Distribution-Based Cluster Structure Selection.
The objective of cluster structure ensemble is to find a unified cluster structure from multiple cluster structures obtained from different datasets. Unfortunately, not all the cluster structures contribute to the unified cluster structure. This paper investigates the problem of how to select the suitable cluster structures in the ensemble which will be summarized to a more representative cluster structure. Specifically, the cluster structure is first represented by a mixture of Gaussian distributions, the parameters of which are estimated using the expectation-maximization algorithm. Then, several distribution-based distance functions are designed to evaluate the similarity between two cluster structures. Based on the similarity comparison results, we propose a new approach, which is referred to as the distribution-based cluster structure ensemble (DCSE) framework, to find the most representative unified cluster structure. We then design a new technique, the distribution-based cluster structure selection strategy (DCSSS), to select a subset of cluster structures. Finally, we propose using a distribution-based normalized hypergraph cut algorithm to generate the final result. In our experiments, a nonparametric test is adopted to evaluate the difference between DCSE and its competitors. We adopt 20 real-world datasets obtained from the University of California, Irvine and knowledge extraction based on evolutionary learning repositories, and a number of cancer gene expression profiles to evaluate the performance of the proposed methods. The experimental results show that: 1) DCSE works well on the real-world datasets and 2) DCSE based on DCSSS can further improve the performance of the algorithm.


Accurate prediction of nonadiabatic transitions through avoided crossings.
In the case of one nuclear degree of freedom, we derive an explicit formula for the nuclear wave function transmitted through an avoided crossing, and show that it agrees to high accuracy with precise numerical calculations.


A simple, effective and well-tolerated treatment regime for West syndrome.
The authors systematically treated 94 patients with West syndrome using the same protocol of sodium valproate and steroids, starting with hydrocortisone (HC) orally for two weeks. If seizures stopped, HC was withdrawn; if they persisted, tetracosactrin (TA; synthetic ACTH) was administered for another two weeks then HC was slowly withdrawn. 90 per cent of the symptomatic cases were controlled by HC, the remainder by TA. 65 per cent of symptomatic cases were controlled by HC; this rose to 78 per cent if patients treated by HC then TA were included. At 31 months follow-up, the percentage of favourable results was 72 per cent for cryptogenic and 60 per cent for symptomatic cases. For the latter, best results were obtained in patients with periventricular leukomalacia, postnatal distress and porencephaly. Patients suffering from sequelae of full-term distress or encephalopathy of unknown aetiology were the most resistant.


Efficacy and Safety of Uninterrupted Low-Intensity Warfarin for Radiofrequency Catheter Ablation of Atrial Fibrillation in the Elderly.
No previous studies exist investigating the optimal intensity of uninterrupted anticoagulation with warfarin during radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) in the elderly. Evaluate the efficacy and safety of continuous low-intensity warfarin therapy throughout the periprocedural period of RFCA for AF in the elderly. This is a prospective randomized study. We enrolled AF patients (age ≥ 70 years) who underwent first-time RFCA for AF. Enrolled patients were randomized to group A and group B. The international normalized ratios before ablation were maintained at 1.5 to 2.0 and 2.0 to 2.5 in group A and B, respectively. Primary end points were periprocedural thromboembolic complications and major bleeding. Secondary end points included periprocedural asymptomatic cerebral emboli (ACE) and minor bleeding. A total of 101 patients were enrolled in our study (group A: 52; group B: 49). Baseline characteristics were well balanced between the 2 groups. Only 1 patient suffered from stroke in group B. No major bleeding events occurred in either group. The incidence of new ACE lesions was comparable between the 2 groups (11.5% vs 8.2%, P = 0.82). Minor bleeding occurred in 1 of 52 (1.9%) patients in group A and in 5 of 49 (10.2%) patients in group B ( P = 0.10). Uninterrupted low-intensity warfarin for RFCA of AF might be as effective as standard-intensity warfarin in preventing periprocedural thromboembolic complications and might be associated with fewer bleeding events in the elderly.


Cell-based systems to assess nuclear receptor activation and their use in drug development.
The evolution of scientific information relating to the regulation of xenobiotic disposition has extended to the discovery of an intricate group of receptor systems now recognized as master regulators. These ligand-activated transcription factors are commonly designated as "nuclear receptors", and include CAR (NR1I3), PXR (NR1I2), PPAR (NR1C1, NR1C2, and NR1C3) and AhR (HLHE76). As regulators of gene expression, activation of these receptors can elicit a plethora of drug-drug interactions. The aforementioned nuclear receptors bind a wide range of structurally-unrelated ligands, such as steroid hormones, bile acids, and small drug-type molecules. A pivotal nuclear receptor with regards to regulation of drug-drug interactions is the pregnane X receptor (PXR). Gene expression profiling has demonstrated that PXR regulates over 60 human genes that are involved not only in physiological functions but also in the metabolism of xenobiotics. Moreover, chemical library screening suggests that about 10% of the compounds comprising the U. S. Food and Drug Administration 1 and 2, Sigma-Aldrich LOPAC collection, Biomol, and Tocris/TimTec bioactive collection libraries exhibit some form of PXR binding. For these reasons, efficient, rapid and economical systems have been developed to identify nuclear receptor ligands. Cell-based assays encompassing transiently and stably-transfected cells and mammalian two-hybrid systems are currently being employed by the pharmaceutical industry to screen compounds for binding to and/or activation of nuclear receptors. Overall, these systems have the ability to predict in vivo responses to receptor activation that culminate in drug-drug interactions and adverse drug effects.


Mothers' reflections on raising a child with a craniofacial anomaly.
To conduct a qualitative evaluation of parenting among families with school-aged and young adolescent children with craniofacial anomalies (CFAs). Interview responses were obtained from nine mothers of children ages 9 to 14 years old with CFAs. Mothers were asked to describe their perceptions of their children, their children's special needs because of CFAs, and their parenting strategies. Narratives were coded into categories, including maternal concerns and worries, children's strengths, proactive maternal behaviors, and role of CFAs in the families' lives. Mothers' responses indicated concern and protectiveness because of the challenges of having a CFA, as well as parenting strategies intended to promote autonomy and positive social and emotional adjustment.


Laparoscopic vs open resection for patients with rectal cancer: comparison of perioperative outcomes and long-term survival.
The aim of the study is to assess the safety and oncologic feasibility of laparoscopic-assisted resection for rectal cancer vs open rectal resection as a phase II pilot study for a planned randomized control trial. A case-matched controlled prospective analysis of 54 patients who underwent laparoscopic-assisted resection for stage I to III (no T4) rectal cancer within 12 cm of the anal verge from 2002 to 2005 was performed. Patients were matched with contemporary patients who underwent open rectal cancer surgery (n = 108) in a 1 to 2 fashion. The perioperative clinical outcomes, postoperative pathology, and oncologic outcomes were compared between the groups. The demographic data did not differ significantly between the groups. The laparoscopic group manifested early return of bowel function (P = .003). The complication rate was 22.2% in the laparoscopic group and 32.4% in the open group (P = .178). Local recurrence was similar (2.0% laparoscopic, 4.2% open, P = .417). The 5-year overall and disease-free survival rate also were similar (overall survival, 90.8% laparoscopic, 88.5% open, P = .261; disease-free survival, 80.8% laparoscopic, 75.8% open. P = .390). The laparoscopic-assisted resection for rectal cancer was acceptable in terms of oncologic outcomes and perioperative clinical outcomes. The present data are the basis for a large-scale randomized trial for comparison of laparoscopic and open rectal cancer surgeries (American College of Surgeons Oncology Group Z6051).


Investigation of adsorption characteristics of four toxic gases (nitric oxide, nitrogen dioxide, sulfur dioxide, and hydrogen chloride) on the inner surface of nickel-coated manganese steel cylinders and aluminum cylinders.
To develop standard toxic gas mixtures, it is essential to identify adsorption characteristics of each toxic gas on the inner surface of a gas cylinder. Thus, this study quantified adsorbed amounts of the four toxic gases (nitric oxide [NO], nitrogen dioxide [NO2], sulfur dioxide [SO2], and hydrogen chloride [HCl]) on the inner surface of aluminum cylinders and nickel-coated manganese steel cylinders. After eluting adsorbed gases on the inside of cylinders with ultrapure water, a quantitative analysis was performed on an ion chromatograph. To evaluate the reaction characteristics of the toxic gases with cylinder materials, quantitative analyses of nickel (Ni), iron (Fe), and aluminum (Al) were also performed by inductively coupled plasma optical emission spectrometry (ICP-OES). It was found that the amounts of NO, NO2, and SO2 adsorbed on the inner surface of aluminum cylinders were less than 1.0% at the level of 100 μmol/mol mixing ratio, whereas the signal for most heavy metal elements were below their respective detection limits. This study found that the amounts of HCl adsorbed on the inner surface of nickel-coated manganese steel cylinders were less than 5% at the level of 100 μmol/mol mixing ratio, whereas Ni (86 μmol) and Fe (28 μmol) were detected in the same cylinders. It was revealed that the adsorption mainly took place via the reaction of HCl with inner surface material of nickel-coated manganese steel cylinders. On the other hand, in the case of aluminum cylinders, the amounts of the adsorption were determined to be less than 1% at the level of HCl 100 μmol/mol mixing ratio, whereas most of Ni, Fe, and Al were detected at levels similar to their limits of detection. As a result, this study found that aluminum cylinders are more suitable for preparing HCl gas mixtures than nickel-coated manganese steel cylinders. Implications: To develop a standard toxic gas mixture, it is essential to understand the adsorption characteristics of each toxic gas inside a gas cylinder. It was found that the amounts of NO, NO2, and SO2 adsorbed inside aluminum cylinders were less than 1.0% at the level of 100 μmol/mol mixing ratio. The amounts of HCl adsorbed inside nickel-coated manganese steel cylinders were less than 5% at the level of 100 μmol/mol mixing ratio, whereas those inside aluminum cylinders were less than 1%, indicating that aluminum cylinders are more suitable for preparing HCl gas mixtures.


Endoscopic treatment of early gastric cancer: polypectomy and laser treatment.
With the tremendous development of gastroenterological endoscopy, it has become possible to treat some types of early gastric cancer by endoscopy. There are two principal methods for this purpose, endoscopic polypectomy using a high frequency electric current and laser endoscopy. We developed the technic and instruments of endoscopic polypectomy, in 1972. Since then, we have experienced 358 cases of gastric polypoid lesions treated by endoscopic polypectomy. Nineteen patients with the elevated type of early gastric cancer were treated by endoscopic polypectomy. Seven patients were operated on after polypectomy and 12 were followed without surgery. Out of the 12 patients, nine are alive after more than five years. On the other hand, we started research to apply lasers for treating early gastric cancer in 1978. Since then, 18 patients have been treated by laser endoscopy, with Nd-YAG laser, argon dye laser or a combination of both lasers. We have established criteria for these treatments for early gastric cancer.


Investigation of doxorubicin tissue toxicity: does amifostine provide chemoprotection? An experimental study.
This experimental animal study of 12-weeks' duration, involving Wistar rats, tested the possible chemoprotection of Doxorubicin (adriamycin), cardiomyopathy and other toxicities by Amifostine. One hundred and five animals were divided into 3 groups: Groups A, B and C, which had Doxorubicin, simultaneous Doxorubicin and Amifostine treatment and normal saline for control, respectively. Treatment was administered once weekly for 12 consecutive weeks. The doses of each drug were appropriately calculated on the basis of other experiments in the literature and given in analogous dosage to human kilograms of body weight. Euthanasias and autopsies of six animals at a time from each animal group were performed on weeks 3, 6, 8, 10 and 12. The blood, heart, lung, liver, aorta, thymus, spleen, kidneys, adrenals, testis and ovaries and muscle and lipoid tissue were examined macroscopically and microscopically. Biochemical liver and kidney examinations, full blood count and serum lipids were examined before and during the weeks of treatment and autopsies. Increased cholesterol and triglycerides from the 6th week towards the end of the experiment and a gradual increase in cardiomyopathy were found, particularly in Group A. The findings were similar in Group B, except for the timing (the increase of serum lipids and the serious cardiac lesions were delayed by two weeks). No abnormalities were detected in the controls, Group C. In conclusion, Amifostine does not seem to be cardioprotective when administered with Doxorubicin, since it only delays the onset of cardiac lesions. In in vitro testing, Amifostine was found to be a scavenger of the oxygen-free radicals which are produced by Doxorubicin.


Flexoelectric Polarization in a Nematic Liquid Crystal Enhanced by Dopants with Different Molecular Shape Polarities.
Flexoelectricity may have an important impact on the switching properties of nematic and cholesteric liquid crystals due to the linear coupling between the flexoelectric polarization of the liquid crystal and the applied electric field. This coupling is the origin of the extraordinary electro-optic effect in cholesterics aligned in the uniform lying helix texture, resulting in fast switching and field control of both rise and fall times. Therefore, the flexoelectric properties of the liquid crystals have become an important issue when designing and synthesizing liquid crystal materials and/or preparing their mixtures with appropriate flexoelectric compounds (dopants). Here, we report on the flexoelectric polarization of a highly polar nematic liquid crystal host enhanced by doping it with two newly synthesized dopants SK 1-6 and SK 1-8, possessing a hockey stick molecular shape, and comparing their doping effect with the one of the dimeric dopants CB7CB possessing a symmetric bend molecular shape. All dopants were dissolved in small concentration (5 wt %) in the nematic host so that the linear approximation of the dependence of the difference between splay e s and bend e b flexoelectric constants, that is, (e s - e b), on the concentration of the dopant in the host material can be applied. In this way, (e s - e b) was estimated for the hockey stick dopants SK 1-6 and SK 1-8 to be 0.182 and 0.204 nC/m, respectively. The obtained flexoelectric polarization of these dopants is among the highest reported in the literature so far.


Analysis of the factors that stabilize a designed two-stranded antiparallel beta-sheet.
Autonomously folding beta-hairpins (two-strand antiparallel beta-sheets) have become increasingly valuable tools for probing the forces that control peptide and protein conformational preferences. We examine the effects of variations in sequence and solvent on the stability of a previously designed 12-residue peptide (1). This peptide adopts a beta-hairpin conformation containing a two-residue loop (D-Pro-Gly) and a four-residue interstrand sidechain cluster that is observed in the natural protein GB1. We show that the conformational propensity of the loop segment plays an important role in beta-hairpin stability by comparing 1 with (D)P--> N mutant 2. In addition, we show that the sidechain cluster contributes both to conformational stability and to folding cooperativity by comparing 1 with mutant 3, in which two of the four cluster residues have been changed to serine. Thermodynamic analysis suggests that the high loop-forming propensity of the (D)PG segment decreases the entropic cost of beta-hairpin formation relative to the more flexible NG segment, but that the conformational rigidity of (D)PG may prevent optimal contacts between the sidechains of the GB1-derived cluster. The enthalpic favorability of folding in these designed beta-hairpins suggests that they are excellent scaffolds for studying the fundamental mechanisms by which amino acid sidechains interact with one another in folded proteins.


Phase separation micromolding: a new generic approach for microstructuring various materials.
Phase separation micromolding (PSmicroM) is a versatile microfabrication technique that can be used to structure a very broad range of polymers, including block copolymers and biodegradable and conductive polymers without the need for clean-room facilities. By incorporating a subsequent process step, carbon, ceramic, and metallic microstructures can also be fabricated from a polymeric or hybrid precursor. The replication process is straightforward and cost-effective. It relies on phase separation of a polymer solution while in contact with a structured mold. Intrinsic shrinkage during the phase separation facilitates the release of the replica from the mold, which increases the reliability of the process even at small feature sizes, thin polymer films, or high aspect ratios. Under suitable circumstances perforation of the polymer film can be obtained, resulting in completely open "through" microstructures. Furthermore, porosity can be introduced in a microstructure, which may result in unknown functionalities.


Development of codominant simple sequence repeat, single nucleotide polymorphism and sequence characterized amplified region markers for the pea root rot pathogen, Aphanomyces euteiches.
Three kinds of genetic markers including simple sequence repeats (SSRs), single nucleotide polymorphisms (SNPs) and sequence characterized amplified regions (SCARs) were developed from Aphanomyces euteiches. Of 69 loci tested, seven SSR, two SNP and two SCAR markers were codominantly polymorphic. These codominant markers and dominant markers described herein will facilitate population genetic and evolutionary studies of this important plant pathogen.


Exposure to perflubron is associated with decreased Syk phosphorylation in human neutrophils.
Liquid ventilation with perflubron is associated with reduced neutrophil recruitment into the lung during acute injury. Perflubron also reduces chemotactic responses, the respiratory burst, and cytokine production in neutrophils and in alveolar macrophages in vitro. In the current studies, the effect of perflubron on neutrophil chemotaxis to formyl-Met-Leu-Phe (fMLP) and phagocytosis of opsonized sheep erythrocytes (EA) correlated with decreased phosphorylation of Syk, an important intracellular second messenger in pathways regulating neutrophil functional responses. Brief (5 min) exposure of neutrophils to perflubron resulted in a dose-dependent reduction in chemotaxis to fMLP and reduced phagocytosis of EA but no apparent morphological changes as seen by electron microscopy. Concurrently, there was a reduction in both total cytosolic tyrosine phosphorylation and Syk phosphorylation. Binding studies indicated that this effect was neither a result of impaired ligand-receptor affinity nor a change in the number of fMLP receptors available on the neutrophil surface. These results suggest that perflubron nonspecifically affects cellular activation as measured by tyrosine phosphorylation perhaps by interfering with transmembrane signal transduction.


Human alveolar epithelial cells induce nitric oxide synthase-2 expression in alveolar macrophages.
It was hypothesized that cell-to-cell interaction between human alveolar macrophages (AM) and alveolar epithelium, might be an important factor leading to nitric oxide synthase-2 (NOS2) messenger ribonucleic acid (mRNA) and protein expression by constituent cells of the alveolar wall and/or AM. NOS2 mRNA and the protein expression patterns of human AM and alveolar epithelial cells type II (AEC-II) isolated from normal parts of lung resections of patients with pulmonary malignancies were determined. In addition, NOS2 mRNA expression in human AM co-cultured with autologous AEC-II in the presence of pro-inflammatory cytokines interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma or lipopolysaccharide (LPS) was investigated. The effect of human surfactant protein-A (SP-A) on IFN-gamma-mediated NOS2 mRNA expression in human AM was also studied. Neither NOS2 mRNA nor protein could be detected in freshly isolated, unstimulated or cytokine-stimulated AEC-II. In contrast, freshly isolated AM from bronchoalveolar lavage or lung tissue samples expressed immunoreactivity for NOS2 protein, but no NOS2 mRNA could be detected by reverse transcriptase polymerase chain reaction. All stimuli tested failed to induce NOS2 mRNA expression in human AM in vitro. Only AM-AEC-II co-culture in the presence of IFN-gamma led to NOS2 mRNA and protein expression. In situ hybridization of NOS2 mRNA on lung tissue explants and immunohistochemical staining of cytospin preparations of AM-AEC-II co-cultures demonstrated that NOS2 is expressed in AM but not in AEC-II. This co-culture effect could not be reproduced by substitution of AEC-II with SP-A. These data give evidence of a regulatory network controlling human nitric oxide synthase-2 expression in the lower respiratory tract.


Prevalence and Antimicrobial Resistance of Salmonella in Market Raw Oysters in Taiwan.
We tested 137 samples of domestic shucked oysters and 114 samples of imported oysters collected from traditional retail markets and supermarkets during 2010 and 2011 in Taiwan for the presence of Salmonella. We obtained a total of 91 Salmonella isolates, representing nine serotypes, from 80 of the domestic samples. We did not find any Salmonella in the imported oysters. The presence of Salmonella contamination tended to be specific to the area from which the oysters were harvested: the Dongshih area had a significantly higher contamination rate (68.8%) than the Budai (20.0%) and Wanggong (9.1%) areas. In addition, the rate of Salmonella contamination was higher in oysters that were packed or sold with water (P < 0.05). The most commonly identified Salmonella serotypes were Saintpaul (26.4%), Newport (22.0%), and Infantis (13.2%). We screened the isolates for susceptibility to nine antimicrobials and compared them genetically by using PCR for the class 1 integron (int1), tetA, tetB, and blaPSE-1 genes. Eighteen isolates (19.8%) were resistant to at least one antimicrobial agent, and the most frequent resistances were those to tetracycline and oxytetracycline (n = 12, 14.3%).We detected the antimicrobial resistance genes int1, tetA, tetB, and blaPSE-1 in 16.5, 26.4, 6.6, and 22.0% of the isolates, respectively. Eleven of the 18 antimicrobial-resistant isolates contained one or two int1 cassettes, suggesting that the presence of int1 is highly correlated with antimicrobial resistance in Salmonella isolates from oysters. The consumption of oysters is increasing in Taiwan, and information related to Salmonella contamination in oysters is rather limited. Our results indicate that raw oyster consumption from retail markets in Taiwan is associated with a human health hazard owing to Salmonella, including multidrug-resistant Salmonella strains.


Control of stem cell activity in the carpel margin meristem (CMM) in Arabidopsis.
Overview of the current understanding of the molecular mechanisms that regulate meristem activity in the CMM compared to the SAM. Meristems are undifferentiated cells responsible for post-embryonic plant development. The meristems are able to form new organs continuously by carefully balancing between stem cell proliferation and cell differentiation. The plant stem cell niche in each meristem harbors the stem cells that are important to maintain each meristem. The shoot apical meristem (SAM) produces all above-parts of a plant and the molecular mechanisms active in the SAM are actively studied since many years, and models are available. During the reproductive phase of the plant, the inflorescence meristem gives rise to floral meristems, which give rise to the flowers. During floral development, the gynoecium forms that contains a new meristem inside, called the carpel margin meristem (CMM). In Arabidopsis, the gynoecium consists out of two fused carpels, where the CMM forms along the fused carpel margins. In this review, we focus on the molecular mechanisms taking place in the CMM, and we discuss similarities and differences found in the SAM.


Dynamic Stability and Risk of Tripping during the Timed Up and Go Test in Hemiparetic and Healthy Subjects.
The Timed Up and Go (TUG) test is often used to estimate risk of falls. Foot clearance and displacement of the center of mass (COM), which are related to risk of tripping and dynamic stability have never been evaluated during the TUG. Accurate assessment of these parameters using instrumented measurements would provide a comprehensive assessment of risk of falls in hemiparetic patients. The aims of this study were to analyze correlations between TUG performance time and displacement of the COM and foot clearance in patients with stroke-related hemiparesis and healthy subjects during the walking and turning sub-tasks of the TUG and to compare these parameters between fallers and non-fallers. 29 hemiparetic patients and 25 healthy subjects underwent three-dimensional gait analysis during the TUG test. COM and foot clearance were analyzed during the walking and turning sub-tasks of the TUG. Lateral displacement of the COM was greater and faster during the walking sub-tasks and vertical displacement of the COM was greater during the turn in the patients compared to the healthy subjects (respectively p<0.01 and p<0.05). Paretic foot clearance was greater during walking and displacement of the COM was slower during the turn in the patients (p<0.01). COM displacement and velocity during the turn were correlated with TUG performance in the patients, however, vertical COM displacement was not. These correlations were significant in the healthy subjects. There were no differences between COM parameters or foot clearance in fallers and non-fallers. Hemiparetic patients are less stable than healthy subjects, but compensate with a cautious gait to avoid tripping. Instrumented analysis of the TUG test appears relevant for the assessment of dynamic stability in hemiparetic patients, providing more information than straight-line gait.


Molecular Fluorescent Probes for Imaging and Evaluation of Hypochlorite Fluctuations during Diagnosis and Therapy of Osteoarthritis in Cells and in a Mouse Model.
The early diagnosis of osteoarthritis (OA) can halt or delay the progression of the disease, and it is essentially beneficial to its treatment. However, biomarkers with sufficient sensitivity for dynamically identifying early OA are still yet to be determined. The overproduced hypochlorous acid (HOCl) has been proposed as an obvious symptom in early OA. Herein, based on the oxidation reaction of the sulfur atom in phenothiazine into sulfoxide, we design and synthesize a phenothiazine-derived coumarin fluorescent probe PDC for the detection of ClO- in cells and in an OA mouse model. The probe PDC exhibits excellent selectivity and sensitivity for ClO- detection with a limit of detection as low as 16.1 nM. Taking advantage of the probe PDC, we visualize and evaluate the level changes of ClO- in macrophage cells, which is stimulated by various inflammatory factors. The anti-inflammatory and therapeutic effects of selenocysteine and methotrexate in inflamed cells are also confirmed. Finally, with in vivo imaging of ClO- concentration changes in OA BALB/c mouse models, we successfully inspected the relationship between OA phenotypes and the burst of ClO-. We suggest that abnormal changes in HOCl concentration may be considered as a new biomarker for the early OA diagnosis.


Presurgical blood metabolites and risk of postsurgical pelvic pain in young patients with endometriosis.
To identify metabolites in presurgical blood associated with risk of persistent postsurgical pelvic pain 1 year after endometriosis surgery in adolescent and young adult patients. Prospective observational study within the Women's Health Study: From Adolescence to Adulthood, a US-based longitudinal cohort of adolescents and women enrolled from 2012-2018. Two tertiary care hospitals. Laparoscopically confirmed endometriosis patients (n = 180) with blood collected before their endometriosis surgery. Of these, 77 patients additionally provided blood samples 5 weeks to 6 months after their surgery. We measured plasma metabolites using liquid chromatography tandem mass spectrometry, and a total of 390 known metabolites were included in our analysis. None. Persistent postsurgical pelvic pain, defined as severe, life-impacting pelvic pain 1 year after endometriosis surgery. Most patients (>95%) were at stage I/II of the revised American Society for Reproductive Medicine classification. Their average age at diagnosis was 18.7 years, with 36% reporting persistent postsurgical pelvic pain. Of the 21 metabolites in presurgical blood that were associated with risk of persistent postsurgical pelvic pain, 19 metabolites, which were mainly lipid metabolites, were associated with increased risk. Only 2 metabolites-pregnenolone sulfate (odds ratio = 0.64, 95% confidence interval = 0.44-0.92) and fucose (odds ratio = 0.69, 95% confidence interval = 0.47-0.97)-were associated with decreased risk. Metabolite set enrichment analysis revealed that higher levels of lysophosphatidylethanolamines (false discovery rate = 0.01) and lysophosphatidylcholines (false discovery rate = 0.01) in presurgical blood were associated with increased risk of persistent postsurgical pelvic pain. Our results suggest that dysregulation of multiple groups of lipid metabolites may play a role in the persistence of pelvic pain postsurgery among young endometriosis patients.


Decreased number of peripheral blood CD4 + CD29+ lymphocytes and increased in vitro spontaneous production of anti-DNA antibodies in patients with active systemic lupus erythematosus.
Flow cytometric 2-color analysis of peripheral blood lymphocytes from patients with systemic lupus erythematosus (SLE) showed a reduction of relative and absolute number of CD4+ CD29+ cells compared to matched healthy individuals. This abnormality was more marked in patients with active/very active disease. Absolute number of CD4+ CD29+ cells was negatively correlated with spontaneous anti-DNA Ig production that we demonstrated to be a laboratory index strongly correlated with a clinical disease activity score. A decrease of the percentage of CD8+ CD29+ lymphocytes in patients with active disease was also observed.


Immunogenomic profile at baseline predicts host susceptibility to clinical malaria.
Host gene and protein expression impact susceptibility to clinical malaria, but the balance of immune cell populations, cytokines and genes that contributes to protection, remains incompletely understood. Little is known about the determinants of host susceptibility to clinical malaria at a time when acquired immunity is developing. We analyzed peripheral blood mononuclear cells (PBMCs) collected from children who differed in susceptibility to clinical malaria, all from a small town in Mali. PBMCs were collected from children aged 4-6 years at the start, peak and end of the malaria season. We characterized the immune cell composition and cytokine secretion for a subset of 20 children per timepoint (10 children with no symptomatic malaria age-matched to 10 children with >2 symptomatic malarial illnesses), and gene expression patterns for six children (three per cohort) per timepoint. We observed differences between the two groups of children in the expression of genes related to cell death and inflammation; in particular, inflammatory genes such as CXCL10 and STAT1 and apoptotic genes such as XAF1 were upregulated in susceptible children before the transmission season began. We also noted higher frequency of HLA-DR+ CD4 T cells in protected children during the peak of the malaria season and comparable levels cytokine secretion after stimulation with malaria schizonts across all three time points. This study highlights the importance of baseline immune signatures in determining disease outcome. Our data suggests that differences in apoptotic and inflammatory gene expression patterns can serve as predictive markers of susceptibility to clinical malaria.


High Throughput Screening Assay to Identify Modulators of IL-17 Expression.
Herein we demonstrate the successful development of a new RORγt-enhanced IL-17F promoter-luciferase reporter assay and its use in a parallel high throughput screening approach, alongside a RORγt TR-FRET assay, to rapidly identify new small molecule RORγt/IL-17 inhibitors and evaluate their mode of action. We sought to identify cell-permeable small-molecule inhibitors of RORγt for rapid progression into hit-to-lead chemistry. As such, we developed the IL-17F promoter luciferase reporter assay in a stable human T-cell (Jurkat) line expressing the RORγt receptor and miniaturised it to a final volume of 8 µL in 1536 well plates for HTS use in screening a library of > 350k compounds. In parallel, a RORγt TR-FRET binding assay was employed to cross-screen the same set of compounds. This enabled the rapid identification of a small number of cell permeable RORγt antagonists showing promising activity in both assays and also highlighted a larger group of potentially very interesting hits which inhibited IL-17 reporter activity, but did not appear to modulate RORγt directly. A rigorous triaging process of the novel non-RORγt IL-17 antagonists was followed, making use of in-silico filtering, historical screening data, selectivity screening using an IL-2 reporter assay with an identical cellular background, and final profiling in a phenotypic PBMC IL-17A production assay. This resulted in the identification of a set of promising small molecule compounds which show IL-17 inhibition via potentially novel pathways. This technique for the fast identification of cell-permeable IL-17 modulators acting through different mechanisms, highlights the benefits of adopting a parallel approach combining high throughput profiling of hits in multiple assay formats, with robust in-silico triaging.


[Results of residual ametropia correction using CIRCLE technology after femtosecond laser SMILE surgery].
to evaluate functional results of reoperation performed according to the CIRCLE technology and using the VisuMax femtosecond laser and MEL-80 excimer laser in cases of regression of the refractive effect after SMILE surgery. We studied a group of post-SMILE patients. In those, who showed regression of the refractive effect at 1 year, reoperation was performed according to the CIRCLE technology and using the VisuMax femtosecond laser. The corneal flap was separated from the stromal bed and turned aside. Excimer laser ablation of the stromal bed was performed with the MEL 80 machine. The corneal flap was then placed back and rinsed from both sides. Uncorrected (UCVA) and corrected (BCVA) visual acuity as well as spherical equivalent (SE) were estimated before reoperation, on day 1, and at 1 month. After reoperation, BCVA and UCVA improved. Patient refraction became close to emmetropia. Specifically, UCVA was 0.23±0.18 at baseline (i.e. 1 year after SMILE) and 0.93±0.11 after the CIRCLE procedure (p<0.05). The absolute value of SE was 1.86±1.15 D and 0±0 D before and after CIRCLE, respectively (p<0.05). BCVA change was not statistically significant - from 0.95±0.1 to 0.93±0.11 (p>0.05). Reoperation performed according to the CIRCLE technology and using the VisuMax femtosecond laser and MEL-80 excimer laser provides an increase in visual acuity in case of post-SMILE regression of the refractive effect.


Common generic measures of health related quality of life in injured patients.
The measurement of health-related quality of life (HRQOL) through generic outcome instruments is important for comparisons of populations across disease states and interventions. The growing number of questionnaires available has made selection and interpretation more difficult. Profile instruments such as the SF-36 and Sickness Impact Profile provide insight into various domains of health with established population norms. Preference-based measures, including the EQ-5D, Health Utilities Index, SF-6D, and QWB-SA are used to generate utility scores, which can be used for cost-effectiveness analysis and therefore have particular relevance in health policy. Both types of generic measures have been used in clinical trials in injured populations to assess the relative impact of interventions on quality-of-life. Comparisons of internal consistency and test-retest reliability across measures reveal minimal differences between instruments, and reported values are acceptable for group comparisons but insufficient for individual clinical use. There is a dearth of studies evaluating the validity of these measures in the trauma population, but available data suggest most of the available instruments are acceptable. Populations that may require special consideration are patients with head, spinal cord, and upper-extremity injuries. Practical issues to consider in selecting a questionnaire include time for completion, which ranges from less than 2 min for the EQ-5D to 20-30 min for the Sickness Impact Profile. Selection of the appropriate measure ultimately depends largely on the population to be studied and whether utility-estimation is desired.


Functional domains within FEN-1 and RAD2 define a family of structure-specific endonucleases: implications for nucleotide excision repair.
Structure-specific nucleases catalyze critical reactions in DNA replication, recombination, and repair. Recently, a structure-specific endonuclease, FEN-1, has been purified and shown to cleave DNA flap structures. Here, we describe the cloning of the murine FEN-1 gene. The nucleotide sequence of FEN-1 is highly homologous to the Saccharomyces cerevisiae genes YKL510 and RAD2. We show that YKL510 and a truncated RAD2 protein are also structure-specific endonucleases. The substrate specificity of the truncated RAD2 protein implicates branched DNA structures as important intermediates in nucleotide excision repair. The polarity of these branched DNA structures allows us to predict the placement of DNA scissions by RAD2 and RAD1/RAD10 in this reaction.


Ventilation-induced changes correlate to pulmonary vascular response and VEGF, VEGFR-1/2, and eNOS expression in the rat model of postnatal hypoxia.
Neonatal asphyxia occurs due to reduction in oxygen supply to vital organs in the newborn. Rapid restoration of oxygen to the lungs after a long period of asphyxia can cause lung injury and decline of respiratory function, which result from the activity of molecules that induce vascular changes in the lung such as nitric oxide (NO) and vascular endothelial growth factors (VEGF). In this study, we evaluated the pulmonary and vascular morphometry of rats submitted to the model of neonatal asphyxia and mechanical ventilation, their expression of pulmonary VEGF, VEGF receptors (VEGFR-1/VEGFR-2), and endothelial NO synthase (eNOS). Neonate Sprague-Dawley rats (CEUA #043/2011) were divided into four groups (n=8 each): control (C), control submitted to ventilation (CV), hypoxia (H), and hypoxia submitted to ventilation (HV). The fetuses were harvested at 21.5 days of gestation. The morphometric variables measured were body weight (BW), total lung weight (TLW), left lung weight (LLW), and TLW/BW ratio. Pulmonary vascular measurements, VEGFR-1, VEGFR-2, VEGF, and eNOS immunohistochemistry were performed. The morphometric analysis showed decreased TLW and TLW/BW ratio in HV compared to C and H (P<0.005). Immunohistochemistry showed increased VEGFR-2/VEGF and decreased VEGFR-1 expression in H (P<0.05) and lower eNOS expression in H and HV. Median wall thickness was increased in H, and the expression of VEGFR-1, VEGFR-2, VEGF, and eNOS was altered, especially in neonates undergoing H and HV. These data suggested the occurrence of arteriolar wall changes mediated by NO and VEGF signaling in neonatal hypoxia.


Influence of the dye presence on the conformational preferences of CREKA, a tumor homing linear pentapeptide.
The conformational properties of the Cys-Arg-Glu-Lys-Ala (CREKA) peptide sequence labeled with fluorescein, a fluorescent dye attached to the Cys through a flexible linker have been examined using molecular dynamics simulations. The CREKA sequence has been identified as a tumor-homing peptide that effectively binds to clotted plasma proteins. Before conformational exploration, the molecular geometry, basicity and spectroscopic properties of this dye, which is essential for the imaging the peptide activity, have been examined using quantum mechanical calculations, with the results also allowing determination of the force-field parameters required for classical simulations. Minimum energy conformations derived from the conformational search have been classified using clustering analyses with criteria based on both the existence of interactions and backbone geometric similarity. The results have been compared with those reported for isolated CREKA (peptide without dye). We found that the fluorescein affects the energy distribution of the minimum energy conformations, with the repulsive steric interactions induced by the dye producing shifting the distribution towards higher energy values. Interestingly, although the structural characteristics of the bioactive conformation identified for CREKA are not perturbed by the dye, it is less stable when the peptide is attached to the dye than in other chemical environments previously studied (isolated peptide, peptide attached to the surface of a protein, and peptide inserted in a phage display protein).


Healthcare costs of burn patients from homes without fire sprinklers.
The treatment of burn injuries requires high-cost services for healthcare and society. Automatic fire sprinklers are a preventive measure that can decrease fire injuries, deaths, property damage, and environmental toxins. This study's aim was to conduct a cost analysis of patients with burn or inhalation injuries caused by residential fires and to compare this with the cost of implementing residential automatic fire sprinklers. We conducted a cohort analysis of adult burn patients admitted to our provincial burn center (1995-2012). Patient demographics and injury characteristics were collected from medical records and clinical and coroner databases. Resource costs included average cost per day at our intensive care and rehabilitation program, transportation, and property loss. During the study period, there were 1557 residential fire-related deaths province-wide and 1139 patients were admitted to our provincial burn center as a result of a flame injury occurring at home. At our burn center, the average cost was CAN$84,678 per patient with a total cost of CAN$96,448,194. All resources totaled CAN$3,605,775,200. This study shows the considerable healthcare costs of burn patients from homes without fire sprinklers.


Concurrent septic arthritis and urinary tract infection in a patient with nephrocalcinosis and vesicoureteral reflux.
An eight-month-old boy who presented with a 15-day history of vomiting was revealed to be suffering from urinary tract infection and nephrocalcinosis caused by vitamin D intoxication. During the treatment of vitamin D intoxication (alendronate, 5 mg/day), he developed urinary tract infection and septic arthritis of the left hip joint. Escherchia coli was isolated from his blood, urine, and joint fluid culture. He was operated, joint drainage was performed and appropriate intravenous antibiotic treatment was given for four weeks. After discharge, a voiding cystoureterogram revealed grade 4 vesicoureteral reflux in the right ureter. Combination of complex urinary anomalies associated with stagnation of urine flow and altered urinary dynamics, and metabolic urinary anomalies, such as hypercalciuria/nephrocalcinosis, may facilitate the occurrence of rare systemic complications of urinary tract infection.


Quercetin ameliorates atrazine-induced changes in the testicular function of rats.
The protective effect of quercetin (QT) on atrazine (ATZ)-induced testicular damage in rats was investigated. Sexually mature male Wistar rats (weighing 220-250 g) divided into four groups with six animals in each group were given ATZ (120 mg kg(-1); 1/16 of the median lethal dose for an oral dose) and/or QT (10 mg kg(-1)) daily via gavage for 16 days. By the end of day 16, rats given ATZ alone had significantly lower sperm counts, daily spermatozoa production, and sperm motility and significantly higher abnormal sperm numbers than the untreated control rats. The rats given ATZ alone also had significantly decreased 3β-hydroxtsteroid dehydrogenase (HSD) and 17β-HSD activities than the control rats. Lactate dehydrogenase activity and malondialdehyde levels were significantly increased, whereas superoxide dismutase activity decreased but glutathione levels remain unaffected after ATZ exposure. These changes were reversed toward control values in the QT + ATZ-treated animals, though the sperm motility was 28% below the control levels but was still higher than in the ATZ-treated rats. The results indicate that QT might improve testicular function of rats exposed to ATZ, but its protective effect on sperm motility might be partial.


Are Chileans exposed to dietary furan?
Chilean consumer preferences include foods that may contain considerable amounts of furan, a potential human carcinogen. However, there is no information regarding dietary exposure to furan in Chile. Thus, the objective of this work was to determine the Chilean exposure to dietary furan. To accomplish this objective, the furan concentration of 14 types of commercial foods processed at high temperature were analysed based on a modified headspace-GC/MS (HS-GC/MS) method in which the limits of detection for different food matrices ranged from 0.01 to 0.6 ng g(-1). In addition, a risk assessment was made with exposure estimates based on dietary data from national studies on different age groups (9-month-old babies, school children, adults and elderly people). Of the food items surveyed "American"-type coffee (espresso coffee plus hot water) obtained from automatic coffee machine (936 ng g(-1)) and low moisture starchy products like crisps and "soda"-type crackers showed the highest furan concentrations (259 and 91 ng g(-1), respectively). Furthermore, furan was also found in samples of breakfast cereals (approximately 20 ng g(-1)), jarred fruit baby foods (8.5 ng g(-1)) and orange juice (7.0 ng g(-1)). School children (aged 9-13 years) represented the highest intake of furan (about 500 ng kg(-1)(bw) day(-1)), with margins of exposure of 2479 and 2411, respectively, which points to a possible public health risk.


The effect of a high phosphorus diet on the parathyroid cell cycle.
High extracellular phosphorus directly increases parathyroid hormone (PTH) secretion and gene transcription. The present study evaluates the effect of high phosphorus diet on the parathyroid cell cycle in rats with normal renal function. Rats were divided into two groups, receiving either a high phosphorus diet (HPD, P=1.2%) or a normal phosphorus diet (NPD, P=0.6%). The dietary calcium content was 0.6% in both diets. Rats were pair fed and sacrificed on days 0, 1, 5, 10 and 15 after initiation of the diet. The parathyroid glands were removed and parathyroid cells dispersed for evaluation of cell cycle and apoptosis by flow cytometry. Serum calcium, phosphorus, PTH and calcitriol were measured. As compared with NPD, the ingestion of a HPD resulted in an increased number of cells in the S phase of the cell cycle from day 1 to 10 (1.2+/-0.09% vs 0.6+/-0.04% for day 1, 1.2+/-0.11% vs 0.6+/-0.06% for day 5 and 1.0+/-0.09% vs 0.5+/-0.04% for day 10, P<0.01). By day 15, the percentage of cells in the S phase in NPD and HPD were not different. In the rats fed the HPD, serum PTH increased significantly from day 5 through 15 (P<0.01). Parathyroid cell apoptosis was minimal and unaffected by the diet. At day 15, the parathyroid gland size in HPD was increased by 27% as compared with NPD (P<0.05). This increase should be attributed to cell proliferation since parathyroid cell size remained unchanged. Serum calcitriol and calcium were not significantly different in the two groups. In HPD, an increase in serum phosphorus was observed only on day 1. The results show that an HPD results in the stimulation of the parathyroid cell cycle independently of changes in calcium and calcitriol.


Support for Complicated Grief in Military Primary Care: Associations, Challenges, and Opportunities.
This study examined whether service members and their families engage in communication with their primary care managers (PCMs) regarding their losses and to what extent PCMs provide counseling or referrals for grief-related concerns. Additionally, the study explored the potential associations between ethnicity, age, military status (dependent, service member, or veteran), gender, patients' disclosure of loss to their PCM, receipt of referrals for grief-related services, and treatment seeking. A survey was administered to 161 patients enrolled in primary care at William Beaumont Army Medical Center, with 138 reporting a significant loss. Bereaved respondents completed the Inventory of Complicated Grief and the Prolonged Grief Disorder-13 Revised scale (PG-13). Respondents were also asked questions related to their loss and their interactions with their PCM related to the loss. One hundred twenty-five bereaved respondents completed the measures, 13 had missing information related to PCM interactions. Twenty-nine percent (n = 36) of the 112 respondents reported a significant loss to their PCM. These respondents exhibited significantly higher symptom severity, as indicated by their total mean scores on the Inventory of Complicated Grief and the PG13. Seventeen percent (n = 6) of these respondents reported receiving counseling on topics related to grief or a referral for grief care from their PCM. A moderate relationship was identified between military status and communication with PCM, such that current service members were least likely to report, followed by veterans, then dependents. A moderate relationship was also found between ethnicity and treatment seeking. The study's findings have implications for primary care and highlight opportunities for improved outcomes, including the development of appropriate assessment protocols, interventions, and educational initiatives to address grief-related concerns within the military healthcare system. Future research should further investigate the specific needs and preferences of military personnel and their families to enhance the delivery of targeted and effective healthcare services.


Insecticide toxicity to oriental fruit fly Bactrocera dorsalis (Diptera: Tephritidae) is influenced by environmental factors.
In this study, we investigated the effects of environmental factors (temperature, dose, dietary source, and feeding density) on the insecticide tolerance of Bactrocera dorsalis (Hendel) (Diptera: Tephritidae). The results indicated that the toxicities of trichlorphon and abamectin to B. dorsalis increased with an increase in temperature. At 15-35 degrees C, the toxicity of beta-cypermethrin decreased with an increase in temperature at low doses (0.82 and 1.86 mg/L), but was similar at a high dose (4.18 mg/L). These results demonstrated that the temperature coefficient of beta-cypermethrin was related to both temperature and dosage. The insecticide sensitivity of B. dorsalis reared on different dietary sources was significantly different. Trichlorphon sensitivity of B. dorsalis fed on banana was the highest with an LC50 of 1.61 mg/L, followed by on apple, carambola, semiartificial diet, pear, mango, guava, orange, and papaya. With an increasing feeding density, the sensitivity of B. dorsalis adults to trichlorphon increased, while the sensitivities of B. dorsalis adults to abamectin and beta-cypermethrin decreased. The differences between LC50 values of insects reared at densities of 10 and 13 eggs/g of semiartificial diet to trichlorphon, abamectin and beta-cypermethrin were not significant. This result suggested that representative toxicity could be obtained by using adults developed at a feeding density between 10-13 eggs/g of semiartificial diet. Adult body weight was positively correlated with the LC50 value of trichlorphon, but was negatively correlated with the toxicities of abamectin and beta-cypermethrin. These results suggested that the effects of adult body weight on the toxicity of insecticides were different among different chemicals.


Commentary on paradigms and key word index for NDPLS articles 1997-2006.
Although a paradigm shift in the sense of a postmodern worldview might be taking shape in society at large, the core concepts of nonlinear science date back a century, and are only tangentially influenced by other intellectual developments. Relative to contemporary science it offers new concepts concerning events that transpire over time, new hypotheses, new methods for answering new questions, some efficient answers, and a new perspective for understanding what we do not know in addition to knowing how we know what we know. Paradoxically, nonlinear science can be viewed as a narrow specialty within a specific discipline and as a general systems theory that identifies common themes that underlie phenomena found in a wide range of disciplines and specialties. The key word index illustrates the breadth of concepts and applications found in NDPLS, and some pathways for continued growth of the field.


Modeling out-of-plane actuation in thin-film nematic polymer networks: From chiral ribbons to auto-origami boxes via twist and topology.
Various experimental and theoretical studies demonstrate that complex stimulus-responsive out-of-plane distortions such as twist of different chirality, emergence of cones, simple and anticlastic bending can be engineered and pre-programmed in a liquid crystalline rubbery material given a well-controlled director microstructure. Via 3-d finite element simulation studies, we demonstrate director-encoded chiral shape actuation in thin-film nematic polymer networks under external stimulus. Furthermore, we design two complex director fields with twisted nematic domains and nematic disclinations that encode a pattern of folds for an auto-origami box. This actuator will be flat at a reference nematic state and form four well-controlled bend distortions as orientational order changes. Device fabrication is applicable via current experimental techniques. These results are in qualitative agreement with theoretical predictions, provide insight into experimental observations, and demonstrate the value of finite element methods at the continuum level for designing and engineering liquid crystal polymeric devices.


Plant antimutagenic agents, 3. Coumarins.
Several coumarins were isolated from crude plant extracts by means of an antimutagenic assay procedure. These coumarins included psoralen from Psoralea corylifolia and imperatorin and osthol from Selinum monniere. Studies of structure-activity relationships of these and several other available coumarins were carried out with four mutagens. All of the coumarins were nontoxic and in particular showed high activity in the inhibition of the mutagenicity of benzo[a]pyrene.


Family Carers of People with Dementia in Japan, Spain, and the UK: A Cross-Cultural Comparison of the Relationships between Experiential Avoidance, Cognitive Fusion, and Carer Depression.
Objective and research design This study investigated whether the relationship between experiential avoidance and carer depression is mediated by cognitive fusion using path analysis and whether this model differs between family carers from Japan, Spain, and the UK using multi-group path analysis. Results The whole sample model (N = 745) showed a good fit to the data. The direct effect of experiential avoidance on carer depression (β = .10) and its indirect effect on carer depression through cognitive fusion (β = .15) were significant. Examined variables accounted for 45% of the variance of depression. Multi-group path analysis confirmed the same pattern of indirect path across 3 countries, while the direct path was no longer significant in Spanish and UK samples.Conclusion These findings suggest that targeting cognitive fusion may be particularly critical in culturally diverse carers and pre-emptive efforts to reduce experiential avoidance using psychological techniques may be beneficial among family carers prone to cognitive fusion regardless of cultural differences.


Host range and distribution of small mammal fleas in South Africa, with a focus on species of medical and veterinary importance.
The host range and distribution of flea species on rodents and insectivores across multiple vegetation types in South Africa were investigated. Habitat suitability for flea species considered as important vectors of disease in humans and domestic animals was modelled. Data originated from fleas that were recovered from small mammals captured at 29 localities during 2009-2013 and published literature searched for flea records. Climate-based predictor variables, widely used in arthropod vector distribution, were selected and habitat suitability modelled for 10 flea vector species. A total of 2469 flea individuals representing 33 species and subspecies were collected from 1185 small mammals. Ten of each of the flea and rodent species are plague vectors and reservoirs, respectively. Multiple novel flea-host associations and locality records were noted. Three vector species were recorded from insectivores. Geographic distributions of flea species ranged from broad, across-biome distributions to narrower distributions within one or two biomes. Habitat suitability models performed excellently for the majority of flea vectors and identified regions of summer and all-year rainfall as representing suitable habitats for most vector species. Current knowledge of vector and disease ecology can benefit from similar sampling approaches that will be important not only for South Africa, but also for the sub-region.


Genetics of Tinnitus: Still in its Infancy.
Tinnitus is the perception of a phantom sound that affects between 10 and 15% of the general population. Despite this considerable prevalence, treatments for tinnitus are presently lacking. Tinnitus exhibits a diverse array of recognized risk factors and extreme clinical heterogeneity. Furthermore, it can involve an unknown number of auditory and non-auditory networks and molecular pathways. This complex combination has hampered advancements in the field. The identification of specific genetic factors has been at the forefront of several research investigations in the past decade. Nine studies have examined genes in a case-control association approach. Recently, a genome-wide association study has highlighted several potentially significant pathways that are implicated in tinnitus. Two twin studies have calculated a moderate heritability for tinnitus and disclosed a greater concordance rate in monozygotic twins compared to dizygotic twins. Despite the more recent data alluding to genetic factors in tinnitus, a strong association with any specific genetic locus is lacking and a genetic study with sufficient statistical power has yet to be designed. Future research endeavors must overcome the many inherent limitations in previous study designs. This review summarizes the previously embarked upon tinnitus genetic investigations and summarizes the hurdles that have been encountered. The identification of candidate genes responsible for tinnitus may afford gene based diagnostic approaches, effective therapy development, and personalized therapeutic intervention.


Multiple cutaneous leiomyomas leading to discovery of novel splice mutation in the fumarate hydratase gene associated with HLRCC.
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant condition, which manifests as cutaneous leiomyomas (CL), uterine fibroids and renal cell cancer (RCC). We describe the case of a 53-year-old woman who presented with multiple CL with a novel heterozygous canonical splice site mutation in intron 9 of the fumarate hydratase (FH) gene IVS 9-1 G>C (NM_000143.3:c 1391-1 G>C) that was not detected on initial screening of a mutation hotspot but was picked up on sequencing the remaining exons and splice site junctions. This report highlights the importance of clinical suspicion in the diagnosis of HLRCC in the absence of a family or personal history of cancer and despite initial genetic testing being negative.


KAT4IA: K-Means Assisted Training for Image Analysis of Field-Grown Plant Phenotypes.
High-throughput phenotyping enables the efficient collection of plant trait data at scale. One example involves using imaging systems over key phases of a crop growing season. Although the resulting images provide rich data for statistical analyses of plant phenotypes, image processing for trait extraction is required as a prerequisite. Current methods for trait extraction are mainly based on supervised learning with human labeled data or semisupervised learning with a mixture of human labeled data and unsupervised data. Unfortunately, preparing a sufficiently large training data is both time and labor-intensive. We describe a self-supervised pipeline (KAT4IA) that uses K-means clustering on greenhouse images to construct training data for extracting and analyzing plant traits from an image-based field phenotyping system. The KAT4IA pipeline includes these main steps: self-supervised training set construction, plant segmentation from images of field-grown plants, automatic separation of target plants, calculation of plant traits, and functional curve fitting of the extracted traits. To deal with the challenge of separating target plants from noisy backgrounds in field images, we describe a novel approach using row-cuts and column-cuts on images segmented by transform domain neural network learning, which utilizes plant pixels identified from greenhouse images to train a segmentation model for field images. This approach is efficient and does not require human intervention. Our results show that KAT4IA is able to accurately extract plant pixels and estimate plant heights.


The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways.
Quercetin is the most abundant flavonoid and is assumed to have protective roles against the pathogenesis of multiple diseases associated with oxidative stress. In the present study, we investigated the molecular mechanisms by which quercetin affects adipogenesis and apoptosis in 3T3-L1 cells. The exposure of 3T3-L1 preadipocytes to quercetin resulted in attenuated adipogenesis and decreased expression of adipogenesis-related factors and enzymes. Moreover, quercetin exposure up-regulated the levels of phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylase (ACC). Treatment of 3T3-L1 adipocytes with quercetin resulted in the induction of apoptosis and a concomitant decrease in ERK and JNK phosphorylation. Taken together, these data indicate that quercetin exerts anti-adipogenesis activity by activating the AMPK signal pathway in 3T3-L1 preadipocytes, while the quercetin-induced apoptosis of mature adipocytes was mediated by modulation of the ERK and JNK pathways, which play pivotal roles during apoptosis.


Performance evaluation of a natural treatment system for small communities, composed of a UASB reactor, maturation ponds (baffled and unbaffled) and a granular rock filter in series.
Post-treatment of anaerobic reactor effluent with maturation ponds is a good option for small to medium-sized communities in tropical climates. The treatment line investigated, operating in Brazil, with an equivalent capacity to treat domestic sewage from 250 inhabitants, comprised a upflow anaerobic sludge blanket reactor followed by two shallow maturation ponds (unbaffled and baffled) and a granular rock filter (decreasing grain size) in series, requiring an area of only 1.5 m2 inhabitant-1. With an overall hydraulic retention time of only 6.7 days, the performance was excellent for a natural treatment system. Based on over two years of continuous monitoring, median removal efficiencies were: biochemical oxygen demand = 93%, chemical oxygen demand = 79%, total suspended solids = 87%, ammonia = 43% and Escherichia coli = 6.1 log units. The final effluent complied with European discharge standards and WHO guidelines for some forms of irrigation, and appeared to be a suitable alternative for treating domestic sewage for small communities in warm areas, especially in developing countries.


New type of POU domain in germ line-specific protein Oct-4.
Members of a family of murine octamer-binding proteins interact specifically with the octamer motif, a transcription regulatory element found in the promoter and enhancer regions of many genes. Oct-4 is a maternally expressed protein that is also present in the pre-implantation mouse embryo. Although many regulatory proteins are expressed in post-implantation embryos, transcription factors regulating pre-implantation processes have remained elusive. The Oct-4 gene is therefore a prime candidate for an early developmental control gene. Here we report the complementary DNA cloning of the mouse Oct-4 gene, and the characterization of the encoded protein(s) by sequential in vitro transcription, translation, DNA-binding and protease-clipping analysis. Deletion analysis shows that the DNA-binding activity is mediated by a POU domain encoded in an open reading frame corresponding to a 324-amino-acid protein. Sequence comparison with known POU domains reveals that Oct-4 is a novel member of the POU-family.


Indoor air pollution in rural China: cooking fuels, stoves, and health status.
Solid fuels are a major source of indoor air pollution, but in less developed countries the short-term health effects of indoor air pollution are poorly understood. The authors conducted a large cross-sectional study of rural Chinese households to determine associations between individual health status and domestic cooking as a source of indoor air pollution. The study included measures of health status as well as measures of indoor air-pollution sources, such as solid cooking fuels and cooking stoves. Compared with other fuel types, coal was associated with a lower health status, including negative impacts on exhaled carbon monoxide level, forced vital capacity, lifetime prevalence of chronic obstructive pulmonary disease and asthma, and health care utilization. Decreasing household coal use, increasing use of improved stove technology, and increasing kitchen ventilation may decrease the short-term health effects of indoor air pollution.


[Expression, purification of recombinant Luxi yellow cattle IFN-alpha fusion protein and its antiviral activities].
Interferon a gene was cloned from genomic DNA of Chinese Luxi yellow cattle by PCR, and the PCR product was inserted into vector pET32a( + ) to make a recombinant plasmid pET32a( + )/BoIFN-alpha. The expression of BoIFN-alpha in Escherichia coli was induced by addition of IPTG. Sequence analysis showed that the Chinese Luxi yellow cattle IFN-alpha gene is composed of 498 nucleotides, encoding a mature polypeptide of 166 amino acids. Compared with other BoIFN-alpha subtypes, it shares the highest identity of 97.6% to the C-subtype. SDS-PAGE results showed that recombinant proteins were expressed in inclusion bodies in Escherichia coli with molecular weight of 40 kD and the recombinant proteins accounted for 26.7% of the whole proteins.The expressed product was purified by affinity chromatography with immobilized nickel chelating NTA (Ni-NTA) and its antiviral activities were tested on MDBK/VSV cell system. Its antiviral activities were 5 x 10(5) u/mg on MDBK/VSV cell system. The results showed that the expression plasmid was successfully constructed and BoIFN-alpha C2 protein was expressed in Escherichia coli. Moreover the purification had good effects on antiviral activities.


Secretory leukocyte protease inhibitor mediates proliferation of human endometrial epithelial cells by positive and negative regulation of growth-associated genes.
Secretory leukocyte protease inhibitor (SLPI) inhibits chymotrypsin, trypsin, elastase, and cathepsin G. This protein also exhibits proliferative effects, although little is known about the molecular mechanisms underlying this activity. We have generated SLPI-ablated epithelial sublines by stably transfecting the Ishikawa human endometrial cell line with an antisense human SLPI RNA expression vector. We demonstrate a positive correlation between cellular SLPI production and proliferation. We further show that Ishikawa sublines expressing low to undetectable SLPI have correspondingly increased and decreased expression, respectively, of transforming growth factor-beta 1 and cyclin D1 genes, relative to parental cells. SLPI selectively increased cyclin D1 gene expression, with the effect occurring in part at the level of promoter activity. Cellular SLPI levels negatively influenced the anti-proliferative and pro-apoptotic insulin-like growth factor-binding protein-3 expression. We also identified lysyl oxidase, a phenotypic inhibitor of the ras oncogenic pathway and a tumor suppressor, as SLPI-repressed gene, whose expression is up-regulated by transforming growth factor-beta1. Our results suggest that SLPI acts at the node(s) of at least three major interacting growth inhibitory pathways. Because expression of SLPI is generally high in epithelial cells exhibiting abnormal proliferation such as in carcinomas, SLPI may define a novel pathway by which cellular growth is modulated.


Reactive oxygen products in heterologous anti-glomerular basement membrane nephritis in rats.
The effect of 'scavengers' of reactive oxygen products (ROPs) was studied in the heterologous phase of anti-glomerular basement (anti-GBM) nephritis induced in rats. Glomerulonephritis was induced by the intravenous administration of sheep anti-GBM antibody (5 mg/100 g) to rats on day 0. The intraperitoneal administration of superoxide dismutase (SOD) 30 mg/kg/day or 150 mg/kg/day leads to a significant reduction in proteinuria on day 1 and also on day 3 in animals given SOD 30 mg/kg/day. Proteinuria was not significantly reduced by the intraperitoneal administration of inactivated SOD (150 mg/kg/day). In rats given polyethylene glycol coupled catalase (PEG-catalase) intraperitoneally at a dose of 10,000 iu/kg/day and 100,000 iu/kg/day proteinuria was lower than in rats with unmodified anti-GBM nephritis. These differences were significant on day 1 (P less than 0.05) in rats given PEG-catalase 100,000 iu/kg/day and on days 3 and 5 in rats treated with either dose of PEG-catalase (P less than 0.01). These data suggest a role for superoxide anion and hydrogen peroxide, or a product of their interaction such as hydroxyl radical, in glomerular injury induced by anti-GBM antibody.


An Exploration of Self-Reported Medicinal Cannabis Use Among a Sample of Eastern Canadian Postsecondary Students.
In October 2018, prior to the legalization of cannabis in Canada, a survey was completed by 1050 Memorial University of Newfoundland students. Both descriptive quantitative and thematic qualitative data analyzes were used. Approximately 16% of the sample reported ever using cannabis for medicinal purposes (n=175), with only 16.6% of medicinal users reporting authorization by a healthcare provider (HCP). The majority (80.2%) were aware of possible side effects of cannabis. Prior personal experience (65.3%) and peer influence (59.5%) informed participants' medicinal use. Approximately 40% reported having replaced/reduced prescribed medication. Roughly 60% of medicinal users had not disclosed their use to their HCP. Consistent with previous studies, medicinal cannabis use among postsecondary students appears to be largely motivated for mental health related conditions and is grounded in personal experience versus evidence-based guidelines. There is a need for increased communication between HCPs and patients to promote lower-risk use among medicinal cannabis users.


SO2 capture and detection using a Cu(II)-metal-organic polyhedron.
The SO2 adsorption-desorption capacity at room temperature and 1 bar of the metal-organic polyhedron MOP-CDC was investigated. In addition, the qualitative solid-state absorption-emission properties of this material (before and after SO2 exposure) were measured and tested, and it demonstrated remarkable capability for SO2 detection. Our results represent the first example of fluorimetric SO2 detection in a MOP.


Optimal indicators of home BP variability in perimenopausal women and associations with albuminuria and reproducibility: The J-HOT home BP study.
This study investigated the associations between various indicators of home blood pressure (BP) variability and albuminuria as well as the reproducibility of these indicators in perimenopausal women, who are likely to exhibit increased BP variability. As a measure of organ damage, urinary albumin/creatinine ratio (UACR) was examined at baseline in 151 women aged 40-59 years. Home BP was measured in duplicate in both morning and evening for 12 weeks using a home BP monitor. The following home BP variability indicators were calculated biweekly: mean, maximum, minimum, difference between maximum and minimum, average real variability (ARV), SD, and coefficient of variation. In simple correlation, the ARV of systolic BP (SBP) (morning + evening and morning), maximum SBP (evening), and maximum diastolic BP (all time points) were most strongly correlated with UACR. In multivariate linear regression, the maximum, minimum, and ARV of SBP (morning) and both mean and maximum SBP (evening) were significantly associated with Box-Cox transformed UACR after adjustment for age, body mass index, and lifestyle. In particular, maximum SBP had the lowest P value among those BP indicators. Furthermore, maximum morning SBP tended to distinguish high-normal albuminuria (UACR ≥ 10 mg/g Cr) more clearly than mean morning SBP. The mean, maximum, and minimum values of home BP demonstrated the greatest reproducibility among all indicators. Maximum home BP is associated with UACR and exhibits high reproducibility in perimenopausal women. These findings raise the hypothesis that maximum home SBP may be suitable to detect kidney damage.


Iron-Catalyzed Regioselective Direct Arylation at the C-3 Position of N-Alkyl-2-pyridone.
A number of pharmaceutical compounds possess an arylated 2-pyridone moiety. The existing reports using expensive starting materials and/or superstoichiometric metal salts have prompted us to explore a possible user-friendly method for their synthesis. In this report, we demonstrate an easy-to-handle reaction condition with an iron catalyst for the exclusive generation of C-3-arylated pyridone via C-H functionalization.


Non-autophagic roles of autophagy-related proteins.
Autophagy and autophagy-related processes are fundamentally important in human health and disease. These processes are viewed primarily as cellular degradative pathways that recycle macromolecules and dysfunctional or redundant organelles into amino acids, sugars and lipids, especially during starvation. However, the ubiquitin-like autophagy proteins and other components of the autophagic machinery additionally participate in cellular reprogramming. We highlight these non-autophagic roles of autophagy proteins with the aim of drawing attention to this growing, but unexplored, research topic. We focus on the non-autophagic functions of autophagy proteins in cell survival and apoptosis, modulation of cellular traffic, protein secretion, cell signalling, transcription, translation and membrane reorganization.


FLT3 expressing leukemias are selectively sensitive to inhibitors of the molecular chaperone heat shock protein 90 through destabilization of signal transduction-associated kinases.
We conducted studies to evaluate the hypothesis that FLT3 is a client of heat shock protein (Hsp) 90 and inhibitors of Hsp90 may be useful for therapy of leukemia. The effects of the Hsp90-inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) on cell growth, expression of signal transduction kinases, apoptosis, FLT3 phosphorylation and interaction with Hsp90 was determined in FLT3(+) human leukemias. We found that FLT3 is included in a multiprotein complex that includes Hsp90 and p23. 17-AAG inhibited FLT3 phosphorylation and interaction with Hsp90. FLT3(+) leukemias were significantly more sensitive to the Hsp90 inhibitors 17-AAG and Herbimycin A in cell growth assays than FLT3-negative leukemias. Cells transfected with FLT3 became sensitive to 17-AAG. Cell cycle inhibition and apoptosis were induced by 17-AAG. Cells with constitutive expression of FLT3, as a result of internal tandem duplication, were the most sensitive; cells with wild-type FLT3 were intermediate in sensitivity, and FLT3-negative cells were the least sensitive. 17-AAG resulted in reduced cellular mass of FLT3, RAF, and AKT. The mass of another Hsp, Hsp70, was increased. The expression level of MLL-AF4 fusion protein was not reduced by 17-AAG in human leukemia cells. FLT3(+) leukemias are sensitive to 17-AAG and Herbimycin A. 17-AAG inhibits leukemia cells with either FLT3-internal tandem duplication or wild-type FLT3, in part through destabilization of client kinases including FLT3, RAF, and AKT. 17-AAG is potentially useful for therapy of FLT3-expressing leukemias, including the mixed lineage leukemia fusion gene leukemias.


Phenomenological study of nurses caring for dying patients.
Little is known about how nurses experience caring for dying patients. Yet, entering the patient's world often involves dealing with death and dying and is a major challenge to oncology nurses. The purpose of this article is to describe the shared practices of oncology nurses caring for dying patients. Stories from staff nurses on an oncology unit were analyzed using a hermeneutic method to identify and describe four themes: knowing the patient, preserving hope, easing the struggle, and providing for privacy. The four themes contribute to knowledge development about how nurses enter into and experience caring for dying patients. The growing body of knowledge previously reported has included descriptions of critical behaviors in caring for dying patients, coping strategies nurses used when caring for dying patients and their families, and the meaning of oncology nursing practice. The four themes described in this article expand our understanding of the nurses' experience in caring for dying patients.


Serum albumin. A CAP survey.
The results of a 1974 survey of albumin measurements as performed by more than 1,300 laboratories are presented. The most widely used methods are the dye-binding technics: bromcresol green (BCG) and 2-(4'-hydroxyazobenzene) benzoic acid (HABA). These are followed by electrophoresis and salt fractionation. All methods yielded comparable albumin concentrations except electrophoresis, which manifested a consistent low bias. This close agreement is attributed, in part, to the normal-range concentration of albumin in the test specimen. Type of standardization, i.e., commercial serum, bovine serum albumin, human serum albumin, or pooled serum, did not appear to be a factor in the estimation of albumin in the normal serum submitted for analysis. Surprisingly, interlaboratory variation, from method means, was the lowest for salt fractionation and electrophoretic technics.


Chromosomal damage in peripheral blood lymphocytes of traffic policemen and taxi drivers exposed to urban air pollution.
Urban air contains a diversity of chemical compounds, some of which are genotoxins. An increased risk of cancer has also been reported in occupations with heavy exposure to traffic-related pollution. The aim of this study was to assess the cytogenetic effects of urban air pollution by analyzing the chromosomal aberration (CA) frequencies in lymphocytes and to estimate the polycyclic aromatic hydrocarbons (PAHs) exposure by measuring urinary 1-hydroxypyrene (1-OHP) levels. A total of 15 traffic policemen and 17 taxi drivers working in the city of Ankara were the exposed groups and 23 healthy men working in the office departments were the control group. The overall mean +/- S.D. values of 1-OHP excretions of traffic policemen, taxi drivers and control subjects were 0.59 +/- 0.40 micromol/mol creatinine, 0.32 +/- 0.25 micromol/mol creatinine and 0.57 +/- 0.36 micromol/mol creatinine, respectively. Urinary 1-OHP levels of non-smoking policemen were significantly greater than those of nonsmoking control subjects (p < 0.05). The overall mean +/- S.D. values for CA frequencies (%) from policemen, taxi drivers and control group were 1.29 +/- 1.59, 1.81 +/- 1.79, and 0.26 +/- 0.73, respectively. There was a significantly greater frequency of CAs in exposed groups relative to the matched control population (p < 0.05; p < 0.01). Age, sex and smoking habits have not influenced the cytogenetic end-point in this study. Our results demonstrate that occupational exposure to urban air pollutants leads to a significant induction of cytogenetic damage in peripheral lymphocytes of traffic policemen and taxi drivers.


Exploring the Potential of Seaweed Derivatives for the Development of Biodegradable Plastics: A Comparative Study.
Biodegradable films made from biopolymer materials have the potential to replace conventional plastics, which can reduce waste disposal problems. This study aims to explore the potential of different seaweed derivate films consisting of 2% (w/w) of kappaphycus alverezi (KA), kappa carrageenan (KC), refined carrageenan (RC) and semi-refined carrageenan (SRC) as bio-based materials with 0.9% (w/w) glycerol (G), and reinforced with different concentrations of cellulose nanofibers (CNFs) derived from palm waste. A characterization of the glycerol-plasticized seaweed derivatives containing 0, 5, 10, and 15% (v/w) cellulose nanofiber is carried out. The CNFs were studied based on their mechanical, physical and thermal properties including mechanical properties, thickness, moisture content, opacity, water solubility, water vapor permeability and thermal stability. The hydrogen bonding was determined using the DFT calculation generated by Gauss view software version 9.6. The KA + G + 10%CNF film exhibited a surface with slight cracks, roughness, and larger lumps and dents, resulting in inferior mechanical properties (18.50 Mpa), making it unsuitable for biofilm production. The KC + G + 10%CNF film exhibited mechanical properties 24.97 Mpa and water vapor permeability of 1.42311 × 10-11 g s-1 m-1 Pa-1. The RC/G/10%CNF film displayed the highest TS (48.23 MPa) and water vapor permeability (1.4168 × 10-11 g s-1 m-1 Pa-1), but it also had higher solubility in water (66%). In contrast, the SRC + G + 10%CNF film demonstrated excellent mechanical properties (45.98 MPa), low water solubility (42.59%), low water vapor permeability (1.3719 × 10-11 g s-1 m-1 Pa-1), and a high decomposition temperature (250.62 °C) compared to KA, KC and RC. These attributes develop films suitable for various applications, including food packaging with enhanced properties and stability.


Differential susceptibility of human mononuclear cells to infection with HTLV-I.
Infection with human T-cell leukaemia/lymphoma (HTLV-I) preferentially affects T cells of the OKT-4 phenotype. The aim of the present study was to determine whether distinct T-cell subsets exhibit differences in susceptibility to virus infection. T cells from peripheral blood were separated according to cell densities by 7-step Percoll gradients. Separated T-cell subpopulations were infected with HTLV-I, using cocultivation with irradiated virus producer MT-2 cell line. Percentages of HTLV-I-infected cells and their phenotypes were assayed by immunofluorescence assay (IFA), using highly specific mouse monoclonal antibody directed against HTLV-I P-19 core protein, and other surface markers. The results showed that different T-cell subpopulations were susceptible to HTLV-I infection with the exception of large granular lymphocytes (LGL) which exhibit high cell-mediated natural cytotoxicity (CMNC).


Coexisting with clonal evolution and BCR-ABL mutant in CML patients treated with second-generation tyrosine kinase inhibitors predict the discrepancy of in vitro drug sensitivity.
Second-generation tyrosine kinase inhibitors (second TKIs) such as nilotinib and dasatinib control the activity of most ABL kinase domain mutations observed in patients with imatinib resistance. Although in vitro data show that both agents can inhibit all mutations except T315I, some discrepancies have been observed in a small subset of mutation clones. Cytogenetic clonal evolution is the important resistance mechanism of chronic myeloid leukemia (CML). Accordingly, we observed the clinical significance of coexisting with clonal evolution and BCR-ABL mutant in CML patients treated with second TKIs. We monitored BCR-ABL transcript kinetics, interrelationship of clones expressing non-mutated and mutant transcripts and clonal aberrations within Philadelphia (Ph) positive and negative clones, respectively, in eight patients with CML receiving dasatinib or nilotinib for 3~41 months. Clinical responses were correlated with in vitro sensitivity of the BCR-ABL mutants to the second TKIs in four patients. Four patients showed resistance to the second TKIs as compared to in vitro observations; three of them developed chromosomal abnormalities in the Ph chromosome positive or negative metaphases. Another patient lost the original mutation but acquired a more resistant new mutation and became resistant to the second TKI. Cytogenetic clonal evolution is an independent poor prognostic factor in CML, which could explain the onset of mechanisms for second TKIs resistance to ABL kinase domain mutations. The results indicate that an additional evaluation of chromosomal abnormalities is warranted when BCR-ABL mutants are more resistant than indicated by in vitro data.


Near-infrared absorbing ligand-oxidized dinuclear phthalocyanines.
Ligand-oxidized annulated dinuclear phthalocyanine zinc(II) and lithium(I) complexes absorbing in the NIR region (lambda=1000-2200 nm) with high extinction coefficients are described. Analogous mononuclear Pc complexes were used for comparison. The oxidized Pcs were characterized in solution by electronic absorption, EPR and NMR spectra. The NIR transitions were explained by using MO diagrams calculated semiempirically. The reversible oxidation behavior of the phthalocyanine complexes was also estimated by cyclic voltammetry. These new extremely long wavelength absorbing phthalocyanines are interesting as materials with new electronic properties.


Optimization of the mechanical performance of bacterial cellulose/poly(L-lactic) acid composites.
Understanding the nature of the interface between nanofibers and polymer resins in composite materials is challenging because of the complexity of interactions that may occur between fibers and between the matrix and the fibers. The ability to select the most efficient amount of reinforcement for stress transfer, making a saving on both cost and weight, is also a key part of composite design. The use of Raman spectroscopy to investigate micromechanical properties of laminated bacterial cellulose (BC)/poly(l-lactic) acid (PLLA) resin composites is reported for the first time as a means for understanding the fundamental stress-transfer processes in these composites, but also as a tool to select appropriate processing and volume fraction of the reinforcing fibers. Two forms of BC networks are investigated, namely, one cultured for 3 days and another for 6 days. The mechanical properties of the latter were found to be higher than the former in terms of Young's modulus, stress at failure, and work of fracture. However, their specific Young's moduli (divided by density) were found to be similar. Young's modulus and stress at failure of transparent predominantly amorphous PLLA films were found to increase by 100 and 315%, respectively, for an 18% volume fraction of BC fibers. BC networks cultured for 3 days were shown to exhibit enhanced interaction with PLLA because of their higher total surface area compared, as measured by nitrogen adsorption, to the material cultured for 6 days. This enhanced interaction is confirmed by using the Raman spectroscopic approach, whereby larger band shift rates, of a peak initially located at 1095 cm(-1), with respect to both strain and stress, are observed, which is a quantitative measure of enhanced stress transfer. Thermal analysis (differential scanning calorimetry) and electron microscopy imaging (scanning electron microscopy) of the samples also confirms the enhanced coupling between the resin and the BC networks cultured for 3 days, compared to those cultured for 6 days. These results are shown to have implications for the use of BC networks for composite reinforcement, whereby less material can be used for the same specific mechanical properties. The technique also gives opportunities to study the interfaces in these composite materials in detail.


Assessing the Performance of Thin-Film Nanofiltration Membranes with Embedded Montmorillonites.
In this study, the basal spacing of montmorillonite (MMT) was modified through ion exchange. Two kinds of MMT were used: sodium-modified MMT (Na-MMT) and organo-modified MMT (O-MMT). These two particles were incorporated separately into the thin-film nanocomposite polyamide membrane through the interfacial polymerization of piperazine and trimesoyl chloride in n-hexane. The membrane with O-MMT (TFNO-MMT) has a more hydrophilic surface compared to that of membrane with Na-MMT (TFNNa-MMT). When various types of MMT were dispersed in the n-hexane solution with trimesoyl chloride (TMC), O-MMT was well-dispersed than Na-MMT. The poor dispersion of Na-MMT in n-hexane led to the aggregation of Na-MMT on the surface of TFNNa-MMT. TFNO-MMT displayed a uniform distribution of O-MMT on the surface, because O-MMT was well-dispersed in n-hexane. In comparison with the pristine and TFNNa-MMT membranes, TFNO-MMT delivered the highest pure water flux of 53.15 ± 3.30 L∙m-2∙h-1 at 6 bar, while its salt rejection for divalent ions remained at 95%-99%. Furthermore, it had stable performance in wide operating condition, and it exhibited a magnificent antifouling property. Therefore, a suitable type of MMT could lead to high separation efficiency.


Commensurate CO2 Capture, and Shape Selectivity for HCCH over H2CCH2, in Zigzag Channels of a Robust Cu(I)(CN)(L) Metal-Organic Framework.
A novel copper(I) metal-organic framework (MOF), {[Cu(I)2(py-pzpypz)2(μ-CN)2]·MeCN}n (1·MeCN), with an unusual topology is shown to be robust, retaining crystallinity during desolvation to give 1, which has also been structurally characterized [py-pzpypz is 4-(4-pyridyl)-2,5-dipyrazylpyridine)]. Zigzag-shaped channels, which in 1·MeCN were occupied by disordered MeCN molecules, run along the c axis of 1, resulting in a significant solvent-accessible void space (9.6% of the unit cell volume). These tight zigzags, bordered by (Cu(I)CN)n chains, make 1 an ideal candidate for investigations into shape-based selectivity. MOF 1 shows a moderate enthalpy of adsorption for binding CO2 (-32 kJ mol(-1) at moderate loadings), which results in a good selectivity for CO2 over N2 of 4.8:1 under real-world operating conditions of a 15:85 CO2/N2 mixture at 1 bar. Furthermore, 1 was investigated for shape-based selectivity of small hydrocarbons, revealing preferential uptake of linear acetylene gas over ethylene and methane, partially due to kinetic trapping of the guests with larger kinetic diameters.


Treatment with vitamin D and calcium reduces bone loss after renal transplantation: a randomized study.
A decrease in bone mineral density (BMD) is a major complication of renal transplantation (RTx), predominantly occurring within the first 6 mo after RTx. The most important causative factor is the use of corticosteroids, but persisting hyperparathyroidism and abnormalities in vitamin D metabolism play a role too. This study examines the effect of treatment with calcium and active vitamin D on the loss of BMD in the first 6 mo after RTx. A total of 111 renal transplant recipients (65 men, 46 women; age, 47 +/- 13 yr) were randomized to either treatment with active vitamin D (0.25 microg/d) plus calcium (1000 mg/d) (CaD group), or to no treatment (NoT group). Immunosuppressive therapy consisted of cyclosporine, prednisone, and mycophenolate mofetil. Laboratory parameters and BMD (lumbar spine and hip) were measured at 0, 1 (laboratory only), 3, and 6 mo after RTx. Lumbar BMD was nearly normal at the time of RTx. In both groups, a significant decrease in lumbar BMD was observed during the first 3 mo (CaD, -3.3 +/- 4.3%; P < 0.0001; NoT, -4.1 +/- 4.8%; P < 0.0001). Between the third day and sixth month, lumbar BMD slightly recovered in the CaD group, but it decreased further in the NoT group (total loss 0 to 6 mo: CaD, -2.6 +/- 5.0% [P < 0.001]; NoT, -5.0 +/- 4.7% [P < 0.0001]). As a result, the amount of bone loss at 6 mo was significantly lower in the CaD group (P = 0.02). Loss of BMD at the different femoral sites was also significantly reduced in the CaD group. Apart from a trend toward more frequent hypercalcemia in the CaD group, no clinical or biochemical differences existed between the groups. Treatment with a low dose of active vitamin D and calcium partially prevents bone loss at the lumbar spine and proximal femur during the first 6 mo after RTx.


Recursive Factorization of the Inverse Overlap Matrix in Linear-Scaling Quantum Molecular Dynamics Simulations.
We present a reduced complexity algorithm to compute the inverse overlap factors required to solve the generalized eigenvalue problem in a quantum-based molecular dynamics (MD) simulation. Our method is based on the recursive, iterative refinement of an initial guess of Z (inverse square root of the overlap matrix S). The initial guess of Z is obtained beforehand by using either an approximate divide-and-conquer technique or dynamical methods, propagated within an extended Lagrangian dynamics from previous MD time steps. With this formulation, we achieve long-term stability and energy conservation even under the incomplete, approximate, iterative refinement of Z. Linear-scaling performance is obtained using numerically thresholded sparse matrix algebra based on the ELLPACK-R sparse matrix data format, which also enables efficient shared-memory parallelization. As we show in this article using self-consistent density-functional-based tight-binding MD, our approach is faster than conventional methods based on the diagonalization of overlap matrix S for systems as small as a few hundred atoms, substantially accelerating quantum-based simulations even for molecular structures of intermediate size. For a 4158-atom water-solvated polyalanine system, we find an average speedup factor of 122 for the computation of Z in each MD step.


Effect of bioaugmentation on digestate metal concentrations in anaerobic digestion of sewage sludge.
This study examined the influence of bioaugmentation on metal concentrations (aluminum, cadmium, chromium, cobalt, copper, iron, lead, manganese, molybdenum, nickel and zinc) in anaerobically digested sewage sludge. To improve the digestion efficiency, bioaugmentation with a mixture of wild-living Archaea and Bacteria (MAB) from Yellowstone National Park, USA, was used. The total concentration of all metals was higher in the digestate than in the feedstock. During anaerobic digestion, the percent increase in the concentration of most of metals was slightly higher in the bioaugmented runs than in the un-augmented runs, but these differences were not statistically significant. However, the percent increase in cadmium and cobalt concentration was significantly higher in the bioaugmented runs than in the un-augmented runs. At MAB doses of 9 and 13% v/v, cadmium concentration in the digestate was 211 and 308% higher than in the feedstock, respectively, and cobalt concentration was 138 and 165%, respectively. Bioaugmentation increased over 4 times the percentage of Pseudomonas sp. in the biomass that are able to efficiently accumulate metals by both extracellular adsorption and intracellular uptake. Biogas production was not affected by the increased metal concentrations. In conclusion, bioaugmentation increased the concentration of metals in dry sludge, which means that it could potentially have negative effects on the environment.