Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential signalling by muscarinic receptors in smooth muscle: m2-mediated inactivation of myosin light chain kinase via Gi3, Cdc42/Rac1 and p21-activated kinase 1 pathway, and m3-mediated MLC20 (20 kDa regulatory light chain of myosin II) phosphorylation via Rho-associated kinase/myosin phosphat

Signalling via m3 and m2 receptors in smooth muscles involved activation of two G-protein-dependent pathways by each receptor. m2 receptors were coupled via Gbetagammai3 with activation of phospholipase C-beta3, phosphoinositide 3-kinase and Cdc42/Rac1 (where Cdc stands for cell division cycle) and p21-activated kinase 1 (PAK1), resulting in phosphorylation and inactivation of myosin light chain kinase (MLCK). Each step was inhibited by methoctramine and pertussis toxin. PAK1 activity was abolished in cells expressing both Cdc42-DN (where DN stands for dominant negative) and Rac1-DN. MLCK phosphorylation was inhibited by PAK1 antibody, and in cells expressing Cdc42-DN and Rac1-DN. m3 receptors were coupled via Galpha(q/11) with activation of phospholipase C-beta1 and via RhoA with activation of Rho-associated kinase (Rho kinase), phospholipase D and protein kinase C (PKC). Rho kinase and phospholipase D activities were inhibited by C3 exoenzyme and in cells expressing RhoA-DN. PKC activity was inhibited by bisindolylmaleimide, and in cells expressing RhoA-DN; PKC activity was also inhibited partly by Y27632 (44+/-5%). PKC-induced phosphorylation of PKC-activated 17 kDa inhibitor protein of type 1 phosphatase (CPI-17) at Thr38 was abolished by bisindolylmaleimide and inhibited partly by Y27632 (28+/-3%). Rho-kinase-induced phosphorylation of myosin phosphatase targeting subunit (MYPT1) and was abolished by Y27632. Sustained phosphorylation of 20 kDa regulatory light chain of myosin II (MLC20) and contraction were abolished by bisindolylmaleimide Y27632 and C3 exoenzyme and in cells expressing RhoA-DN. The results suggest that Rho-kinase-dependent phosphorylation of MYPT1 and PKC-dependent phosphorylation and enhancement of CPI-17 binding to the catalytic subunit of MLC phosphatase (MLCP) act co-operatively to inhibit MLCP activity, leading to sustained stimulation of MLC20 phosphorylation and contraction. Because Y27632 inhibited both Rho kinase and PKC activities, it could not be used to ascertain the contribution of MYPT1 to inhibition of MLCP activity. m2-dependent phosphorylation and inactivation of MLCK precluded its involvement in sustained MLC20 phosphorylation and contraction.
Utility Maximization and Indifference Value under Risk and Information Constraints for a Market with a Change Point

In this article we consider an optimization problem of expected utility maximization of continuous-time trading in a financial market. This trading is constrained by a benchmark for a utility-based shortfall risk measure. The market consists of one asset whose price process is modeled by a Geometric Brownian motion where the market parameters change at a random time. The information flow is modeled by initially and progressively enlarged filtrations which represent the knowledge about the price process, the Brownian motion and the random time. We solve the maximization problem and give the optimal terminal wealth depending on these different filtrations for general utility functions by using martingale representation results for the corresponding filtration. Moreover, for a special utility function and risk measure we calculate the utility indifference value which measures the gain of further information for the investor.
Quantitative evaluation of single-arm versus randomized phase II cancer clinical trials

Background There is a debate among cancer researchers about the use of single-arm or randomized phase II clinical trial designs; however, there is limited published objective evaluation of this issue. Purpose To objectively quantify the impact on phase III clinical trials of a policy of all single-arm versus all randomized phase II trials. Methods A simulation study was performed comparing optimal single-arm and randomized phase II trial designs with a variety of commonly used α and β error rates. Parameters modeled included: between-institution variability in the standard of care response rate, between-institution variability in the treatment effect, between-institution variability in the estimate of historical control rate (for selecting H0), presence of historical bias, and proportion of phase II trials conducted using active agents. Results Using single-arm phase II trials resulted in a higher percentage of phase III trials conducted using active agents when there was minimal standard of care activity, or in the presence of a positive historical bias (H0 estimated to be greater than truth). Randomized phase II trials performed better in the presence of a negative historical bias, in the presence of high variability, and were more consistent across variation of historical bias. The proportion of phase III trials conducted using active agents was increased by reducing the α error. Presence of historical bias and the proportion of active agents studied in phase II had the greatest influence on results. Limitations It was estimated that between 5% and 20% of agents studied in phase II trials are active; however, the conclusions could change if this estimate is incorrect. This study did not account for the possibility of a new drug application submission immediately following phase II. The primary outcome looked at was response rate, although some investigators have suggested that time-to-event outcomes should be used in phase II, particularly for randomized phase II trials. Conclusions Both single-arm and randomized phase II trials appear warranted in certain situations. Investigators should increase consideration of the potential impact on phase III trials to optimally select the proper trial design prior to phase II study implementation.
The Effect Of Vessel Supply On Ship-Demolition Prices

The ship-demolition is one of the four main markets that form the shipping industry and plays an important role on the seaborne trade, as it mitigates imbalances between supply and demand for transportation services by adjusting the merchant fleet supply. The aim of this study is to examine whether the factors that determine the supply of vessels for demolition are capable of affecting materially the ship-demolition price formation. The availability of ships for demolition is primarily a function of the fleet’s age and the conditions on the freight and secondhand markets. The analysis is conducted on the crude tanker and the bulk carrier segments and the vector autoregressive model methodology is employed, whereby the effect of both the supply and the demand factors on the ship-demolition prices is examined. The results indicate that the supply side has limited effect on the price formation in the industry, which is driven by the demand for the steel-scrap commodity.
[The influence of afterload on the normal and ischemic myocardium in the dog].

The influence of an instantaneous increase in afterload on the hemodynamics and regional myocardial function was studied in five anesthetized dogs before and after occlusion of the left anterior descending coronary artery. By inflation of an intaaortic balloon during single ejections, an instantaneous increase in afterload was obtained. From biplane cineventriculograms, the following parameters were calculated: left ventricular volumes (EDV, ESV), stroke volume (SV), ejection fraction (EF). Mean circumferential fiber shortening (V CF) was calculated in three ventricular diameters in the RAO projection. Simultaneously PLV, PLVED, PAo, and LV dp/dt were obtained. In the control ventriculograms, an increased afterload (delta PLV 16.4 +/- 8 mm Hg) caused only a minor decrease of SV (2.6 +/- 2.5 ml), EF (4.2 +/- 2.4%), and V CF (0.20 circ . s -1). After coronary occlusion (delta PLV 14.5 +/- 6.7 mm Hg),the reduction of SV (5.9 +/- 2.7 ml) and EF (8.2 +/- 2.6%) was more pronounced. This was caused mainly by a significant reduction of V CF in the center of ischemia (delta V CF -93%). For the evaluation of regional myocardial function by ventriculography, the marked influence of afterload in ischemic areas must be taken into consideration. This is of special interest in comparative ventriculograms, such as those before and after coronary bypass surgery.
Use of proteomics and physiological characteristics to elucidate ecotoxic effects of methyl tert‐butyl ether in Pseudomonas putida KT2440

We monitored rates of growth, ATP‐synthesis, respiration, and death to assess the sensitivity of the model organism Pseudomonas putida KT2440 to methyl tert‐butyl ether (MTBE), and its degree of toxicity. The physiological data obtained suggested that the energy conservation system was the most sensitive site. However, with the help of proteomic analysis we obtained further information and deeper insight into the molecular mechanisms involved. This analysis indicated that sensitivity involves oxidative stress since alkylhydroperoxide reductase C (AhpC) and two superoxide dismutases (SodM, SodF) were amplified in the presence of MTBE. Thus, proteomics has major advantages in ecotoxicological investigations where the aims include elucidation of the molecular mechanisms as well as characterization of the ecostress and the potency of the stressor(s).
Selective inhibition of inducible nitric oxide synthase enhances intraglomerular coagulation in chronic anti-Thy 1 nephritis.

BACKGROUND A particular Lewis rat substrain (LEW/Maa) develops chronic glomerulonephritis in the anti-Thy 1 model (aThy 1-GN) characterized by increased microaneurysm formation, chronic glomerular sclerosis and persistent albuminuria. This phenotype is accompanied by increased and prolonged glomerular induction of inducible nitric oxide synthase (iNOS) when compared to the LEW/Moe substrain, in which aThy 1-GN resolves quickly. We investigated the effect of selective iNOS inhibition by l-N6-(1-iminoethyl)-lysine (L-NIL) administration on aThy 1-GN in LEW/Maa rats. METHODS Nephritic rats were studied over a period of 7 days. L-NIL-treated animals received 20 mg/day L-NIL in the drinking water starting two days prior to disease induction. iNOS activity was determined in cultured glomeruli and in urine samples, respectively. Severity of aThy 1-GN was determined by scoring glomerular matrix expansion and microaneurysm formation, and by albuminuria measurements (ELISA). Immunohistochemical evaluation was performed including staining for macrophages (ED-1), platelets (PL-1) and fibrin deposition. RESULTS L-NIL treated rats (+NIL) showed a significant decrease in peak nitrate production by ex vivo cultured glomeruli, and in urinary nitrate excretion versus untreated nephritic rats (-NIL). Mean arterial pressure remained unchanged in both +NIL and -NIL rats. +NIL rats developed significantly increased albuminuria (+44%) associated with a significant increase in glomerular platelet (+45%) and fibrin deposition (+48%). CONCLUSIONS Selective inhibition of iNOS aggravated albuminuria in chronic aThy 1-GN in LEW/Maa rats. Induction of iNOS during the inflammatory phase of this model may be a partially protective mechanism by interfering with intraglomerular coagulation processes.
Job resources and demands for expatriate academics

Purpose While there is a growing interest in expatriate academics, their specific role as teachers with daily contact to local students seems to have been largely ignored when examining their adjustment and work outcomes. Based on the job demands-resources model the authors predict that good teacher-student relations, as a supportive job resource, will have a positive effect on expatriate academics’ job satisfaction. This effect, however, will be even stronger for individuals experiencing high job demands and challenges in terms of intercultural job adjustment. In other words, expatriate academics that have difficulties adjusting will benefit more from the social support that can originate from good relations to their students. The paper aims to discuss these issues. Design/methodology/approach The authors surveyed expatriate academics adjusting to a university position in China by use of 124 responses from foreign university employees. Findings The authors found that teacher-student relations had a positive association with job satisfaction and that positive teacher-student relations increased job satisfaction more for individuals being slow to adjust. Originality/value This is one of the few papers to explore the impact that students can have on expatriate academics and treat this relationship as a potential resource for universities to capitalize upon in socializing their new foreign academic staff members.
Premorbid social functioning in schizophrenia and bipolar disorder: similarities and differences.

OBJECTIVE This research examined social functioning in childhood and adolescence among patients with schizophrenia and patients with bipolar disorder compared with healthy subjects and investigated the relation between premorbid adjustment and risk factors for psychosis. METHOD Maternal recall was used to assess the premorbid adjustment of patients with schizophrenia (N = 70) and patients with bipolar disorder (N = 28) recruited from a survey of consecutive hospital admissions for psychosis and of healthy comparison subjects (N = 100) drawn from the same catchment area. RESULTS The patients with schizophrenia had significantly poorer premorbid adjustment in childhood and adolescence than the comparison subjects and were impaired in both sociability and school adjustment. The patients with bipolar disorder exhibited poorer social impairment in adolescence than the comparison subjects, though to a lesser degree than the schizophrenic subjects, but functioned well at school. There were significant linear trends in the risk of psychosis with worsening premorbid functioning, which was most marked in the schizophrenic group, and a specific linear relation between low birth weight and poor premorbid adjustment among the schizophrenic patients. CONCLUSIONS Impaired premorbid social functioning is not specific to schizophrenia and is seen also in bipolar disorder. The data support the view that poor premorbid social adjustment is one manifestation of vulnerability to adult psychotic disorders. These results are consistent with other findings pointing to early developmental deficits in patients who subsequently develop psychosis.
Pulse wave velocity. A new calculation method.

BACKGROUND The increase in aortic Pulse Wave Velocity (PWV) is considered a surrogate marker of vascular disease; it can be non-invasively assessed by means of an indirect method calculating the time that the pulse wave takes to travel a definite distance along the vasculature; the distance/time ratio corresponds to the velocity measure. The presentation of a new calculation method is the aim of the present study. METHODS A duplex scanner at the common carotid artery, the abdominal aorta at the prebifurcation site and the femoral common artery levels, was performed on 127 out-patients with risk factors, 38 of which were affected by clinical vascular disease, and on 50 healthy subjects (control group). The spectral analysis from these three sites was registered simultaneously with an ECG trace and the interval between the R wave apex and the spectral complex systolic foot was measured. The Transit Time (TT) was calculated by the difference between the values obtained from the proximal and distal measurement sites and PWV dividing the distance between them by the TT (PWV = Distance/TT); statistical significance and intra and inter observer variation coefficient, expressed as mean +/- standard deviation, were calculated by the analysis of variance and Turkey test, the correlation with the major risk factors and the intima-media thickness by the multivariate analysis. RESULTS The PWV is increased in the patients group compared to control group (p < 0.001). Multivariate analysis shows a positive correlation with age, hypercholesterolemia, arterial hypertension, diabetes mellitus, intima-media thickness and arterial disease, no correlation was found with the smoking habit. The "patients" group shows an increased PWV in those with atherosclerotic plaques and/or clinical vascular disease compared to non atherosclerotic patients with risk factors (p < 0.001); the intra and inter observer variation coefficient ranged between 4.87 +/- 1.82% and 8.06 +/- 3.16% respectively. CONCLUSIONS The proposed PWV measurement method is simple, quick, reproducible and repeatable, it can separate healthy subjects from patients with risk factors, atherosclerotic plaques and clinical vascular disease. Due to the strong correlation with age, normal values in different age groups are necessary before the PWV can be used as a marker of vascular disease.
A preliminary analysis of reconstructed nerve function using targeted muscle reinnervation in a rat model

The previous studies have demonstrated that by transferring residual nerves to alternative muscle sites, the targeted muscle reinnervation (TMR) technique could provide a rich source of motor control information to improve myoelectrical control of a multifunctional prosthesis in patients with above-elbow amputations. However, it seems to lack the detailed investigations about the recovery progress of the targeted muscle function after reinnervation surgery, which may be important for further improving the TMR surgery and prosthesis control. In this study, a rat TMR model was developed by transferred the medial nerve of the rats into their pectoralis major muscle and was used to investigate the electrophysiological function of the targeted muscle. An implanted electrode was used to record the intramuscular myoelectric signals from the targeted muscle in the TMR rats and the histomorphometric analysis was performed to visualize the reinnervation of the medial nerve within the pectoralis major muscle. Our results of this pilot study showed that the myoelectric signals from the reinnervated muscle could be clearly recorded about one week post TMR and the newly growing fibers in the targeted muscle could be for the first time observed.
Who Benefits from Longer Lending Relationships? An Analysis on European SMEs

This paper empirically investigates the impact of lending relationships duration on SMEs financial stability. Our research hypothesis is that the balance between benefits and costs of longer bank‐firm ties may be different depending on the degree of firms' financial health. Using a large sample of European manufacturing SMEs that excludes firms that have defaulted and those with less than ten employees, we find that the overall positive effect of enduring lending relationships tends to progressively increase for more stable firms, being greater when the main bank operates nearby the firm. Our findings, yet, are conditional on firm survival and may not be generalized to the smallest of firms.
Source Memory in Parkinson's Disease

Three experiments (ns= 14 per group) are reported which investigated the ability of Parkinson patients to remember the characteristics of conditions under which a memory was acquired. In Exp. 1, subjects were required to indicate for each item in a recognition memory test whether it was spoken by Experimenter 1 or by Experimenter 2 (external-external source memory). In Exp. 2, subjects had to indicate for each item whether it was generated by themselves or by the experimenter (internal-external source memory). In Exp. 3, subjects had to judge whether an item was generated by themselves in saying or in thinking (internal-internal source memory). We found that patients with Parkinson's disease were not impaired in the previous two kinds of source memory (Exp. 1 and 2) but were impaired in internal-internal source memory (Exp. 3) relative to the age-matched control groups. In addition, both groups' performance could be improved when given distinctive cues, i.e., perceptual cues in Exp. 1 and different-domain cues in Exp. 2. These results suggest that the availability of cues was critical for Parkinson's disease in source memory. Finally, the result of Exp. 2 also showed generation effects for patients with Parkinson's disease. The generation effect refers to better memory of information by people when they had to produce it, e.g., producing associates to a word, compared with memory of information given to them.
REGIONAL POPULATION STRUCTURE IN POSTCLASSIC MEXICO

Abstract The majority of our knowledge about population structure in Mexico during the Postclassic period (a.d. 900–1520) is based on archaeological data. During this time, populations were in contact with each other through extensive trade networks and via the expansion of powerful empires in central and west Mexico. Though archaeological data provides a wealth of information about these relationships, little is known about the effects of these processes on population structure and biological, morphological variation or whether these effects vary across geographic regions. In this study, dental morphological observations are used as a proxy for genetic data in order to assess the differences in regional population structures throughout Mexico. Our analyses show differences in population structure between the various cultural and geographic areas around Mexico. We further conclude that population structures are affected by economic, political, or religious processes. This study provides bioarchaeological support for archaeological interpretations of population structure in Postclassic Mexico.
Fibronectin Fibrillogenesis Involves the Heparin II Binding Domain of Fibronectin*

Fibronectin matrix assembly is thought to involve binding interactions between the amino-terminal I1–5repeats and the first type III repeat (III1). Here we report that a third site, located within the III12–14repeats of the carboxyl-terminal heparin II domain of fibronectin, is also involved in fibrillogenesis. Heparin II fragments inhibited fibril formation and binding of 125I-labeled fibronectin and/or 70-kDa fragments to the cell surface, deoxycholate-insoluble matrix, and adsorbed 160-kDa cell adhesion fragments of fibronectin. The inhibitory effects of heparin II fragments were as large or up to 20 times larger than those of a 44-kDa fibronectin fragment containing the III1 repeat. Under physiological conditions, amino-terminal fragments of fibronectin containing the I1–5 repeats interacted preferentially with proteolytically derived heparin II fragments and a recombinant III12–14 peptide both in solution and in solid phase, indicating that matrix assembly may involve direct interactions between I1–5 and III12–14 repeats. Interactions between the I1–5 repeats and 160-kDa fragments containing the III12–14 and III1 repeats could be inhibited by ≥ 90% by either an anti-III13–14 monoclonal antibody (mAb) (IST-2) or an anti-III1 mAb (9D2), suggesting that cooperative interactions between III12–14and III1 repeats may also promote binding of the I1–5 repeats. Neither mAb IST-2 nor mAb 9D2, alone or in combination, inhibited binding of 125I-labeled 70-kDa fragments to cycloheximide-treated cells plated on the 160-kDa substrate, suggesting that additional I1–5 binding sites, independent of the III1 and III12–14 repeats, may be involved in fibrillogenesis.