Miracle-dz/UniFAR-FTUs huggingface dataset:
Population Pharmacokinetics and Use of Monte Carlo Simulation To Evaluate Currently Recommended Dosing Regimens of Ciprofloxacin in Adult Patients with Cystic Fibrosis

ABSTRACT Pharmacodynamic data on ciprofloxacin indicate that a target area under the concentration-time curve from 0 to 24 h (AUC0–24)/MIC ratio of ≥125 is necessary to achieve optimal bactericidal activity for the treatment of gram-negative pneumonia. The purpose of this prospective study was to (i) develop a pharmacokinetic (PK) model to be utilized for therapeutic drug monitoring (TDM) of ciprofloxacin and (ii) evaluate current ciprofloxacin dosing regimens for pneumonias in cystic fibrosis (CF) patients. Twelve adult CF patients received a single 400-mg dose of IV ciprofloxacin. Six blood samples were obtained over a 12-h interval. Serum drug concentrations were determined by high-pressure liquid chromotography and were fitted to one- and two-compartment models by using NPEM2. Ciprofloxacin MIC data for Pseudomonas aeruginosa were obtained from 1,213 CF patients enrolled in a large clinical trial. A Monte Carlo simulation was performed to estimate the fractional attainment of an AUC0–24/MIC ratio of ≥125. A two-compartment model best describes the serum drug concentration data. The mean fitted PK parameter values are volume of distribution in the central compartment, 0.29 liter/kg; volume of distribution at steady state, 1.1 liters/kg; total clearance, 0.34 liter/h/kg; distributional clearance, 0.89 liter/h/kg; half-life at α phase, 0.16 h; and half-life at β phase, 2.9 h. The overall fractional attainment of achieving an AUC0–24/MIC ratio of ≥125 against P. aeruginosa isolates with ciprofloxacin (400 mg every 12 h [q12h] and 8 qh) were 10 and 30%, respectively. A clinical breakpoint MIC of <0.5 μg/ml for susceptibility is suggested, based on an examination of the fractional attainment of the AUC0–24/MIC target at each MIC. The recommended doses of 400 mg q8h or q12h may be inadequate to treat an acute pulmonary exacerbation when given alone. The poor and variable AUC0–24/MIC ratios support the use of TDM to monitor and adjust the dosage to optimize the efficacy of ciprofloxacin therapy in these patients.
Ligand-Specific Activation of Escherichia coli Chemoreceptor Transmethylation

ABSTRACT Adaptation in the chemosensory pathways of bacteria like Escherichia coli is mediated by the enzyme-catalyzed methylation (and demethylation) of glutamate residues in the signaling domains of methyl-accepting chemotaxis proteins (MCPs). MCPs can be methylated in trans, where the methyltransferase (CheR) molecule catalyzing methyl group transfer is tethered to the C terminus of a neighboring receptor. Here, it was shown that E. coli cells exhibited adaptation to attractant stimuli mediated through either engineered or naturally occurring MCPs that were unable to tether CheR as long as another MCP capable of tethering CheR was also present, e.g., either the full-length aspartate or serine receptor (Tar or Tsr). Methylation of isolated membrane samples in which engineered tethering and substrate receptors were coexpressed demonstrated that the truncated substrate receptors (trTsr) were efficiently methylated in the presence of tethering receptors (Tar with methylation sites blocked) relative to samples in which none of the MCPs had tethering sites. The effects of ligand binding on methylation were investigated, and an increase in rate was produced only with serine (the ligand specific for the substrate receptor trTsr); no significant change in rate was produced by aspartate (the ligand specific for the tethering receptor Tar). Although the overall efficiency of methylation was lower, receptor-specific effects were also observed in trTar- and trTsr-containing samples, where neither Tar nor Tsr possessed the CheR binding site at the C terminus. Altogether, the results are consistent with a ligand-induced conformational change that is limited to the methylated receptor dimer and does not spread to adjacent receptor dimers.
Relationship Between Respiratory Dynamics and Body Mass Index in Patients Undergoing General Anesthesia with Laryngeal Mask Airway (LMA) and Comparison Between Lithotomy and Supine Positions

Background This study aimed to compare respiratory dynamics in patients undergoing general anesthesia with a laryngeal mask airway (LMA) in lithotomy and supine positions and to validate the impact of operational position on effectiveness of LMA ventilation. Material/Methods A total of 90 patients (age range, 18–65 years) who underwent general anesthesia were selected and divided into supine position (SP group) and lithotomy position groups (LP group). Vital signs and respiratory dynamic parameters of the 2 groups were measured at different time points and after implantation of an LMA. The arterial blood gas was monitored at 15 min after induction. The intraoperative changes of hemodynamic indexes and postoperative adverse reactions of LMA were recorded. The possible correlation between body mass index (BMI) and respiratory dynamic indexes was analyzed. Results With prolonged duration of the operation, the inspiratory plateau pressure (Pplat), inspiratory resistance (RI), and work of breathing (WOB) gradually increased, while chest-lung compliance (Compl) and partial pressure of carbon dioxide in end-expiratory gas (PetCO2) gradually decreased (all P value <0.05). The mean airway pressure (Pmean), Pplat, and expiratory resistance (Re) in the LP group were significantly higher than in the SP group (P<0.05), while the peak inspiratory flow (FImax), peak expiratory flow (FEmax), WOB, and Compl in the LP group were significantly lower than in the SP group (P<0.05). BMI was positively correlated with peak airway pressure (PIP/Ppeak), Pplat, and airway resistance (Raw) and was negatively correlated with Compl; the differences among patients in lithotomy position were more remarkable (P<0.05). Conclusions The inspiratory plateau pressure and airway resistance increased with prolonged duration of the operation, accompanied by decreased chest-lung compliance. Peak airway pressure and airway resistance were positively correlated with BMI, and chest-lung compliance was negatively correlated with BMI. Changes among patients in lithotomy position were more remarkable than those in supine position.
Performance analysis of OSTBC over generalized Gaussian MIMO channels

Based on the theory of optimum diversity combining, this paper presents original results for the error rate calculations for the Orthogonal Space-Time Block Codes (OSTBC) in generalized Gaussian MIMO channels. A simple bound for the symbol rate performance is derived, allowing to track contribution of channel parameters to the performance. Channel hardening is then investigated from the probability of error point of view. Results of the application of different signal constellation's choice are shown from the prospective of the trade- off between the error performance and spectral efficiency.
ARE GREEN POLITICAL PARTIES MORE POST-MATERIALIST THAN OTHER PARTIES?

ABSTRACT Among other social and political changes, post-materialist theory anticipated the need to strengthen democracy in political institutions in post-industrial societies. This change in political values would mean that in addition to growth in post-materialist values, parties would be pushed to take an alternative view of politics that would entail greater assimilation of democratic procedures. This paper partially and empirically tests the validity of this explanation in four European party systems. The Greens are the focus, since they are considered the parties that best fit the post-materialist profile. In particular, the paper aims to ascertain whether the Greens display a significantly better positioning in respect to support for democracy and the congruence of their voters than other parties, as theory leads us to believe. The explanation of higher levels of party congruence is also expected to be related to post-materialist party features. The findings of this research did not show enough evidence to validate our theoretical expectations.
Variation Tolerant Differential 8T SRAM Cell for Ultralow Power Applications

Low power and noise tolerant static random access memory (SRAM) cells are in high demand today. This paper presents a stable differential SRAM cell that consumes low power. The proposed cell has similar structure to conventional 6T SRAM cell with the addition of two buffer transistors, one tail transistor and one complementary word line. Due to stacking effect, the proposed cell achieves lower power dissipation. In this paper, impact of process parameters variations on various design metrics of the proposed cell are presented and compared with conventional differential 6T (D6T), transmission gate-based 8T (TG8T), and single ended 8T (SE8T) SRAM cells. Impact of process variation, like threshold voltage and length, on different design metrics of an SRAM cell like, read static noise margin (RSNM), read access time (TRA), and write access time (TWA) are also presented. The proposed cell achieves 1.12×/1.43×/5.62× improvement in TRA compared to TG8T/D6T/SE8T at a penalty of 1.1×/4.88× in TWA compared to D6T/TG8T and 1.19×/1.18× in read/write power consumption compared to D6T. An improvement of 1.12×/2.15× in RSNM is observed compared to D6T/TG8T. The proposed cell consumes 5.38× less power during hold mode and also shows 2.33x narrower spread in hold power @ VDD = 0.4 V compared to D6T SRAM cell.
A self‐directed home yoga programme for women with breast cancer during chemotherapy: A feasibility study

Recent studies suggest yoga as a promising approach for improving the cognitive function of cancer survivors. We studied whether a self‐directed home yoga programme was feasible for patients with breast cancer who were undergoing chemotherapy. Participants' preferences for the type of yoga course and the clinical effects of the programme were also assessed. In this study, 18 women (mean age, 43.9 years) were enrolled (44.7% recruitment rate). Of the participants, 63.6% had stage II cancer and 71.4% received adjuvant chemotherapy. Favourable retention (86%), adherence (94.4%) and acceptability (96.5%) rates were determined. Most (94.4%) of the women practiced the home programme more than twice a week on average. The participants preferred to gradually increase the intensity of the exercises. We only observed improvements in the cognitive aspects of fatigue. No serious adverse events were encountered during the programme. This self‐directed home yoga programme was safe and feasible for patients with breast cancer undergoing chemotherapy.
Temporal Metabolic Profiling of Plasma During Endotoxemia in Humans

ABSTRACT Endotoxemia induced by the administration of low-dose lipopolysaccharide (LPS) to healthy human volunteers is a well-established experimental protocol and has served as a reproducible platform for investigating the responses to systemic inflammation. Because metabolic composition of a tissue or body fluid is uniquely altered by stimuli and provides information about the dominant regulatory mechanisms at various cellular processes, understanding the global metabolic response to systemic inflammation constitutes a major part in this investigation complementing the studies undertaken so far in both clinical and systems biology fields. This article communicates the first proof-of-principle metabonomic analysis, which comprised global biochemical profiles in human plasma samples from healthy subjects given intravenous endotoxin at 2 ng/kg. Concentrations of a total of 366 plasma biochemicals were determined in archived blood samples collected from 15 endotoxin-treated subjects at five time points within 24 h after treatment and compared with control samples collected from four saline-treated subjects. Principal component analysis within this data set determined the sixth hour as a critical time point separating development and recovery phases of the LPS-induced metabolic changes. Consensus clustering of the differential metabolites identified two distinct subsets of metabolites that displayed common coherent profiles with opposing directionality. The first group of metabolites, which were mostly associated with pathways related to lipid metabolism, was upregulated within the first 6 h and downregulated by the 24th hour following LPS administration. The second group of metabolites, in contrast, was first downregulated until the sixth hour, then upregulated. Metabolites in this group were predominantly amino acids or their derivatives. In summary, nontargeted biochemical profiling and unsupervised multivariate analyses highlighted the prominent roles of lipid and protein metabolism in regulating the response to systemic inflammation while also revealing their dynamics in opposite directions.
Formative Geographies of Belonging in White Australia: Constructing the National Self and Other in Parliamentary Debate, 1901

The relationship between nationally unified calls for immigration restriction in the White Australia period and the emergence of an imagined national identity has been the focus of much valuable historical research. Through the method of content analysis, a geographical lens was used to re-examine the Commonwealth Parliamentary debates regarding the development of the Immigration Restriction Act 1901 and to provide empirical support to the existing scholarship. The content analysis provided statistical evidence for the ways in which immigration restriction in this specific historical context was legitimised and rationalised by social constructions that reproduced racisms. Constructions of the Self and the Other were fundamental in defining exclusion and inclusion during the White Australia era. The national Self was complexly defined by overlapping constructions of the Self as Australian, British (racially and culturally) and White. This is indicative of the tensions and negotiations between national interests and cultural, historical and ‘racial’ ties to Britain at the time. Additionally, content analysis provided nuanced insight into the ways in which the designation of inherent (and diametrically opposing) racial attributes to the White Self and non-White Other justified the ways in which ‘they’ were different from ‘us’. In this way the Other was characterised as an intrinsic threat to the development of the nation and the wellbeing of its peoples. ‘We’, on the other hand, were integral to the development of White Australia.
Association of STAT4 with Rheumatoid Arthritis in the Korean Population

A recent study in the North American White population has documented the association of a common STAT4 haplotype (tagged by rs7574865) with risk for rheumatoid arthritis (RA) and systemic lupus erythematosus. To replicate this finding in the Korean population, we performed a case-control association study. We genotyped 67 single nucleotide polymorphisms (SNPs) within the STAT1 and STAT4 regions in 1123 Korean patients with RA and 1008 ethnicity-matched controls. The most significant four risk SNPs (rs11889341, rs7574865, rs8179673, and rs10181656 located within the third intron of STAT4) among 67 SNPs are identical with those in the North American study. All four SNPs have modest risk for RA susceptibility (odds ratio 1.21–1.27). A common haplotype defined by these markers (TTCG) carries significant risk for RA in Koreans [34 percent versus 28 percent, P = 0.0027, OR (95 percent CI) = 1.33 (1.10–1.60)]. By logistic regression analysis, this haplotype is an independent risk factor in addition to the classical shared epitope alleles at the HLA-DRB1 locus. There were no significant associations with age of disease onset, radiographic progression, or serologic status using either allelic or haplotypic analysis. Unlike several other risk genes for RA such as PTPN22, PADI4, and FCRL3, a haplotype of the STAT4 gene shows consistent association with RA susceptibility across Whites and Asians, suggesting that this risk haplotype predates the divergence of the major racial groups.
Modeling effects of intrinsic and extrinsic rewards on the competition between striatal learning systems

A common assumption in psychology, economics, and other fields holds that higher performance will result if extrinsic rewards (such as money) are offered as an incentive. While this principle seems to work well for tasks that require the execution of the same sequence of steps over and over, with little uncertainty about the process, in other cases, especially where creative problem solving is required due to the difficulty in finding the optimal sequence of actions, external rewards can actually be detrimental to task performance. Furthermore, they have the potential to undermine intrinsic motivation to do an otherwise interesting activity. In this work, we extend a computational model of the dorsomedial and dorsolateral striatal reinforcement learning systems to account for the effects of extrinsic and intrinsic rewards. The model assumes that the brain employs both a goal-directed and a habitual learning system, and competition between both is based on the trade-off between the cost of the reasoning process and value of information. The goal-directed system elicits internal rewards when its models of the environment improve, while the habitual system, being model-free, does not. Our results account for the phenomena that initial extrinsic reward leads to reduced activity after extinction compared to the case without any initial extrinsic rewards, and that performance in complex task settings drops when higher external rewards are promised. We also test the hypothesis that external rewards bias the competition in favor of the computationally efficient, but cruder and less flexible habitual system, which can negatively influence intrinsic motivation and task performance in the class of tasks we consider.
Intermittent compressive force induces human mandibular‐derived osteoblast differentiation via WNT/β‐catenin signaling

Mechanical force induces an efflux of ATP that regulates osteoblast differentiation. However, the effect of mechanical force‐induced ATP efflux on WNT/β‐catenin signaling remains unclarified. The aim of this study was to investigate the effect of intermittent compressive force (ICF) and ICF‐induced extracellular ATP on osteoblast differentiation via WNT/β‐catenin signaling in human mandibular‐derived osteoblast precursors (hMOBPs). The hMOBPs were subjected to ICF (1.5 g/cm2, 0.3 Hz) for 20 h. To investigate the role of ATP, Apyrase (0.5 units/mL), an enzyme that hydrolyzes ATP, was added 30 min before ICF was applied. The extracellular ATP levels were measured immediately after ICF was removed. The mRNA expression of osteogenic related genes, including WNT was evaluated via quantitative real time polymerase chain reaction. In vitro mineralization was determined by Alizarin Red S staining. The localization of β‐catenin was detected using immunofluorescence staining and lentiviral‐TOP‐dGFP reporter assay. The results demonstrated that ICF increased ATP efflux and in vitro mineralization by hMOBPs. In addition, OSX, ALP, and WNT3A mRNA expression and β‐catenin nuclear translocation increased when ICF was applied. The upregulation of these genes was reduced by Apyrase, suggesting the role of ICF‐induced ATP on osteoblast differentiation. Notably, ICF altered the mRNA expression of purinergic 2X receptors (P2XRs). A P2X1R antagonist (NF449) downregulated ICF‐induced WNT3A, OSX, and ALP mRNA expression. Moreover, when 25 μM α, β‐meATP, a P2X1R agonist, was added, WNT3A, and OSX expression increased. In conclusion, our results demonstrate that ICF‐induced ATP enhanced hMOBP differentiation. This enhancement was associated with WNT/β‐catenin signaling and P2X1R activation.
Reduction of hysteresis for carbon nanotube mobility measurements using pulsed characterization

We describe a pulsed measurement technique for suppressing hysteresis for carbon nanotube (CNT) device measurements in air, vacuum, and over a wide temperature range (80–453 K). Varying the gate pulse width and duty cycle probes the relaxation times associated with charge trapping near the CNT, found to be up to the 0.1–10 s range. Longer off times between voltage pulses enable consistent, hysteresis-free measurements of CNT mobility. A tunneling front model for charge trapping and relaxation is also described, suggesting trap depths up to 4–8 nm for CNTs on SiO2. Pulsed measurements will also be applicable for other nanoscale devices such as graphene, nanowires, or molecular electronics, and could enable probing trap relaxation times in a variety of material system interfaces.
Investigating the relationships among breathing, attachment, and emotion-regulation

The escalating prevalence of psychological distress among young adults is a systemic issue with a generational impact as evidenced by patterns of insecure attachment, maladaptive self-regulation, and, accordingly, mental health problems (Stallard, Norman, Huline-Dickens, Salter, & Cribb, 2004). There is a call for holistic approaches to prevention, assessment, and treatment that reduce the occurrence and impact of mental health problems among adults and their families (WHO, 2004). As such, researchers have identified a need to investigate the psychobiology of attachment (Diamond & Hicks, 2004), including emotional and physiological processes involved in self-regulation. Breathing is a physiological process that is critical to both physiological (Courtney, Cohen, & van Dixhoorn, 2011a) and emotional regulation (Koole, 2009). Exploration of the psychobiology of attachment could inform the advancement of holistic strategies in mental health (Diamond & Fagundes, 2010) and breathing appears to be a logical construct for examination in this context. An exploratory cross-sectional correlational study was used to examine the relationships among the variables of adult romantic attachment, emotion-regulation difficulty, and symptoms of dysfunctional breathing in a sample of 203 young adults. Results of Pearson correlations indicated that there were statistically significant bivariate positive relationships among attachment anxiety, attachment avoidance, difficulty regulating emotion, symptoms of hyperventilation, and symptoms of dysfunctional breathing. Three one-way ANOVA's indicated that there were significant differences in scores of attachment anxiety, attachment avoidance, and difficulty in emotion regulation among individuals who reported symptoms of hyperventilation who indicated either normal, mild, or clinically significant symptoms. The results of two multiple regression analyses indicated that a significant portion of the variance in both attachment avoidance and attachment anxiety was accounted for by symptoms of hyperventilation. Another multiple regression indicated that attachment dimensions, dysfunctional breathing, and hyperventilation accounted for 45% of the variance in emotion regulation difficulty. A hierarchical multiple regression indicated that the relationship between dysfunctional breathing, hyperventilation, and difficulty regulating emotion was not moderated by attachment insecurity. Though causal conclusions cannot be drawn, these results indicate preliminary support that addressing issues of dysfunctional breathing could complement mental health approaches aimed at promoting secure attachment and adaptive self-regulation.