Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of ursodeoxycholic acid on the kinetics of the major hydrophobic bile acids in health and in chronic cholestatic liver disease

Beneficial effects of ursodeoxycholic acid in chronic cholestatic liver diseases have been attributed to displacement of hydrophobic bile acids from the endogenous bile acid pool. To test this hypothesis, we determined pool sizes, fractional turnover rates, synthesisiinput rates and serum levels of deoxycholic acid and chenodeoxycholic acid before and 1 mo after the start of treatment with ursodeoxycholic acid (13 to 15 mg/kg body wt/day) in four healthy volunteers and five patients with chronic cholestatic liver diseases (three with primary biliary cirrhosis and two with primary sclerosing cholangitis). Bile acid kinetics were determined by combined capillary gas chromatographyisotope ratio mass spectrometry in serum samples after administration of [2H4] deoxycholic acid and [13C]chenodeoxycholic acid. In healthy volunteers, deoxycholic acid pool sizes decreased during administration of ursodeoxycholic acid by 72%. In patients with cholestatic liver diseases, deoxycholic acid pool sizes before ursodeoxycholic acid treatment were only 13% of those in healthy volunteers and were unaffected by ursodeoxycholic acid treatment. Chenodeoxycholic acid pool sizes were not different in healthy volunteers and in patients with cholestatic liver disease, and were not altered by ursodeoxycholic acid treatment. In both healthy volunteers and patients with cholestatic liver disease, synthesidinput rates and serum levels of deoxycholic acid and chenodeoxycholic acid were not altered by ursodeoxycholic acid treatment. Because in our patients improvement of serum liver tests during short‐term ursodeoxycholic acid treatment was noted without a decrease of the pool sizes of the major hydrophobic bile acids, we conclude that displacement of hydrophobic endogenous bile acids is not the mechanism of action of ursodeoxycholic acid in chronic cholestatic liver disease. (Hepatology 1992; 15603‐608).
Neuroimmune endocrine effects of antidepressants

Antidepressant pharmacotherapy is to date the most often used treatment for depression, but the exact mechanism of action underlying its therapeutic effect is still unclear. Many theories have been put forward to account for depression, as well as antidepressant activity, but none of them is exhaustive. Neuroimmune endocrine impairment is found in depressed patients; high levels of circulating corticosteroids along with hyperactivation of the immune system, high levels of proinflammatory cytokines, low levels of melatonin in plasma and urine, and disentrainment of circadian rhythms have been demonstrated. Moreover, antidepressant treatment seems to correct or at least to interfere with these alterations. In this review, we summarize the complex neuroimmune endocrine and chronobiological alterations found in patients with depression and how these systems interact with each other. We also explain how antidepressant therapy can modify these systems, along with some possible mechanisms of action shown in animal and human models.
Can Stubborn Sets Be Optimal?

Literature on the stubborn set and similar state space reduction methods presents numerous seemingly ad-hoc conditions for selecting the transitions that are investigated in the current state. There are good reasons to believe that the choice between them has a significant effect on reduction results, but not much has been published on this topic. This article presents theoretical results and examples that aim at shedding light on the issue. Because the topic is extensive, we only consider the detection of deadlocks. We distinguish between different places where choices can be made and investigate their effects. It is usually impractical to aim at choices that are “best” in some sense. However, one non-trivial practical optimality result is proven.
Endo-Lysosomal Dysfunction in Human Proximal Tubular Epithelial Cells Deficient for Lysosomal Cystine Transporter Cystinosin

Nephropathic cystinosis is a lysosomal storage disorder caused by mutations in the CTNS gene encoding cystine transporter cystinosin that results in accumulation of amino acid cystine in the lysosomes throughout the body and especially affects kidneys. Early manifestations of the disease include renal Fanconi syndrome, a generalized proximal tubular dysfunction. Current therapy of cystinosis is based on cystine-lowering drug cysteamine that postpones the disease progression but offers no cure for the Fanconi syndrome. We studied the mechanisms of impaired reabsorption in human proximal tubular epithelial cells (PTEC) deficient for cystinosin and investigated the endo-lysosomal compartments of cystinosin-deficient PTEC by means of light and electron microscopy. We demonstrate that cystinosin-deficient cells had abnormal shape and distribution of the endo-lysosomal compartments and impaired endocytosis, with decreased surface expression of multiligand receptors and delayed lysosomal cargo processing. Treatment with cysteamine improved surface expression and lysosomal cargo processing but did not lead to a complete restoration and had no effect on the abnormal morphology of endo-lysosomal compartments. The obtained results improve our understanding of the mechanism of proximal tubular dysfunction in cystinosis and indicate that impaired protein reabsorption can, at least partially, be explained by abnormal trafficking of endosomal vesicles.
Can Chronic Disability Be Prevented?: A Randomized Trial of a Cognitive-Behavior Intervention and Two Forms of Information for Patients With Spinal Pain

Study Design. A randomized controlled design superimposed on treatment as usual was used to compare the effects of a cognitive-behavior intervention aimed at preventing chronicity with two different forms of information. Objective. To develop a coping-oriented preventive intervention applicable in primary care, and to compare its impact with educational information. Summary of Background Data. Preventing long-term disability resulting from spinal pain has proved difficult. The information provided by health care professions and early interventions aimed at preventing long-term disability may be important, but little scientific evidence exists concerning their use. Methods. A protocol for a six-session cognitive-behavior group intervention was developed on the basis of earlier research. The main focus was to prevent long-term disability by changing patients’ behaviors and beliefs so they can cope better with their problems. Comparison groups received either a pamphlet shown earlier to have an effect, or a more extensive information package consisting of six installments. All the groups continued to receive treatment as usual in primary care. There were 243 patients with acute or subacute spinal pain who perceived that they were at risk for developing a chronic problem. These patients were randomized to the cognitive-behavioral intervention or one of the two information groups. Because the aim was to prevent long-term disability, the key outcome variables at the 1-year follow-up assessment were sick absenteeism and health care use. Other variables were pain, function, fear-avoidance beliefs, and cognitions. Results. The comparison groups reported benefits. However, the risk for a long-term sick absence developing was lowered ninefold for the cognitive-behavior intervention group as compared with the risk for the information groups (relative risk, 9.3). Participants in the cognitive-behavior group also reported a significant decrease in perceived risk. In addition, the cognitive-behavior group demonstrated a significant decrease in physician and physical therapy use as compared with two groups receiving information, in which such use increased. All three groups tended to improve on the variables of pain, fear-avoidance, and cognitions. Conclusions. This study demonstrates that a cognitive-behavior group intervention can lower the risk of a long-term disability developing. These findings underscore the significance of early interventions that specifically aim to prevent chronic problems. This approach might be applied to primary care settings.
Carotid and lower extremity arterial disease in patients with renal artery atherosclerosis.

BACKGROUND Atherosclerotic lesions of the carotid and lower extremity arteries may be associated with renal artery stenosis and influence the management of patients with renal artery disease. OBJECTIVE To document the prevalence and clinical features of carotid and lower extremity arterial disease in patients with renal artery atherosclerosis. METHODS An analysis of baseline data on 149 patients enrolled in a prospective natural history study of atherosclerotic renal artery stenosis. Patients with at least 1 abnormal renal artery by duplex scanning were eligible. Carotid artery disease was evaluated by duplex scanning, and ankle/brachial indices were used to assess the lower extremity arteries. Disease at each of the 3 arterial sites was classified as mild, moderate, or severe based on the extent of involvement on both sides. Serum urea nitrogen, creatinine, and lipid levels were also measured. RESULTS Severe renal, carotid, or lower extremity arterial disease was present in 44%, 19%, and 21% of the patients, respectively. There was a trend for patients with increasing degrees of renal artery disease to have increasing degrees of carotid and lower extremity arterial disease. The prevalence of severe carotid artery disease increased from 7% in the mild renal artery group to 28% in the severe renal artery group. Clinical factors that were most predictive of severe disease were elevated apolipoprotein B levels for the renal arteries, high serum urea nitrogen or creatinine levels for the carotid arteries, and smoking for the lower extremity arteries. CONCLUSIONS There was a strong association between severe renal artery atherosclerosis and severe carotid artery disease. Patients with renal artery disease also had a high prevalence of lower extremity arterial disease. In this patient population, screening for lower extremity arterial disease can be reserved for those with signs or symptoms of peripheral ischemia. Noninvasive carotid screening is justified in patients with renal artery disease to detect asymptomatic lesions that require either immediate surgical treatment or serial follow-up for disease progression.
Expression of cell-adhesion molecules in embryonic induction. II. Morphogenesis of adult feathers

The developmental appearance of cell-adhesion molecules (CAMs) was mapped during the morphogenesis of the adult chicken feather. Neural CAM (N-CAM), liver CAM (L-CAM), and neuron-glia CAM (Ng-CAM), as well as substrate molecules (laminin and fibronectin), were compared in newborn chicken skin by immunohistochemical means. N-CAM was found to be enriched in the dermal papilla, which was closely apposed to L-CAM- positive papillar ectoderm. The two CAMs were then co-expressed in cells of the collar epithelium. Subsequently generated barb epithelia expressed only L-CAM, but N-CAM reappeared periodically on cells between developing barbs and barbules. N-CAM first appeared on a single L-CAM-positive basilar cell located in each valley flanked by two adjacent barb ridges. Subsequently, the expression of N-CAM extended one cell after another to include the whole basilar layer. N-CAM also appeared in the L-CAM-positive axial-plate epithelia, beginning in a single cell located at the ridge base. The two collectives of N-CAM- positive epithelia constituting the marginal and axial plates then disintegrated, leaving interdigitating spaces between keratinized structures that had previously expressed L-CAM. The morphological transformation from an epithelial cylinder to a three-level branched feather pattern is thus achieved by coupling alternating CAM expression in linked cell collectives with specific differentiation events, such as keratinization. During all of these morphogenetic processes, laminin and fibronectin formed a continuous basement membrane separating pulp from feather epithelia, and were excluded from the sites involved in periodic appearances of N-CAM. The same staining pattern described for developing chickens persisted in the feather follicles of adult chicken tissue that have gone through several cycles of molting. Cyclic expression of the two different CAMs underlies each of the different morphological events that are generated epigenetically during feather morphogenesis.
Changes in the state of actin during the exocytotic reaction of permeabilized rat mast cells

The major part of mast cell actin is Triton-soluble and behaves as a monomer in the DNase I inhibition assay. Thus, actin exists predominantly in monomeric or short filament form, through filamentous actin is clearly apparent in the cortical region after rhodamine- phalloidin (RP) staining. The minimum actin content is estimated to be approximately 2.5 micrograms/10(6) cells (cytosolic concentration approximately 110 microM. After permeabilization of mast cells by the bacterial cytolysin streptolysin-O, approximately 60% of the Triton- soluble actin leaks out within 10 min. However, the staining of the cortical region by RP remains undiminished, and the cells are still capable of exocytosis when stimulated by GTP-gamma-S together with Ca2+. In the presence of cytochalasin E the requirement for Ca2+ is decreased, indicating that disassembly of the cytoskeleton may be a prerequisite for exocytosis. This disassembly is likely to be controlled by Ca2(+)-dependent actin regulatory proteins; their presence is indicated by a Ca2(+)-dependent inhibition of polymerization of extraneous pyrene-G-actin by a Triton extract of mast cells. The effect of cytochalasin E on secretion is similar to that of phorbol myristate acetate, an activator of protein kinase C; both agents enhance the apparent affinity for Ca2+ and cause variable extents of Ca2(+)-independent secretion. Exposing the permeabilized cells to increasing concentrations of Ca2+ caused a progressive decrease in F-actin levels as measured by flow cytometry of RP-stained cells. In this respect, both cytochalasin E and phorbol ester mimicked the effects of calcium. GTP-gamma-S was not required for the Ca2(+)- dependent cortical disassembly. Thus, since conditions have not yet been identified where secretion can occur in its absence, cortical disassembly may be essential (though it is not sufficient) for exocytosis to occur.
Associations of Unscavenged Anesthetic Gases and Long Working Hours With Preterm Delivery in Female Veterinarians

OBJECTIVE: To examine whether occupational hazards such as anesthetic gases, radiation, pesticides, and working hours in veterinary practice are associated with preterm delivery (before 37 weeks of gestation) in female veterinarians. METHODS: The Health Risks of Australian Veterinarians project was conducted as a questionnaire-based survey of all graduates of Australian veterinary schools during the 40-year period 1960–2000. Approximately 1,200 female veterinarians participated in the survey. Pregnancy was defined as the unit of analysis. We restricted analyses to pregnancies of those women who reported being employed when the pregnancy began and were working only in clinical practice. Of 1,355 pregnancies in total in the file, 744 pregnancies were eligible for the final analysis. RESULTS: The prevalence of preterm birth in women exposed to unscavenged anesthetic gases was 7.3% compared with 5.7% in the general population. In a Cox proportional hazards model controlling for the potential confounders, there was a significant 2.5-fold increase (hazard ratio 2.56, 95% confidence interval [CI] 1.33–4.91) in the risk of preterm delivery in women exposed to unscavenged anesthetic gases for 1 or more hours per week compared with the unexposed group (women who did not perform surgery and those who performed surgery in the presence of a scavenger system). A dose–response relation also was found within this group when exposure was divided into finer categories. There was also a strong and monotonic increase in risk of preterm delivery and the number of hours worked per week with veterinarians working more than 45 hours a week (hazard ratio 3.69, 95% CI 1.40–9.72) compared with those working fewer than 45 hours per week. CONCLUSION: Long working hours and performing surgery in the absence of a scavenger system for anesthetic gases are important risk factors for preterm birth in female veterinarians. LEVEL OF EVIDENCE: II
Comparative teratogenicity of nine retinoids in the rat.

he comparative teratogenicity of nine retinoids in Wistar rats was investigated. The compounds studied and dose levels tested (mg/kg) were: all-trans-retinoic acid (TRA), 6.25, 12.5, 25, 50, 100; etretinate (ETR), 25, 50; acitretin (ACIT), 25, 50; 13-cis-retinoic acid (13CRA), 100, 200; and five retinamides, each at 300 and 600 mg/kg, N-(4-hydroxyphenyl)-retinamide (4HPR); N-tetrazol-5-ylretinamide (TZR); N-butylretinamide (NBR); N-ethylretinamide (NER); 13-cis-N-ethylretinamide (13CNER). Retinoids were administered by oral intubation on days 10 and 11 post coitum (p.c.). Dams were killed on day 22 p.c. and examinations carried out to assess teratogenic potential. TRA, ETR, ACIT, 13CRA and 4HPR increased the incidence of resorptions. The incidence of abnormal fetuses, irrespective of the specific abnormalities induced, was markedly increased (50-100%) by TRA, ETR, ACIT, 13CRA and 4HPR, whereas TZR and NBR caused moderate increases (20-50%), and NER and 13CNER induced mild increases (10-20%). The incidences of CNS, craniofacial and urinogenital defects were generally high with TRA, ETR, ACIT and 13CRA. Cardiac vessel defects were markedly increased by 4HPR. Using a number of criteria, a generalized ranking order of the toxicity of the compounds was drawn up: TRA > ETR > ACIT > 13CRA > 4HPR > TZR identical to NBR > NER identical to 13CNER. The ranked order of relative in-vivo teratogenicity for the nine retinoids is compared with a previously reported in-vitro assessment of the compounds using a rat whole embryo culture technique.
Optimum Linear Transmitter Design for MIMO Systems with Two QPSK Data Streams

We present the optimum design of a linear transmitter for a multi-input multi-output communication system when the input data consists of two QPSK streams and the receiver performs maximum likelihood detection. The transmitter design is optimal in the sense that it minimizes the worst-case pairwise error probability. We prove that the resulting linear transmitter constructs, as a function of the two input QPSK streams, a new signal constellation. Moreover, we show that this new signal constellation is such that the minimum distance among the points of the received constellation is maximized and, indirectly, the number of neighbors at minimum distance is also maximized.
CAIRNS: The Cluster and Infall Region Nearby Survey. I. Redshifts and Mass Profiles

The CAIRNS (Cluster and Infall Region Nearby Survey) project is a spectroscopic survey of the infall regions surrounding eight nearby, rich, X-ray–luminous clusters of galaxies. We have collected 15,654 redshifts (3471 new or remeasured) within ∼5–10 h-1 Mpc of the centers of the clusters, making it the largest study of the infall regions of clusters. We determine cluster membership and the mass profiles of the clusters based on the phase-space distribution of the galaxies. All of the clusters display decreasing velocity dispersion profiles. The mass profiles are fitted well by functional forms based on numerical simulations but exclude an isothermal sphere. Specifically, NFW and Hernquist models provide good descriptions of cluster mass profiles to their turnaround radii. Our sample shows that the predicted infall pattern is ubiquitous in rich, X-ray–luminous clusters over a large mass range. The caustic mass estimates are in excellent agreement with independent X-ray estimates at small radii and with virial estimates at intermediate radii. The mean ratio of the caustic mass to the X-ray mass is 1.03 ± 0.11, and the mean ratio of the caustic mass to the virial mass (when corrected for the surface pressure term) is 0.93 ± 0.07. We further demonstrate that the caustic technique provides reasonable mass estimates even in merging clusters.
Playing with Fire: Transactional Memory Revisited for Error-Resilient and Energy-Efficient MPSoC Execution

As silicon integration technology pushes toward atomic dimensions, errors due to static and dynamic variability are an increasing concern. To avoid such errors, designers often turn to "guardband" restrictions on the operating frequency and voltage. If guardbands are too conservative, they limit performance and waste energy, but less conservative guardbands risk moving the system closer to its Critical Operating Point (COP), a frequency-voltage pair that, if surpassed, causes massive instruction failures. In this paper, we propose a novel scheme that allows to dynamically adjust to an evolving COP and operate at highly reduced margins, while guaranteeing forward progress. Specifically, our scheme dynamically monitors the platform and adaptively adjusts to the COP among multiple cores, using lightweight checkpointing and roll-back mechanisms adopted from Hardware Transactional Memory (HTM) for error recovery. Experiments demonstrate that our technique is particularly effective in saving energy while also offering safe execution guarantees. To the best of our knowledge, this work is the first to describe a full-fledged HTM implementation for error-resilient and energy-efficient MPSoC execution.
An Artificial miRNA against HPSE Suppresses Melanoma Invasion Properties, Correlating with a Down-Regulation of Chemokines and MAPK Phosphorylation

Ribonucleic acid interference (RNAi) based on microRNA (miRNA) context may provide an efficient and safe therapeutic knockdown effect and can be driven by ribonucleic acid polymerase II (RNAP II). In this study, we designed and synthesized miR155-based artificial miRNAs against heparanase (HPSE) constructed with BLOCK-iT™ Pol II miR RNAi Expression Vector Kit. The expression levels of HPSE declined significantly in both the mRNA and protein levels in HPSE-miRNA transfected melanoma cells that exhibited reduction of adhesion, migration, and invasion ability in vitro and in vivo. We also observed that HPSE miRNA could inhibit the expressions of chemokines of interleukin-8 (IL8) and chemokine (C-X-C motif) ligand 1 (CXCL1), at both the transcriptional and translational levels. Further study on its probable mechanism declared that down-regulation of IL8 and CXCL1 by HPSE-miRNA may be correlated with reduced growth-factor simulated mitogen-activated kinase (MAPK) phosphorylation including p38 MAPK, c-Jun N-terminal kinase (JNK) and extracellular-signal-regulated kinase (ERK) 1 and 2, which could be rescued by miRNA incompatible mutated HPSE cDNA. In conclusion, we demonstrated that artificial miRNAs against HPSE might serve as an alterative mean of therapy to low HPSE expression and to block the adhesion, invasion, and metastasis of melanoma cells. Furthermore, miRNA-based RNAi was also a powerful tool for gene function study.