology Dataset for Helicobacter pylori Infection Diagnosis

Emerging deep learning-based applications in precision medicine include computational histopathological analysis. However, there is a lack of the required training image datasets to generate classification and detection models. This phenomenon occurs mainly due to human factors that make it difficult to obtain well-annotated data. The present study provides a curated public collection of histopathological images (DeepHP) and a convolutional neural network model for diagnosing gastritis. Images from gastric biopsy histopathological exams were used to investigate the performance of the proposed model in detecting gastric mucosa with Helicobacter pylori infection. The DeepHP database comprises 394,926 histopathological images, of which 111 K were labeled as Helicobacter pylori positive and 283 K were Helicobacter pylori negative. We investigated the classification performance of three Convolutional Neural Network architectures. The models were tested and validated with two distinct image sets of 15% (59K patches) chosen randomly. The VGG16 architecture showed the best results with an Area Under the Curve of 0.998%. The results showed that CNN could be used to classify histopathological images from gastric mucosa with marked precision. Our model evidenced high potential and application in the computational pathology field.     

CRISPR/Cas9-Based Knock-Out of the PMR4 Gene Reduces Susceptibility to Late Blight in Two Tomato Cultivars

Phytophthora infestans, the causal agent of late blight (LB) in tomato (Solanum lycopersicum L.), is a devastating disease and a serious concern for plant productivity. The presence of susceptibility (S) genes in plants facilitates pathogen proliferation; thus, disabling these genes may help provide a broad-spectrum and durable type of tolerance/resistance. Previous studies on Arabidopsis and tomato have highlighted that knock-out mutants of the PMR4 susceptibility gene are tolerant to powdery mildew. Moreover, PMR4 knock-down in potato has been shown to confer tolerance to LB. To verify the same effect in tomato in the present study, a CRISPR–Cas9 vector containing four single guide RNAs (sgRNAs: sgRNA1, sgRNA6, sgRNA7, and sgRNA8), targeting as many SlPMR4 regions, was introduced via Agrobacterium-tumefaciens-mediated transformation into two widely grown Italian tomato cultivars: ‘San Marzano’ (SM) and ‘Oxheart’ (OX). Thirty-five plants (twenty-six SM and nine OX) were selected and screened to identify the CRISPR/Cas9-induced mutations. The different sgRNAs caused mutation frequencies ranging from 22.1 to 100% and alternatively precise insertions (sgRNA6) or deletions (sgRNA7, sgRNA1, and sgRNA8). Notably, sgRNA7 induced in seven SM genotypes a −7 bp deletion in the homozygous status, whereas sgRNA8 led to the production of fifteen SM genotypes with a biallelic mutation (−7 bp and −2 bp). Selected edited lines were inoculated with P. infestans, and four of them, fully knocked out at the PMR4 locus, showed reduced disease symptoms (reduction in susceptibility from 55 to 80%) compared to control plants. The four SM lines were sequenced using Illumina whole-genome sequencing for deeper characterization without exhibiting any evidence of mutations in the candidate off-target regions. Our results showed, for the first time, a reduced susceptibility to Phytophtora infestans in pmr4 tomato mutants confirming the role of KO PMR4 in providing broad-spectrum protection against pathogens.