Miracle-dz/UniFAR-FTUs huggingface dataset:
Incretin Concepts

Central nervous system effects of glucagon-like peptide 1 At a symposium on nonislet effects of glucagon-like peptide 1 (GLP-1) at the American Diabetes Association (ADA) Scientific Sessions, Remy Burcelin (Toulouse, France) reviewed the controversy as to the extent of GLP-1 action mediated in the central nervous system versus peripheral effects, advancing the concept that a central effect of GLP-1 may be to induce insulin secretion, but showing studies suggesting that central administration of GLP-1 decreases muscle glycogen—an effect blocked with a GLP-1 receptor antagonist (1). If the central effect of GLP-1 is to increase insulin secretion and to reduce peripheral glucose utilization, it would be expected to increase hepatic glycogen stores, which could be useful in preparation for situations of decreased nutrient availability. The nature of the signal sent to muscle may be understood by recognizing that muscle glucose utilization is controlled by muscle blood flow (2). In his group’s study of muscle blood flow, central GLP-1 administration blocked the increase in muscle blood flow seen with insulin and glucose. Mice not expressing the GLP-1 receptor do not show this inhibition of vasodilation and therefore have greater insulin sensitivity with administration of GLP-1. Addressing central GLP-1 signaling mechanisms, Burcelin noted that hypothalamic protein kinase C (PKC) is increased with central GLP-1, whereas the central administration of the PKC inhibitor calphostin C prevented the inhibitory effect of GLP-1 on muscle glucose uptake. In contrast, activation of brain PKC by phorbol-12-myristate, 13-acetate infusion induced insulin resistance and inhibited vasodilation. Although there are more than 12 PKCs, anti-PKC ε appears to block this GLP-1 effect. High-fat diet– induced diabetes is associated with insulin resistance (not seen in mice not expressing the GLP-1 receptor) and increased GLP-1– dependent brain PKC activity, with PKC inhibition reversing the insulin resistance and restoring the vasodilatory action of insulin plus glucose. Burcelin hypothesized that the central effect of GLP-1 activates the sympathetic nervous system causing vasoconstriction, while the peripheral effect of GLP-1 has the opposing action of causing vasodilation.
Synovial cells are potent antigen‐presenting cells for superantigen, staphylococcal enterotoxin B (SEB)

There is ample evidence suggesting that superantigens may act as a triggering factor in the pathogenesis of rheumatoid arthritis (RA). We investigated whether superantigen could activate T cells in the presence of synovial cells. T cells were cultured with SEB in the presence of interferongamma (IFN‐γ)‐treated synovial cells. T cell proliferation and activation were assessed by 3H‐thymidine incorporation and IL‐2 production. The expression of HLA class II antigens and adhesion molecules on synovial ceils was detected by flow cytometer. In the presence of IFN‐γ‐treated synovial cells, T cells proliferated vigorously and produced IL‐2 in response to SEB. A low SEB‐induced T cell response was noticed in the presence of untreated synovial cells. Allogeneic as well as autologous IFN‐γ‐treated synovial cells markedly enhanced SEB‐induced T cell proliferation. IFN‐γ‐treated synovial cells had increased expression of HLA class II antigens and intercellular adhesion molecule‐1 (ICAM‐1) adhesion molecules. MoAbs towards these antigens markedly inhibited the SEB‐induced T cell response. These results indicate that activated synovial cells are potent antigen‐presenting cells for SEB to T cells, and that superantigens may play a critical role in the pathogenesis of RA through activated synovial cells.
Hematopoiesis in the embryonic mouse spleen: an electron microscopic study.

The events of hematopoiesis in the C57/BI6J embryonic mouse spleen are described, beginning with the appearance of the splenic rudiment (12th gestational day). Immature erythroid precursors appear on day 12 of embryonic development, but foci of mature red cell precursors were not seen until day 15. Red cell precursors were observed in the spleen up to day 19 after birth. Mature polymorphonuclear leukocytes were present by day 12, whereas megakaryocytic precursors appear on day 12. Although young cells of the lymphocytic series were identified on the 16th gestational day, a marked proliferation of lymphatic cells was noted at the end of the gestational period and immediately after birth.
A Review on Multiple Potential of Aroid: Amorphophallus paeoniifolius

Amorphophallus paeoniifolius commonly known as “Jimikand”, “Elephant foot yam” is one of the underutilized aroid of araceae family. It is tuberous, stout indigenous herbs used in ayurvedic medicine system for treating various human ailments. In recent years the popularity of complementary medicine has increased. The present review compiles the existing literature related to botanical description propagation, nutrient composition, phyto-chemical constituents, traditional uses, pharmacological actions and production of value added products of Amorphophallus paeoniifolius.
Multi-faceted Index driven Navigation for Educational Videos in Mobile Phones

One of the challenges that is holding back wide spread consumption of educational videos on mobile devices is the lack of mobile interfaces which can provide efficient video navigation capabilities. In this paper, we utilize multi-modal data analysis techniques which include analysis of the spoken content and the written content of the video, to create a multi-faceted index. We present a novel and first-of-its-kind mobile interface which uses aforementioned multi-faceted index to provide intuitive, usable, and efficient way to navigate through a video. The efficacy of the proposed multi-faceted index driven mobile interface for non-linear navigation is demonstrated through a preliminary user study of 15 participants. We demonstrate that the proposed interface leads to statistically significant savings in navigation time as compared to that of a baseline interface used by leading e-learning providers.
Fibrinogen‐CD11b/CD18 interaction activates the NF‐κB pathway and delays apoptosis in human neutrophils

The regulation of neutrophil half‐life by members of the coagulation cascade is critical for the resolution of the inflammatory response. We have demonstrated that soluble fibrinogen (sFbg) delays human neutrophil (PMN) apoptosis through a mechanism that involves CD11b interactions, and phosphorylation of focal adhesion kinase (FAK) and extracellular signal‐regulated kinase 1/2 (ERK1/2). Since NF‐κB is a key element in the regulation of apoptotic mechanisms in several immune cells, we investigated whether NF‐κB is involved in the control of PMN survival by sFbg. We showthat sFbg triggers inhibitor protein κB (IκB‐α) degradation and NF‐κB activation. Furthermore, pharmacological inhibition of NF‐κB abrogates sFbg effects on apoptosis. In addition, specific inhibition of MAPK ERK1/2 significantly reduces NF‐κB translocation by sFbg, suggesting a relationship between ERK1/2 and NF‐κB activation. Similar results are obtained when granulocytic‐differentiated HL‐60 cells are treated with sFbg, making this model highly attractive for integrin‐induced gene expression studies. It can be concluded that NF‐κB participates in the prevention of apoptosis induced by sFbg with the participation of MAPK ERK1/2. These results shed light on the molecular mechanisms that control human granulocyte apoptosis, and suggest that NF‐κB regulation may be of benefit for the resolution of the inflammatory response.
The Performance of Regularized Discriminant Analysis Versus Non-Parametric Classifiers Applied to Hi

Classification of very-high-dimensional images is of the utmost interest in remote sensing applications. Storage space, and mainly the computational effort required for classifying these kinds of images, are the main drawbacks in practice. Moreover, it is well known that a number of spectral classifiers may not be useful (even not valid) in practice for classifying very-high-dimensional images. Even if they are valid, they do not provide high-accuracy classifications when the training sets are high-overlapping in the representation space due to the shape of the decision boundaries they impose. In these cases, it is preferable to adopt a classifier that may adjust the decision boundaries in a better fashion. To do so, classification based on regularized discriminant analysis (RDA) was compared with a number of non-parametric classifiers. Two synthetic image databases consisting of high-dimensional images were used for testing the performance of the classifiers. These datasets were created using a procedure.
Monoacylglycerols Are Components of Root Waxes and Can Be Produced in the Aerial Cuticle by Ectopic Expression of a Suberin-Associated Acyltransferase1[W][OA]

The interface between plants and the environment is provided for aerial organs by epicuticular waxes that have been extensively studied. By contrast, little is known about the nature, biosynthesis, and role of waxes at the root-rhizosphere interface. Waxes isolated by rapid immersion of Arabidopsis (Arabidopsis thaliana) roots in organic solvents were rich in saturated C18-C22 alkyl esters of p-hydroxycinnamic acids, but also contained significant amounts of both α- and β-isomers of monoacylglycerols with C22 and C24 saturated acyl groups and the corresponding free fatty acids. Production of these compounds in root waxes was positively correlated to the expression of sn-glycerol-3-P acyltransferase5 (GPAT5), a gene encoding an acyltransferase previously shown to be involved in aliphatic suberin synthesis. This suggests a direct metabolic relationship between suberin and some root waxes. Furthermore, when ectopically expressed in Arabidopsis, GPAT5 produced very-long-chain saturated monoacylglycerols and free fatty acids as novel components of cuticular waxes. The crystal morphology of stem waxes was altered and the load of total stem wax compounds was doubled, although the major components typical of the waxes found on wild-type plants decreased. These results strongly suggest that GPAT5 functions in vivo as an acyltransferase to a glycerol-containing acceptor and has access to the same pool of acyl intermediates and/or may be targeted to the same membrane domain as that of wax synthesis in aerial organs.
Processing of the Incentive for Social Approval in the Ventral Striatum during Charitable Donation

Human behaviors are motivated not only by materialistic rewards but also by abstract social rewards, such as the approval of others. When choosing an action in social situations, to evaluate each action, the brain must convert different types of reward (such as money or social approval) into a common scale. Here using fMRI, we investigated the neural correlates of such valuation computations while individuals freely decided whether to donate to real charities or to take the money for themselves in the presence or absence of observers. Behavioral evidence showed that the mere presence of observers increased donation rates, and neuroimaging results revealed that activation in the ventral striatum before the same choice (“donate” or “not donate”) was significantly modulated by the presence of observers. Particularly high striatal activations were observed when a high social reward was expected (donation in public) and when there was the potential for monetary gain without social cost (no donation in the absence of observers). These findings highlight the importance of this area in representing both social and monetary rewards as a “decision utility” and add to the understanding of how the brain makes a choice using a “common neural currency” in social situations.
Monitoring Cyber-Physical Systems

The term Cyber-Physical Systems (CPS) typically refers to to engineering, physical and biological systems monitored and/or controlled by an embedded computational core. The behavior of a CPS over time is generally characterized by the evolution of physical quantities and discrete software and hardware states. In general, these can be mathematically modeled by the evolution of continuous state variables for the physical components interleaved with discrete events. Despite large effort and progress in the exhaustive verification of such hybrid systems, the complexity of CPS models limits formal verification of their safe behavior only to small instances. An alternative approach, closer to the practice of simulation and testing, is to monitor and to predict CPS behaviors at simulation-time or at runtime. In this chapter we attempt to summarize the state-of-the-art techniques for qualitative and quantitative monitoring of CPS behaviors. We present an overview of some of the important applications and, finally, we describe the tools supporting CPS monitoring and compare their main features.
Influence of the Degree of Stimulation of the Pituitary by Gonadotropin-Releasing Hormone on the Action of Inhibin and Testosterone to Suppress the Secretion of the Gonadotropins in Rams1

Abstract This experiment determined if the degree of stimulation of the pituitary gland by GnRH affects the suppressive actions of inhibin and testosterone on gonadotropin secretion in rams. Two groups (n = 5) of castrated adult rams underwent hypothalamopituitary disconnection and were given two i.v. injections of vehicle or 0.64 μg/kg of recombinant human inhibin A (rh-inhibin) 6 h apart when treated with i.m. injections of oil and testosterone propionate every 12 h for at least 7 days. Each treatment was administered when the rams were infused i.v. with 125 ng of GnRH every 4 h (i.e., slow-pulse frequency) and 125 ng of GnRH every hour (i.e., fast-pulse frequency). The FSH concentrations and LH pulse amplitude were lower and the LH concentrations higher during the fast GnRH pulse frequency. The GnRH pulse frequency did not influence the ability of rh-inhibin and testosterone to suppress FSH secretion. Testosterone did not affect LH secretion. Following rh-inhibin treatment, LH pulse amplitude decreased at the slow, but not at the fast, GnRH pulse frequency, and LH concentrations decreased at both GnRH pulse frequencies. We conclude that the degree of stimulation of the pituitary by GnRH does not influence the ability of inhibin or testosterone to suppress FSH secretion in rams. Inhibin may be capable of suppressing LH secretion under conditions of low GnRH.
Inferential networked control with accessibility constraints in both the sensor and actuator channels

The predictor and controller design for an inferential control scheme over a network is addressed. A linear plant with disturbances and measurement noise is assumed to be controlled by a controller that communicates with the sensors and the actuators through a constrained network. An algorithm is proposed such that the scarce available outputs are used to make a prediction of the system evolution with an observer that takes into account the amount of lost data between successful measurements transmissions. The state prediction is then used to calculate the control actions sent to the actuator. The possibility of control action drop due to network constraints is taken into account. This networked control scheme is analysed and both the predictor and controller designs are addressed taking into account the disturbances, the measurement noise, the scarce availability of output samples and the scarce capability of control actions update. The time-varying sampling periods that result for the process inputs and outputs due to network constraints have been determined as a function of the probability of successful transmission on a specified time with a Bernoulli distribution. For both designs performance has been established and linear matrix inequality (LMI) design techniques have been used to achieve a numerical solution.
Transfer of samples in batch reinforcement learning

The main objective of transfer in reinforcement learning is to reduce the complexity of learning the solution of a target task by effectively reusing the knowledge retained from solving a set of source tasks. In this paper, we introduce a novel algorithm that transfers samples (i.e., tuples ⟨s, a, s', r⟩) from source to target tasks. Under the assumption that tasks have similar transition models and reward functions, we propose a method to select samples from the source tasks that are mostly similar to the target task, and, then, to use them as input for batch reinforcement-learning algorithms. As a result, the number of samples an agent needs to collect from the target task to learn its solution is reduced. We empirically show that, following the proposed approach, the transfer of samples is effective in reducing the learning complexity, even when some source tasks are significantly different from the target task.
Highly active electrocatalysis of the hydrogen evolution reaction by cobalt phosphide nanoparticles.

Nanoparticles of cobalt phosphide, CoP, have been prepared and evaluated as electrocatalysts for the hydrogen evolution reaction (HER) under strongly acidic conditions (0.50 M H2SO4, pH 0.3). Uniform, multi-faceted CoP nanoparticles were synthesized by reacting Co nanoparticles with trioctylphosphine. Electrodes comprised of CoP nanoparticles on a Ti support (2 mg cm(-2) mass loading) produced a cathodic current density of 20 mA cm(-2) at an overpotential of -85 mV. The CoP/Ti electrodes were stable over 24 h of sustained hydrogen production in 0.50 M H2SO4. The activity was essentially unchanged after 400 cyclic voltammetric sweeps, suggesting long-term viability under operating conditions. CoP is therefore amongst the most active, acid-stable, earth-abundant HER electrocatalysts reported to date.
Involvement of Extracellular Signal-Regulated Kinase 5 in Kinin B1 Receptor Upregulation in Isolated Human Umbilical Veins

The upregulated kinin B1 receptors exert a pivotal role in modulating inflammatory processes. In isolated human umbilical veins (HUVs), kinin B1 receptor is upregulated as a function of in vitro incubation time and proinflammatory stimuli. The aim of this study was to evaluate, using functional and biochemical methods, the involvement of extracellular signal-regulated kinase 5 (ERK5), p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase 1/2 (ERK1/2) on the kinin B1 receptor upregulation process in HUV. Real-time polymerase chain reaction analysis revealed for the first time that kinin B1 receptor mRNA expression closely parallels the functional sensitization to kinin B1 receptor selective agonist des-Arg10-kallidin (DAKD) in HUV. Moreover, the selective inhibition of ERK5, p38 MAPK, and JNK, but not ERK1/2, produced a dose-dependent rightward shift of the concentration-response curves to DAKD after 5-hour incubation and a reduction in kinin B1 receptor mRNA expression. Biochemical analyses showed that ERK5, p38 MAPK, and JNK phosphorylation is maximal during the first 2 hours postisolation, followed by a significant reduction in the last 3 hours. None of the treatments modified the responses to serotonin, an unrelated agonist, suggesting a specific effect on kinin B1 receptor upregulation. The present work provides for the first time pharmacologic evidence indicating that ERK5 plays a significant role on kinin B1 receptor upregulation. Furthermore, we confirm the relevance of p38 MAPK and JNK as well as the lack of effect of ERK1/2 in this process. This study may contribute to a better understanding of MAPK involvement in inflammatory and immunologic diseases.
The Management of Phaeochromocytomas and Paragangliomas in the Era of Precision Medicine: Where Are We Now? Evidence-Based Systemic Treatment Options and Future Cluster Oriented Perspectives

Pheochromocytomas (PCCs) and Paragangliomas (PGLs), commonly known as PPGLs to include both entities, are rare neuroendocrine tumors that may arise in the context of hereditary syndromes or be sporadic. However, even among sporadic PPGLs, identifiable somatic alterations in at least one of the known susceptibility genes can be detected. Therefore, about 3/4 of all PPGL patients can be assigned to one of the three molecular clusters that have been identified in the last years with difference in the underlying pathogenetic mechanisms, biochemical phenotype, metastatic potential, and prognosis. While surgery represents the mainstay of treatment for localized PPGLs, several therapeutic options are available in advanced and/or metastatic setting. However, only few of them hinge upon prospective data and a cluster-oriented approach has not yet been established. In order to render management even more personalized and improve the prognosis of this molecularly complex disease, it is undoubtable that genetic testing for germline mutations as well as genome profiling for somatic mutations, where available, must be improved and become standard practice. This review summarizes the current evidence regarding diagnosis and treatment of PPGLs, supporting the need of a more cluster-specific approach in clinical practice.
Prevalence and characteristics of genetic disease in adult kidney stone formers.

BACKGROUND Molecular mechanisms of kidney stone formation remain unknown in most patients. Previous studies showed high a heritability of nephrolithiasis, but data on prevalence and characteristics of genetic disease in unselected adults with nephrolithiasis are lacking. This study was conducted to fill this important knowledge gap. METHODS We performed whole exome sequencing in 787 participants of the Bern Kidney Stone Registry, an unselected cohort of adults with ≥ 1 past kidney stone episode (KSF), and 114 non-stone-forming individuals (NKSF). An exome-based panel of 34 established nephrolithiasis genes was analyzed and variants assessed according to ACMG criteria. Pathogenic (P) or likely pathogenic (LP) variants were considered diagnostic. RESULTS Mean age of KSF was 47±15 years, and 18% were first time KSF. A Mendelian kidney stone disease was present in 2.9% (23 of 787) of KSF. The most common genetic diagnoses were cystinuria (SLC3A1, SLC7A9; n=13), Vitamin D-24 hydroxylase deficiency (CYP24A1; n=5) and primary hyperoxaluria (AGXT, GRHPR, HOGA1; n=3). 8.1% (64 of 787) of KSF were monoallelic for LP/P variants predisposing to nephrolithiasis, most frequently in SLC34A1/A3 or SLC9A3R1 (n=37), CLDN16 (n=8) and CYP24A1 (n=8). KSF with Mendelian disease had a lower age at the first stone event (30±14 years vs. 36±14 years, p=0.003), were more likely to have cystine stones (23.4% vs. 1.4%) and less likely to have calcium oxalate monohydrates stones (31.9% vs. 52.5%) compared to KSF without genetic diagnosis. The phenotype of KSF with variants predisposing to nephrolithiasis was subtle and showed significant overlap with KSF without diagnostic variants. In NKSF, no Mendelian disease was detected, and LP/P variants were significantly less prevalent compared to KSF (1.8% vs. 8.1%). CONCLUSION Mendelian disease is uncommon in unselected adult KSF, yet variants predisposing to nephrolithiasis are significantly enriched in adult KSF.
Metaplanning for Multiple Agents

We present an extension to classical planning techniques that facilitates their use in complex multi-agent domains. The approach implements a form of metaplanning that enables a planner to reason about properties of multiple plans in a single plan network. With this approach, a planning agent can simultaneously generate an individual plan, repair a second, and, together with a group, execute a third. This provides some of the key functionality of sophisticated multi-agent reasoning techniques, such as Grosz and Kraus’ shared plans, but within the context of better understood classical planning techniques. As such, it helps bridge the gap between planning and multi-agent research.