Miracle-dz/UniFAR-FTUs huggingface dataset:
Relationship between cellular response and behavioral variability in bacterial chemotaxis

Over the last decades, bacterial chemotaxis in Escherichia coli has emerged as a canonical system for the study of signal transduction. A remarkable feature of this system is the coexistence of a robust adaptive behavior observed at the population level with a large fluctuating behavior in single cells [Korobkova E, Emonet T, Vilar JMG, Shimizu TS, Cluzel P (2004) Nature 428:574–578]. Using a unified stochastic model, we demonstrate that this coexistence is not fortuitous but a direct consequence of the architecture of this adaptive system. The methylation and demethylation cycles that regulate the activity of receptor-kinase complexes are ultrasensitive because they operate outside the region of first-order kinetics. As a result, the receptor-kinase that governs cellular behavior exhibits a sigmoidal activation curve. We propose that the steepness of this kinase activation curve simultaneously controls the behavioral variability in nonstimulated individual bacteria and the duration of the adaptive response to small stimuli. We predict that the fluctuating behavior and the chemotactic response of individual cells both peak within the transition region of this sigmoidal curve. Large-scale simulations of digital bacteria suggest that the chemotaxis network is tuned to simultaneously maximize both the random spread of cells in the absence of nutrients and the cellular response to gradients of attractant. This study highlights a fundamental relation from which the behavioral variability of nonstimulated cells is used to infer the timing of the cellular response to small stimuli.
Clinical evaluation of near-infrared spectroscopy for testing cerebrovascular reactivity in patients with carotid artery disease.

BACKGROUND AND PURPOSE Near-infrared spectroscopy (NIRS) derives information about the concentrations of oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb) from measurements of light attenuation caused by these chromosphores. The aim of this study was to assess NIRS as a tool for testing CO2 reactivity in patients with carotid artery disease. METHODS One hundred patients with symptomatic carotid occlusive disease were examined (age range, 44 to 83 years). The severity of stenosis ranged from 30% to 100% (median, 80%) on the ipsilateral side and 0% to 100% (median, 30%) on the contralateral side. Monitored parameters included transcranial Doppler flow velocity, changes in concentration of HbO2 and Hb, cutaneous laser-Doppler blood flow, endtidal CO2, arterial blood pressure, and arterial oxygen saturation. Hypercapnia was induced with the use of a 5% CO2/air mixture for inhalation. To estimate the contribution of skin flow to NIRS during reactivity testing, the superficial temporal artery was compressed, and the NIRS changes in response to the fall in laser-Doppler blood flow were recorded. Finally, reproducibility of reactivity testing was assessed in 10 patients who were subjected to repeated examinations over 3 days. RESULTS Flow velocity- and HbO2-derived reactivity values were related to the severity of the stenosis (P = .0001 and P = .017, respectively). The correlation between the two reactivity modalities was significant (r = .49, P < .000001). The median estimated contribution of skin flow to NIRS changes was 15.8%. Another variable affecting HbO2 signal changes during the CO2 challenge was arterial blood pressure (P = .025). Reproducibility of HbO2 reactivity was similar to flow velocity reactivity (14.3% and 18.6% variation, respectively). CONCLUSIONS NIRS shows potential as an alternative technique for testing CO2 reactivity in patients with carotid disease provided that conditions are carefully controlled. Marked changes in arterial blood pressure may render the NIRS reactivity indices unreliable, and the contribution from extracranial tissue must be taken into account when significant.
Nicastrin Is Dispensable for γ-Secretase Protease Activity in the Presence of Specific Presenilin Mutations*S⃞

γ-Secretase is a multisubunit membrane protein complex consisting of presenilin (PS1), nicastrin (NCT), anterior pharynx-1, and presenilin enhancer 2. To analyze the activity of familial Alzheimer disease mutants and to understand the roles of the subunits, we established a yeast transcriptional activator Gal4p system with artificial γ-secretase substrates containing amyloid precursor protein or Notch fragments. The γ-secretase activities were evaluated by transcriptional activation of reporter genes upon Gal4p release from the membrane-bound substrates, i.e. growth of yeast on histidine and adenine, or β-galactosidase assay. We screened and evaluated γ-secretase mutants using this reconstitution system in yeast, which does not possess endogenous γ-secretase activity. When we introduced familial Alzheimer mutants of PS1 in this system, their activities were shown to be loss of function. Although the protease activity of wild type PS1 depends on the other three subunits introduced, we obtained 15 new PS1 mutants, which are active in the absence of NCT. They possessed a S438P mutation at the ninth transmembrane domain (TM9) together with one missense mutation distributed through transmembrane and loop regions. These mutations were not related to familial Alzheimer mutations of PS1 as identified so far. The S438P mutant was partially active but required other mutations for full activation. Results of the β-galactosidase assay suggested that they have wild type protease activities, which were further confirmed by the endoproteolysis of PS1, amyloid β peptides, and Notch intracellular domain production in mammalian cells. These results suggest that NCT is dispensable for the protease activity of γ-secretase.
Automated micro-roll-back self-recovery synthesis

The problem and efficient solution of automated synthesis of a self-recovery chip using micro-roll-back and checkpoint insertion techniques is discussed and proposed. An efficient design of micro-roll-back and checkpoint insertion can be achieved by considering them during the scheduling and allocation steps. The rollback and recovery scheme is designed to satisfy the constraints of the available number of registers and the maximum allowable recovery time. The proposed checkpointing( rollback point) algorithm will allow the system to recover from most transient faults.
On the use of stable oxygen isotope (δ18O) measurements for tracking avian movements in North America

Tracking migratory animals has benefitted using measurements of naturally occurring stable isotopes of hydrogen (δ2H) in keratinous tissues such as hair and feathers to link animal origins to continental patterns or isoscapes of δ2H in precipitation. However, for most taxa, much less information exists on the use of stable oxygen isotope ratios (δ18O) despite the fact that δ2H and δ18O are strongly linked in environmental waters through the meteoric relationship and the possibility of using both isotopes to infer greater information on origins and climatic conditions where tissues are grown. A fundamental requirement of using stable isotopes to assign individuals and populations to origins is the development of a rescaling function linking environmental food web signals to the tissue of interest and for birds, this has not been carried out. Here, we derived the relationship between H and O isotopes in known source feathers of 104 individuals representing 11 species of insectivorous passerines sampled across the strong precipitation isoscape of North America. We determined again a strong expected relationship between feather δ2H (δ2Hf) and long-term amount-weighted precipitation δ2H (δ2Hp; r2 = 0.77), but the corresponding relationship between δ18Of and δ18Op was poor (r2 = 0.32) for the same samples. This suggests that δ2H measurements are currently more useful for assignment of insectivorous songbirds to precipitation isoscapes but does not preclude other uses of the δ18Of data. Currently, mechanisms responsible for the decoupling of H and O isotopes in food webs is poorly known, and we advocate a much broader sampling of both isotopes in the same keratinous tissues across precipitation isotope gradients and across taxa to resolve this issue and to increase the power of using water isotopes to track migratory animals.
Stem Cell Microvesicles Transfer Cystinosin to Human Cystinotic Cells and Reduce Cystine Accumulation In Vitro

Cystinosis is a rare disease caused by homozygous mutations of the CTNS gene, encoding a cystine efflux channel in the lysosomal membrane. In Ctns knockout mice, the pathologic intralysosomal accumulation of cystine that drives progressive organ damage can be reversed by infusion of wildtype bone marrow-derived stem cells, but the mechanism involved is unclear since the exogeneous stem cells are rarely integrated into renal tubules. Here we show that human mesenchymal stem cells, from amniotic fluid or bone marrow, reduce pathologic cystine accumulation in co-cultured CTNS mutant fibroblasts or proximal tubular cells from cystinosis patients. This paracrine effect is associated with release into the culture medium of stem cell microvesicles (100–400 nm diameter) containing wildtype cystinosin protein and CTNS mRNA. Isolated stem cell microvesicles reduce target cell cystine accumulation in a dose-dependent, Annexin V-sensitive manner. Microvesicles from stem cells expressing CTNSRed transfer tagged CTNS protein to the lysosome/endosome compartment of cystinotic fibroblasts. Our observations suggest that exogenous stem cells may reprogram the biology of mutant tissues by direct microvesicle transfer of membrane-associated wildtype molecules.
Actuating a simple 3D passive dynamic walker

The passive dynamic walker described in this paper is a robot with a minimal number of degrees of freedom which is still capable of stable 3D dynamic walking. First, we present the reduced-order dynamic models used to tune the characteristics of the robot's passive gait. Our sagittal plane model is closely related to the compass gait model, but the steady state trajectory passively converges from a much larger range of initial conditions. We then experimentally quantify the stability of the mechanical device. Finally, we present an actuated version of the robot and some preliminary active control strategies. The control problem for the actuated version of the robot is interesting because although it is theoretically challenging (4 degrees of under-actuation), the mechanical design of the robot made it relatively easy to create controllers which allowed the robot to walk stably on flat terrain and even up a small slope.
Artificial neural networks as alternative tool for minimizing error predictions in manufacturing ultradeformable nanoliposome formulations

Abstract This work was aimed at determining the feasibility of artificial neural networks (ANN) by implementing backpropagation algorithms with default settings to generate better predictive models than multiple linear regression (MLR) analysis. The study was hypothesized on timolol-loaded liposomes. As tutorial data for ANN, causal factors were used, which were fed into the computer program. The number of training cycles has been identified in order to optimize the performance of the ANN. The optimization was performed by minimizing the error between the predicted and real response values in the training step. The results showed that training was stopped at 10 000 training cycles with 80% of the pattern values, because at this point the ANN generalizes better. Minimum validation error was achieved at 12 hidden neurons in a single layer. MLR has great prediction ability, with errors between predicted and real values lower than 1% in some of the parameters evaluated. Thus, the performance of this model was compared to that of the MLR using a factorial design. Optimal formulations were identified by minimizing the distance among measured and theoretical parameters, by estimating the prediction errors. Results indicate that the ANN shows much better predictive ability than the MLR model. These findings demonstrate the increased efficiency of the combination of ANN and design of experiments, compared to the conventional MLR modeling techniques.
Mutational activation of the K-ras oncogene and the effect of chemotherapy in advanced adenocarcinoma of the lung: a prospective study.

PURPOSE To determine whether the clinical course and the response to chemotherapy of patients with advanced adenocarcinoma of the lung depends on the presence or absence of a ras mutation in the tumor. Mutational activation of K-ras is a strong adverse prognostic factor in stage I or II lung cancer and laboratory studies have suggested that ras mutations lead to resistance against ionizing radiation and chemotherapy. PATIENTS AND METHODS Patients with advanced adenocarcinoma of the lung with measurable or assessable disease received chemotherapy with mesna, ifosfamide, carboplatin, and etoposide (MICE). Archival biopsies, fresh biopsies, or fine-needle aspirations were tested for the presence of ras gene mutations. Associations of ras mutations with clinical characteristics, response to chemotherapy, and survival were studied. RESULTS The presence or absence of ras gene mutations could be established in 69 of 83 patients (83%). A total of 261 courses of MICE were administered to 62 informative patients, 16 of whom were shown to have a K-ras mutation-positive tumor. The frequency of mutations (26%) and the type of mutations closely matched the pattern we have previously reported in operable disease. Patients with a ras mutation in their tumor were more likely to have a close relative with lung cancer, but other clinical characteristics, such as pattern of metastases, response, and survival, were similar between the ras mutation-positive and ras mutation-negative groups. CONCLUSION Patients with advanced lung adenocarcinoma who harbor a ras mutation may have major responses to chemotherapy and have similar progression-free and overall survival as patients with ras mutation-negative tumors. K-ras mutations may represent one of several ways in which early tumors are enabled to metastasize to distant sites.
The role of clinical parapapillary atrophy evaluation in the diagnosis of open angle glaucoma

Purpose: To determine if clinical evaluation of parapapillary atrophy (PPA) significantly improves the ability to distinguish open-angle glaucoma (OAG) patients from glaucoma suspects. Methods: Patients in this study were under evaluation for glaucoma and had open angles, at least one reliable 24-2 SITA-standard automatic perimetry, and digital stereophotographs of the optic disc. PPA was identified clinically as a parapapillary region of absent (βPPA) or hyper/hypopigmented (αPPA) retinal pigment epithelium. A single masked observer evaluated photos for: vertical cup-to-disc ratio (CDR), clock hours of total and βPPA, βPPA as percentage width of the optic disc, presence or absence of βPPA at each disc quadrant, and ordinal rating of total PPA. Generalized linear models were used to determine odds of an abnormal or borderline glaucoma hemifield test (GHT) as a function of PPA variables and covariates; model fit was assessed using the log-likelihood ratio test. Results: Of 410 consecutive patients, 540 eyes (of 294 patients) met inclusion criteria. Mean age was greater among patients with abnormal compared with normal GHT (P < 0.001), but sex and race/ethnicity did not differ between groups (P ≥ 0.22). Age, central corneal thickness (CCT) and CDR (P ≤ 0.006), but not intraocular pressure (IOP) (P = 0.71), were significant univariable predictors of the odds of an abnormal GHT. All PPA parameters significantly predicted GHT (P ≤ 0.03), except presence of temporal βPPA (P = 0.25). Adjustment for age, CCT, IOP, and CDR reduced the association between PPA and GHT, and model fit was not greatly improved by addition of PPA variables. Conclusions: Addition of most PPA parameters to a model already containing commonly assessed variables including age, CCT, IOP, and CDR does not significantly improve the ability to distinguish OAG patients from glaucoma suspects.
Direct evidence from intraneural recordings for increased central sympathetic outflow in patients with heart failure.

Patients with heart failure have increased vascular resistance and evidence for increased neurohumoral drive. High levels of circulating norepinephrine are found in patients with heart failure, but it is not known whether they reflect increased sympathetic neural activity or result from altered synthesis, release, or metabolism of norepinephrine. We used microneurography (peroneal nerve) to directly record sympathetic nerve activity to muscle (mSNA) and also measured plasma norepinephrine levels in patients with heart failure and in normal control subjects. Our goal was to determine whether sympathetic nerve activity is increased in patients with heart failure and whether plasma norepinephrine levels correlate with levels of mSNA in heart failure. Resting muscle sympathetic nerve activity in 16 patients with moderate to severe heart failure (54 +/- 5 bursts/min, mean +/- SE) was significantly higher (p less than .01) than the levels of activity in either nine age-matched normal control subjects (25 +/- 4 bursts/min) or 19 "young" normal control subjects (24 +/- 2 bursts/min). We found a significant correlation between plasma norepinephrine levels and mSNA (r = .73, p less than .05). Neither mSNA nor plasma norepinephrine levels correlated with total systemic vascular resistance, cardiac index, left ventricular ejection fraction, or heart rate. However, both mSNA and plasma norepinephrine levels showed significant positive correlations (p less than .05) with left ventricular filling pressures (r = .80, mSNA vs filling pressures; r = .82, norepinephrine levels vs filling pressures) and mean right atrial pressure. (ABSTRACT TRUNCATED AT 250 WORDS)
The Challenges of the 'New Economy' for Monetary Policy

The advent and spread of information and communication technologies (ICTs) increase potential output growth . It is uncertain to what extent and for how long they do so. We use the term "new economy" (NE) to describe the acceleration in potential output growth and the attendant and partly temporary slowdown in inflation. Assessing the NE is however a complicated and delicate task. The impact of the NE on the conduct of monetary policy may differ depending on the time scale. In a long-run perspective, the central bank could capitalise on the NE to set lower inflation targets. In the short to medium term, central banks should be cautious when identifying changing patterns in potential output growth, as temporary errors in appreciation may have an asymmetrical impact on economic stability: the production instability that could result from central banks mistakenly perceiving the advent of a NE would be greater than that generated by the failure to recognise a genuine rise in potential output growth.
Associations between the 2007 Medicare reimbursement reduction for bone mineral density testing and osteoporosis drug therapy patterns of female Medicare beneficiaries

Objective To examine how drug therapy patterns for osteoporosis have changed after the Medicare Physician Fee Schedule (MPFS) reimbursement reduction in 2007, in relation to follow-up bone mineral density (BMD) testing status. Methods We used a retrospective temporal shift design to examine changes in drug therapy patterns before (Phase 1: January 1, 2005–December 31, 2006) and after (Phase 2: July 1, 2007–June 30, 2009) the MPFS reimbursement reduction in 2007, Cleveland, OH, USA. Participants were osteoporotic older women in Phase 1 (n=1,340) and Phase 2 (n=1,437). The main outcomes were a) adherence, b) adjustment, c) occurrence of an extended gap, and d) restarting drug therapy after an extended gap. Follow-up BMD testing status by study phase and location were also analyzed. Results BMD testing rates at physicians’ offices decreased from 64.5% in Phase 1 to 58.4% in Phase 2 (P=0.02); however, testing rates in hospital outpatient settings increased (from 20.8% to 24.5%). There were also decreases in drug therapy adjustment from 15.9% in Phase 1 to 11.6% in Phase 2 (odds ratio [OR]: 0.73; P<0.01) and in restarting drug therapy after an extended gap (55.4% in Phase 1 and 43.6% in Phase 2; OR: 0.76; P<0.01). Conclusion There were no changes in the overall rate of follow-up BMD testing. The rates of drug adjustments and restarting drug therapy after an extended gap did decrease. These decreases were more evident when follow-up BMD testing was not performed.
Toll‐like receptor ligand links innate and adaptive immune responses by the production of heat‐shock proteins

The report shows that CpG can exert additional adjuvant effects by inducing cells that are normally inferior antigen (Ag)‐presenting cells to participate in immune induction by cross‐priming. Macrophages (Mφ) exposed to protein Ag in the presence of bioactive CpG DNA released material that induced primary CD8+ T cell responses in DC‐naïve T cell cultures. This cross‐priming event was accompanied by up‐regulation of the stress protein response as well as inflammatory cytokine expression in treated Mφ. The material released was indicated to contain inducible heat shock protein‐70 and epitope peptide, which in turn, were presented by dendritic cells (DCs) to responder T cells. Such an adjuvant effect by CpG may serve to salvage immunogenic material from otherwise inert depot cellular sites and additionally stimulate DCs to effectively cross‐prime. The cross‐priming, shown also to occur in vivo, may be particularly useful when Ag doses are low and have minimal opportunity for delivery to DCs for consequent direct priming.
Cell‐Free DNA and DNase Activity in Dogs with Immune‐Mediated Hemolytic Anemia

Background Immune‐mediated hemolytic anemia (IMHA) in dogs has a high risk of thrombosis and is associated with marked neutrophilia and necrosis. Cell death and release of neutrophil extracellular traps contribute to increased serum concentrations of cell‐free DNA, and in human autoimmune disease reduced DNase activity further increases cell‐free DNA. Free DNA in blood has prothrombotic properties and could contribute to hypercoagulability in IMHA. Hypothesis Cell‐free DNA is elevated and DNase activity reduced in dogs with IMHA compared to healthy dogs. Animals Dogs presenting to two referral hospitals with IMHA (n = 28) and healthy controls (n = 20). Methods Prospective observational study. Blood was collected and death and thrombotic events occurring in the first 14 days after hospitalization recorded. DNA was extracted from plasma with a commercial kit and quantified by PicoGreen fluorescence. DNase activity of serum was measured by radial diffusion assay. Results Cell‐free DNA was significantly higher in cases (median: 45 ng/mL, range: 10–2334 ng/mL) than controls (26 ng/mL, range 1–151 ng/mL, P = 0.0084). DNase activity was not different between cases and controls (P = 0.36). Four cases died and there were five suspected or confirmed thrombotic events. Cell‐free DNA concentration was associated with death (odds ratio for upper quartile versus lower 3 quartiles: 15; 95% confidence interval 1.62–201; P = 0.03) but not thrombosis (P = 0.57). Conclusions and Clinical Importance Cell‐free DNA is elevated in dogs with IMHA and likely reflects increased release rather than impaired degradation of DNA. Cell‐free DNA concentration is potentially associated with death and might be a prognostic indicator, but this requires confirmation in a larger population.