bluuebunny/crossref_metadata_2025 huggingface dataset:
Diversity and Distribution of Phytophthora Species in Protected Natural Areas in Sicily
Authors: Jung Thomas , La Spada Federico , Pane Antonella , Aloi Francesco , Evoli Maria , Horta Jung Marilia , Scanu Bruno , Faedda Roberto , Rizza Cinzia , Puglisi Ivana , Magnano di San Lio Gaetano , Schena Leonardo , Cacciola Santa Olga
Published: March 2019

The aim of this study was to investigate the occurrence, diversity, and distribution of Phytophthora species in Protected Natural Areas (PNAs), including forest stands, rivers, and riparian ecosystems, in Sicily (Italy), and assessing correlations with natural vegetation and host plants. Fifteen forest stands and 14 rivers in 10 Sicilian PNAs were studied. Phytophthora isolations from soil and stream water were performed using leaf baitings. Isolates were identified using both morphological characters and sequence analysis of the internal transcribed spacer (ITS) region. A rich community of 20 Phytophthora species from eight phylogenetic clades, including three new Phytophthora taxa, was recovered (17 species in rhizosphere soil from forest stands and 12 species in rivers). New knowledge about the distribution, host associations, and ecology of several Phytophthora species was provided.
Production of d-Lactate from Avocado Seed Hydrolysates by Metabolically Engineered Escherichia coli JU15
Authors: Palmerín-Carreño Dulce María , Hernández-Orihuela Ana Lilia , Martínez-Antonio Agustino
Published: March 2019

Agroindustry residues can be used to produce valuable chemicals such as lactic acid, which is a primary chemical platform with many industrial applications. Biotechnological processes are the main approach of lactic acid production; however, culture media has an important impact on their costs. As a result, researchers are exploring various methods of production that use residual or waste biomass as raw materials, most of which are rich in lignocellulose. Nevertheless, starch and micronutrients such as those contained in avocado seeds stand out as promising feedstock for the bioprocess as well. In this study, the lactogenic Escherichia coli strain JU15 was evaluated for producing d-lactate using an avocado seed hydrolysate medium in a controlled stirred-tank bioreactor. The highest lactic acid concentration achieved was 37.8 g L−1 using 120 g L−1 as the content of initial reducing sugars. The results showed that d-lactate can be produced from avocado seed, which hydrolysates to 0.52 g L−1 h−1 using the engineered E. coli JU15. This study may serve as a starting point to further develop bioprocesses for producing metabolites using avocado seed hydrolysates.
Surface Fire to Crown Fire: Fire History in the Taos Valley Watersheds, New Mexico, USA
Authors: Johnson Lane B. , Margolis Ellis Q.
Published: March 2019

Tree-ring fire scars, tree ages, historical photographs, and historical surveys indicate that, for centuries, fire played different ecological roles across gradients of elevation, forest, and fire regimes in the Taos Valley Watersheds. Historical fire regimes collapsed across the three watersheds by 1899, leaving all sites without fire for at least 119 years. Historical photographs and quaking aspen (Populus tremuloides Michx.) ages indicate that a high-severity fire historically burned at multiple high-elevation subalpine plots in today’s Village of Taos Ski Valley, with large high-severity patches (>640 ha). Low-severity, frequent (9–29-year median interval) surface fires burned on the south aspects in nearby lower elevation dry conifer forests in all watersheds. Fires were associated with drought during the fire year. Widespread fires commonly burned synchronously in multiple watersheds during more severe drought years, preceded by wet years, including fire in all three watersheds in 1664, 1715, and 1842. In contrast, recent local “large” wildfires have only burned within single watersheds and may not be considered large in a historical context. Management to promote repeated low-severity fires and the associated open stand structures is within the historical range of variability in the dry conifer forests of these watersheds. In the high-elevation, subalpine forests, different management approaches are needed, which balance ecological and socioeconomic values while providing public safety.
Assessment of Tryptophan, Tryptophan Ethylester, and Melatonin Derivatives in Red Wine by SPE-HPLC-FL and SPE-HPLC-MS Methods
Authors: Fracassetti Daniela , Vigentini Ileana , Lo Faro Alfredo , De Nisi Patrizia , Foschino Roberto , Tirelli Antonio , Orioli Marica , Iriti Marcello
Published: March 2019

Melatonin (MEL) is an indoleamine produced mainly by the pineal gland in vertebrates. It plays a significant role in the regulation of circadian rhythms, mitigation of sleeping disorders, and jet lag. This compound is synthetized from tryptophan (TRP) and it has been found in seeds, fruits, and fermented beverages, including wine. Wine is also a source of other tryptophan derivatives, the tryptophan ethylester (TEE) and MEL isomers (MISs), for which the biological properties need to be elucidated. An analytical method for the simultaneous quantification of TRP, TEE, and MEL was developed by a Solid Phase Extraction (SPE) of a preconcentration of wine followed by high performance liquid chromatography (HPLC) analysis either with fluorescence or mass spectrometer detectors. The analytical method showed a relative standard deviation (RSD) lower than 8%, except for TRP (RSD 10.5% in wine). The recovery was higher than 76%. The versatility of SPE preconcentrations allowed for the adequate preconcentration of wine sample as well as detection of low concentrations, an important aspect especially for MEL (detection limit 0.0023 µg/L). The proposed method proved to be suitable for assessing the investigated compounds in some red wine samples, where 74.4–256.2 µg/L and 0.038–0.063 µg/L of TEE and MEL were detected, respectively. Five MISs were also found in wine samples in concentrations up to 1.97 µg/L.
Collections in the Expanded Field: Relationality and the Provenance of Artefacts and Archives
Authors: Jones Michael
Published: March 2019

In 2017 archaeological evidence was published which indicates that modern humans first arrived in Australia around 65,000 years ago. Through the countless generations since, Aboriginal and Torres Strait Islander peoples built deep connections to the landscape, developed rich material culture infused with story and myth, and used oral and ceremonial traditions to transmit knowledge over thousands of years. Yet, since European invasion at the end of the eighteenth century, the provenance of ethnographic and institutional collections has largely been documented with reference to white collectors and colonial institutions. Attitudes are starting to change. Recent decades have seen significant moves away from the idea of the authoritative institution toward relational museums and the co-creation of knowledge. But the structure and content of much museum documentation continues to lag behind contemporary attitudes. This paper looks at the documentation of Australian ethnographic and anthropological collections through the lens of changing perspectives on provenance, including archival notions of parallel and societal provenance. When placed in the context of recent developments in material culture theory, these collections help to highlight the limitations of existing documentation. The paper concludes with a call for community involvement and a more relational approach to documentation which better encompasses the complexities of provenance and the entangled institutional, archival, oral, and community perspectives that accumulate around artefacts in museums.
A Molecular Docking Approach to Evaluate the Pharmacological Properties of Natural and Synthetic Treatment Candidates for Use against Hypertension
Authors: Attique Syed Awais , Hassan Muhammad , Usman Muhammad , Atif Rana Muhammad , Mahboob Shahid , Al-Ghanim Khalid A. , Bilal Muhammad , Nawaz Muhammad Zohaib
Published: March 2019

Cardiovascular diseases (CVDs) have become the leading cause of disability and death worldwide, particularly in low- and middle-income countries. Hypertension, a major cause of CVD progression, is widely attributable to genetic, behavioral, and environmental risk factors. Among the genetic reasons, angiotensin II enzyme, produced as a result of abnormal functioning of the renin–angiotensin system, is reported as the foremost cause of hypertension. A cascade of genes, including those encoding for WNK kinases (WNK1 and WNK4), Bp1, Bp2, angiotensinogen, and other enzymes, is involved in the conversion of angiotensin I to angiotensin II. However, the angiotensin-converting enzyme (ACE) plays a crucial role in this pathway. Therefore, ACE could be a potential therapeutic target in regulating the conversion of angiotensin I to angiotensin II and eventually controlling hypertension. In this study, a molecular docking-based approach was utilized for identifying and evaluating potential inhibitors of ACE present in herbs, other natural sources, and synthetic sources, on the basis of these compounds’ binding affinities and other physicochemical features. In addition, the suitability of these inhibitors as drugs for biological systems, considering their adsorption, distribution, metabolism, and excretion (ADME), was predicted using Lipinski’s rule. In conclusion, our study provides a novel and clearer insight into the interaction properties of known putative inhibitors of ACE.
Innovative Therapeutic Strategies for Effective Treatment of Brain Metastases
Authors: Lim Malcolm , Puttick Simon , Houston Zachary H. , Thurecht Kristofer J. , Kalita-de Croft Priyakshi , Mahler Stephen , Rose Stephen E. , Jeffree Rosalind L. , Mazzieri Roberta , Dolcetti Riccardo , Lakhani Sunil R. , Saunus Jodi M.
Published: March 2019

Brain metastases are the most prevalent of intracranial malignancies. They are associated with a very poor prognosis and near 100% mortality. This has been the case for decades, largely because we lack effective therapeutics to augment surgery and radiotherapy. Notwithstanding improvements in the precision and efficacy of these life-prolonging treatments, with no reliable options for adjunct systemic therapy, brain recurrences are virtually inevitable. The factors limiting intracranial efficacy of existing agents are both physiological and molecular in nature. For example, heterogeneous permeability, abnormal perfusion and high interstitial pressure oppose the conventional convective delivery of circulating drugs, thus new delivery strategies are needed to achieve uniform drug uptake at therapeutic concentrations. Brain metastases are also highly adapted to their microenvironment, with complex cross-talk between the tumor, the stroma and the neural compartments driving speciation and drug resistance. New strategies must account for resistance mechanisms that are frequently engaged in this milieu, such as HER3 and other receptor tyrosine kinases that become induced and activated in the brain microenvironment. Here, we discuss molecular and physiological factors that contribute to the recalcitrance of these tumors, and review emerging therapeutic strategies, including agents targeting the PI3K axis, immunotherapies, nanomedicines and MRI-guided focused ultrasound for externally controlling drug delivery.
Transcriptional Regulation: Molecules, Involved Mechanisms, and Misregulation
Authors: Casamassimi Amelia , Ciccodicola Alfredo
Published: March 2019

Transcriptional regulation is a critical biological process that allows the cell or an organism to respond to a variety of intra- and extra-cellular signals, to define cell identity during development, to maintain it throughout its lifetime, and to coordinate cellular activity [...]
Global Gene Expression of Seed Coat Tissues Reveals a Potential Mechanism of Regulating Seed Size Formation in Castor Bean
Authors: Yu Anmin , Wang Zaiqing , Zhang Yang , Li Fei , Liu Aizhong
Published: March 2019

The physiological and molecular basis of seed size formation is complex, and the development of seed coat (derived from integument cells) might be a critical factor that determines seed size formation for many endospermic seeds. Castor bean (Ricinus communis L.), a model system of studying seed biology, has large and persistent endosperm with a hard seed coat at maturity. Here, we investigated the potential molecular mechanisms underlying seed size formation in castor bean by comparing the difference between global gene expression within developing seed coat tissues between the large-seed ZB107 and small-seed ZB306. First, we observed the cell size of seed coat and concluded that the large seed coat area of ZB107 resulted from more cell numbers (rather than cell size). Furthermore, we found that the lignin proportion of seed coat was higher in ZB306. An investigation into global gene expression of developing seed coat tissues revealed that 815 genes were up-regulated and 813 were down-regulated in ZB306 relative to ZB107. Interestingly, we found that many genes involved in regulating cell division were up-regulated in ZB107, whereas many genes involved in regulating lignin biosynthesis (including several NAC members, as well as MYB46/83 and MYB58/63) and in mediating programmed cell death (such as CysEP1 and βVPE) were up-regulated in ZB306. Furthermore, the expression patterns of the genes mentioned above indicated that the lignification of seed coat tissues was enhanced and occurred earlier in the developing seeds of ZB306. Taken together, we tentatively proposed a potential scenario for explaining the molecular mechanisms of seed coat governing seed size formation in castor bean by increasing the cell number and delaying the onset of lignification in seed coat tissues in large-seed ZB107. This study not only presents new information for possible modulation of seed coat related genes to improve castor seed yield, but also provides new insights into understanding the molecular basis of seed size formation in endospermic seeds with hard seed coat.
Killing Mechanisms of Chimeric Antigen Receptor (CAR) T Cells
Authors: Benmebarek Mohamed-Reda , Karches Clara Helke , Cadilha Bruno Loureiro , Lesch Stefanie , Endres Stefan , Kobold Sebastian
Published: March 2019

Effective adoptive T cell therapy (ACT) comprises the killing of cancer cells through the therapeutic use of transferred T cells. One of the main ACT approaches is chimeric antigen receptor (CAR) T cell therapy. CAR T cells mediate MHC-unrestricted tumor cell killing by enabling T cells to bind target cell surface antigens through a single-chain variable fragment (scFv) recognition domain. Upon engagement, CAR T cells form a non-classical immune synapse (IS), required for their effector function. These cells then mediate their anti-tumoral effects through the perforin and granzyme axis, the Fas and Fas ligand axis, as well as the release of cytokines to sensitize the tumor stroma. Their persistence in the host and functional outputs are tightly dependent on the receptor’s individual components—scFv, spacer domain, and costimulatory domains—and how said component functions converge to augment CAR T cell performance. In this review, we bring forth the successes and limitations of CAR T cell therapy. We delve further into the current understanding of how CAR T cells are designed to function, survive, and ultimately mediate their anti-tumoral effects.
Long Noncoding RNA and Protein Interactions: From Experimental Results to Computational Models Based on Network Methods
Authors: Zhang Hui , Liang Yanchun , Han Siyu , Peng Cheng , Li Ying
Published: March 2019

Non-coding RNAs with a length of more than 200 nucleotides are long non-coding RNAs (lncRNAs), which have gained tremendous attention in recent decades. Many studies have confirmed that lncRNAs have important influence in post-transcriptional gene regulation; for example, lncRNAs affect the stability and translation of splicing factor proteins. The mutations and malfunctions of lncRNAs are closely related to human disorders. As lncRNAs interact with a variety of proteins, predicting the interaction between lncRNAs and proteins is a significant way to depth exploration functions and enrich annotations of lncRNAs. Experimental approaches for lncRNA–protein interactions are expensive and time-consuming. Computational approaches to predict lncRNA–protein interactions can be grouped into two broad categories. The first category is based on sequence, structural information and physicochemical property. The second category is based on network method through fusing heterogeneous data to construct lncRNA related heterogeneous network. The network-based methods can capture the implicit feature information in the topological structure of related biological heterogeneous networks containing lncRNAs, which is often ignored by sequence-based methods. In this paper, we summarize and discuss the materials, interaction score calculation algorithms, advantages and disadvantages of state-of-the-art algorithms of lncRNA–protein interaction prediction based on network methods to assist researchers in selecting a suitable method for acquiring more dependable results. All the related different network data are also collected and processed in convenience of users, and are available at https://github.com/HAN-Siyu/APINet/.
Revisiting Histone Deacetylases in Human Tumorigenesis: The Paradigm of Urothelial Bladder Cancer
Authors: Giannopoulou Aikaterini F. , Velentzas Athanassios D. , Konstantakou Eumorphia G. , Avgeris Margaritis , Katarachia Stamatia A. , Papandreou Nikos C. , Kalavros Nikolas I. , Mpakou Vassiliki E. , Iconomidou Vassiliki , Anastasiadou Ema , Kostakis Ioannis K. , Papassideri Issidora S. , Voutsinas Gerassimos E. , Scorilas Andreas , Stravopodis Dimitrios J.
Published: March 2019

Urinary bladder cancer is a common malignancy, being characterized by substantial patient mortality and management cost. Its high somatic-mutation frequency and molecular heterogeneity usually renders tumors refractory to the applied regimens. Hitherto, methotrexate-vinblastine-adriamycin-cisplatin and gemcitabine-cisplatin represent the backbone of systemic chemotherapy. However, despite the initial chemosensitivity, the majority of treated patients will eventually develop chemoresistance, which severely reduces their survival expectancy. Since chromatin regulation genes are more frequently mutated in muscle-invasive bladder cancer, as compared to other epithelial tumors, targeted therapies against chromatin aberrations in chemoresistant clones may prove beneficial for the disease. “Acetyl-chromatin” homeostasis is regulated by the opposing functions of histone acetyltransferases (HATs) and histone deacetylases (HDACs). The HDAC/SIRT (super-)family contains 18 members, which are divided in five classes, with each family member being differentially expressed in normal urinary bladder tissues. Since a strong association between irregular HDAC expression/activity and tumorigenesis has been previously demonstrated, we herein attempt to review the accumulated published evidences that implicate HDACs/SIRTs as critical regulators in urothelial bladder cancer. Moreover, the most extensively investigated HDAC inhibitors (HDACis) are also analyzed, and the respective clinical trials are also described. Interestingly, it seems that HDACis should be preferably used in drug-combination therapeutic schemes, including radiation.
Association between Striatal Brain Iron Deposition, Microbleeds and Cognition 1 Year After a Minor Ischaemic Stroke
Authors: Valdés Hernández Maria del C. , Case Tessa , Chappell Francesca M. , Glatz Andreas , Makin Stephen , Doubal Fergus , Wardlaw Joanna M.
Published: March 2019

Brain iron deposits (IDs) are inversely associated with cognitive function in community-dwelling older people, but their association with cognition after ischemic stroke, and whether that differs from microbleeds, is unknown. We quantified basal ganglia IDs (BGID) and microbleeds (BMBs) semi-automatically on brain magnetic resonance images from patients with minor stroke (NIHSS < 7), at presentation and 12 months after stroke. We administered the National Adult Reading Test (NART, estimates premorbid or peak adult cognition) and the Revised Addenbrooke’s Cognitive Examination (ACE-R; current cognition) at 1 and 12 months after stroke. We adjusted analyses for baseline cognition, age, gender, white matter hyperintensity (WMH) volume and vascular risk factors. In 200 patients, mean age 65 years, striatal IDs and BMBs volumes did not change over the 12 months. Baseline BGID volumes correlated positively with NART scores at both times (ρ = 0.19, p < 0.01). Baseline and follow-up BGID volumes correlated positively with age (ρ = 0.248, p < 0.001 and ρ = 0.271, p < 0.001 respectively), but only baseline (and not follow-up) BMB volume correlated with age (ρ = 0.129, p < 0.05). Both smoking and baseline WMH burden predicted verbal fluency and visuospatial abilities scores (B = −1.13, p < 0.02 and B = −0.22, p = 0.001 respectively) at 12 months after stroke. BGIDs and BMBs are associated differently with cognition post-stroke; studies of imaging and post-stroke cognition should adjust for premorbid cognition. The positive correlation of BGID with NART may reflect the lower premorbid cognition in patients with stroke at younger vs older ages.
Interleukin-1 Receptor Antagonist Modulates Liver Inflammation and Fibrosis in Mice in a Model-Dependent Manner
Authors: Meier Raphael P. H. , Meyer Jeremy , Montanari Elisa , Lacotte Stephanie , Balaphas Alexandre , Muller Yannick D. , Clément Sophie , Negro Francesco , Toso Christian , Morel Philippe , Buhler Leo H.
Published: March 2019

Background: Interleukin-1 (IL-1)β and IL-1 receptor antagonist (IL-1Ra) have been proposed as important mediators during chronic liver diseases. We aimed to determine whether the modulation of IL-1β signaling with IL-1Ra impacts on liver fibrosis. Methods: We assessed the effects of IL-1β on human hepatic stellate cells (HSC) and in mouse models of liver fibrosis induced by bile duct ligation (BDL) or carbon tetrachloride treatment (CCl-4). Results: Human HSCs treated with IL-1β had increased IL-1β, IL-1Ra, and MMP-9 expressions in vitro. HSCs treated with IL-1β had reduced α-smooth muscle actin expression. These effects were all prevented by IL-1Ra treatment. In the BDL model, liver fibrosis and Kuppfer cell numbers were increased in IL-1Ra KO mice compared to wild type mice and wild type mice treated with IL-1Ra. In contrast, after CCl-4 treatment, fibrosis, HSC and Kupffer cell numbers were decreased in IL-1Ra KO mice compared to the other groups. IL-1Ra treatment provided a modest protective effect in the BDL model and was pro-fibrotic in the CCl-4 model. Conclusions: We demonstrated bivalent effects of IL-1Ra during liver fibrosis in mice. IL-1Ra was detrimental in the CCl-4 model, whereas it was protective in the BDL model. Altogether these data suggest that blocking IL-1-mediated inflammation may be beneficial only in selective liver fibrotic disease.
The Inescapable Effects of Ribosomes on In-Cell NMR Spectroscopy and the Implications for Regulation of Biological Activity
Authors: Burz David S. , Breindel Leonard , Shekhtman Alexander
Published: March 2019

The effects of RNA on in-cell NMR spectroscopy and ribosomes on the kinetic activity of several metabolic enzymes are reviewed. Quinary interactions between labelled target proteins and RNA broaden in-cell NMR spectra yielding apparent megadalton molecular weights in-cell. The in-cell spectra can be resolved by using cross relaxation-induced polarization transfer (CRINEPT), heteronuclear multiple quantum coherence (HMQC), transverse relaxation-optimized, NMR spectroscopy (TROSY). The effect is reproduced in vitro by using reconstituted total cellular RNA and purified ribosome preparations. Furthermore, ribosomal binding antibiotics alter protein quinary structure through protein-ribosome and protein-mRNA-ribosome interactions. The quinary interactions of Adenylate kinase, Thymidylate synthase and Dihydrofolate reductase alter kinetic properties of the enzymes. The results demonstrate that ribosomes may specifically contribute to the regulation of biological activity.
Methoxsalen and Bergapten Prevent Diabetes-Induced Osteoporosis by the Suppression of Osteoclastogenic Gene Expression in Mice
Authors: Ham Ju Ri , Choi Ra-Yeong , Lee Hae-In , Lee Mi-Kyung
Published: March 2019

This study evaluated whether bergapten and methoxsalen could prevent diabetes-induced osteoporosis and its underlying mechanism. For 10 weeks, bergapten or methoxsalen (0.02%, w/w) was applied to diabetic mice that were provided with a high-fat diet and streptozotocin. Bone mineral density (BMD) and microarchitecture quality were significantly reduced in the diabetic control group; however, both bergapten and methoxsalen reversed serum osteocalcin, bone-alkaline phosphatase and femur BMD. These coumarin derivatives significantly increased bone volume density and trabecular number, whereas they decreased the structure model index of femur tissue in diabetic mice. Conversely, tartrate-resistant acid phosphatase 5 (TRAP) staining revealed that these derivatives reduced osteoclast numbers and formation in diabetic bone tissue. Additionally, both bergapten and methoxsalen tended to downregulate the expression of osteoclast-related genes such as receptor activator of nuclear factor kappa-B ligand (RANKL), nuclear of activated T-cells, cytoplasmic 1 (NFATc1) and TRAP in diabetic femurs, with NFATc1 and TRAP expression showing significant reductions. Our data suggest that both bergapten and methoxsalen prevent diabetic osteoporosis by suppressing bone resorption.
ER Stress is Involved in Epithelial-To-Mesenchymal Transition of Alveolar Epithelial Cells Exposed to a Hypoxic Microenvironment
Authors: Delbrel Eva , Uzunhan Yurdagül , Soumare Abdoulaye , Gille Thomas , Marchant Dominique , Planès Carole , Boncoeur Emilie
Published: March 2019

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal interstitial lung disease of unknown origin. Alveolar epithelial cells (AECs) play an important role in the fibrotic process as they undergo sustained endoplasmic reticulum (ER) stress, and may acquire a mesenchymal phenotype through epithelial-to-mesenchymal transition (EMT), two phenomena that could be induced by localized alveolar hypoxia. Here we investigated the potential links between hypoxia, ER stress and EMT in AECs. Methods: ER stress and EMT markers were assessed by immunohistochemistry, western blot and qPCR analysis, both in vivo in rat lungs exposed to normoxia or hypoxia (equivalent to 8% O2) for 48 h, and in vitro in primary rat AECs exposed to normoxia or hypoxia (1.5% O2) for 2–6 days. Results: Hypoxia induced expression of mesenchymal markers, pro-EMT transcription factors, and the activation of ER stress markers both in vivo in rat lungs, and in vitro in AECs. In vitro, pharmacological inhibition of ER stress by 4-PBA limited hypoxia-induced EMT. Calcium chelation or hypoxia-inducible factor (HIF) inhibition also prevented EMT induction under hypoxic condition. Conclusions: Hypoxia and intracellular calcium are both involved in EMT induction of AECs, mainly through the activation of ER stress and HIF signaling pathways.
Effectiveness of Vitamin D Supplementation in the Management of Multiple Sclerosis: A Systematic Review
Authors: Berezowska Monika , Coe Shelly , Dawes Helen
Published: March 2019

Objective: to examine the extent of effect vitamin D in Multiple Sclerosis (MS) on pathology and symptoms. Methods: A literature search was performed in November 2018 (CRD42018103615). Eligibility criteria: randomised control trials in English from 2012 to 2018; a clinical diagnosis of MS; interventions containing vitamin D supplementation (vitamin D3 or calcitriol) in disease activity compared to a control/placebo; improvement in: serum 25(OH)D, relapse rates, disability status by Expanded Disability Status Scale (EDSS) scores, cytokine profile, quality of life, mobility, T2 lesion load and new T2 or T1 Gd enhancing lesions, safety and adverse effects. Risk of bias was evaluated. Results: Ten studies were selected. The study size ranged from 40 to 94 people. All studies evaluated the use of vitamin D supplementation (ranging from 10 to 98,000 IU), comparing to a placebo or low dose vitamin D. The duration of the intervention ranged from 12 to 96 weeks. One trial found a significant effect on EDSS score, three demonstrated a significant change in serum cytokines level, one found benefits to current enhancing lesions and three studies evaluating the safety and tolerability of vitamin D reported no serious adverse events. Disease measures improved to a greater extent overall in those with lower baseline serum 25(OH)D levels. Conclusions: As shown in 3 out of 10 studies, improvement in disease measures may be more apparent in those with lower baseline vitamin D levels.
An Artificial Neural Network Approach to Forecast the Environmental Impact of Data Centers
Authors: Ferreira Joao , Callou Gustavo , Josua Albert , Tutsch Dietmar , Maciel Paulo
Published: March 2019

Due to the high demands of new technologies such as social networks, e-commerce and cloud computing, more energy is being consumed in order to store all the data produced and provide the high availability required. Over the years, this increase in energy consumption has brought about a rise in both the environmental impacts and operational costs. Some companies have adopted the concept of a green data center, which is related to electricity consumption and CO2 emissions, according to the utility power source adopted. In Brazil, almost 70% of electrical power is derived from clean electricity generation, whereas in China 65% of generated electricity comes from coal. In addition, the value per kWh in the US is much lower than in other countries surveyed. In the present work, we conducted an integrated evaluation of costs and CO2 emissions of the electrical infrastructure in data centers, considering the different energy sources adopted by each country. We used a multi-layered artificial neural network, which could forecast consumption over the following months, based on the energy consumption history of the data center. All these features were supported by a tool, the applicability of which was demonstrated through a case study that computed the CO2 emissions and operational costs of a data center using the energy mix adopted in Brazil, China, Germany and the US. China presented the highest CO2 emissions, with 41,445 tons per year in 2014, followed by the US and Germany, with 37,177 and 35,883, respectively. Brazil, with 8459 tons, proved to be the cleanest. Additionally, this study also estimated the operational costs assuming that the same data center consumes energy as if it were in China, Germany and Brazil. China presented the highest kWh/year. Therefore, the best choice according to operational costs, considering the price of energy per kWh, is the US and the worst is China. Considering both operational costs and CO2 emissions, Brazil would be the best option.
Synthesis and Structural Characterization of Two New Main Group Element Carboranylamidinates
Authors: Liebing Phil , Harmgarth Nicole , Zörner Florian , Engelhardt Felix , Hilfert Liane , Busse Sabine , Edelmann Frank T.
Published: March 2019

Two new main group element carboranylamidinates were synthesized using a bottom-up approach starting from o-carborane, ortho-C2B10H12 (1, = 1,2-dicarba-closo-dodecaborane). The first divalent germanium carboranylamidinate, GeCl[HLCy] (3, [HLCy]− = [o-C2B10H10C(NCy)(NHCy)]−, Cy = cyclohexyl), was synthesized by treatment of GeCl2(dioxane) with 1 equiv. of in situ-prepared Li[HLCy] (2a) in THF and isolated in 47% yield. In a similar manner, the first antimony(III) carboranylamidinate, SbCl2[HLiPr] (4, [HLiPr]− = [o-C2B10H10C(NiPr)(NHiPr)]−), was obtained from a reaction of SbCl3 with 1 equiv. of Li[HLiPr] in THF (56% yield). The title compounds were fully characterized by analytical and spectroscopic methods as well as single-crystal X-ray diffraction. Both compounds 3 and 4 are monomeric species in the solid state, and the molecular geometries are governed by a stereo-active lone pair at the metal centers.
Ecological and Societal Services of Aquatic Diptera
Authors: Adler Peter H. , Courtney Gregory W.
Published: March 2019

More than any other group of macro-organisms, true flies (Diptera) dominate the freshwater environment. Nearly one-third of all flies—roughly 46,000 species—have some developmental connection with an aquatic environment. Their abundance, ubiquity, and diversity of adaptations to the aquatic environment position them as major drivers of ecosystem processes and as sources of products and bioinspiration for the benefit of human society. Larval flies are well represented as ecosystem engineers and keystone species that alter the abiotic and biotic environments through activities such as burrowing, grazing, suspension feeding, and predation. The enormous populations sometimes achieved by aquatic flies can provide the sole or major dietary component for other organisms. Harnessing the services of aquatic Diptera for human benefit depends on the ingenuity of the scientific community. Aquatic flies have played a role as indicators of water quality from the earliest years of bioassessment. They serve as indicators of historical and future ecological and climate change. As predators and herbivores, they can serve as biological control agents. The association of flies with animal carcasses in aquatic environments provides an additional set of tools for forensic science. The extremophilic attributes of numerous species of Diptera offer solutions for human adaptation to harsh terrestrial and extraterrestrial environments. The potential pharmaceutical and industrial applications of the symbiotic microbial community in extremophilic Diptera are better explored than are those of dipteran chemistry. Many flies provide valuable ecological and human services as aquatic immatures, but are also pests and vectors of disease agents as terrestrial adults. The scientific community, thus, is challenged with balancing the benefits and costs of aquatic Diptera, while maintaining sustainable populations as more species face extinction.
Heterologous Expression of Aedes aegypti Cation Chloride Cotransporter 2 (aeCCC2) in Xenopus laevis Oocytes Induces an Enigmatic Na+/Li+ Conductance
Authors: Kalsi Megha , Gillen Christopher , Piermarini Peter M.
Published: March 2019

The yellow fever mosquito Aedes aegypti possesses three genes encoding putative Na+-coupled cation chloride cotransporters (CCCs): aeNKCC1, aeCCC2, and aeCCC3. To date, none of the aeCCCs have been functionally characterized. Here we expressed aeCCC2 heterologously in Xenopus oocytes and measured the uptake of Li+ (a tracer for Na+) and Rb+ (a tracer for K+). Compared to control (H2O-injected) oocytes, the aeCCC2-expressing oocytes exhibited significantly greater uptake of Li+, but not Rb+. However, the uptake of Li+ was neither Cl−-dependent nor inhibited by thiazide, loop diuretics, or amiloride, suggesting unconventional CCC activity. To determine if the Li+-uptake was mediated by a conductive pathway, we performed two-electrode voltage clamping (TEVC) on the oocytes. The aeCCC2 oocytes were characterized by an enhanced conductance for Li+ and Na+, but not K+, compared to control oocytes. It remains to be determined whether aeCCC2 directly mediates the Na+/Li+ conductance or whether heterologous expression of aeCCC2 stimulates an endogenous cation channel in the oocyte plasma membrane.
Morphology and Morphometry of the Midgut in the Stingless Bee Friesella schrottkyi (Hymenoptera: Apidae)
Authors: Oliveira André H. , Gonçalves Wagner G. , Fernandes Kenner M. , Barcellos Marcelo S. , Sampaio Wagner M. S. , Lopes Marcos P. , Martins Gustavo F. , Serrão José E.
Published: March 2019

Friesella schrottkyi is a small stingless bee (3-mm long) important for agricultural and native forest pollination. This study describes the morphology and morphometry of the midgut in F. schrottkyi forager workers. The F. schrottkyi midgut presents a single-layered epithelium with digestive, regenerative and endocrine cells. The digestive cells are similar along the entire midgut length with a spherical nucleus, apex with long striated border, cytoplasmic granules in the apical region and well-developed basal labyrinth associated with mitochondria, suggesting they are multifunctional, synthesizing digestive enzymes and peritrophic matrix compounds and absorbing nutrients. Regenerative cells are located around the basal region organized in nests with some cells with a spherical nucleus. Phe-Met-Arg-Phe-NH2-amide (FMRFamide) positive endocrine cells are restricted to the posterior midgut region, suggesting a paracrine function in the midgut. This is the first morphological description of the F. schrottkyi midgut contributing to the comprehension of the digestive process of this bee.
Full Statistics of Conjugated Thermodynamic Ensembles in Chains of Bistable Units
Authors: Benedito Manon , Manca Fabio , Giordano Stefano
Published: March 2019

The statistical mechanics and the thermodynamics of small systems are characterized by the non-equivalence of the statistical ensembles. When concerning a polymer chain or an arbitrary chain of independent units, this concept leads to different force-extension responses for the isotensional (Gibbs) and the isometric (Helmholtz) thermodynamic ensembles for a limited number of units (far from the thermodynamic limit). While the average force-extension response has been largely investigated in both Gibbs and Helmholtz ensembles, the full statistical characterization of this thermo-mechanical behavior has not been approached by evaluating the corresponding probability densities. Therefore, we elaborate in this paper a technique for obtaining the probability density of the extension when force is applied (Gibbs ensemble) and the probability density of the force when the extension is prescribed (Helmholtz ensemble). This methodology, here developed at thermodynamic equilibrium, is applied to a specific chain composed of units characterized by a bistable potential energy, which is able to mimic the folding and unfolding of several macromolecules of biological origin.
Effects of a Combined Community Exercise Program in Obstructive Sleep Apnea Syndrome: A Randomized Clinical Trial
Authors: Torres-Castro Rodrigo , Vilaró Jordi , Martí Joan-Daniel , Garmendia Onintza , Gimeno-Santos Elena , Romano-Andrioni Bárbara , Embid Cristina , Montserrat Josep M.
Published: March 2019

Physical activity is associated with a decreased prevalence of obstructive sleep apnea and improved sleep efficiency. Studies on the effects of a comprehensive exercise program in a community setting remain limited. Our objective was to investigate the effects of a combined physical and oropharyngeal exercise program on the apnea-hypopnea index in patients with moderate to severe obstructive sleep apnea. This was a randomized clinical trial where the intervention group followed an eight-week urban-walking program, oropharyngeal exercises, and diet and sleep recommendations. The control group followed diet and sleep recommendations. A total of 33 patients were enrolled and randomized and, finally, 27 patients were included in the study (IG, 14; CG, 13) Obstructive sleep apnea patients were analyzed with a median age of 67 (52–74) and median apnea-hypopnea index of 32 events/h (25–41). The apnea-hypopnea index did not differ between groups pre- and post-intervention. However, in intervention patients younger than 60 (n = 6) a reduction of the apnea-hypopnea index from 29.5 (21.8–48.3) to 15.5 (11–34) events/h (p = 0.028) was observed. While a comprehensive multimodal program does not modify the apnea-hypopnea index, it could reduce body weight and increase the walking distance of patients with moderate to severe obstructive sleep apnea. Patients younger than 60 may also present a decreased apnea-hypopnea index after intervention.
The Ideal Goal of Testosterone Replacement Therapy: Maintaining Testosterone Levels or Managing Symptoms?
Authors: Moon Du Geon , Park Hyun Jun
Published: March 2019

Typically, the goal of testosterone replacement therapy (TRT) is to restore blood testosterone to normal levels [...]
Serotonergic, Dopaminergic, and Noradrenergic Modulation of Erotic Stimulus Processing in the Male Human Brain
Authors: Graf Heiko , Malejko Kathrin , Metzger Coraline Danielle , Walter Martin , Grön Georg , Abler Birgit
Published: March 2019

Human sexual behavior is mediated by a complex interplay of cerebral and spinal centers, as well as hormonal, peripheral, and autonomic functions. Neuroimaging studies identified central neural signatures of human sexual responses comprising neural emotional, motivational, autonomic, and cognitive components. However, empirical evidence regarding the neuromodulation of these neural signatures of human sexual responses was scarce for decades. Pharmacological functional magnetic resonance imaging (fMRI) provides a valuable tool to examine the interaction between neuromodulator systems and functional network anatomy relevant for human sexual behavior. In addition, this approach enables the examination of potential neural mechanisms regarding treatment-related sexual dysfunction under psychopharmacological agents. In this article, we introduce common neurobiological concepts regarding cerebral sexual responses based on neuroimaging findings and we discuss challenges and findings regarding investigating the neuromodulation of neural sexual stimulus processing. In particular, we summarize findings from our research program investigating how neural correlates of sexual stimulus processing are modulated by serotonergic, dopaminergic, and noradrenergic antidepressant medication in healthy males.
Influence of Process Fluctuations on Residual Stress Evolution in Rotary Swaging of Steel Tubes
Authors: Ishkina Svetlana , Charni Dhia , Herrmann Marius , Liu Yang , Epp Jérémy , Schenck Christian , Kuhfuss Bernd , Zoch Hans-Werner
Published: March 2019

Infeed rotary swaging is a cold forming production technique to reduce the diameter of axisymmetric components. The forming is achieved discontinuously by a series of radial strokes that are spread over the shell of the part. Due to tolerances within the rotary swaging machine, these strokes perform individually and the resulting stroke pattern is not homogeneous with regards to circumferential and longitudinal distribution. Nevertheless, in combination with the high number of performed strokes and the large contact area between the dies and the part, the external part properties, such as diameter, roundness and surface roughness, show even values along the finished part. In contrast, strength-defining internal part properties, like microstructure and residual stress components, are more sensitive to the actual pattern and temporal sequence of the individual strokes, which is investigated in this study. The impact of process fluctuations during the conventional process, which are induced by the tolerances of machine tool components, was verified by numerical simulations, physical tests and measurements of residual stress distributions at the surface and at depth. Furthermore, a method is introduced to maintain the stroke following angle ∆φ at zero by flat dies, and thus the actual pattern and temporal sequence of the strokes was homogenized. The results show that the residual stress fluctuations at the surface could be controlled and reduced. Furthermore, it is demonstrated that the depth profile of the residual stresses at a distance of 300 µm from the surface developed independently from the process fluctuations.
Hybrid Superconducting-Ferromagnetic [Bi2Sr2(Ca,Y)2Cu3O10]0.99(La2/3Ba1/3MnO3)0.01 Composite Thick Films
Authors: Mejía-Salazar J. Ricardo , Perea José Darío , Castillo Roberto , Diosa Jesús Evelio , Baca Eval
Published: March 2019

We report here on the development of composite thick films exhibiting hybrid superconducting and ferromagnetic properties, produced through a low-cost, fast, and versatile process. These films were made of high Tc cuprate superconductor Bi2Sr2(Ca,Y)2Cu3O10 (with Y:Ca ratio of 5%) and ferromagnetic perovskite La2/3Ba1/3MnO3, synthesized by melting-quenching annealing process on a MgO substrate. Curie temperature for La2/3Ba1/3MnO3 was determined (~336 K ) by magnetic field assisted thermogravimetric analysis (TGA), while superconducting behavior of Bi2Sr2(Ca,Y)2Cu3O10/MgO films was observed through temperature-dependent resistance measurements. Superconducting features in our hybrid compound were corroborated by temperature-dependent resistivity and magnetic susceptibility.
A Neural Network Approximation Based on a Parametric Sigmoidal Function
Authors: Yun Beong In
Published: March 2019

It is well known that feed-forward neural networks can be used for approximation to functions based on an appropriate activation function. In this paper, employing a new sigmoidal function with a parameter for an activation function, we consider a constructive feed-forward neural network approximation on a closed interval. The developed approximation method takes a simple form of a superposition of the parametric sigmoidal function. It is shown that the proposed method is very effective in approximation of discontinuous functions as well as continuous ones. For some examples, the availability of the presented method is demonstrated by comparing its numerical results with those of an existing neural network approximation method. Furthermore, the efficiency of the method in extended application to the multivariate function is also illustrated.
Computing the Moments of the Complex Gaussian: Full and Sparse Covariance Matrix
Authors: Fassino Claudia , Pistone Giovanni , Rogantin Maria Piera
Published: March 2019

Given a multivariate complex centered Gaussian vector Z = ( Z 1 , ⋯ , Z p ) with non-singular covariance matrix Σ , we derive sufficient conditions on the nullity of the complex moments and we give a closed-form expression for the non-null complex moments. We present conditions for the factorisation of the complex moments. Computational consequences of these results are discussed.
An Efficient Numerical Technique for the Nonlinear Fractional Kolmogorov–Petrovskii–Piskunov Equation
Authors: Veeresha Pundikala , Prakasha Doddabhadrappla , Baleanu Dumitru
Published: March 2019

The q -homotopy analysis transform method ( q -HATM) is employed to find the solution for the fractional Kolmogorov–Petrovskii–Piskunov (FKPP) equation in the present frame work. To ensure the applicability and efficiency of the proposed algorithm, we consider three distinct initial conditions with two of them having Jacobi elliptic functions. The numerical simulations have been conducted to verify that the proposed scheme is reliable and accurate. Moreover, the uniqueness and convergence analysis for the projected problem is also presented. The obtained results elucidate that the proposed technique is easy to implement and very effective to analyze the complex problems arising in science and technology.
Study on the Isolation of Two Atrazine-Degrading Bacteria and the Development of a Microbial Agent
Authors: Zhu Jiangwei , Fu Li , Jin Caihua , Meng Zili , Yang Ning
Published: March 2019

Two bacteria capable of efficiently degrading atrazine were isolated from soil, and named ATLJ-5 and ATLJ-11. ATLJ-5 and ATLJ-11 were identified as Bacillus licheniformis and Bacillus megaterium, respectively. The degradation efficiency of atrazine (50 mg/L) by strain ATLJ-5 can reach about 98.6% after 7 days, and strain ATLJ-11 can reach 99.6% under the same conditions. The degradation of atrazine is faster when two strains are used in combination. Adding the proper amount of fresh soil during the degradation of atrazine by these two strains can also increase the degradation efficiency. The strains ATLJ-5 and ATLJ-11 have high tolerance to atrazine, and can tolerate at least 1000 mg/L of atrazine. In addition, the strains ATLJ-5 and ATLJ-11 have been successfully made into a microbial agent that can be used to treat atrazine residues in soil. The degradation efficiency of atrazine (50 mg/kg) could reach 99.0% by this microbial agent after 7 days. These results suggest that the strains ATLJ-5 and ATLJ-11 can be used for the treatment of atrazine pollution.