Universidade Federal de Alfenas

The chemical composition of small organic molecules is often very similar to amino acid side chains or the bases in nucleic acids, and hence there is no a priori reason why a molecular mechanics force field could not describe both organic liquids and biomolecules with a single parameter set. Here, we devise a benchmark for force fields in order to test the ability of existing force fields to reproduce some key properties of organic liquids, namely, the density, enthalpy of vaporization, the surface tension, the heat capacity at constant volume and pressure, the isothermal compressibility, the volumetric expansion coefficient, and the static dielectric constant. Well over 1200 experimental measurements were used for comparison to the simulations of 146 organic liquids. Novel polynomial interpolations of the dielectric constant (32 molecules), heat capacity at constant pressure (three molecules), and the isothermal compressibility (53 molecules) as a function of the temperature have been made, based on experimental data, in order to be able to compare simulation results to them. To compute the heat capacities, we applied the two phase thermodynamics method (Lin et al. J. Chem. Phys.2003, 119, 11792), which allows one to compute thermodynamic properties on the basis of the density of states as derived from the velocity autocorrelation function. The method is implemented in a new utility within the GROMACS molecular simulation package, named g_dos, and a detailed exposé of the underlying equations is presented. The purpose of this work is to establish the state of the art of two popular force fields, OPLS/AA (all-atom optimized potential for liquid simulation) and GAFF (generalized Amber force field), to find common bottlenecks, i.e., particularly difficult molecules, and to serve as a reference point for future force field development. To make for a fair playing field, all molecules were evaluated with the same parameter settings, such as thermostats and barostats, treatment of electrostatic interactions, and system size (1000 molecules). The densities and enthalpy of vaporization from an independent data set based on simulations using the CHARMM General Force Field (CGenFF) presented by Vanommeslaeghe et al. (J. Comput. Chem.2010, 31, 671) are included for comparison. We find that, overall, the OPLS/AA force field performs somewhat better than GAFF, but there are significant issues with reproduction of the surface tension and dielectric constants for both force fields.

A.4 Constraining the flux in the ND A.4.1 Neutrino-electron elastic scattering A.4.2 The low- method A.4.3 Coherent neutrino-nucleus scattering A.4.4 Beam e content A.5 Movable components of the ND and the DUNE-PRISM program A.5.1 Introduction to DUNE-PRISM A.5.2 LArTPC component in the DUNE ND: ArgonCube A.5.3 Multipurpose detector A.5.4 The DUNE-PRISM program A.6 Fixed on-axis component of the DUNE ND A.6.1 Motivation and introduction A.6.2 Three-dimensional projection scintillator tracker spectrometer A.7 Meeting the near detector requirements A.7.1 Overarching requirements A.7.2 Event rate and flux measurements A.7.3 Control of systematic errors B ND hall and construction C Computing roles and collaborative projects C.1 Roles C.2 Specific collaborative computing projects C.2.1 LArSoft for event reconstruction C.2.2 WLCG/OSG and the HEP Software Foundation C.2.3 Evaluations of other important infrastructure

Analysis of variance (ANOVA) is a usual way for analysing experiments. However, depending on the design and/or the analysis scheme, it can be a hard task. ExpDes, acronym for Experimental Designs, is a package that intends to turn such task easier. Devoted to fixed models and balanced experiments (no missing data), ExpDes allows user to deal with additional treatments in a single run, several experiment designs and exhibits standard and easy-to-interpret outputs. It was developed at the Exact Sciences Institute of the Federal University of Alfenas, Brazil. Stable versions of package ExpDes are available on CRAN (Comprehensive R Archive Network) since 2012. Based on users’ feedback, the package was used to illustrate graduation and post-graduation classes and to carry out data analysis, in Brazil and many other countries. Package ExpDes differs from the other R tools in its easiness in use and cleanliness of output.

Probiotics are defined as microorganisms that live in symbiosis with the human host. When ingested in adequate quantities, probiotics may modulate biological functions, with health benefits. Different biological properties have been reported for probiotics, including antimicrobial activity. However, there are few studies investigating the use of probiotics as candidates for alternative antimicrobial therapy or as a source of new antibiotics. Thus, in this review we provide a general approach to the current situation of probiotic antimicrobial research and point out future directions in the field. Despite the promising benefits of probiotics on intestinal health, there remains no consensus or standardization on the development of delivery systems and on the application of probiotic formulations for antimicrobial therapy. Thus, further bioguided studies and clinical trials are needed to address the existing gaps in the knowledge. Future research should focus on the isolation, doses, clinical efficacy, safety and mechanisms of action of probiotics in humans.

This review presents some of the hottest topics in biotechnological applications: proteases in biocatalysis. Obviously, one of the most relevant areas of application is in the hydrolysis of proteins in food technology, and that has led to a massive use on proteomics. The aim is to identify via peptide maps the different proteins obtained after a specific protease hydrolysis. However, concepts like degradomics are also taking on a more relevant importance in the use and study of proteases and will also be discussed. Other protease applications, as seem in cleaning (detergent development), the pharmaceutical industry, and in fine chemistry, will be analyzed. This review progresses from basic areas such as protease classification to a discussion of the preparation of protease-immobilized biocatalysts, considering the different problems raised by the use of immobilized proteases due to the peculiar features of the substrates, usually large macromolecules. Production of bioactive peptides via limited hydrolysis of proteins will occupy an important place in this review.

It is essential to acknowledge the efforts made thus far to manage or eliminate various disease burden faced by humankind. However, the rising global trends of the so-called incurable diseases continue to put pressure on Pharma industries and other drug discovery platforms. In the past, drugs with more than one target were deemed as undesirable options with interest being on the one-drug-single target. Despite the successes of the single-target drugs, it is currently beyond doubt that these drugs have limited efficacy against complex diseases in which the pathogenesis is dependent on a set of biochemical events and several bioreceptors operating concomitantly. Different approaches have thus been proposed to come up with effective drugs to combat even the complex diseases. In the past, the focus was on producing drugs from screening plant compounds; today, we talk about combination therapy and multi-targeting drugs. The multi-target drugs have recently attracted much attention as promising tools to fight against most challenging diseases, and thus a new research focus area. This review will discuss the potential impact of multi-target drug approach on various complex diseases with focus on malaria, tuberculosis (TB), diabetes and neurodegenerative diseases as the main representatives of multifactorial diseases. We will also discuss alternative ideas to solve the current problems bearing in mind the fourth industrial revolution on drug discovery.

The skin barrier function has been attributed to the stratum corneum and represents a major challenge in clinical practice pertaining to cutaneous administration of drugs. Despite this, a large number of bioactive compounds have been successfully administered via cutaneous administration because of advances in the design of topical and transdermal formulations. In vitro and in vivo evaluations of these novel drug delivery systems are necessary to characterize their quality and efficacy. This review covers the most well-known methods for assessing the cutaneous absorption of drugs as an auxiliary tool for pharmaceutical formulation scientists in the design of drug delivery systems. In vitro methods as skin permeation assays using Franz-type diffusion cells, cutaneous retention and tape-stripping methods to study the cutaneous penetration of drugs, and in vivo evaluations as pre-clinical pharmacokinetic studies in animal models are discussed. Alternative approaches to cutaneous microdialysis are also covered. Recent advances in research on skin absorption of drugs and the effect of skin absorption enhancers, as investigated using confocal laser scanning microscopy, Raman confocal microscopy, and attenuated total reflectance Fourier-transform infrared spectroscopy, are reviewed.

Dental erosion is defined as the loss of tooth substance by acid exposure not involving bacteria. The etiology of erosion is related to different behavioral, biological and chemical factors. Based on an overview of the current literature, this paper presents a summary of the preventive strategies relevant for patients suffering from dental erosion. Behavioral factors, such as special drinking habits, unhealthy lifestyle factors or occupational acid exposure, might modify the extent of dental erosion. Thus, preventive strategies have to include measures to reduce the frequency and duration of acid exposure as well as adequate oral hygiene measures, as it is known that eroded surfaces are more susceptible to abrasion. Biological factors, such as saliva or acquired pellicle, act protectively against erosive demineralization. Therefore, the production of saliva should be enhanced, especially in patients with hyposalivation or xerostomia. With regard to chemical factors, the modification of acidic solutions with ions, especially calcium, was shown to reduce the demineralization, but the efficacy depends on the other chemical factors, such as the type of acid. To enhance the remineralization of eroded surfaces and to prevent further progression of dental wear, high-concentrated fluoride applications are recommended. Currently, little information is available about the efficacy of other preventive strategies, such as calcium and laser application, as well as the use of matrix metalloproteinase inhibitors. Further studies considering these factors are required. In conclusion, preventive strategies for patients suffering from erosion are mainly obtained from in vitro and in situ studies and include dietary counseling, stimulation of salivary flow, optimization of fluoride regimens, modification of erosive beverages and adequate oral hygiene measures.

Red propolis is a new type of Brazilian propolis. This material, as well as the secretions of 20 plant species that are often mentioned as its probable botanical source, have been investigated by RP-HPTLC. Phytochemical evidence based on UV-VIS spectra, RP-HPLC and GC-MS, showed Dalbergia ecastophyllum (L.) Taub. to be the main source of red propolis in Alagoas state. The propolis and plant resin showed high relative percentages of the isoflavonoids 3-Hydroxy-8,9-dimethoxypterocarpan and medicarpin. To our knowledge this is the first report of the secretion of a leguminous species being the source of propolis.

Antimicrobial bacterial cellulose-silver nanoparticles composite membranes have been obtained by “in situ” preparation of Ag nanoparticles from hydrolytic decomposition of silver nitrate solution using triethanolamine as reducing and complexing agent. The formation of silver nanoparticles was evidenced by the X-ray diffraction, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and absorption in the UV-Visible (350 nm to 600 nm). Thermal and mechanical properties together with swelling behavior for water were considered. TEA concentration was observed to be important in order to obtain only Ag particles and not a mixture of silver oxides. It was also observed to control particle size and amount of silver contents in bacterial cellulose. The composite membranes exhibited strong antimicrobial activity against Gram-negative and Gram-positive bacteria.

Despite evidence of pollinator declines from many regions across the globe, the threat this poses to plant populations is not clear because plants can often produce seeds without animal pollinators. Here, we quantify pollinator contribution to seed production by comparing fertility in the presence versus the absence of pollinators for a global dataset of 1174 plant species. We estimate that, without pollinators, a third of flowering plant species would produce no seeds and half would suffer an 80% or more reduction in fertility. Pollinator contribution to plant reproduction is higher in plants with tree growth form, multiple reproductive episodes, more specialized pollination systems, and tropical distributions, making these groups especially vulnerable to reduced service from pollinators. These results suggest that, without mitigating efforts, pollinator declines have the potential to reduce reproduction for most plant species, increasing the risk of population declines.

Studies have revealed more positive effects of berries’ components over the years, representing a growing trend in their consumption. Phenolic compounds, such as anthocyanins, flavonols, and phenolic acids occur in different concentrations depending on the berry type. Significant trends to exploit the beneficial compounds were collected, with mostly novel and environmentally friendly techniques, such as ultrasound, microwave, and high-pressure technologies. Abundant phenolic compounds present in different berries (raspberry, blueberry, goji berry, blackcurrant, strawberry, cranberry, and blackberry) were summarized based on up-to-date information and their beneficial health effects. The antioxidant, anti-inflammatory, antihypertensive, and antihyperglycemic activities in vitro and in vivo were comprehensively reviewed. Recent studies allied to in vivo results and positive findings to reduce oxidative stress, for example, support that berries and their functional products represent a prominent economic potential to maintain human health and function.

Abstract Protecting riparian vegetation around streams is vital in reducing the detrimental effects of environmental change on freshwater ecosystems and in maintaining aquatic biodiversity. Thus, identifying ecological thresholds is useful for defining regulatory limits and for guiding the management of riparian zones towards the conservation of freshwater biota. Using nationwide data on fish and invertebrates occurring in small Brazilian streams, we estimated thresholds of native vegetation loss in which there are abrupt changes in the occurrence and abundance of freshwater bioindicators and tested whether there are congruent responses among different biomes, biological groups and riparian buffer sizes. Mean thresholds of native vegetation cover loss varied widely among biomes, buffer sizes and biological groups: ranging from 0.5% to 77.4% for fish, from 2.9% to 37.0% for aquatic invertebrates and from 3.8% to 43.2% for a subset of aquatic invertebrates. Confidence intervals for thresholds were wide, but the minimum values of these intervals were lower for the smaller riparian buffers (50 and 100 m) than larger ones (200 and 500 m), indicating that land use should be kept away from the streams. Also, thresholds occurred at a lower percentage of riparian vegetation loss in the smaller buffers, and were critically lower for invertebrates: reducing only 6.5% of native vegetation cover within a 50‐m riparian buffer is enough to cross thresholds for invertebrates. Synthesis and applications . The high variability in biodiversity responses to loss of native riparian vegetation suggests caution in the use of a single riparian width for conservation actions or policy definitions nationwide. The most sensitive bioindicators can be used as early warning signals of abrupt changes in freshwater biodiversity. In practice, maintaining at least 50‐m wide riparian reserves on each side of streams would be more effective to protect freshwater biodiversity in Brazil. However, incentives and conservation strategies to protect even wider riparian reserves (~100 m) and also taking into consideration the regional context will promote a greater benefit. This information should be used to set conservation goals and to create complementary mechanisms and policies to protect wider riparian reserves than those currently required by the federal law.

The increasing demand for food production has necessitated the development of sensitive and reliable methods of analysis, which allow for the optimization of storage and distribution while ensuring food safety. Methods to quantify and monitor volatile and biogenic amines are key to minimizing the waste of high-protein foods and to enable the safe consumption of fresh products. Novel materials and device designs have allowed the development of portable and reliable sensors that make use of different transduction methods for amine detection and food quality monitoring. Herein, we review the past decade's advances in volatile amine sensors for food quality monitoring. First, the role of volatile and biogenic amines as a food-quality index is presented. Moreover, a comprehensive overview of the distinct amine gas sensors is provided according to the transduction method, operation strategies, and distinct materials (e.g., metal oxide semiconductors, conjugated polymers, carbon nanotubes, graphene and its derivatives, transition metal dichalcogenides, metal organic frameworks, MXenes, quantum dots, and dyes, among others) employed in each case. These include chemoresistive, fluorometric, colorimetric, and microgravimetric sensors. Emphasis is also given to sensor arrays that record the food quality fingerprints and wireless devices that operate as radiofrequency identification (RFID) tags. Finally, challenges and future opportunities on the development of new amine sensors are presented aiming to encourage further research and technological development of reliable, integrated, and remotely accessible devices for food-quality monitoring.

Despite a plethora of in situ studies and clinical trials evaluating the efficacy of fluoridated dentifrices on caries control, in vitro pH cycling models are still broadly used because they mimic the dynamics of mineral loss and gain involved in caries formation. This paper critically reviews the current literature on existing pH-cycling models for the in vitro evaluation of the efficacy of fluoridated dentifrices for caries control, focusing on their strengths and limitations. A search was undertaken in the MEDLINE electronic journal database using the keywords "pH-cycling", "demineralization", "remineralization", "in vitro", "fluoride", "dentifrice". The primary outcome was the decrease of demineralization or the increase of remineralization as measured by different methods (e.g.: transverse microradiography) or tooth fluoride uptake. Inclusion of studies, data extraction and quality assessment were undertaken independently and in duplicate by two members of the review team. Disagreements were solved by discussion and consensus or by a third party. One hundred and sixteen studies were included, of which 42 addressed specifically the comparison of dentifrices using different pH-cycling models. The other studies included meta-analysis or reviews, data about the effect of different fluoride sources on de-remineralization, different methods for analysis de-remineralization and chemical variables and characteristics of dental hard tissues that might have influence on de-remineralization processes. Generally, the studies presented ability to detect known results established by clinical trials, to demonstrate dose-related responses in the fluoride content of the dentifrices, and to provide repeatability and reproducibility between tests. In order to accomplish these features satisfactorily, it is mandatory to take into account the type of substrate and baseline artificial lesion, as well as the adequate response variables and statistical approaches to be used. This critical review of literature showed that the currently available pH-cycling models are appropriate to detect dose-response and pH-response of fluoride dentifrices, and to evaluate the impact of new active principles on the effect of fluoridated dentifrices, as well as their association with other anti-caries treatments.

OBJECTIVE: Evaluating the occurrence of anxiety in pregnant women and the factors associated with its occurrence; comparing the presence of anxiety in each gestational trimester. METHOD: A descriptive, correlational cross-sectional study. Data were collected from January to May 2013 using the Hospital Anxiety Subscale and a form composed of socioeconomic characterization; gestational anamnesis; life-changing habits and events; preexisting conditions and interpersonal relationships. RESULTS: A total of 209 pregnant women from a municipality in the south of Minas Gerais, Brazil, participated in the study. Anxiety was present in 26.8% of the pregnant women, being more frequent in the third trimester (42.9%). Occupation (p=0.04), complications in previous pregnancies (p=0.00), history of miscarriage risk of preterm birth (p=0.05), maternal desire regarding the pregnancy (p=0.01), number of abortions (p=0.02), number of cigarettes smoked daily (p=0.00) and drug use (p=0.01) were statistically associated with the occurrence of anxiety during pregnancy. CONCLUSION: Anxiety occurred frequently during pregnancy. Understanding the factors associated with its occurrence allows for elaborating preventive measures in prenatal care. OBJETIVO: Avaliar a ocorrência da ansiedade em gestantes e os fatores associados à sua ocorrência; comparar a presença de ansiedade em cada trimestre gestacional. MÉTODO: Estudo descritivo, correlacional, de corte transversal. A coleta de dados ocorreu de janeiro a maio de 2013, utilizou-se da Subescala Hospitalar de Ansiedade e de um formulário composto por caracterização socioeconômica; anamnese gestacional; hábitos e eventos marcantes de vida; patologias preexistentes e relacionamentos interpessoais. RESULTADOS: Participaram do estudo 209 gestantes de um município do sul de Minas Gerais. A ansiedade esteve presente em 26,8% das gestantes, sendo mais frequente no terceiro trimestre (42,9%). Ocupação (p=0,04), complicações em gestações anteriores (p=0,00), histórico de abortamento/ameaça de parto prematuro (p=0,05), desejo materno em relação à gravidez (p=0,01), número de abortamentos (p=0,02), quantidade de cigarros consumidos diariamente (p=0,00) e uso de drogas (p=0,01) apresentaram associação estatisticamente significativa com a ocorrência da ansiedade na gravidez. CONCLUSÃO: A ansiedade se mostrou frequente na gestação. O conhecimento dos fatores associados a sua ocorrência oportuniza a elaboração de medidas preventivas na assistência pré-natal.

The Deep Underground Neutrino Experiment (DUNE) is an international, world-class experiment aimed at exploring fundamental questions about the universe that are at the forefront of astrophysics and particle physics research. DUNE will study questions pertaining to the preponderance of matter over antimatter in the early universe, the dynamics of supernovae, the subtleties of neutrino interaction physics, and a number of beyond the Standard Model topics accessible in a powerful neutrino beam. A critical component of the DUNE physics program involves the study of changes in a powerful beam of neutrinos, i.e., neutrino oscillations, as the neutrinos propagate a long distance. The experiment consists of a near detector, sited close to the source of the beam, and a far detector, sited along the beam at a large distance. This document, the DUNE Near Detector Conceptual Design Report (CDR), describes the design of the DUNE near detector and the science program that drives the design and technology choices. The goals and requirements underlying the design, along with projected performance are given. It serves as a starting point for a more detailed design that will be described in future documents.

This study deals with the regulation of the output voltage of photovoltaic (PV) arrays. As a case study, the DC–DC buck converter is used as an interface between the PV array and the load, but other types of converters can be used for the same purpose. The input voltage of the converter is controlled in order to regulate the operating point of the array. Besides reducing losses and stress because of the bandwidth-limited regulation of the converter duty cycle, controlling the converter input voltage reduces the settling time and avoids oscillation and overshoot, making easier the functioning of maximum power point tracking (MPPT) methods. The voltage regulation problem is addressed with a detailed analysis that starts with the modelling of the PV array and the converter. This analysis is followed by study, design, simulation and practical experiments of three closed-loop control strategies for the buck converter. Control stability and implementation considerations are presented.

We report a measurement of the energy spectrum of cosmic rays for energies above 2.5×1018 eV based on 215,030 events recorded with zenith angles below 60°. A key feature of the work is that the estimates of the energies are independent of assumptions about the unknown hadronic physics or of the primary mass composition. The measurement is the most precise made hitherto with the accumulated exposure being so large that the measurements of the flux are dominated by systematic uncertainties except at energies above 5×1019 eV. The principal conclusions are:\n(1) The flattening of the spectrum near 5×1018 eV, the so-called “ankle,” is confirmed.\n(2) The steepening of the spectrum at around 5×1019 eV is confirmed.\n(3) A new feature has been identified in the spectrum: in the region above the ankle the spectral index γ of the particle flux (∝E−γ) changes from 2.51±0.03 (stat)±0.05 (syst) to 3.05±0.05 (stat)±0.10 (syst) before changing sharply to 5.1±0.3 (stat)±0.1 (syst) above 5×1019 eV.\n(4) No evidence for any dependence of the spectrum on declination has been found other than a mild excess from the Southern Hemisphere that is consistent with the anisotropy observed above 8×1018 eV.

The objective of this study was to evaluate anti-inflammatory and antimicrobial activities of neovestitol and vestitol isolated from Brazilian red propolis (BRP). BRP ethanolic extract (EEP), neovestitol, and vestitol were evaluated by anti-inflammatory properties using a neutrophil migration assay. The antimicrobial activity was evaluated by minimal inhibitory and bactericidal concentrations (MIC and MBC) against Streptococcus mutans , Streptococcus sobrinus , Staphylococcus aureus , and Actinomyces naeslundii . Neovestitol, vestitol, and EEP inhibited neutrophil migration at a dose of 10 mg/kg. Regarding antimicrobial activity, neovestitol showed MICs ranging from <6.25 to 25-50 μg/mL and MBCs ranging from 25-50 to 50-100 μg/mL, while vestitol showed MICs ranging from 25-50 to 50-100 μg/mL and MBCs ranging from 25-50 to 50-100 μg/mL. Both isoflavonoids neovestitol and vestitol are consistent bioactive compounds displaying anti-inflammatory and antimicrobial activities that can strongly act in a low dose and concentration and have a promising potential to be applied in the pharmaceutical and food industries.