Miracle-dz/UniFAR-FTUs huggingface dataset:
The potential effect of excessive coffee consumption on nicotine metabolism: CYP2A6 inhibition by caffeic acid and quercetin

Over the past decade interest in the biochemical and biological properties of polyphenols has grown considerably, as epidemiological evidence for their beneficial effects on health continues to increase. Dietary polyphenol antioxidants are reported to have many ‘health promoting’ properties, including anti-inflammatory, vasoprotection, anti-cancer and anti-obesity effects. However, their absorption and metabolism are as yet not fully elucidated, particularly with regard to their interactions with other metabolized compounds, such as nicotine. Epidemiological studies have shown that coffee-drinking cigarette smokers are more likely to smoke less in comparison to non-coffee drinking cigarette smokers. Nicotine is primarily metabolized by the hepatic cytochrome P450 enzyme CYP2A6 and may be inhibited by the metal chelating properties of polyphenols via haem interactions with their hydroxyl groups. To model nicotine metabolism, bovine liver microsomes, shown to suitably represent human CYP2A6 metabolism, were isolated by calcium precipitation and differential centrifugation. Fluorometric analysis of 7-hydroxycoumarin, the CYP2A6 metabolite of coumarin and known probe for CYP2A6 activity, was used to model nicotine metabolism in vitro and to quantify the degree of CYP2A6 inhibition imposed by caffeic acid and quercetin. It was found that both caffeic acid and quercetin, major polyphenolic constituents of caffeine containing beverages, significantly inhibited CYP2A6 activity in vitro by 37.9% (P < 0.05) and 48.2% (P < 0.05), respectively. Thus, this study demonstrates the first reported biochemical evidence in support of previous epidemiological observations, where it is suggested that polyphenol interaction with CYP2A6 prolongs the pharmacological effects of nicotine by decreasing its rate of elimination.
Monolithic electronic-photonic integration in state-of-the-art CMOS processes

As silicon CMOS transistors have scaled, increasing the density and energy efficiency of computation on a single chip, the off-chip communication link to memory has emerged as the major bottleneck within modern processors. Photonic devices promise to break this bottleneck with superior bandwidth-density and energy-efficiency. Initial work by many research groups to adapt photonic device designs to a silicon-based material platform demonstrated suitable independent performance for such links. However, electronicphotonic integration attempts to date have been limited by the high cost and complexity associated with modifying CMOS platforms suitable for modern high-performance computing applications. In this work, we instead utilize existing state-of-the-art electronic CMOS processes to fabricate integrated photonics by: modifying designs to match the existing process; preparing a design-rule compliant layout within industry-standard CAD tools; and locallyremoving the handle silicon substrate in the photonic region through post-processing. This effort has resulted in the fabrication of seven test chips from two major foundries in 28, 45, 65 and 90 nm CMOS processes. Of these efforts, a single die fabricated through a widely available 45nm SOI-CMOS mask-share foundry with integrated waveguides with 3.7 dB/cm propagation loss alongside unmodified electronics with less than 5 ps inverter stage delay serves as a proof-of-concept for this approach. Demonstrated photonic devices include high-extinction carrier-injection modulators, 8-channel wavelength division multiplexing filter banks and low-efficiency silicon germanium photodetectors. Simultaneous electronicphotonic functionality is verified by recording a 600 Mb/s eye diagram from a resonant modulator driven by integrated digital circuits. Initial work towards photonic device integration within the peripheral CMOS flow of a memory process that has resulted in polysilicon waveguide propagation losses of 6.4 dB/cm will also be presented. Thesis Supervisor: Rajeev J. Ram Title: Professor of Electrical Engineering
Structural basis underlying the dual gate properties of KcsA

KcsA is a prokaryotic pH-dependent potassium (K) channel. Its activation, by a decrease in the intracellular pH, is coupled with its subsequent inactivation, but the underlying mechanisms remain elusive. Here, we have investigated the conformational changes and equilibrium of KcsA by using solution NMR spectroscopy. Controlling the temperature and pH of KcsA samples produced three distinct methyl-TROSY and NOESY spectra, corresponding to the resting, activated, and inactivated states. The pH-dependence of the signals from the extracellular side was affected by the mutation of H25 on the intracellular side, indicating the coupled conformational changes of the extracellular and intracellular gates. K+ titration and NOE experiments revealed that the inactivated state was obtained by the replacement of K+ with H2O, which may interfere with the K+-permeation. This structural basis of the activation-coupled inactivation is closely related to the C-type inactivation of other K channels.
Cooking rice in excess water reduces both arsenic and enriched vitamins in the cooked grain

Abstract This paper reports the effects of rinsing rice and cooking it in variable amounts of water on total arsenic, inorganic arsenic, iron, cadmium, manganese, folate, thiamin and niacin in the cooked grain. We prepared multiple rice varietals both rinsed and unrinsed and with varying amounts of cooking water. Rinsing rice before cooking has a minimal effect on the arsenic (As) content of the cooked grain, but washes enriched iron, folate, thiamin and niacin from polished and parboiled rice. Cooking rice in excess water efficiently reduces the amount of As in the cooked grain. Excess water cooking reduces average inorganic As by 40% from long grain polished, 60% from parboiled and 50% from brown rice. Iron, folate, niacin and thiamin are reduced by 50–70% for enriched polished and parboiled rice, but significantly less so for brown rice, which is not enriched. Graphical Abstract
The Temperature of Bupivacaine 0.5% Affects the Sensory Level of Spinal Anesthesia

Three milliliters of plain bupivacaine 0.5% was injected intrathecally in two groups of 20 patients. Group 1 received a solution that had been equilibrated to 37°C, group 2 received a solution that had been equilibrated to 4°C. Patients were kept sitting for 3 minutes after injection. All observations were observer-blind. The differences between segmental levels of sensory loss between groups 1 and 2 (T4 and T9, respectively) and of temperature loss (T3 and T8, respectively) 10 and 20 minutes after injection of bupivacaine were statistically significant. It is concluded that the time needed forthermal equilibration in the cerebrospinal fluid and hence temperature of the injected solution plays an important role in the seasory spread of plain bupivacaine 0.5%.
Standards for Local Recurrence Rates in Both Open and Laparoscopic Rectal Cancer Surgery. How do you Measure Up

Local recurrence of rectal cancer is the result either of potentially removable tumor cells left in situ or cells already disseminated to areas where surgery cannot reach them. The first scenario infers inadequate surgery, the second implies unfavorable biology. Surgeons who operate for rectal cancer must know local recurrence rates in their patients, and be able to relate them to outcomes achieved by others. We have performed this study to facilitate such a comparison. Methods: Systematic review of the literature from 1990 to 2010 was performed for publications which reported local recurrence after proctectomy for rectal cancer. Inclusion criteria were: studies of more than 80 patients and local recurrence stratified by histopathologic stage. Pooled local recurrence rates were tabulated by 5 percentile levels, stratified according to TNM stage (I,II,III) and surgical technique (total mesorectal excision or standard), as well as laparoscopic versus open. Results: Thirty-six studies comprising 16425 patients were pooled for final analysis: Mean follow-up is 40.9 months (1.3-188mths). The table shows local recurrence stratified by tumor biology (stage), operative technique (total mesorectal excision vs. standard) and operative approach (open vs. laparoscopic). The percentiles provide standards against which surgeons can compare their own outcomes Conclusion: Oncologic outcome of the treatment of rectal cancer is the result of interaction of therapeutic expertise and tumor biology. The percentile tables allow the use of local recurrence rates as an indirect parameter of surgical quality.
In-register homodimers of smooth muscle tropomyosin.

Gizzard smooth muscle tropomyosin dimer molecules were dissociated by guanidinium chloride and reassociated by dialysis against 1 M NaCl. Several properties of the protein were changed by this treatment. There was a large decrease in tropomyosin's low-salt viscosity, owing to reduced end-to-end polymerization, the helix unfolding profile changed from a one-step to a two-step process, and the ability to form intramolecular, interchain, disulfide-cross-linked homodimers increased dramatically. Thus, the native molecule, though to exist predominantly as by the beta gamma heterodimer which cannot form disulfide cross-links [Sanders, C. , Burtnick, L.D. , & Smillie, L. B. (1986) J. Biol. Chem. 261, 12774-12778], reassembles, after dissociation, to form predominantly parallel, in-register beta beta and gamma gamma homodimers able to form disulfide cross-links. This suggests that the physical properties, including the end-to-end interaction, of gizzard tropomyosin homodimers differ considerably from those of the heterodimer. This is a first step toward a molecular understanding of the end-to-end interaction of smooth muscle tropomyosin.
Phagocytosis Affects Biguanide Sensitivity of Acanthamoeba spp

ABSTRACT The incidence of Acanthamoeba keratitis, a disease associated with contact lens wear, has been in apparent decline with the advent of multipurpose contact lens solutions. The concentrations of the biguanides chlorhexidine digluconate (CHX) and particularly polyhexamethylene biguanide (PHMB) included in multipurpose solutions (MPSs) are sublethal for amoebae. We evaluated by flow cytometry the effects of these two biguanides on phagocytosis of particles and the survival of trophozoites of Acanthamoeba castellanii and A. polyphaga. Trophozoites of A. castellanii and A. polyphaga (106/ml) were exposed to solutions of 5 and 50 μg of PHMB and CHX per ml in the presence and absence of particles (i.e., heat-killed yeasts and bacteria and latex beads). In addition, trophozoites were exposed to particles treated with these concentrations of the two biguanides. In the absence of particles, trophozoites of A. polyphaga appeared to be more resistant to the biguanides than those of A. castellanii. In the presence of particles, the rates of survival of both species were decreased. In most instances, particles treated with sublethal concentrations of both biguanides that were adsorbed onto the particles reduced the incidence of phagocytosis. Particles present in MPSs in contact lens cases may be involved in the decreased incidence of Acanthamoeba keratitis.
Alterations in neurofilament protein(s) in human leprous nerves: morphology, immunohistochemistry and Western immunoblot correlative study

Using a specific antibody (SMI 31), the state of phosphorylation of high and medium molecular weight neurofilaments (NF‐H and NF‐M) was studied in 22 leprous and four nonleprous human peripheral nerves by means of immunohistochemistry, sodium dodecyl sulfate‐poly acrylamide gel electrophoresis (SDS‐PAGE) and Western immunoblot (WB). The results thus obtained were compared with morphological changes in the respective nerves studied through light and electron microscopy. Many of the leprous nerves showing minimal pathology revealed lack of or weak staining with SMI 31, denoting dephosphorylation. Remyelinated fibres stained intensely with SMI 31 antibody. The WB analysis of Triton X‐100 insoluble cytoskeletal preparation showed absence of regular SMI 31 reactive bands corresponding to 200 and 150 kDa molecular weight (NF‐H and NF‐M, respectively) in 10 nerves. Three of the 10 nerves revealed presence of NF protein bands in SDS‐PAGE but not in WB. Presence of additional protein band (following NF‐M) was seen in four nerves. Two nerves revealed NF‐H band but not NF‐M band and one nerve showed trace positivity. In the remaining five nerves presence of all the three NF bands was seen. Thus, 77.3% (17/22) of human leprous nerves studied showed abnormal phosphorylation of NF protein(s). The ultrastructural study showed abnormal compaction and arraying of NF at the periphery of the axons in the fibres with altered axon to myelin thickness ratio (atrophied fibres) as well as at the Schmidt‐Lantermann (S‐L) cleft region. Such NF changes were more pronounced in the severely atrophied axons suggesting a direct correlation. The observed well‐spaced NF in the remyelinated fibres under ultrastructural study was in keeping with both intense SMI 31 staining and presence of NF triplet bands seen in WBs in four of leprous nerves that showed a large number of regenerating fibres suggesting reversal of changes with regeneration. Findings in the present study suggest that atrophy, that is, the reduction in axonal calibre and paranodal demyelination, seen in leprous nerves may result from dephosphorylation of NF‐H and NF‐M proteins.
Zur Situation der Doktoranden in Deutschland - Ergebnisse einer bundesweiten Doktorandenbefragung

In diesem Beitrag werden zentrale Ergebnisse der bundesweiten Doktorandenbefragung der Promovierenden- und Promovierten-initiative THESIS e. V. vorgestellt. Beginnend bei den Motiven fur die Aufnahme einer Promotion, uber die Finanzierung der Promotionsphase und die Organisation der Betreuung deckt die Studie ein breites Themenspektrum der Situation von Doktoranden in Deutschland ab. Die Untersuchung kommt zu dem Ergebnis, dass es keinen einheitlichen Weg zur Promotion gibt; die Promotionsbedingungen unterscheiden sich zwischen den Fachergruppen, den Promotionsmodellen und den Geschlechtern.
Bimodal Speech Perception in Infant Hearing Aid and Cochlear Implant Users

Methods: A total of 10 infants with hearing loss, aged 4 to 24 months, were assessed at least once prior to cochlear implantation and previous to implant stimulation. The Split-Screen Preferential Looking Procedure was used to evaluate the bimodal perception skills of these infants. Results: Examples of individual bimodal perception data and preliminary group data are presented. A difference in performance across preimplant and postimplant test sessions was noted for the individuals and the group.
Phase II study of pemetrexed and carboplatin plus bevacizumab, followed by maintenance pemetrexed and bevacizumab in Japanese patients with non-squamous non-small cell lung cancer

The present study evaluated the efficacy and safety of pemetrexed, carboplatin and bevacizumab, followed by maintenance pemetrexed and bevacizumab, in chemotherapy-naïve patients with stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC). The patients were administered pemetrexed (500 mg/m2), carboplatin (area under the concentration-time curve, 6.0 mg/ml × min) and bevacizumab (15 mg/kg) intravenously every three weeks for up to six cycles. Patients who did not experience tumor progression remained on maintenance pemetrexed and bevacizumab until disease progression or unacceptable toxicity occurred. The primary endpoint was the overall response rate. Of the 26 patients enrolled between March 2010 and April 2011, three were excluded due to brain metastases, therefore the intention-to-treat (ITT) population consisted of 23 patients. The median age was 64 years (range, 40–74 years) and 15 patients were male. In total, six patients had a performance status of 0, and 20 had stage IV tumors. The response rate was 69.6% [95% confidence interval (CI), 47.1–86.8], the disease control rate was 100% and the time to response was 1.2 months (95% CI, 0.72–1.93). The median progression-free survival time was 8.6 months (95% CI, 5.9–10.9) and the median overall survival time was 18.6 months (95% CI, 12.9–24.8). There were no grade 3 or worse hemorrhagic events and the feasibility was modest. Overall, pemetrexed and carboplatin plus bevacizumab, followed by maintenance pemetrexed and bevacizumab, was effective and tolerable in the patients with non-squamous NSCLC, and the time to response was relatively short.
Understanding Oral Glucose Tolerance: Comparison of Glucose or Insulin Measurements During the Oral Glucose Tolerance Test with Specific Measurements of Insulin Resistance and Insulin Secretion

The extent to which the oral glucose tolerance test can be used to estimate insulin secretion and insulin resistance has been evaluated by comparing glucose and insulin concentrations during an oral glucose tolerance test with specific measurements of insulin secretion and insulin resistance in 85 normoglycaemic subjects and 23 subjects with impaired glucose tolerance (IGT). Insulin secretion was measured by the first phase insulin response to intravenous glucose and insulin resistance by the insulin tolerance test which measures the decline of plasma glucose after the injection of a bolus of insulin. The best measure of insulin secretion was the ratio of the 30 min increment in insulin concentration to the 30 min increment in glucose concentration following oral glucose loading. This correlated with the first phase insulin release following intravenous glucose (r=0.61, p < 0.001) but not insulin resistance (r= −0.05, p >0.05). Insulin resistance could be estimated by the fasting insulin, proinsulin, or split proinsulin concentrations. However, fasting split proinsulin appeared to discriminate best between insulin resistance (r = −0.53, p < 0.001) and insulin secretion (r = 0.07, p > 0.05). Relative insulin resistance estimated by homeostasis model assessment (HOMA) also correlated well with insulin resistance (r= −0.57, p < 0.001) but not insulin secretion (r= 0.01, p > 0.05). We conclude that the oral glucose tolerance test can be used to derive estimates of the relative roles of insulin secretion and insulin resistance in population studies of glucose tolerance.
Dialectical Behavior Therapy for the Treatment of Stalking Offenders

The need for effective mental health interventions for specific offender populations has become clear in recent decades. In particular, individuals who engage in stalking and harassment have increasingly attracted the attention of the public and mental health and criminal justice professionals, however no evidence-based treatment currently exists for this population. We adapted Dialectical Behavior Therapy (DBT) for the treatment of this offender group, in part because of the high prevalence of personality disorders. This study describes the application of a 6-month treatment program to a sample of 29 individuals, 14 of whom completed treatment. Treated offenders were significantly less likely to re-offend with another stalking offense (0 of 14) compared to treatment drop-outs (26.7%) or to published recidivism data (47%). Measures intended to help determine the nature of changes revealed increased thought suppression, but are qualified by the high degree of defensive responding. These preliminary data suggest that DBT holds promise for reducing stalking behaviors and warrants further study.
Performance analysis of variable Smart Grid traffic over ad hoc Wireless Mesh Networks

Recent advances in ad hoc Wireless Mesh Networks (WMN) has posited it as a strong candidate in Smart Grid's Neighbourhood Area Network (NAN) for Advanced Metering Infrastructure (AMI). However, its abysmal capacity and poor multi-hoping performance in harsh dynamic environment will require an improvement to its protocol stacks in order for it to effectively support the variable requirements of application traffic in Smart Grid. This paper presents a classification of Smart Grid traffics and examines the performance of HWMP (which is the default routing protocol of the IEEE 802.11s standard) with the Optimised Link State Routing (OLSR) protocol in a NAN based ad hoc WMN. Results from simulations in ns-3 show that HWMP does not outperform OLSR. This indicates that cross layer modifications can be developed in OLSR protocol to address the routing challenges in a NAN based ad hoc WMN.
Shoulder girdle rotation, forelimb movement and the influence of carapace shape on locomotion in Testudo hermanni (Testudinidae)

ABSTRACT Studies into the function of structures are crucial for making connections between morphology and behaviour of organisms, but are still rare for the terrestrial Testudinidae. We investigated the kinematics of shoulder girdle and forelimb motion in Hermann's tortoise Testudo hermanni using biplanar X-ray fluoroscopy with a twofold aim: firstly, to understand how the derived shapes of shoulder girdle and carapace together influence rotation of the girdle; and, secondly, to understand how girdle rotation affects forelimb excursion. The total degree of shoulder rotation in the horizontal plane is similar to a species with a less domed shell, but because of the long and nearly vertically oriented scapular prong, shoulder girdle rotation contributes more than 30% to the horizontal arc of the humerus and nearly 40% to the rotational component of step length. The antebrachium and manus, which act as a functional unit, contribute roughly 50% to this component of the step length because of their large excursion almost parallel to the mid-sagittal plane. This large excursion is the result of the complex interplay between humerus long-axis rotation, counter-rotation of the antebrachium, and elbow flexion and extension. A significant proportion of forelimb step length results from body translation that is due to the propulsive effect of the other limbs during their stance phases. Traits that are similar to other tortoises and terrestrial or semi-aquatic turtles are the overall slow walk because of a low stride frequency, and the lateral-sequence, diagonally coupled footfall pattern with high duty factors. Intraspecific variation of carapace shape and shoulder girdle dimensions has a corresponding effect on forelimb kinematics. Summary: X-ray fluoroscopy of shoulder girdle and forelimb movements in Testudo hermanni identifies kinematic mechanisms that enhance locomotor performance within the inherent framework of structural and physiological constraints of Testudines.
Pharmacokinetics of Saquinavir With Atazanavir or Low‐Dose Ritonavir Administered Once Daily (ASPIRE I) or Twice Daily (ASPIRE II) in Seronegative Volunteers

ASPIRE I and II were prospective, 3‐way sequential crossover studies in healthy volunteers to compare the safety and pharmacokinetics of saquinavir/ritonavir (SQV/RTV) with saquinavir/atazanavir (SQV/ATV) administered either once daily (QD, ASPIRE I) or twice daily (BID, ASPIRE II). Treatments were separated by 10 days, and pharmacokinetic analyses were performed on days 11, 32, and 53. SQV pharmacokinetics were significantly higher when dosed with RTV compared to ATV (P < .05 for all comparisons). ATV pharmacokinetics were similar within treatment arms. ATV Cmin increased approximately 60%, and Cmax decreased approximately 35% with BID dosing compared with QD dosing. Women had higher exposure for all 3 protease inhibitors (PIs) compared with men after adjusting for weight. Adverse effects were primarily gastrointestinal‐related with SQV/RTV and hyperbilirubinemia with SQV/ATV. Although SQV plasma concentrations were higher when coadministered with RTV, a combination of SQV/ATV administered BID may be a viable alternative in HIV‐infected, PI‐naive subjects intolerant to RTV.