Miracle-dz/UniFAR-FTUs huggingface dataset:
The Small GTP-binding Protein Rho Activates c-Jun N-terminal Kinases/Stress-activated Protein Kinases in Human Kidney 293T Cells

Work from a number of laboratories has established a role for certain small GTP-binding proteins in controlling the enzymatic activity of a family of serine-threonine kinases known as itogen-ctivated rotein inases (MAPKs). MAPKs have been classified into three subfamilies: xtracellular signal-egulated inases (ERKs), also known as MAPKs; c-un -terminal inases (JNKs); and p38 kinase. Whereas Ras controls the activation of MAPKs, we and others have recently observed that in certain cells, the small GTP-binding proteins Rac1 and Cdc42 but not Rho regulate the activity of JNKs. Furthermore, because Rac1 and Cdc42 but not Rho bind and activate a kinase known as Pak1, it has been suggested that Pak1 is the most upstream component of the pathway linking these GTPases to JNK. However, in both yeast and mammalian cells, Rho1p, a Rho homologue, and RhoA, respectively, directly interact with a number of proteins, including kinases related to protein kinase C. In addition, in yeast, Rho1p controls the activity of a MAPK cascade involved in bud formation. Considering this diversity of target molecules for small GTP-binding proteins, their likely tissue specific distribution, and the potential role for Rho in signaling to a kinase cascade, we decided to extend our initial analysis, exploring the ability of Ras and Rho-related GTP-binding proteins to activate MAPK or JNK in a variety of cell lines. We found that in the human kidney epithelial cell line, 293T, Cdc42 and all Rho proteins, RhoA, RhoB, and RhoC, but not Rac or Ras can induce activation of JNK. Furthermore, we provide evidence that signaling from Rho proteins to JNK in 293T cells does not involve Pak1. Taken together these findings demonstrate that Rho signals to JNK in a cell type-specific manner and suggest the existence of a novel, Pak1-independent signaling route communicating the Rho family of small GTP-binding proteins to the JNK pathway.
Safety and Immunogenicity of an Enterotoxigenic Escherichia coli Vaccine Patch Containing Heat-Labile Toxin: Use of Skin Pretreatment To Disrupt the Stratum Corneum

ABSTRACT Transcutaneous immunization allows safe delivery of native heat-labile enterotoxin (LT) from Escherichia coli via application of a simple patch. Physical disruption of the stratum corneum can improve the efficiency of delivery. In the current study, the stratum corneum was disrupted using an electrocardiogram prep pad prior to patch application. The effects were quantified using transepidermal water loss (TEWL) and were correlated with the immune responses. Sixty adults received 50 μg of LT from three lots of LT (20 adults per group) administered in a patch on days 0 and 21. The immunizations were well tolerated. There were no differences in the anti-LT immunoglobulin G (IgG) titers between the three LT lots; the seroconversion rate was 100%, and the mean anti-LT IgG titer was 12,185 enzyme-linked immunosorbent assay units (EU) (a 24-fold increase). TEWL measurements obtained at the time of the second immunization were found to correlate with the day 42 individual increases in the anti-LT IgG titer (r = 0.59, P < 0.001). In a comparative assessment of the immune responses, sera after an LT+ ST+ (E2447A) oral ETEC challenge, which induced moderate to severe diarrhea in 81% of the recipients, had anti-LT IgG titers of 3,245 EU (a 10.8-fold increase). Similarly, the anti-LT IgG titer after administration of an oral cholera toxin B subunit-containing cholera vaccine, which cross-reacts with LT and protects against LT and LT/heat-stable toxin ETEC disease in the field, was 6,741 EU (a 3.3-fold increase). This study confirmed that a well-tolerated regimen for stratum corneum disruption before vaccine patch application results in robust immunity comparable to natural immunity and vaccine-induced immunity and that the magnitude of stratum corneum disruption correlates with the immune response.
PRICE-RESPONSE ASYMMETRY IN DOMESTIC WHOLESALE AND RETAIL DIESEL 2 MARKETS IN PERU

This paper tests and confirms the hypothesis that retail and wholesale Diesel 2 prices respond more quickly to increases than to decreases in wholesale and crude oil prices, respectively. Among the possible sources of this asymmetry, we find: production / inventory adjustment lags, refining adjustments, market power of some sellers, searching costs, among others. By analyzing price transmission at different points of the distribution chain, this paper attempts to shed light on these theories for the Peruvian oil industry. Wholesale prices for Diesel 2 show asymmetry in responding to crude oil price changes, which may refl ect inventory adjustment effects. Asymmetry also appears in the response that retail prices give to wholesale price changes, presumably indicating short-run local market power among retailers or the existence of searching costs.
Immunomodulation Induced by Avène Spring Water on Th1- and Th2-Dependent Cytokine Production in Healthy Subjects and Atopic Dermatitis Patients

Avène spring water (ASW) is commonly used in France for treating atopic dermatitis and psoriasis. Previous works demonstrated modulation of cell membrane fluidity by ASW. The aims of the present study were (a) to investigate a possible in vitro effect of ASW on Th1- and Th2-dependent cytokine production using peripheral blood mononuclear cells from healthy individuals and (b) to investigate both the in vitro effect of ASW on AD patients’ cells and the in vivo cellular and clinical modifications induced by a 3-week Avène Medical Spa water cure (AMSWC). The effect of ASW was tested on lymphocyte cultures, which were stimulated in vitro by various mitogens and a superantigen of staphylococcal origin. The lymphocyte proliferation and the production of the cytokines IL-2, IL-4 and IFN-γ were tested. The results showed that ASW-containing medium enhanced the lymphoproliferative response to some mitogens. IL-2 and IFN-γ production were also increased in stimulated culture supernatants. Conversely, ASW-containing medium induced a decrease in IL-4 production by normal peripheral blood lymphocytes. Furthermore, AMSWC was able to amend the clinical features as well as the immunological Th2 profile of atopic dermatitis.
OPTIMAL HARVESTING OF FOREST AGE CLASSES UNDER PRICE UNCERTAINTY AND RISK AVERSION

ABSTRACT. We analyze optimal forest harvesting under mean reverting and random walk timber price and include multiple age classes, forest owners' consumption‐savings decisions and risk aversion. This framework generalizes existing studies that assume a single stand and risk neutrality or include ad hoc risk aversion and obtain the result that uncertainty lengthens the optimal rotation. Including planting cost implies that price stochasticity may shorten the rotation period. Under the mean reverting price process, optimal harvesting becomes more sensitive to periodic price level, as compared to the random walk case. Including risk aversion completely changes the harvesting policy in the sense that, if the forest initially consists of just one age class, it is optimal to smooth the age class structure and have more frequent cuttings from younger age classes. With risk aversion, optimal cuttings depend on price level, even under a random walk price and zero replanting and harvesting costs. In addition, harvesting decisions become dependent on subjective time preference and forest owners' wealth.
The effect of leisure activity golf practice on motor imagery: an fMRI study in middle adulthood

Much is known about practice-induced plasticity of the motor system. But it is not clear how a physical training influences the mental rehearsal of the practiced task and its associated hemodynamic responses. In the present longitudinal study with two measurement time-points, we used the method of functional magnetic resonance imaging (fMRI) and a motor imagery task, in order to explore the dynamic neuro-functional changes induced by a highly complex physical training. The 11 golf novices between the age of 40 and 60 years practiced the motor training as leisure activity. Additionally, data from an age and sex-matched control group without golf training was collected. As a main result, we demonstrate that changes between the two measurement time-points were only found in the golf novice group. The golf novices showed a decrease in hemodynamic responses during the mental rehearsal of the golf swing in non-primary motor areas after the 40 h of golf practice. Thus, the results indicate that a complex physical leisure activity induces functional neuroplasticity in the seldom studied population of middle-aged adults, and that this effect is evident during mental rehearsal of the practiced task. This finding supports the idea that (a) a skill improvement is associated with a modified activation pattern in the associated neuronal network that can be identified during mental rehearsal of the practiced task, and that (b) a strict training protocol is not necessary to induce functional neuroplasticity.
Cable Wrapping Phenomenon in Cable-Driven Parallel Manipulators

In the study of cable-driven parallel manipulators, the interference between the cable and the rigid link(s) of the mechanisms have generally been excluded when considering the workspace. This leads to the loss of perfectly feasible and useful regions of workspace. In this paper, such phenomenon is modelled by allowing the cable to wrap around the rigid link and the resulting pose to be included in the workspace consideration. A kinematic model of the path of a cable in a cable-driven parallel manipulator is constructed to include the segment of the cable wrapped over the surface of the rigid link, in addition to the conventional modelling of the straight (unwrapped) segments of the actuation cables. The path described by the cable wrapping about the rigid link is a function of the displacement of the rigid link(s). When wrapping occurs, the contact between the cable and the rigid link is no longer restricted to a stationary point with respect to the body attached frame, as in the case of a conventional cable-driven parallel manipulator, but is now a function of the pose of the rigid link. It is assumed that the cable remains taut at all times, therefore finding the cable configuration is equivalent to finding a geodesic solution on a convex hull of a rigid body. In this paper, the analysis is first presented for the basic case of finding the path of a single cable wrapped over an arbitrary (convex) rigid body, with specific illustration performed for cylindrical-shaped rigid body. Modelling and analysis is then applied to the case of a selected cable-driven parallel manipulator that allows wrapped cable segments in its operation.
Dosimetric evaluation of new approaches in GRID therapy using nonconventional radiation sources.

PURPOSE Spatial fractionation of the dose has proven to be a promising approach to increase the tolerance of healthy tissue, which is the main limitation of radiotherapy. A good example of that is GRID therapy, which has been successfully used in the management of large tumors with low toxicity. The aim of this work is to explore new avenues using nonconventional sources: GRID therapy by using kilovoltage (synchrotron) x-rays, the use of very high-energy electrons, and proton GRID therapy. They share in common the use of the smallest possible grid sizes in order to exploit the dose-volume effects. METHODS Monte Carlo simulations (penelope/peneasy and geant4/GATE codes) were used as a method to study dose distributions resulting from irradiations in different configurations of the three proposed techniques. As figure of merit, percentage (peak and valley) depth dose curves, penumbras, and central peak-to-valley dose ratios (PVDR) were evaluated. As shown in previous biological experiments, high PVDR values are requested for healthy tissue sparing. A superior tumor control may benefit from a lower PVDR. RESULTS High PVDR values were obtained in the healthy tissue for the three cases studied. When low energy photons are used, the treatment of deep-seated tumors can still be performed with submillimetric grid sizes. Superior PVDR values were reached with the other two approaches in the first centimeters along the beam path. The use of protons has the advantage of delivering a uniform dose distribution in the tumor, while healthy tissue benefits from the spatial fractionation of the dose. In the three evaluated techniques, there is a net reduction in penumbra with respect to radiosurgery. CONCLUSIONS The high PVDR values in the healthy tissue and the use of small grid sizes in the three presented approaches might constitute a promising alternative to treat tumors with such spatially fractionated radiotherapy techniques. The dosimetric results presented here support the interest of performing radiobiology experiments in order to evaluate these new avenues.
Continuous Muscle Stretch Prevents Disuse Muscle Atrophy and Deterioration of Its Oxidative Capacity in Rat Tail–Suspension Models

Sasa T, Sairyo K, Yoshida N, Fukunaga M, Koga K, Ishikawa M, Yasui N: Continuous muscle stretch prevents disuse muscle atrophy and deterioration of its oxidative capacity in rat tail–suspension models. Am J Phys Med Rehabil 2004;83:851–856. Objective:The purpose of this study was to evaluate the effect of continuous muscle stretch on disuse-atrophied muscles. Design:Sprague-Dawley rats were used and divided into five groups: control group, hind limb suspended for 3 and 7 days, and hind-limb suspension plus strenuous continuous muscle stretch for 3 and 7 days. In the hind-limb suspension plus strenuous continuous muscle stretch groups, the gastrocnemius-plantaris-soleus muscles were stretched using a plastic plate that immobilized the ankle joint at the maximum dorsal flexed position during the hind-limb suspension period. The intracellular energy metabolism of the working muscle during electric stimulation was evaluated by phosphorus-31 magnetic resonance spectroscopy in vivo. Changes in phosphocreatine, inorganic phosphate, and the intracellular pH were monitored to evaluate intramuscular oxidative capacity. Maximum tension and muscle wet mass were also measured. Results:The oxidative capacity, muscle wet weight, and maximum tension decreased after hind-limb suspension. The muscle oxidative capacity at control levels was maintained during the first 3 days in muscles subjected to continuous strenuous stretch. It was also effective to prevent the decrease in muscle mass and maximum twitch tension during the initial 3 days. However, the effects did not persist. Conclusion:Continuous strenuous stretch was effective to prevent disuse muscle atrophy and its functional deterioration; however, its effects did not last long.
The Effects of GABA Agonists on Glutamic Acid Decarboxylase, GABA‐Transaminase, Activin, Salmon Gonadotrophin‐Releasing Hormone and Tyrosine Hydroxylase mRNA in the Goldfish (Carassius auratus) Neuroendocrine Brain

GABA plays a pivotal role in reproduction by regulating luteinising hormone (LH) release from the anterior pituitary. Current evidence indicates that there is a prominent stimulatory effect of GABA on LH release in teleost fish which results from enhanced gonadotrophin‐releasing hormone (GnRH) release and decreased dopamine turnover in the brain and pituitary. We hypothesised that there may be additional mechanisms underlying LH release in goldfish and investigated the relative mRNA levels of GABA synthesising enzymes (GAD65 and GAD67), degrading enzyme (GABA‐T), activin βa and βb, salmon GnRH (sGnRH), and tyrosine hydroxylase (TH) with the real‐time reverse transcriptase‐polymerase chain reaction after GABA agonist treatment. Sexually regressed female goldfish were i.p. injected with either the GABAA agonist muscimol (1 µg/g body weight) or the GABAB agonist baclofen (10 µg/g body weight). Both agonists significantly increased serum LH after 6 h. Muscimol decreased GAD65 (approximately ten‐fold), GABA‐T (approximately 15‐fold) and TH (approximately three‐fold) mRNA in the telencephalon. Baclofen significantly reduced GAD67 (approximately two‐fold) and GABA‐T (approximately two‐fold) mRNA levels in the hypothalamus. Activin βa, but not activin βb, steady‐state mRNA was increased approximately three‐ to four‐fold in both the hypothalamus and telencephalon after baclofen treatment. There was no change in sGnRH mRNA levels in either tissue after GABA agonist treatment. We show that the GABAA and GABAB receptor agonists have differing and rapid effects on gene transcription in the goldfish neuroendocrine brain and, by affecting specific targets, we identify putative genomic mechanisms underlying GABA‐stimulated LH release in fish.
Vehicle Yaw Stability Control by Coordinated Active Front Steering and Differential Braking in the Tire Sideslip Angles Domain

Vehicle active safety receives ever increasing attention in the attempt to achieve zero accidents on the road. In this paper, we investigate a control architecture that has the potential of improving yaw stability control by achieving faster convergence and reduced impact on the longitudinal dynamics. We consider a system where active front steering and differential braking are available and propose a model predictive control (MPC) strategy to coordinate the actuators. We formulate the vehicle dynamics with respect to the tire slip angles and use a piecewise affine (PWA) approximation of the tire force characteristics. The resulting PWA system is used as prediction model in a hybrid MPC strategy. After assessing the benefits of the proposed approach, we synthesize the controller by using a switched MPC strategy, where the tire conditions (linear/saturated) are assumed not to change during the prediction horizon. The assessment of the controller computational load and memory requirements indicates that it is capable of real-time execution in automotive-grade electronic control units. Experimental tests in different maneuvers executed on low-friction surfaces demonstrate the high performance of the controller.
Valuation of Loan Credit Default Swaps Correlated Prepayment and Default Risks with Stochastic Recovery Rate

In this paper, we establish an intensity based multi-factor model to value LCDS. The pricing model incorporates the modeling of default, prepayment and recovery risks. Using one factor model, negative correlation between the default and prepayment intensities and positive correlation between the default intensity and the loss given default are described. The interest rate and the house price are chosen as the relevant factors. Under these assumption, a Cauthy problem of PDE is derived, which has a closed-form solution. Based on the solution, numerical examples are provided.
Channel profile engineering of 0.1 /spl mu/m-Si MOSFETs by through-the-gate implantation

A novel approach to the super-steep retrograde (SSR) channel profile formation for MOSFETs is suggested, with dopant implantation in the late stages of the processing, with the gate, source/drain already in place ("TGi"). Only a single damage/activation anneal and the back-end thermal budget are experienced by the implanted dopants, which results in steep profiles even when light boron ions are used. High-performance NMOS devices with excellent SCE control designed for low-voltage digital, analog and RF operation were realized using this technique. For PMOS the use of TGi is restricted by significant diffusion of source/drain extensions due to the TGi damage induced TED.
Testing New Theories of Choice under Uncertainty using the Common Consequence Effect

A generalised common consequence problem is used to contrast the predictions of expected utility theory and several new theories of choice under uncertainty. An experiment designed to test these predictions is reported. Systematic violations of expected utility theory are detected but although a consistent pattern emerges from the data, it offers little support for any of the new theories. The analysis is extended to test predictions which are unique to regret theory and significant regret effects are detected.
Addiction Severity Index Profile of Persons who Reenter Treatment for Substance use Disorders

Background Despite a growing interest in persons with multiple treatment reentries, few studies have defined their clinical profile. The aim of this study was to compare the severity profile of substance use disorder and related problems of persons who reenter treatment with the profile of those who come in for treatment for the first time. Methods A data bank containing 6651 Addiction Severity Index (ASI) interviews from 3 rehabilitation centers was used for the analyses. Results All the ASI composite scores were significantly higher among persons who reentered treatment than among those who came for the first time. Conclusion The results support the hypothesis of a more severe ASI profile and substance use–related problems among persons who reenter treatment compared with those who come for the first time. Consequently, they have greater needs, and the treatment offered should be adjusted accordingly.
Phylogenomics of tomato chloroplasts using assembly and alignment-free method

Abstract Phylogenetics and population genetics are central disciplines in evolutionary biology. Both are based on the comparison of single DNA sequences, or a concatenation of a number of these. However, with the advent of next-generation DNA sequencing technologies, the approaches that consider large genomic data sets are of growing importance for the elucidation of evolutionary relationships among species. Among these approaches, the assembly and alignment-free methods which allow an efficient distance computation and phylogeny reconstruction are of great importance. However, it is not yet clear under what quality conditions and abundance of genomic data such methods are able to infer phylogenies accurately. In the present study we assess the method originally proposed by Fan et al. for whole genome data, in the elucidation of Tomatoes' chloroplast phylogenetics using short read sequences. We find that this assembly and alignment-free method is capable of reproducing previous results under conditions of high coverage, given that low frequency k-mers (i.e. error prone data) are effectively filtered out. Finally, we present a complete chloroplast phylogeny for the best data quality candidates of the recently published 360 tomato genomes.
Rapid treatment of “wearing off” in Parkinson’s disease

Patients with advanced Parkinson’s disease (PD) may develop a variety of motor complications associated with levodopa therapy. Motor fluctuations, such as early morning akinesia and “wearing-off,” may respond to individualized medical management with titrated combinations of levodopa, dopamine agonists, COMT inhibitors and amantadine. Often with disease progression, dyskinesias and unpredictable, rapid “off” periods will also emerge. These motor complications are less amenable to traditional anti-parkinson therapy manipulation. This manuscript reviews approaches for “rescue” therapy in PD patients with “wearing off,” sudden “offs,” early morning akinesia, and variable response to individual doses of oral medications. Strategies for preparing and administering liquid levodopa are discussed within the context of gastric emptying, intestinal absorption, and active transport across the blood brain barrier. In addition other levodopa preparations in early development, including the orally administered levodopa methyl ester and the potential for a subcutaneously administered levodopa ethyl ester are reviewed. Furthermore, practical guidelines regarding the dosing, administration, use of the antiemetic trimethobenzamide (Tigan®), time to “on,” duration of benefit, and potential side effects associated with subcutaneously injected apomorphine are provided.