Miracle-dz/UniFAR-FTUs huggingface dataset:
Stress transforms lateral habenula reward responses into punishment signals

Significance Activity in the lateral habenula (LHb), a brain region implicated in depression, provides a reward prediction error (RPE): rewards reduce, while punishment or expected-reward omission increase LHb activity. These signals are important in shaping future choices. Here, we image the activity of individual LHb neurons in behaving mice. We find that stress, a major risk factor for depression, acutely transforms LHb signals in a remarkable manner: under stress, rewards produce punishment-like LHb output, and reward omission increases its punishment-like output. That is, under stress, LHb signals interpret “good as bad and bad as worse. ” This effect is rapid and coincides with reduced reward responsivity. These results potentially explain why an individual under stress is more prone to depression. Neuronal activity in the lateral habenula (LHb), a brain region implicated in depression [C. D. Proulx, O. Hikosaka, R. Malinow, Nat. Neurosci. 17, 1146–1152 (2014)], decreases during reward and increases during punishment or reward omission [M. Matsumoto, O. Hikosaka, Nature 447, 1111–1115 (2007)]. While stress is a major risk factor for depression and strongly impacts the LHb, its effect on LHb reward signals is unknown. Here we image LHb neuronal activity in behaving mice and find that acute stress transforms LHb reward responses into punishment-like neural signals; punishment-like responses to reward omission also increase. These neural changes matched the onset of anhedonic behavior and were specific to LHb neurons that distinguished reward and its omission. Thus, stress distorts LHb responsivity to positive and negative feedback, which could bias individuals toward negative expectations, a key aspect of the proposed pathogenesis of depression [A. T. Beck, Depression: Clinical, Experimental, and Theoretical Aspects, sixth Ed (1967)].
Exploring the effects of age of alcohol use initiation and psychosocial risk factors on subsequent alcohol misuse.

OBJECTIVE This study examines whether the age of initiation of alcohol use mediates the effects of other variables that predict alcohol misuse among adolescents and also whether the age of initiation of alcohol use accounts for known gender differences in the severity of alcohol misuse. METHOD Data were taken from an ethnically diverse sample of 808 (412 male) students who were recruited in grade 5 at age 10-11 and followed prospectively on an annual basis for the next 7 years to age 17-18. State-of-the-art missing data methodology was used to address nonresponse due to noninitiation of alcohol use. Structural equation modeling was used to examine hypotheses for the prediction of alcohol misuse. RESULTS A younger age of alcohol initiation was strongly related to a higher level of alcohol misuse at age 17-18 and fully mediated the effects of parent drinking, proactive parenting, school bonding, peer alcohol initiation and ethnicity, all measured at age 10-11, and perceived harmfulness of alcohol use, measured at age 10-11 and age 11-12. However, age of alcohol initiation did not fully account for gender differences in the level of alcohol misuse at age 17-18. To further examine the role of gender, interactions between gender and school bonding, and gender and friend's alcohol initiation, were evaluated. However, neither of the interaction terms had direct effects on either age of initiation or level of alcohol-related problems. CONCLUSIONS Most measured risk factors for alcohol misuse were mediated through age of alcohol initiation. Only gender differences in alcohol misuse at age 17-18 were not mediated by age of alcohol initiation. Variables associated with these differences require further study. The results of this study indicate the importance of prevention strategies to delay the age of initiation of alcohol use.
Fast 2D filter with low false positive for network packet inspection

Deep packet inspection (DPI) represents the major process in network intrusion detection and prevention systems. In DPI each security threat is represented as a signature, and the payload of every incoming data packet is matched against the set of current signatures. Moreover, DPI is also used for other networking applications such as packet classification, quality of service techniques, protocol identification and so on. DPI exhausts extra central processing unit and memory resources, and as a result, several attempts have been proposed to improve this process. In this study, the authors proposed a fast two-dimensional (2D) filter with low false positive (FP) rate for DPI purposes. It consists of 2D array that employs single hash function and has very low FP rate. Using this filter as an identification tool in a DPI technique will result in more accurate and higher throughput than other systems that employ Bloom (BFs) and quotient filters (QFs). Our experiments show that the proposed solution has time improvement up to 94% over others that employ BFs or QFs and the achieved average throughput is 1.8 Gbps.
DETECTION OF MOVING OBJECTS FOR ROBOTIC MANIPULATION APPLICATIONS IN NON-STRUCTURED ENVIRONMENTS

Robotic manipulation tasks, particularly in unstructured environments, require detailed information about the manipulator surroundings. Location and form of objects to be manipulated are especially important information. Due to the emergence of RGB-D cameras, e.g. the Microsoft Kinect, the research community w as able to develop important results related to 3D environment mapping, scene segmentation and object detection. Calibration between two cameras, depth camera and RGB camera provided in the RGB-D devices has been theme of an extensive number of papers. Nevertheless not only the intrinsic and extrinsic cameras parameters are necessary, the transformation between the reference frames of the camera and the reference frame of the manipulator is mandatory information for any arbitrary application. Frequently this measurement procedure is difficult to perform and implies in parameter values deviations. This paper presents an experimental method to obtain the transformation parameters for the two reference frames. The robot modeling is elegantly developed using the product of exponentials approach and the twist between robot and camera reference frames which is obtained, and represents the best solution in a least squares sense. Experimental application using a SCARA 4 D.O. F robot and a Kinect RGB-D camera is conducted to ascertain the method effectiveness. This approach represents an improvement and a flexibilization for robot programming tasks.
Aptitude of Oxidative Enzymes for Treatment of Wastewater Pollutants: A Laccase Perspective

Natural water sources are very often contaminated by municipal wastewater discharges which contain either of xenobiotic pollutants and their sometimes more toxic degradation products, or both, which frustrates the universal millenium development goal of provision of the relatively scarce pristine freshwater to water-scarce and -stressed communities, in order to augment their socioeconomic well-being. Seeing that both regulatory measures, as regards the discharge limits of wastewater, and the query for efficient treatment methods remain unanswered, partially, the prospects of enzymatic treatment of wastewater is advisable. Therefore, a reconsideration was assigned to the possible capacity of oxidative enzymes and the respective challenges encountered during their applications in wastewater treatment, and ultimately, the prospects of laccase, a polyphenol oxidase that oxidizes aromatic and inorganic substrates with electron-donating groups in treatment aromatic contaminants of wastewater, in real wastewater situations, since it is assumed to be a vehicle for a greener community. Furthermore, the importance of laccase-driven catalysis toward maintaining mass-energy balance, hence minimizing environmental waste, was comprehensibly elucidated, as well the strategic positioning of laccase in a model wastewater treatment facility for effective treatment of wastewater contaminants.
Phylogenetic relationships of Phaeochorella parinarii and recognition of a new family, Phaeochorellaceae (Diaporthales)

ABSTRACT Species of Phaeochorella are biotrophic leaf parasites with a tropical distribution, traditionally accepted in the family Phyllachoraceae, Phyllachorales in classifications based on morphological characters. Phylogenetic evidence presented here resolves the relationship of Phaeochorella within the Sordariomycetes, based on a multilocus analysis of partial nuc rDNA large subunit (28S) and internal transcribed spacers (ITS1-5.8S-ITS2 = ITS), the DNA-directed RNA polymerase II second largest subunit (RPB2), and the translation elongation factor 1-α (TEF1-α) gene. Phylogenetic analyses indicate that Phaeochorella belongs to the Diaporthales rather than the Phyllachorales. Phaeochorella parinarii, the type species of the genus, present on native hosts from the Brazilian Cerrado, forms a unique clade with a species of Phaeoappendicospora with high support. Thus, a new family, Phaeochorellaceae, Diaporthales, including both genera, is herein proposed. With the exception of P. parinarii and P. zonata, all other species in Phaeochorella (P. artocarpi, P. ciliata, P. machaerii) were excluded from the genus.
Relationship Between HDL Functional Characteristics and Cardiovascular Health and Potential Impact of Dietary Patterns: A Narrative Review

Cardiovascular disease is a leading cause of death around the world. Overall diet quality and dietary behaviors are core contributors to metabolic health. While therapeutic targets have traditionally focused on levels of lipoprotein cholesterol when evaluating cardiovascular risk, current perspectives on high-density lipoprotein (HDL) have shifted to evaluating the functionality of this lipoprotein particle. Effects of diet on cardiovascular health are mediated through multiple pathways, but the impact on HDL composition and function deserves greater attention. Potential areas of investigation involve changes in particle characteristics, distribution, microRNA cargo, and other functional changes such as improvements to cholesterol efflux capacity. Various dietary patterns like the Mediterranean diet and Dietary Approaches to Stop Hypertension (DASH) diet have beneficial effects on cardiovascular health and may prevent cardiovascular events. These healthful dietary patterns tend to be rich in plant-based foods, with cardiovascular benefits likely resulting from synergistic effects of the individual dietary components. The purpose of this review is to summarize current perspectives on selected functions of HDL particles and how various dietary patterns affect cardiovascular health biomarkers, with a focus on HDL functionality.
Slow NMDA-Mediated Excitation Accelerates Offset-Response Latencies Generated via a Post-Inhibitory Rebound Mechanism

Abstract In neural circuits, action potentials (spikes) are conventionally caused by excitatory inputs whereas inhibitory inputs reduce or modulate neuronal excitability. We previously showed that neurons in the superior paraolivary nucleus (SPN) require solely synaptic inhibition to generate their hallmark offset response, a burst of spikes at the end of a sound stimulus, via a post-inhibitory rebound mechanism. In addition SPN neurons receive excitatory inputs, but their functional significance is not yet known. Here we used mice of both sexes to demonstrate that in SPN neurons, the classical roles for excitation and inhibition are switched, with inhibitory inputs driving spike firing and excitatory inputs modulating this response. Hodgkin–Huxley modeling suggests that a slow, NMDA receptor (NMDAR)-mediated excitation would accelerate the offset response. We find corroborating evidence from in vitro and in vivo recordings that lack of excitation prolonged offset-response latencies and rendered them more variable to changing sound intensity levels. Our results reveal an unsuspected function for slow excitation in improving the timing of post-inhibitory rebound firing even when the firing itself does not depend on excitation. This shows the auditory system employs highly specialized mechanisms to encode timing-sensitive features of sound offsets which are crucial for sound-duration encoding and have profound biological importance for encoding the temporal structure of speech.
Harnessing synthetic biology for kelp forest conservation1

Environmental and climatic change is outpacing the ability of organisms to adapt, at an unprecedented level, resulting in range contractions and global ecosystem shifts to novel states. At the same time, scientific advances continue to accelerate, providing never‐before imagined solutions to current and emerging environmental problems. Synthetic biology, the creation of novel and engineered genetic variation, is perhaps the fastest developing and transformative scientific field. Its application to solve extant and emerging environmental problems is vast, at times controversial, and technological advances have outpaced the social, ethical, and practical considerations of its use. Here, we discuss the potential direct and indirect applications of synthetic biology to kelp forest conservation. Rather than advocate or oppose its use, we identify where and when it may play a role in halting or reversing global kelp loss and discuss challenges and identify pathways of research needed to bridge the gap between technological advances and organismal biology and ecology. There is a pressing need for prompt collaboration and dialogue among synthetic biologists, ecologists, and conservationists to identify opportunities for use and ensure that extant research directions are set on trajectories to allow these currently disparate fields to converge toward practical environmental solutions.
Heritabilities, social environment effects and genetic correlations of social behaviours in a cooperatively breeding vertebrate

Social animals interact frequently with conspecifics, and their behaviour is influenced by social context, environmental cues and the behaviours of interaction partners, allowing for adaptive, flexible adjustments to social encounters. This flexibility can be limited by part of the behavioural variation being genetically determined. Furthermore, behaviours can be genetically correlated, potentially constraining independent evolution. Understanding social behaviour thus requires carefully disentangling genetic, environmental, maternal and social sources of variations as well as the correlation structure between behaviours. Here, we assessed heritability, maternal, common environment and social effects of eight social behaviours in Neolamprologus pulcher, a cooperatively breeding cichlid. We bred wild‐caught fish in a paternal half‐sibling design and scored ability to defend a resource against conspecifics, to integrate into a group and the propensity to help defending the group territory (“helping behaviour”). We assessed genetic, social and phenotypic correlations within clusters of behaviours predicted to be functionally related, namely “competition,” “aggression,” “aggression‐sociability,” “integration” and “integration‐help. ” Helping behaviour and two affiliative behaviours were heritable, whereas there was little evidence for a genetic basis in all other traits. Phenotypic social effects explained part of the variation in a sociable and a submissive behaviour, but there were no maternal or common environment effects. Genetic and phenotypic correlation within clusters was mostly positive. A group's social environment influenced covariances of social behaviours. Genetic correlations were similar in magnitude but usually exceeding the phenotypic ones, indicating that conclusions about the evolution of social behaviours in this species could be provisionally drawn from phenotypic data in cases where data for genetic analyses are unobtainable.
Modeling Subcutaneous Absorption of Long-Acting Insulin Glargine in Type 1 Diabetes

<italic>Objective:</italic> Subcutaneous (sc) administration of long-acting insulin analogs is often employed in multiple daily injection (MDI) therapy of type 1 diabetes (T1D) to cover patient's basal insulin needs. Among these, insulin glargine 100 U/mL (Gla-100) and 300 U/mL (Gla-300) are formulations indicated for once daily sc administration in MDI therapy of T1D. A few semi-mechanistic models of sc absorption of insulin glargine have been proposed in the literature, but were not quantitatively assessed on a large dataset. The aim of this paper is to propose a model of sc absorption of insulin glargine able to describe the data and provide precise model parameters estimates with a clear physiological interpretation. <italic>Methods:</italic> Three candidate models were identified on a total of 47 and 77 insulin profiles of T1D subjects receiving a single or repeated sc administration of Gla-100 or Gla-300, respectively. Model comparison and selection were performed on the basis of their ability to describe the data and numerical identifiability. <italic>Results:</italic> The most parsimonious model is linear two-compartment and accounts for the insulin distribution between the two compartments after sc administration through parameter <italic>k</italic>. Between the two formulations, we report a lower fraction of insulin in the first versus second compartment (<italic>k</italic> = 86% versus 94% in Gla-100 versus Gla-300, p < 0.05), a lower dissolution rate from the first to the second compartment (<inline-formula><tex-math notation="LaTeX">$k_{sp}= \text{0.0013}$</tex-math></inline-formula> versus 0.0008 min<sup>−1</sup> in Gla-100 versus Gla-300, p << 0.001), and a similar rate of insulin absorption from the second compartment to plasma (<inline-formula><tex-math notation="LaTeX">$k_{a}= \text{0.0018}$</tex-math></inline-formula> versus 0.0016 min<sup>−1</sup> in Gla-100 versus Gla-300, p = NS), in accordance with the mechanisms of insulin glargine protraction. <italic>Conclusions:</italic> The proposed model is able to both accurately describe plasma insulin data after sc administration and precisely estimate physiologically plausible parameters. <italic>Significance:</italic> The model can be incorporated in simulation platforms potentially usable for optimizing basal insulin treatment strategies.
Emerging Resistance of Neglected Tropical Diseases: A Scoping Review of the Literature

Background: Antimicrobial resistance (AMR) is a global public health threat with the potential to cause millions of deaths. There has been a tremendous increase in the use of antimicrobials, stemming from preventive chemotherapy elimination and control programs addressing neglected tropical diseases (NTDs). This study aims to identify the frequency of drug resistance for 11 major NTDs and 20 treatment drugs within a specific period by systematically analyzing the study design, socio-demographic factors, resistance, and countries of relevant studies. Methods: Adhering to PRISMA guidelines, we performed systematic reviews of the major 11 NTDs to identify publications on drug resistance between 2000 and 2016. A quality assessment tool adapted for evaluating observational and experimental studies was applied to assess the quality of eligible studies. Results: One of the major findings is that six NTDs have information on drug resistance, namely human African trypanosomiasis, leishmaniasis, onchocerciasis, schistosomiasis, soil-transmitted helminths, and trachoma. Many studies recorded resistance due to diagnostic tests, and few studies indicated clinical resistance. Although most studies were performed in Africa where there is the occurrence of several NTDs, there was no link between disease burden and locations of study. Conclusions: Based on this study we deduce that monitoring and surveillance systems need to be strengthened to enable the early detection of AMR and the mitigation of its global spread.
Biocompatible Materials Based on Plasticized Poly(lactic acid), Chitosan and Rosemary Ethanolic Extract I. Effect of Chitosan on the Properties of Plasticized Poly(lactic acid) Materials

The purpose of the present study is to develop new multifunctional environmentally friendly materials having applications both in medical and food packaging fields. New poly(lactic acid) (PLA)-based multifunctional materials containing additives derived from natural resources like chitosan (CS) and rosemary extract (R) were obtained by melt mixing. Each of the selected components has its own specific properties such as: PLA is a biodegradable thermoplastic aliphatic polyester derived from renewable biomass, heat-resistant, with mechanical properties close to those of polystyrene and polyethylene terephthalate, and CS offers good antimicrobial activity and biological functions, while R significantly improves antioxidative action necessary in all applications. A synergy of their combination, an optimum choice of their ratio, and processing parameters led to high performance antimicrobial/antioxidant/biocompatible/environmentally degradable materials. The polyethylene glycol (PEG)-plasticized PLA/chitosan/powdered rosemary extract biocomposites of various compositions were characterized in respect to their mechanical and rheological properties, structure by spectroscopy, antioxidant and antimicrobial activities, and in vitro and in vivo biocompatibility. Scanning electron microscopy images evidence the morphology features added by rosemary powder presence in polymeric materials. Incorporation of additives improved elongation at break, antibacterial and antioxidant activity and also biocompatibility. Migration of bioactive components into D1 simulant is slower for PEG-plasticized PLA containing 6 wt % chitosan and 0.5 wt % rosemary extract (PLA/PEG/6CS/0.5 R) biocomposite and it occurred by a diffusion-controlled mechanism. The biocomposites show high hydrophilicity and good in vitro and in vivo biocompatibility. No hematological, biochemical and immunological modifications are induced by subcutaneous implantation of biocomposites. All characteristics of the PEG-plasticized PLA-based biocomposites recommend them as valuable materials for biomedical implants, and as well as for the design of innovative drug delivery systems. Also, the developed biocomposites could be a potential nature-derived active packaging with controlled release of antimicrobial/antioxidant compounds.
EGFR mutations and AKT phosphorylation are markers for sensitivity to combined MCL-1 and BCL-2/xL inhibition in non-small cell lung cancer

Lung cancer is among the common and deadly cancers. Although the treatment options for late-stage cancer patients have continued to increase in numbers, the overall survival rates for these patients have not shown significant improvement. This highlights the need for new targets and drugs to more effectively treat lung cancer patients. In this study, we characterize the MCL-1 inhibitor maritoclax alone or in combination with a BCL-2/xL inhibitor in a panel of lung cancer cell lines. BCL-2 family proteins, phosphorylated proteins, and apoptosis were monitored following the treatments. We found that maritoclax was effective at inhibiting growth in these lung cancer cells. We also establish that cell lines with EGFR mutations were most sensitive to the combined inhibition of MCL-1 and BCL-2/xL. In addition, a high level of phosphorylated AKT (S473) was identified as a marker for sensitivity to the combination treatment. This work has defined EGFR mutations and AKT phosphorylation as markers for sensitivity to combined MCL-1 and BCL-2/xL targeted therapy and establishes a rationale to explore multiple BCL-2 family members in patients who are refractory to EGFR inhibitor treatment. Our data support the design of a clinical trial that aims to employ inhibitors of the BCL-2 family of proteins in lung cancer patients.