Miracle-dz/UniFAR-FTUs huggingface dataset:
Control of end-point forces of a multijoint limb by functional neuromuscular stimulation

A multivariable feedback controller was designed and tested for regulating the magnitude and orientation of the force vector at the end point of a multijoint limb in contact with an isometric load. The force vector was produced by electrical stimulation of muscles. Two coupling issues must be dealt with by the control system. First, there is a geometric coupling between the end-point force vector and joint torques on which amplitude and orientation of the force vector depend. Second, torques at two joints may be coupled due to activation of muscles that cross them (biarticular coupling). To eliminate the geometric coupling, a transformation of controller error from the Cartesian space to the joint space was employed. A multivariable proportional-plus-integral (PI) control law was used to calculate muscle activation based on the transformed controller error. Centralized and decentralized controls were investigated for decoupling the effects of biarticular muscles. Test results show that the magnitude and orientation of end-point forces could be regulated by this controller. <<ETX>>
MEK inhibitor trametinib does not prevent the growth of anaplastic lymphoma kinase (ALK)–addicted neuroblastomas

MEK inhibitors induce feedback AKT-mTORC2–mediated survival signaling in ALK-addicted neuroblastoma cells. Feedback signaling complicates treatment Trametinib, an inhibitor of the kinase MEK, is clinically approved to treat patients with various types of cancers. Because some cases, particularly relapses, of neuroblastoma often display increased activation of the RAS-MAPK pathway, which includes MEK, trametinib is proposed as a rational combination strategy for treating ALK-addicted neuroblastomas. However, Umapathy et al. found that this may not be effective. The authors evaluated various ALK-addicted and RAS-mutant neuroblastoma cell lines and EML4-ALK–positive NSCLC cell lines in mice and found that trametinib did not inhibit growth. Rather, MEK pathway inhibition by trametinib induced a prosurvival feedback signal mediated by AKT and mTORC2. Thus, although it seems to be a rational therapeutic target, inhibiting the RAS-MAPK pathway would likely not benefit patients with ALK-addicted neuroblastoma. Activation of the RAS-RAF-MEK-ERK signaling pathway is implicated in driving the initiation and progression of multiple cancers. Several inhibitors targeting the RAS-MAPK pathway are clinically approved as single- or polyagent therapies for patients with specific types of cancer. One example is the MEK inhibitor trametinib, which is included as a rational polytherapy strategy for treating EML4-ALK–positive, EGFR-activated, or KRAS-mutant lung cancers and neuroblastomas that also contain activating mutations in the RAS-MAPK pathway. In addition, in neuroblastoma, a heterogeneous disease, relapse cases display an increased rate of mutations in ALK, NRAS, and NF1, leading to increased activation of RAS-MAPK signaling. Co-targeting ALK and the RAS-MAPK pathway is an attractive option, because monotherapies have not yet produced effective results in ALK-addicted neuroblastoma patients. We evaluated the response of neuroblastoma cell lines to MEK-ERK pathway inhibition by trametinib. In contrast to RAS-MAPK pathway-mutated neuroblastoma cell lines, ALK-addicted neuroblastoma cells treated with trametinib showed increased activation (inferred by phosphorylation) of the kinases AKT and ERK5. This feedback response was mediated by the mammalian target of rapamycin complex 2–associated protein SIN1, resulting in increased survival and proliferation that depended on AKT signaling. In xenografts in mice, trametinib inhibited the growth of EML4-ALK–positive non–small cell lung cancer and RAS-mutant neuroblastoma but not ALK-addicted neuroblastoma. Thus, our results advise against the seemingly rational option of using MEK inhibitors to treat ALK-addicted neuroblastoma.
Clinical implications of increased expression of CD40L in patients with acute coronary syndromes.

OBJECTIVE To investigate clinical implications of expression of CD40L in monocytes and changes in serum soluble CD40L in patients with acute coronary syndromes (ACS). METHODS Sixteen control and 56 patients, including 24 with stable angina (SA), 20 with unstable angina (UA) and 12 with acute myocardial infarction (AMI) enrolled in this study. Expression of CD40L in monocytes was analyzed by flow cytometry and sCD40L levels were measured by ELISA. RESULTS Expression of CD40L in monocytes and serum levels of sCD40L in UA and AMI patients were higher than in SA patients and controls. In patients with AMI, sCD40L levels showed no significant increase when compared to patients with UA, while AMI patients had a peak level of sCD40L at 24 hours after AMI. PTCA induced a marked rise in sCD40L levels in all patients, while CD40L expression in monocytes showed no difference between patients with PTCA, before and after. CONCLUSION Enhanced level of serum sCD40L may be a reliable prognostic indicator for ACS and may represent a marker of coronary disease activity.
Inhibitory effects of delphinidin on the proliferation of ovarian cancer cells via PI3K/AKT and ERK 1/2 MAPK signal transduction

Delphinidin is a member of the anthocyanidin family and is a natural pigment in red cabbage, berries, sweet potatoes and grapes. It possesses nutraceutical properties against various chronic diseases and types of cancer. However, little is known about its preventative effects on epithelial ovarian cancer, a disease that is associated with a low survival rate, a poor prognosis and a high rate of recurrence. The results of the present study demonstrated that the proliferation of SKOV3 cells decreased in a dose-dependent manner in response to treatment with delphinidin, and the phosphorylation of carcinogenic protein kinases associated with the progression of epithelial ovarian cancer was affected by delphinidin treatment. The levels of phosphorylated protein kinase B (AKT), ribosomal protein S6 kinase β-1 (P70S6K), ribosomal protein S (S6), extracellular signal-regulated kinase (ERK)1/2 and p38 were suppressed by increasing concentrations of delphinidin. Furthermore, the combination of certain pharmacological inhibitors, including phosphoinositide 3-kinase (PI3K; LY294002), ERK1/2 (U0126) and delphinidin significantly reduced the proliferation of SKOV3 cells and the phosphorylation of each of those target proteins. In addition, delphinidin treatment exerted anti-proliferative effects on paclitaxel-resistant SKOV3 cells, compared with treatment with paclitaxel alone. These results indicate that delphinidin inhibits the proliferation of SKOV3 cells through inactivation of PI3K/AKT and ERK1/2 mitogen-activated protein kinase signaling cascades, and that this cell signaling pathway may be a pivotal therapeutic target for the prevention of epithelial ovarian cancer, including paclitaxel-resistant ovarian cancer.
How China’s nitrogen footprint of food has changed from 1961 to 2010

People have increased the amount of reactive nitrogen (Nr) in the environment as a result of food production methods and consumption choices. However, the connection between dietary choices and environmental impacts over time has not yet been studied in China. Here we combine a nitrogen footprint tool, the N-Calculator, with a food chain model, NUFER (NUtrient flows in Food chains, Environment and Resources use), to analyze the N footprint of food in China. We use the NUFER model to provide a detailed estimation of the amounts and forms of Nr released to the environment during food production, which is then used to calculate virtual nitrogen factors (VNFs, unit: kg N released/kg N in product) of major food items. The food N footprint consists of the food consumption N footprint and food production N footprint. The average per capita food N footprint increased from 4.7 kg N capita−1 yr−1 in the 1960s to 21 kg N capita−1 yr−1 in the 2000s, and the national food N footprint in China increased from 3.4 metric tons (MT) N yr−1 in the 1960s to 28 MT N yr−1 in the 2000s. The proportion of the food N footprint that is animal-derived increased from 37% to 54% during this period. The food production N footprint accounted for 84% of the national food N footprint in the 2000s, compared to 62% in the 1960s. More Nr has been added to the food production systems to produce enough food for a growing population that is increasing its per-capita food consumption. The increasing VNFs in China indicate that an increasing amount of Nr is being lost per unit of N embedded in food products consumed by humans in the past five decades. National N losses from food production increased from 6 MT N yr−1 in the 1960s to 23 MT N yr−1 in the 2000s. N was lost to the environment in four ways: ammonia (NH3) emissions and dinitrogen (N2) emissions through denitrification (each account for nearly 40%), N losses to water systems (20%), and nitrous oxide (N2O) emissions (1%). The average per capita food N footprint in China is relatively high compared with those of developed countries in the 2000s. To reduce the food N footprint in China, it is important to both reduce the Nr losses during food production and encourage diets associated with a lower N footprint, such as shifting towards a more plant-based diet.
DEGRADATION OF MYOFIBRILLAR PROTEINS BY EXTRACTABLE LYSOSOMAL ENZYMES AND m-CALPAIN , AND THE EFFECTS OF ZINC CHLORIDE

A study was conducted to examine the effects that physiological levels of m-calpain (calpain requiring millimolar concentrations of Ca2+) extract and a lysosomal extract have on myofibrillar proteins in vitro, and the effects that zinc has on inhibiting proteolysis by these extracts. During a 22-h incubation period, the lysosomal extract degraded myosin heavy chain, a-actinin, des&, troponin-I, and myosin light chains 1 and 2. The effectiveness of the lysosomal extract to degrade myofibrillar proteins was significantly affected by the presence or absence of EDTA. Zinc, which is a potent inhibitor of cysteine proteinases, prevented most, but not all, of the lysosomal extract-induced myofibrillar protein degradation. Incubation of myofibrils with m-calpain resulted in the hydrolysis of troponin-T, desmin, and a 58-kDa molecular weight protein, possibly vimentin, and 5 mM ZnCl2 completely blocked these changes. Results from this study indicate that the degradation by the lysosomal extract is far more extensive than the degradation that occurs with normal postmortem storage and that possibly a non-cysteine protease is present that is capable of hydrolyzing some myofibrillar proteins under this in vitro condition, because Zn2+ did not block al l proteolysis. However, similar changes were induced by m-calpah incubation and postmortem storage.
Nerve origin of the acoustic neuroma

Two hundred and seventy-one Japanese patients who underwent surgical removal of neuroma from the cerebello-pontine angle using the translabyrinthine approach were retrospectively reviewed in order to investigate the nerve origin on an anatomical basis. In 269 out of the 271 cases, the origin of the neuromas was identified. Among these cases, 84.8 per cent of tumours originated from the inferior vestibular nerve (IVN), followed by the superior vestibular nerve (SVN) (8.9 per cent). Of the 5.6 per cent of tumours arising from the vestibular nerve, however, it could not be determined whether they originated from the SVN or IVN. Two cases of neuromas originating from the facial nerve were seen (0.7 per cent). No neuroma arose from the cochlear nerve. Currently, the diagnosis of acoustic neuromas is best made with Gd-enhanced magnetic resonance imaging (MRI). However, our data indicate that the development of a functional test of the individual IVN can be useful for screening most cases of acoustic neuroma and in facilitating their early diagnosis.
Functional MRI of the immediate impact of transcranial magnetic stimulation on cortical and subcortical motor circuits

Recent studies indicate that the cortical effects of transcranial magnetic stimulation (TMS) may not be localized to the site of stimulation, but spread to other distant areas. Using echo‐planar imaging with blood‐oxygenation‐level‐dependent (BOLD) contrast at 3 Tesla, we measured MRI signal changes in cortical and subcortical motor regions during high‐frequency (3.125 Hz) repetitive TMS (rTMS) of the left sensorimotor cortex (M1/S1) at intensities above and below the active motor threshold in healthy humans. The supra‐ and subthreshold nature of the TMS pulses was confirmed by simultaneous electromyographic monitoring of a hand muscle. Suprathreshold rTMS activated a network of primary and secondary cortical motor regions including M1/S1, supplementary motor area, dorsal premotor cortex, cingulate motor area, the putamen and thalamus. Subthreshold rTMS elicited no MRI‐detectable activity in the stimulated M1/S1, but otherwise led to a similar activation pattern as obtained for suprathreshold stimulation though at reduced intensity. In addition, we observed activations within the auditory system, including the transverse and superior temporal gyrus, inferior colliculus and medial geniculate nucleus. The present findings support the notion that re‐afferent feedback from evoked movements represents the dominant input to the motor system via M1 during suprathreshold stimulation. The BOLD MRI changes in motor areas distant from the site of subthreshold stimulation are likely to originate from altered synaptic transmissions due to induced excitability changes in M1/S1. They reflect the capability of rTMS to target both local and remote brain regions as tightly connected constituents of a cortical and subcortical network.
Functional Outcomes Used to Compare Single Radius and Multiradius of Curvature Designs in Total Knee Arthroplasty

Abstract A recent development to better recreate joint kinematics has been a change from a multiradius (MR) design to a single radius (SR) design. We analyzed 559 primary total knee arthroplasty (TKA) procedures which used either a SR (n = 426 Triathlon®; Stryker Orthopaedics, Mahwah, NJ) or MR of curvature knee system (n = 133 Duracon®; Stryker Orthopaedics, Mahwah, NJ) (79.3% follow-up; 705 total TKA procedures identified). Patients were administered a modification of the Knee Society score (KSS) (3.9 years average follow-up). The SR design showed improvements over the MR design in pain (p = 0.021), stability (p = 0.002), flexion (p = 0.006), ability to completely straighten the knee (p = 0.025), stair climbing (p = 0.0001), walking (p = 0.0001), use of assistive devices (p = 0.0005), postoperative knee score (p = 0.0005), and postoperative function (p < 0.0001). Analysis of the change in KSS knee (p = 0.002) and function scores (p = 0.002) from preoperative visit to postoperative follow-up favored the SR design as well. These data support the use of SR implants and provide evidence of improved outcomes in terms of function, stability, and pain.
Cold‐induced stress stimulates the sympathetic nervous system, causing hypertension and proteinuria in rats

Objective To determine whether cold-stress stimulation of the soles of the paws would produce a preeclampsialike syndrome in rats. Methods Pregnant or nonpregnant rats were kept in 0°C floor and 23°C room temperature cages (the cold-stressed group) or in 23°C floor and 23°C room temperature cages (the control group) for 2 weeks. Their blood pressure, proteinuria, and plasma catecholamines were measured, and histologic studies were performed on all groups. Results There were no significant differences in systolic blood pressure between the two groups during the first week of the experimental period; however, during the last week of gestation the blood pressure of the cold-stressed group did not fall and was significantly higher than that of the control group. A significant increase in urinary protein excretion was observed in the cold-stimulated pregnant rats, in contrast to the control rats. The concentrations of norepinephrine and epinephrine in the cold-stressed pregnant rats were markedly higher than those in the control rats. A decrease in trophoblast invasion, congestion, and fibrinoid deposits of the labyrinth were observed in the cold-stressed rats. A marked increase in subendothelial fibrinoid deposits in the glomerular capillary was found only in the cold- stressed pregnant rats. The blood pressure, biochemical parameters, and histologic findings in the nonpregnant rats were almost the same as those in the pregnant rats. Conclusion Chronic local cold stimulation of the soles of the paws induces preeclampsia-like phenomena in pregnant and nonpregnant rats, and this model suggests that the cause of preeclampsia is involved in chronic stimulation of the sympathetic nerve.
Financial Development in Latin America and the Caribbean: The Road Ahead

The financial systems of the Latin America and the Caribbean region (LAC) are at a crucial juncture. After a history of recurrent instability and crisis (a trademark of the region), they now seem well poised for rapid expansion. Since the last wave of financial crises that swept through the region in the late 1990s and early 2000s, financial systems in LAC have continued to gain in soundness, depth, and diversity. The size of banking systems has increased, albeit from a low base; local currency bond markets have greatly developed, both in volumes and in reach over the yield curve; stock markets have expanded; and derivative markets particularly currency derivatives have grown and multiplied. Institutional investors have become more important relative to banks, making the financial system more complex and diversified. Importantly, much progress has been made in financial inclusion, particularly through the expansion of payments, savings, and credit services to lower income households and microenterprises. As evidence of their new soundness and resiliency, financial systems in the region, except in some Caribbean countries, weathered the recent global financial crisis remarkably well. The progress in financial development in LAC no doubt reflects substantial improvements in the enabling environment, lower macroeconomic volatility, more independent and better-anchored currencies, increased financial liberalization, lower currency mismatches and foreign debt exposures, enhanced effectiveness of regulation and supervision, and notable improvements in the underlying market infrastructures (for example, trading, payments, custody, clearing, and settlement). This regional flagship report aims at providing such a stocktaking and forward looking assessment of the region's financial development. Rather than going into detail about sector-specific issues, the report focuses on the main architectural issues, overall perspectives, and interconnections. The value added of the report thus hinges on its holistic view of the development process, its broad coverage of the financial services industry (not just banking), its emphasis on benchmarking, its systemic perspective, and its explicit effort to incorporate the lessons from the recent global financial crisis.
Consumer dispositions in multicultural contexts: a framework proposition

Objetivo: A globalização tem levado à formação de fluxos culturais através das fronteiras nacionais, resultando em diferentes comportamentos em relação ao consumo de produtos estrangeiros. O objetivo deste estudo é organizar alguns dos construtos que descrevem as disposições do consumidor em contextos multiculturais, rastreando a literatura disponível sobre essas disposições e propondo um quadro conceitual. Metodologia: Foi adotada uma perspectiva conceitual, onde uma revisão sistemática da literatura foi utilizada para organizar as disposições do ingroup e outgroup.Principais resultados: Identificou-se que o estudo das disposições do consumidor é um tema relativamente recente na literatura acadêmica, tendo 35 anos desde o primeiro artigo publicado, sendo 53% deles publicados a partir de 2016. Além disso, os estudos sobre as disposições do ingroup estão em um estágio mais maduro do que aqueles sobre as disposições do outgroup.Originalidade: Os autores propõem uma estrutura bidimensional que combina as perspectivas pró e anti das disposições. Contribuições teóricas: Além da perspectiva pró já presente na literatura, esta pesquisa propõe a combinação dos aspectos pró e anti, chamando a atenção para uma posição neutra do consumidor. Os autores também recomendam a inclusão do exotismo como uma disposição pro-outgroup no comportamento do consumidor.
The Ingenious Interactions Between Macrophages and Functionally Plastic Retinal Pigment Epithelium Cells.

Purpose The purpose of this study was to clarify the interactions between macrophages (MPs) and RPE cells in coculture systems to investigate the functional plasticity of RPE cells. Methods Adherent peritoneal cells or murine MP cell line Raw 264.7 was cocultured with primary RPE cells taken from C57BL/6 mice, with or without lipopolysaccharide (LPS) or TNF-α stimulation. The cytokine levels of the culture supernatants (CSs) were then analyzed with the Bio-Plex murine 23-Plex Panel Assay Kit (Bio-Rad Laboratories). Monocyte chemoattractant protein-1 (MCP-1), IL-6, VEGF, and TNF-α in CS were further quantified by ELISA. The expression profiles, in cocultures, of complement-associated genes, TNF-α, and angiogenesis-associated genes were analyzed by quantitative real-time PCR. Results The production of MCP-1, IL-6, and VEGF was synergistically elevated when primary MPs or RAW264.7 cells and RPE cells were cocultured compared with those derived from sole cultures of MPs and RPE cells. The synergistic effect was confirmed without direct cell contact and was more prominent in the presence of LPS or TNF-α. TNF-α production by MPs was suppressed by RPE cells. Coculture of RPE cells with RAW264.7 cells increased the gene expression of C3, CFB, and VEGF genes, whereas it reduced those of complement regulatory factors CFH, CD59, clusterin, and TNF-α and antiangiogenic pigment epithelium-derived factor (PEDF). Conclusions Our findings indicate the presence of ingenious interactions between MPs and RPE cells that forces the inflammation and complement activation in the vicinity of RPE cells under pathologic conditions.
Electricity–Growth Nexus in Turkey: The Importance Of Capital and Labor

The objective of the study is to examine the relationship between energy consumption and economic growth by including capital and labor as potential determinants of Cobb–Douglas production function in case of Turkey by using the auto-regressive distributed lag (ARDL) model and rolling window approach (RWA) over the period of 1980-2014. The results from this study confirm a co-integration relationship in the long run. There is a feedback effect between variables and electricity consumption; capital and labor positively impact on the economic growth. This results supports the policy recommendation for a better protection and conservation policy on energy consumption, labor and capital in Turkey in the future in order to achieve better economic growth rates.