[Pathomechanisms of podocyte injury in diabetic nephropathy and interventional effects of Chinese herbal medicine].
Podocyte injury is closely related to proteinuria in the progress of diabetic nephropathy(DN). The pathological characters of podocyte injury mainly refer to the change of podocyte form and function, including foot process effacement, reduction of podocyte number and density, podocyte apoptosis, podocyte epithelial-mesenchymal transdifferentiation(EMT)and podocyte hypertrophy. These pathological damages are controlled by multiple signaling pathways in the kidney, such as mammalian target of rapamycin(mTOR)/autophagy pathway, transforming growth factor(TGF)-β1 pathway and Notch pathway. For podocyte injuries induced by high glucose or in murine models of DN, some Chinese herbal medicine(CHM)extracts, such as multiglycoside of Tripterygium wilfordii(GTW), triptolide(TP), astragaloside IV(AS-IV), astragalus polysaccharide(APS)and Panax notoginseng saponins(PNS), have the protective effects in vivo or in vitro. The preliminary studies in China showed that GTW improves podocyte injury in the DN model rats probably through regulating the activity of mTORC1 signaling pathway in the kidney. Therefore, it is the developmental direction for the further study to clarify the interventional effects of CHM based on podocyte injury-related signaling pathway in DN.


Cell-type specific role of the RNA-binding protein, NONO, in the DNA double-strand break response in the mouse testes.
The tandem RNA recognition motif protein, NONO, was previously identified as a candidate DNA double-strand break (DSB) repair factor in a biochemical screen for proteins with end-joining stimulatory activity. Subsequent work showed that NONO and its binding partner, SFPQ, have many of the properties expected for bona fide repair factors in cell-based assays. Their contribution to the DNA damage response in intact tissue in vivo has not, however, been demonstrated. Here we compare DNA damage sensitivity in the testes of wild-type mice versus mice bearing a null allele of the NONO homologue (Nono gt). In wild-type mice, NONO protein was present in Sertoli, peritubular myoid, and interstitial cells, with an increase in expression following induction of DNA damage. As expected for the product of an X-linked gene, NONO was not detected in germ cells. The Nono gt/0 mice had at most a mild testis developmental phenotype in the absence of genotoxic stress. However, following irradiation at sublethal, 2-4 Gy doses, Nono gt/0 mice displayed a number of indicators of radiosensitivity as compared to their wild-type counterparts. These included higher levels of persistent DSB repair foci, increased numbers of apoptotic cells in the seminiferous tubules, and partial degeneration of the blood-testis barrier. There was also an almost complete loss of germ cells at later times following irradiation, evidently arising as an indirect effect reflecting loss of stromal support. Results demonstrate a role for NONO protein in protection against direct and indirect biological effects of ionizing radiation in the whole animal.


Mesoporous silica microparticles gated with a bulky azo derivative for the controlled release of dyes/drugs in colon.
Mesoporous silica microparticles were prepared, loaded with the dye safranin O (M-Saf) or with the drug budesonide (M-Bud) and capped by the grafting of a bulky azo derivative. Cargo release from M-Saf at different pH values (mimicking those found in the gastrointestinal tract) in the absence or presence of sodium dithionite (a reducing agent mimicking azoreductase enzyme present in the colon) was tested. Negligible safranin O release was observed at pH 6.8 and 4.5, whereas a moderate delivery at pH 1.2 was noted and attributed to the hydrolysis of the urea bond that linked the azo derivative onto the external surface of the inorganic scaffold. Moreover, a marked release was observed when sodium dithionite was present and was ascribed to the rupture of the azo bond in the molecular gate. Budesonide release from M-Bud in the presence of sodium dithionite was also assessed by ultraviolet-visible spectroscopy and high performance liquid chromatography measurements. In addition, preliminary in vivo experiments with M-Saf carried out in mice indicated that the chemical integrity of the microparticles remained unaltered in the stomach and the small intestine, and safranin O seemed to be released in the colon.


Elevated serum calcitonin levels in patients with thyroid disorders.
Serum calcitonin was measured by radioimmunoassay (RIA) in 63 patients with hyperthyroidism, 37 with hypothyroidism, 9 with surgically proven medullary thyroid carcinoma (MTC) and 81 normal subjects. Provocative tests of calcitonin by calcium infusion were performed in 11 with hyperthyroidism, 10 with hypothyroidism, 6 with MTC and 14 normal subjects. Changes of calcitonin were also studied before and after treatment in 17 patients with hyperthyroidism and 12 with hypothyroidism. The basal calcitonin levels were increased in both hyperthyroidism (117 +/- 60.1 pg/ml (mean +/- SD): n = 63, P less than 0.001) and hypothyroidism (137 +/- 107 pg/ml, n = 37, P less than 0.001), and significantly increased in MTC 14 765 +/- 25 039 pg/ml, range 390 to 70 400 pg/ml, n = 9, P less than 0.001) compared with those in normal subjects (45.8 +/- 22.3 pg/ml, n = 81). Increases of calcitonin during calcium load (iv 4.5 mg calcium/kg for 10 min) were significantly lower in both hyperthyroidism and hypothyroidism patients than in those in MTC. The calcitonin levels were not correlated with the serum T3, T4, TSH concentrations or titres of serum antithyroid antibodies in hyperthyroidism and hypothyroidism. We found some tendency toward decreasing calcitonin levels with the euthyroid state after treatment in both groups, but the changes were not significant. Although exact mechanisms of increased calcitonin in hyperthyroidism and hypothyroidism were not clear, our findings suggest that a 2- to 3-fold elevation of calcitonin levels in these patients did not indicate malignancy; MTC could be readily differentiated by a calcium infusion test.


Clinical expression and treatment response among children with comorbid obsessive compulsive disorder and attention-deficit/hyperactivity disorder.
Paediatric obsessive-compulsive disorder (OCD) is highly comorbid with other psychological disorders, including attention deficit/hyperactivity disorder (ADHD). Preliminary evidence suggests that youth with comorbid OCD and ADHD may experience greater impairments than children with other comorbidities; however, there is limited research examining the clinical expression and treatment response of these youth. Youth (7 to 17 years) with a primary diagnosis of OCD and comorbid ADHD (n = 40) were compared a sample of age and gender matched youth with OCD and other comorbidity (without ADHD, n = 40). The study investigated symptoms, severity, functioning, comorbidity, family accommodation, in addition to parental psychopathology and rearing styles. Treatment response was investigated at post-treatment and six-month follow-up. Youth with comorbid OCD and ADHD had fewer sexual obsessions, higher rates of comorbidity, poorer executive functioning and higher family impairment. Families of comorbid youth engaged in significantly more accommodation and reported more negative rearing. Finally, comorbid youth were significantly less likely to be responders or remitters at post-treatment. Limitations include the cross-sectional design, relatively small clinical sample, and lack of an experimental control group of youth with ADHD without OCD. Current approaches to treatment may be improved for youth with comorbid OCD and ADHD by addressing cooccurring anxiety, behavioural difficulties, and maladaptive family accommodation and rearing. Moreover, given pronounced deficits in executive function, these youth may require a stronger initial dose of CBT to achieve an adequate response.


[Study of IS-elements aimed at establishing a degree of the relationship of multiple-serotype Streptococcal strains of group B].
The presence and restriction fragment length polymorphism of IS 861 and IS 1548 were analyzed among 113 streptococcal strains of group B. 13 strains were found to possess both IS 861 and IS 1548, 54 strains were found to possess only IS 861, and 46 strains had neither IS 861 nor IS 1548. 9 HindIII and 6 EcoRI restriction patterns, hybridizing correspondingly with IS 861 and IS 1548, were discovered. A certain correlation between IS 1548 and IS 861 hybridizing patterns, on the one hand, and restriction patterns, found by pulse-electrophoresis, on the other hand, was established. It was demonstrated that restriction fragment length polymorphism of IS 1548 and 861 can be used to evaluate the degree of relationship between the strains.


[Inhibitory effects of small interfering RNA targeting c-myc in combination with 5-fluorouracil on the growth in vitro and in vivo].
To observe the effects of small interfere RNA (siRNA) targeting the c-myc in combination with 5-fluorouracil (5-Fu) on the growth of Hep-2 cells in vitro and in vivo. Hep-2 cells transfected with or without c-myc siRNA were treated with 5-Fu for 48 h. C-myc protein levels in Hep-2 cells were detected using the Western blot. The cell cycle was analyzed by flow cytometry. Hep-2 cells were subcutaneously inoculated into the back of BALB/c nude mice to establish the implanted laryngeal squamous carcinoma model. PBS, c-myc siRNA, and 5-Fu, alone or in combinations were administered i.p. The mice were sacrificed after the treatments and the tumor masses were removed to determine the tumor volume and weight. The inhibitory rate was calculated. Expression of c-myc in tumor tissue was detected by immunocytochemistry and cell apoptosis was analyzed by terminal transferase dUTP nick end labeling (TUNEL). The protein levels of c-myc decreased after transfected with c-myc siRNA. C-myc siRNA-transfected cells showed an increase in the percentage of cells in the GO-G1 phase and a decrease in the percentage of cells in the S phase. When combined with 5-Fu, the results were improved. The tumor growth was faster in the control group and was significantly slower in the c-myc siRNA plus 5-Fu group than that in the c-myc siRNA group or 5-Fu group (P < 0.05). The tumor weight in the c-myc siRNA plus 5-Fu group was significantly smaller than that in the c-myc siRNA or 5-Fu group (P < 0.05). Immunohistochemistry showed that c-myc siRNA inhibited the expression of c-myc in tumor tissues in the c-myc siRNA group and c-myc siRNA plus 5-Fu group (P < 0.05). The number of apoptotic cells in the c-myc siRNA plus 5-Fu group was higher than those in the c-myc siRNA groups (P < 0.05). C-myc siRNA inhibits the expression of c-myc in Hep-2 cells and in the tumor tissues of nude mice. C-myc siRNA combined with 5-Fu inhibits the growth of implanted laryngeal squamous carcinoma and promotes cell apoptosis. C-myc could become a novel target for the treatment of laryngeal squamous carcinoma.


Semantic Memory Organization in Japanese Patients With Schizophrenia Examined With Category Fluency.
Disorganization of semantic memory in patients with schizophrenia has been studied by referring to their category fluency performance. Recently, data-mining techniques such as singular value decomposition (SVD) analysis have been reported to be effective in elucidating the latent semantic memory structure in patients with schizophrenia. The aim of this study is to investigate semantic memory organization in patients with schizophrenia using a novel method based on data-mining approach. Category fluency data were collected from 181 patients with schizophrenia and 335 healthy controls at the Department of Psychiatry, Osaka University. The 20 most frequently reported animals were chosen for SVD analysis. In the two-dimensional (2D) solution, item vectors (i.e., animal names) were plotted in the 2D space of each group. In the six-dimensional (6D) solution, inter-item similarities (i.e., cosines) were calculated among items. Cosine charts were also created for the six most frequent items to show the similarities to other animal items. In the 2D spatial representation, the six most frequent items were grouped in the same clusters (i.e., dog, cat as pet cluster, lion, tiger as wild/carnivorous cluster, and elephant, giraffe as wild/herbivorous cluster) for patients and healthy adults. As for 6D spatial cosines, the correlations (Pearson's r) between 17 items commonly generated in the two groups were moderately high. However, cosine charts created for the three pairs from the six most frequent animals (dog-cat, lion-tiger, elephant-giraffe) showed that pair-wise similarities between other animals were less salient in patients with schizophrenia. Semantic memory organization in patients with schizophrenia, revealed by SVD analysis, did not appear to be seriously impaired in the 2D space representation, maintaining a clustering structure similar to that in healthy controls for common animals. However, the coherence of those animals was less salient in 6D space, lacking pair-wise similarities to other members of the animal category. These results suggests subtle but structural differences between the two groups. A data-mining approach by means of SVD analysis seems to be effective in evaluating semantic memory in patients with schizophrenia, providing both a visual representation and an objective measure of the structural alterations.


The effect of esophageal acid volume on arousals from sleep and acid clearance.
To assess the effect of different volumes of acid infused into the esophagus, seven normal volunteers were studied in the waking and sleep state. All subjects were studied for three nights in the sleep laboratory, which included complete polysomnographic monitoring and esophageal pH recording. Multiple infusions of either 5, 15, or 25 ml of 0.1 N HCL were administered each night. Similar infusions were also accomplished in the waking state. The results showed a significant (p less than 0.05) decrease in the arousal from sleep with 25-ml vs 5-ml infusions. During sleep, the latency to the first swallow was significantly (p less than .05) shorter with the 25-ml infusion when compared with that of the 5-ml infusion. While awake, the infusion volume did not affect the latency to the first swallow. The acid clearance times were not significantly altered by the different volumes infused. It is concluded that the larger volumes of acid in the esophagus create an afferent "warning" signal to the central nervous system to produce a rapid arousal from sleep along with a shortened interval to the first swallow. These responses rapidly empty the larger acid volumes from the esophagus.


Expression and organization of basement membranes and focal adhesion proteins in pregnant myometrium is regulated by uterine stretch.
The mechanisms underlying the preparation of the uterus for labor are not fully understood. We have previously found a significant increase in the expression of messenger RNA (mRNAs) encoding extracellular basement membrane (BM) proteins of the smooth muscle cells (SMCs) in late pregnant rat myometrium. At term, the myometrium is stretched by growing fetuses and these mechanical signals are transmitted from extracellular matrix into SMCs through focal adhesions (FA). The aim of this study was to investigate the effect of gravidity on the expression and spatiotemporal distribution of major BM proteins, laminin-gamma2 and collagen IV, as well as typical FA constituents, vinculin and paxillin, in the myometrium during gestation and parturition, using a unilaterally pregnant rat model. We found that the expression of laminin-gamma2 and collagen IV proteins increased significantly with gestational age (P < .05) and was dependent on gravidity whereas vinculin and paxillin proteins were not affected. Near term, BM proteins from gravid horn myometrium demonstrated increased extracellular immunostaining and major rearrangement from sporadic protein distribution to organized, continuous, and regular structures surrounding the plasma membrane of each myocyte. Examination of FA proteins revealed that paxillin was translocated from the cytoplasm to the cell periphery, while vinculin was sequestered specifically to FAs. At labor, BM and FA proteins, organized in similar bead-like structures, were localized on opposing sides of SMC plasma membrane into 2 different compartments. We suggest that these stretch-induced changes facilitate formation of stable cell-matrix adhesions and provide the molecular basis for optimal force transduction during labor contractions.


Nudging Strategies for Arable Land Protection Behavior in China.
Arable land protection is critical to the sustainable development of agriculture in China and acceleration of the realization of the trinity protection goal of the quantity, quality, and ecology of arable land. As a new program of behavioral science to promote social development, nudge has gradually gained the favor of researchers and policy makers due to its unique advantages of small cost and substantial effect. However, current research and practical exploration of arable land protection behavior intervention based on the idea of nudging are still lacking. Implicit nudging strategies directly target the heuristic and analytic systems of arable land protection behavior of each stakeholder and possess more advantages than traditional intervention strategies. Therefore, this article designs six arable land protection behavior nudging strategies from the perspectives of cognition and motivation to realize the theoretical discussion of "generating medium-scale returns with nano-level investment". The nudging strategies of the cognitive perspective include default options, framing effects, and descriptive norms, while those of the motivation perspective aim to stimulate home and country, and heritage and benefit motives to promote arable land protection behavior of various stakeholders. The utility of nudge to arable land protection behavior may be controversial in practice. Therefore, the implementation in China should be based on the division of farmers, the number of options should be appropriate, and the external environment of arable land protection behavior should be fully considered.


[Special aspects of abdominal adhesions in gynecology].
Even minor adhesions in the oviduct or in the ovarial region may lead to infertility. In a controlled trial the adhesion status was documented in 103 patients who underwent microsurgical operations for infertility. Solutions of (a) streptokinase/streptodornase, (b) hydrocortisone acetate or (c) Ringer's solution only were administered intraperitoneally as adhesion prophylaxis. During a control laparoscopy 1 week after the primary operation, newly formed adhesions of mainly intermediate extent were observed in about 10% of the patients. There was no significant difference in efficacy between the prophylactic treatment.


E-nose based rapid prediction of early mouldy grain using probabilistic neural networks.
In this paper, early mouldy grain rapid prediction method using probabilistic neural network (PNN) and electronic nose (e-nose) was studied. E-nose responses to rice, red bean, and oat samples with different qualities were measured and recorded. E-nose data was analyzed using principal component analysis (PCA), back propagation (BP) network, and PNN, respectively. Results indicated that PCA and BP network could not clearly discriminate grain samples with different mouldy status and showed poor predicting accuracy. PNN showed satisfying discriminating abilities to grain samples with an accuracy of 93.75%. E-nose combined with PNN is effective for early mouldy grain prediction.


A case study of 2019-nCoV in Russia using integer and fractional order derivatives.
In this article, we define a mathematical model to analyze the outbreaks of the most deadly disease of the decade named 2019-nCoV by using integer and fractional order derivatives. For the case study, the real data of Russia is taken to perform novel parameter estimation by using the Trust Region Reflective (TRR) algorithm. First, we define an integer order model and then generalize it by using fractional derivatives. A novel optimal control problem is derived to see the impact of possible preventive measures against the spread of 2019-nCoV. We implement the forward-backward sweep method to numerically solve our proposed model and control problem. A number of graphs have been plotted to see the impact of the proposed control practically. The Russian data-based parameter estimation along with the proposal of a mathematical model in the sense of Caputo fractional derivative that contains the memory term in the system are the main novel features of this study.


A programme to create short-course chemotherapy for pulmonary Mycobacterium avium disease based on pharmacokinetics/pharmacodynamics and mathematical forecasting.
Pulmonary Mycobacterium avium complex (MAC) prevalence is on the rise worldwide. The average therapy duration is 1.5 years, which is associated with poor cure rates. Our objective was to develop a programme to design a combination therapy regimen for pulmonary MAC to be administered for 6 months or less with efficacy in > 90% of patients. We performed a literature search for the following MeSH headings 'Mycobacterium avium' AND 'pharmacokinetics/pharmacodynamics' in PubMed up to 2016. The findings were then used to identify steps in the programme to design new regimens with faster microbial kill rates than the current standard regimen. First, we designed a strategy for rapid in vitro screening of all antibiotic classes for repurposing against pulmonary MAC. Secondly, we identified and compared maximal microbial kill rates (Emax), and optimal exposures of eight different antibiotics. These studies had all been performed in the hollow-fibre system model of pulmonary MAC (HFS-MAC). Thirdly, all drugs with a high Emax at clinically achievable optimal exposures will be chosen, and exposures associated with synergy or additivity for two/three drugs identified based on Bliss independence. Fourthly, the time-kill slopes and resistance suppression of the chosen combinations will be compared with those of standard combination therapy in the HFS-MAC. Finally, we will identify the clinical doses best able to achieve synergistic or additive combination exposures by taking into account pharmacokinetic variability. Our stepwise pharmacokinetics/pharmacodynamics approach provides a scientific rationale and a strategy for achieving short-course chemotherapy for pulmonary MAC disease within a few years.


Pharmacokinetics of peptide mediated delivery of anticancer drug ellipticine.
The amino acid pairing peptide EAK16-II (EAK) has shown the ability to stabilize the hydrophobic anticancer agent ellipticine (EPT) in aqueous solution. In this study, we investigate pharmacokinetics of the formulation of EAK-EPT complexes in vivo. The developed formulation can achieve a sufficiently high drug concentration required in vivo animal models. The nanostructure and surface properties of EAK-EPT complexes or nanoparticle were characterized by transmission electron microscopy (TEM) and zeta potential measurements, respectively. 12 healthy male SD rats were divided into EPT group and EAK-EPT group randomly. Rats in EPT group were tail intravenously injected with the EPT (20 mg/kg); rats in EAK-EPT group were injected with EAK-EPT complexes (EPT's concentration is 20 mg/kg). EPT was extracted from rat plasma with dexamethasone sodium phosphate as internal standards (IS). The pharmacokinetic parameters were obtained using high pressure liquid chromatography (HPLC). Significant differences in main pharmacokinetic parameters between EPT and EAK-EPT complexes were observed, demonstrating that the complexation with EAK prolongs the residence time of the drug and enlarges the area under the concentration-time curve (AUC). This means that EAK can serve as a suitable carrier to increase the bioavailability of EPT.


The Development of Chinese Medical Education.
This paper mainly introduces the current situation of Chinese medical education, and reviews the development and transformation of Chinese clinical medical education. Overall, Chinese clinical medical education is gradually towards standardization and internationalization. At the same time, scientific research is playing an increasingly important role in Chinese clinical medical education.


The genetic basis of prezygotic reproductive isolation between Drosophila santomea and D. yakuba due to mating preference.
Sexual isolating mechanisms that act before fertilization are often considered the most important genetic barriers leading to speciation in animals. While progress has been made toward understanding the genetic basis of the postzygotic isolating mechanisms of hybrid sterility and inviability, little is known about the genetic basis of prezygotic sexual isolation. Here, we map quantitative trait loci (QTL) contributing to prezygotic reproductive isolation between the sibling species Drosophila santomea and D. yakuba. We mapped at least three QTL affecting discrimination of D. santomea females against D. yakuba males: one X-linked and one autosomal QTL affected the likelihood of copulation, and a second X chromosome QTL affected copulation latency. Three autosomal QTL also affected mating success of D. yakuba males with D. santomea. No epistasis was detected between QTL affecting sexual isolation. The QTL do not overlap between males and females and are not disproportionately concentrated on the X chromosome. There was some overlap in map locations of QTL affecting sexual isolation between D. santomea and D. yakuba with QTL affecting sexual isolation between D. simulans and D. mauritiana and with QTL affecting differences in pigmentation between D. santomea and D. yakuba. Future high-resolution mapping and, ultimately, positional cloning, will reveal whether these traits do indeed have a common genetic basis.


Induced Dwarf Mutant in Catharanthus roseus with Enhanced Antibacterial Activity.
Evaluation of an ethyl methane sulphonate-induced dwarf mutant of Catharanthus roseus (L.) G. Don revealed that the mutant exhibited marked variation in morphometric parameters. The in vitro antibacterial activity of the aqueous and alcoholic leaf extracts of the mutant and control plants was investigated against medically important bacteria. The mutant leaf extracts showed enhanced antibacterial activity against all the tested bacteria except Bacillus subtilis.


Applying Corrigan's progressive model of self-stigma to people with depression.
The progressive model of self-stigma describes four stages of internalizing stereotypes of mental illness: stereotype awareness, personal agreement, self-concurrence, and harm to self (i.e., self-esteem). Successive stages are postulated to be the most highly related. Endorsement is presumed to decrease by stage. The model has been supported in most but not all elements in various studies. The procedural character has not yet been investigated in one integrative model. The aim of this study was to test the progressive model of self-stigma in three respects: I) successive stages have the strongest associations, II) endorsements decrease with each stage, and III) the procedural character can be represented by one serial mediation model. A cross-sectional computer-based survey was conducted in two samples of patients with depression; one online sample (NA = 550; only self-report) and one clinical face-to-face sample (NB = 180; screening by treatment staff). The inclusion criteria were, age of 18-70 years, sufficient cognitive abilities and German language skills. IBM SPSS statistics 24 was used for Cronbach's alphas, descriptive statistics, Spearman correlations, and Mann-Whitney-U tests. The PROCESS procedure for SPSS Version 3.00 was used for mediation analyses. The results support the progressive model of self-stigma in people with depression in most respects: Endorsements for stereotype awareness were higher than for personal agreement and self-concurrence, and no relevant difference was found between personal agreement and self-concurrence. Successive stages had the strongest associations, with the exception of the association between stereotype awareness and self-esteem, which was higher than the association between stereotype awareness and personal agreement and self-concurrence. The association between stereotype awareness and self-esteem was mediated via personal agreement and self-concurrence. The progressive model of self-stigma offers a theoretical foundation for the process research of self-stigma. Longitudinal research may investigate predictive effects and whether different stages of self-stigma require specific consideration in their prediction, consequences, and potential interventions.


The connecdenn family, Rab35 guanine nucleotide exchange factors interfacing with the clathrin machinery.
Rabs constitute the largest family of monomeric GTPases, yet for the majority of Rabs relatively little is known about their activation and recruitment to vesicle-trafficking pathways. We recently identified connecdenn (DENND1A), which contains an N-terminal DENN (differentially expressed in neoplastic versus normal cells) domain, a common and evolutionarily ancient protein module. Through its DENN domain, connecdenn functions enzymatically as a guanine-nucleotide exchange factor (GEF) for Rab35. Here we identify two additional connecdenn family members and demonstrate that all connecdenns function as Rab35 GEFs, albeit with different levels of activity. The DENN domain of connecdenn 1 and 2 binds Rab35, whereas connecdenn 3 does not, indicating that Rab35 binding and activation are separable functions. Through their highly divergent C termini, each of the connecdenns binds to clathrin and to the clathrin adaptor AP-2. Interestingly, all three connecdenns use different mechanisms to bind AP-2. Characterization of connecdenn 2 reveals binding to the beta2-ear of AP-2 on a site that overlaps with that used by the autosomal recessive hypercholesterolemia protein and betaarrestin, although the sequence used by connecdenn 2 is unique. Loss of connecdenn 2 function through small interference RNA knockdown results in an enlargement of early endosomes, similar to what is observed upon loss of Rab35 activity. Our studies reveal connecdenn DENN domains as generalized GEFs for Rab35 and identify a new AP-2-binding motif, demonstrating a complex link between the clathrin machinery and Rab35 activation.


[Applications of terahertz spectroscopy and imaging techniques in food safety inspection].
With the development of ultra-fast laser technology and the further understanding of the mechanism behind the interaction of terahertz radiation and materials, THz radiation is actively developed as a new-style technology for a wide range of applications. Currently THz spectroscopy and imaging techniques show great promise in security detection, medical diagnosis, wireless communication, pharmaceutical and many other areas. Because of the growing importance of food safety issues, the detection technology of food safety is also faced with great opportunities and challenges, while THz spectroscopy and imaging techniques provide a new solution to the problem. Compared to other technologies, THz radiation with higher signal-to-noise ratio and wide dynamic range can simultaneously obtain both frequency-domain and time-domain information of the sample which relates to the information of physical structure and chemical composition of materials. Above all THz radiation features unique advantages in food safety inspection. In the present paper, the brief concept of terahertz radiation was introduced, while the properties and technical methods of THz wave were also discussed. The most recent progress in THz technology used in food safety inspection was summarized. The prospect and restricted factors of this novel technology in food industry were also discussed.


General practitioner diagnosis of depression and dementia in the elderly: can academic detailing make a difference?
The objective was to improve the ability of general practitioners (GPs) to diagnose depression and dementia compared with standard screening measures. The setting was a retirement village on the outskirts of Sydney, Australia. The study used a prepost design with a 6 month follow-up. The intervention involved a visit to the GP by an academic detailer who spent 15 minutes discussing the diagnosis of depression and dementia. Ratings of depression and dementia on two occasions by GPs, and by independent interviews were made using the Geriatric Depression Scale, Mini-mental State Examination and Canberra Interview for the Elderly. In the case of depression, the level of agreement (Kappa) between the GPs and all instruments increased significantly by a factor of between 2.3 and 3.3. The doctors did not significantly improve in their agreement with the instruments on the diagnosis of dementia. An academic detailing approach to improving GPs' abilities in the diagnosis of depression can be effective. A controlled trial would be justified to confirm this finding.


Iron absorption from infant formula and iron-fortified cow's milk: experimental model in weanling rats.
To compare iron absorption from infant formula and iron-fortified cow's milk. Twenty-four weanling Wistar rats were maintained in metabolic cages during the whole experiment (10 days). On the first day, the animals were divided into three similar groups according to their weight, length, hematocrit and hemoglobin levels: 1) infant formula; 2) powdered whole cow's milk fortified with iron in the same quantity and type as the formula; 3) control--powdered whole cow's milk not fortified with iron. Deionized water and diet were offered ad libitum and the volume consumed was measured. Weight, hematocrit, and hemoglobin levels were measured on the fifth and 10th days when length, fecal occult blood, and hepatic iron levels were also analyzed. Group 1 consumed less diet (450.5+/-26.50 mL) than group 2 (658.8+/-53.73 mL) and control group (532.7+/-19.06 mL, p < 0.001). Hemoglobin levels were higher (p < 0.001) in group 1 (12.1+/-1.13 g/dL) than in group 2 (9.6+/-1.59 g/dL) and in control group (6.2+/-0.97 g/dL). Hepatic iron level showed the same pattern as hemoglobin (p < 0.001). There was no difference in weight and length between the three groups (p = 0.342). There was no fecal occult blood in the any of the animals. Despite the lower volume consumed, the group that received formula presented higher iron absorption and hemoglobin levels than the group fed with fortified whole cow's milk. Growth was similar in the three groups.


Orbital order in ZnV(2)O(4).
In view of recent controversy regarding the orbital order in the frustrated spinel ZnV(2)O(4), we analyze the orbital and magnetic ground state of this system within an ab initio density functional theory approach. While local density approximation+Hubbard U calculations in the presence of a cooperative Jahn-Teller distortion stabilize an A-type staggered orbital order, the consideration of relativistic spin-orbit (SO) effects unquenches the orbital moment and leads to a uniform orbital order with a net magnetic moment close to the experimental one. Our results show that ab initio calculations are able to resolve the existing discrepancies in previous theories and that it is the SO coupling along with electronic correlations which play a significant role in determining the orbital structure in these materials.


Somatic nonhomologous crossing-over between neuropeptide genes in rat hypothalamic neurons.
Molecular biological and immunocytochemical data demonstrate nonhomologous crossing-over between the closely linked vasopressin (VP) and oxytocin (OT) genes in rat hypothalamic neuroendocrine neurons. Reverse transcription of hypothalamic total RNA from wild-type or homozygous Brattleboro aged rats combined with polymerase chain reaction (PCR) amplifications in the presence of appropriate 5' forward and 3' reverse primers deduced from the VP and OT cDNA sequences yielded PCR products that, upon cloning and sequencing, revealed several hybrid transcripts. They encode the N-terminal part of the VP precursor fused to the C-terminal part of the OT precursor (VP/OT transcripts) and vice versa (OT/VP transcripts). VP/OT hybrid precursor proteins have been identified immunocytochemically in enlarged cisternae of the rough endoplasmic reticulum, yet there is no evidence that the products can be secreted from affected cells. Recombination appears to be a rather frequent genetic event affecting about 0.06-0.1% of the rat vasopressinergic magnocellular neurons in aged rats.


Use of gray values in CBCT and MSCT images for determination of density: influence of variation of FOV size.
To determine the effect of field of view (FOV) size on gray values in cone beam computed tomography (CBCT) and multislice computed tomography (MSCT) images. A phantom made up of 3 cylinders containing distilled water, plaster, and motor oil was constructed and inserted into an acrylic cylinder filled with distilled water. The phantom was scanned with a CBCT and MSCT device using 3 FOV sizes. Gray value of each material was evaluated in 40 axial slices, and the comparison between the results obtained with the same FOV size was made. In CBCT examinations, there was significant difference between the gray values of different FOVs for the 3 materials. In the MSCT, there was significant difference for the oil. Gray values showed significant difference between the CBCT and MSCT examinations for the 3 materials in the 3 different FOV sizes. Gray values determined in CBCT images are significantly influenced by the FOV size. Although the gray values obtained in MSCT have shown statistically significant differences between some acquisitions, the analysis of those differences seems to indicate low clinical relevance.


Gene expression changes in thalamus and inferior colliculus associated with inflammation, cellular stress, metabolism and structural damage in thiamine deficiency.
Identification of gene expression changes that promote focal neuronal death and neurological dysfunction can further our understanding of the pathophysiology of these disease states and could lead to new pharmacological and molecular therapies. Impairment of oxidative metabolism is a pathogenetic mechanism underlying neuronal death in many chronic neurodegenerative diseases as well as in Wernicke's encephalopathy (WE), a disorder induced by thiamine deficiency (TD). To identify functional pathways that lead to neuronal damage in this disorder, we have examined gene expression changes in the vulnerable thalamus and inferior colliculus of TD rats using Affymetrix Rat Genome GeneChip analysis in combination with gene ontology and functional categorization assessment utilizing the NetAffx GO Mining Tool. Of the 15 927 transcripts analysed, 125 in thalamus and 141 in inferior colliculus were more abundantly expressed in TD rats compared with control animals. In both regions, the major functional categories of transcripts that were increased in abundance after TD were those associated with inflammation (approximately 33%), stress (approximately 20%), cell death and repair ( approximately 26%), and metabolic perturbation (approximately 19%), together constituting approximately 98% of all transcripts up-regulated. These changes occurred against a background of neuronal cell loss and reactive astro- and microgliosis in both structures. Our results indicate that (i) TD produces changes in gene expression that are consistent with the observed dysfunction and pathology, and (ii) similar alterations in expression occur in thalamus and inferior colliculus, brain regions previously considered to differ in pathology. These findings provide important new insight into processes responsible for lesion development in TD, and possibly WE.


Intra-Colonial Viral Infections in Western Honey Bees (Apis Mellifera).
RNA viruses play a significant role in the current high losses of pollinators. Although many studies have focused on the epidemiology of western honey bee (Apis mellifera) viruses at the colony level, the dynamics of virus infection within colonies remains poorly explored. In this study, the two main variants of the ubiquitous honey bee virus DWV as well as three major honey bee viruses (SBV, ABPV and BQCV) were analyzed from Varroa-destructor-parasitized pupae. More precisely, RT-qPCR was used to quantify and compare virus genome copies across honey bee pupae at the individual and subfamily levels (i.e., patrilines, sharing the same mother queen but with different drones as fathers). Additionally, virus genome copies were compared in cells parasitized by reproducing and non-reproducing mite foundresses to assess the role of this vector. Only DWV was detected in the samples, and the two variants of this virus significantly differed when comparing the sampling period, colonies and patrilines. Moreover, DWV-A and DWV-B exhibited different infection patterns, reflecting contrasting dynamics. Altogether, these results provide new insight into honey bee diseases and stress the need for more studies about the mechanisms of intra-colonial disease variation in social insects.


Using literature as the framework for a new course.
The award-winning book The Spirit Catches You and You Fall Down,(1) a true story of the collision between two cultures (American and Hmong) with heartrending consequences for the patient, the patient's family, and the medical professionals who care for them, has been favorably reviewed(2) and used to stimulate teaching of cultural diversity, ethics, and professionalism to students and residents. We used it as a required text for a new Patient Doctor Society (PDS) course for 184 first- and second-year medical students. This report describes the scope and contexts in which the book was used to meet specific course goals. PDS is a required 90-hour introduction to medical interviewing, which integrates ethics, communication, clinical reasoning, cultural diversity, humanities, spirituality, integrative medicine, nutrition, and behavioral science. To provide a common experience among these diverse topics, faculty members were asked to use examples from the book to achieve their learning objectives. A required faculty development session illustrated strategies for effectively using the text. Focusing on chapter 13 ("Code X"), dramatic portrayals of differences in beliefs about end-of-life care and clinician-family communication, facilitated the introduction of methods including point-of-view writing, role-plays, and faculty-facilitated discussions as techniques for meeting course objectives. At PDS orientation, we used the same chapter, and had faculty members lead small groups of students using the teaching techniques they acquired. About 90% of students read the book prior to orientation. Students favorably reviewed this three-hour session. For the ethics session, unfacilitated small groups of students were asked to identify and discuss the ethical issues in chapter 11 ("The Big One"), which describes a major turning point in the health care provided to the text's central character, Lia. Each group presented its "moral diagnosis" and ethical arguments for resolution. Class discussion then focused on the diverse views presented, to emphasize the importance of justifying decisions and to practice using tools of ethical analysis. In the communication skills workshop, we excerpted dramatic readings from the book. Faculty members played the roles of the author, the patient's mother, and one of Lia's physicians. The interaction became a dialogue to illustrate the points of view of the participants. The dialogue was used to stimulate discussion about potential pitfalls in physician-patient communication and understanding. In a medical humanities session, excerpts from the book were compared with poetry explicating themes of physician arrogance and humility. The Spirit Catches You and You Fall Down provides a context appropriate to teaching students how to listen to, and learn from patient stories. The story will be reintroduced in the pediatrics clerkship. Caution will be exercised to (1) avoid overexposure to the text, (2) counteract the potential to interpret the story too narrowly, and (3) assure that faculty become familiar with the text and its uses. We intend to track outcomes in knowledge, skills and attitudes for each content area, and observe the degree that the book facilitates achievement of objectives. We will follow several cohorts of students to verify longitudinally the learning effects observed.


Fullerene-Perylenediimide (C60-PDI) Based Systems: An Overview and Synthesis of a Versatile Platform for Their Anchor Engineering.
An overview of the different covalent bonding synthetic strategies of two electron acceptors leading to fullerene-perylenediimide (C60-PDI)-based systems, essentially dyads and triads, is presented, as well as their more important applications. To go further in the development of such electron and photoactive assemblies, an original aromatic platform 5-benzyloxy-3-formylbenzoic acid was synthesized to graft both the PDI dye and the fullerene C60. This new C60-PDI dyad exhibits a free anchoring phenolic function that could be used to attach a third electro- and photoactive unit to study cascade electron and/or energy transfer processes or to obtain unprecedented side-chain polymers in which the C60-PDI dyads are attached as pendant moieties onto the main polymer chain. This C60-PDI dyad was fully characterized, and cyclic voltammetry showed the concomitant reduction process onto both C60 and PDI moieties at identical potential. A quasi-quantitative quenching of fluorescence was demonstrated in this C60-PDI dyad, and an intramolecular energy transfer was suggested between these two units. After deprotection of the benzyloxy group, the free hydroxyl functional group of the platform was used as an anchor to reach a new side-chain methyl methacrylate-based polymer in which the PDI-C60 dyad units are located as pendants of the main polymer chain. Such polymer which associates two complementary acceptors could find interesting applications in optoelectronics and in particular in organic solar cells.


Profiles of steady state levels of messenger RNAs coding for type I procollagen, elastin, and fibronectin in hamster lungs undergoing bleomycin-induced interstitial pulmonary fibrosis.
We have characterized the messenger RNAs (mRNAs) coding for procollagen alpha 1(I), elastin, fibronectin, and actin in the lungs of Syrian golden hamsters by Northern blot analyses. While elastin, fibronectin, and beta-actin were each coded for by a single mRNA species of 4.1 kilobases (kb), 9.1 kb, and 2.1 kb in size, respectively, we identified a major (5.4 kb) and a minor (6.5 kb) procollagen alpha 1(I) mRNA species in the hamster lungs. The mRNAs for the three extracellular matrix proteins showed increased accumulation followed by steady decline in the bleomycin-treated lungs. There were significant differences among the three mRNAs in the relative increase and the time of maximum accumulation. After reaching the peak levels between 2-3 wk posttreatment, the levels of procollagen alpha 1(I) and elastin mRNAs declined to near normal values around the fourth week. In contrast, the accumulation of fibronectin mRNA was maximum in the first week after bleomycin treatment. The procollagen alpha 1(I) mRNA accumulated most dramatically (sevenfold above the levels in the untreated animals) compared with a five-fold increase in mRNA coding for fibronectin. Elastin mRNA increased approximately twofold above the control values. Nuclear runoff transcription experiments demonstrated a selective increase in the rates of transcription of genes coding for procollagen alpha 1(I), fibronectin, and elastin; the extent of transcriptional stimulation of procollagen alpha 1(I) and fibronectin genes was significantly greater than that of elastin. Since the amount of actin mRNA, as well as the rate of transcription of actin gene(s), varied only slightly after bleomycin treatment, we conclude that the metabolism of mRNAs coding for extracellular matrix proteins may be preferentially perturbed during pulmonary fibrosis.


Laws of humanity.
The Human Rights Act should underpin everything nurses do in caring for patients. The topic is the subject of an RCN conference to be held in London on October 26.


[Primary study of relationship between serum level of VEGF and non-Hodgkin's lymphoma in children and adolescent patients].
Angiogenesis is an important mechanism in morbility of malignant tumor, vascular endothelial growth factor (VEGF) is the key factor. This study was to investigate the serum level of VEGF in children and adolescent patients with non-Hodgkin's lymphoma (NHL). The serum levels of VEGF(sVEGF) in 24 pretreated NHL patients were detected by ELISA. sVEGF in 10 of the 24 patients who received complete response after treatment were also detected by ELISA. The average serum VEGF level was 745.79 ng/L (40.64-3623.09 ng/L)in 24 NHL patients. It was higher than normal [(294.20+/-23.40) ng/L]. sVEGF in 18 of the patients were higher than the standard, while in 6 of the patients were lower than the standard. The average serum VEGF level was 289.54 ng/L (35.11-826.8 ng/L) in 10 of The CR patients, 8 cases of them had a high VEGF level before treatment but a nearly normal level after first CR. And 2 cases of them had normal level during the course. The serum level of VEGF in NHL patients was higher than normals. The high serum level of VEGF has a tendency to drop to the normal standard after receiving CR. From the clinical data, a high serum level was not found associated with stage, gender, PS. score, IPI score, serum LDH and "B" symptoms et al.


A new superficial needle-scraping method for assessing Demodex density in papulopustular rosacea.
Standardized skin surface biopsy (SSSB) is often performed to determine the density of Demodex mites in facial papulopustular eruptions. We aimed to test the applicability of a new, "superficial needle-scraping" (SNS) method for assessing Demodex density in papulopustular rosacea (PPR). Using SNS method, we measured the Demodex density in patients with PPR, also enrolling the patients with acne vulgaris as controls. SNS was performed by gently scraping off 5 small pustules with the convex surface of the tip of an 18# needle for examination. For comparison, SSSB was also performed in patients with PPR. Demodex density was expressed as "mites per 5 pustules" for SNS and as "mites per cm2 " for SSSB. A total of 40 patients with PPR and 35 patients with acne vulgaris were recruited. There were no statistically significant differences in age or sex between the PPR and acne groups. The Demodex density was 5.6 ± 4.2 in the PPR group versus 0.3 ± 1.0 in the acne group (P < .001). The cutoff of "≥3 Demodex mites per 5 pustules" gave a sensitivity of 78% and a specificity of 97%, and the area under the receiver operating characteristic curve was 0.89. Moreover, SNS and SSSB gave mutually concordant results (positive or negative) in half of the patients. Our study suggests that SNS is a simple and convenient method for assessing Demodex density of pustules in PPR and can be a useful alternative or addition to SSSB for evaluation of Demodex-associated facial papulopustular eruptions.


New data on some crickets of the subfamilies Landrevinae, Phaloriinae and Podoscirtinae (Orthoptera: Grylloidea) from Laguna (Philippines: Luzon Island).
Recent orthopteran sampling at Laguna in Luzon Island of the Philippines revealed noteworthy crickets from the subfamilies Landrevinae, Phaloriinae and Podoscirtinae. We describe one species new to science from the subfamily Podoscirtinae: Mnesibulus laguna n. sp. We record new locality and complete the genitalia description of Phaloria (Phaloria) modulator (Saussure, 1878), previously described with incomplete parts of genitalia in the holotype. We also differentiate Duolandrevus (Jorama) curtipennis Chopard, 1937 from Laguna which varies slightly from the subspecies from Palawan and Mindoro.


Ontogeny and characterization of basic somatomedin receptors in rat placenta.
We investigated the binding of [125I]basic somatomedin (B-SM) (insulin-like growth factor-I/SM-C in rat placenta. Low but specific [125I]B-SM binding to placenta was detected in rats from the end of the second week (14 days) of gestation. The binding increased until about 17 days of gestation and then reached a plateau. Binding characteristics did not alter during gestation. In contrast to previous observations [125I]B-SM binding to the tissue was competed more effectively by B-SM than multiplication stimulating activity (a rat counterpart of IGF-II). Insulin competed for the binding at a higher concentration. The Scatchard plot derived from the binding competition data was curvilinear. Autoradiograms of affinity labeled B-SM receptors in placentas at different gestational age subsequent to sodium dodecyl sulfate-gel (7.5%) electrophoresis revealed labeled constituents with approximate mol wt greater than 330 K and 140 K in the presence of reductant and greater than 330 K in the absence of reductant. Detailed analysis of the receptor in term placenta subsequent to 5-13% gradient gel containing sodium dodecyl sulfate revealed two more labeled components (mol wt, 250 K and 36 K) irrespective of the reductant. However, the intensity of the 250 K and 36K was low compared to 140 K and 330 K components. These results suggest that B-SM receptor in rat placenta, similar to human placenta, binds preferentially to type I or 140 K subunit of the 330 K oligomeric SM receptor.


New arylthioindoles and related bioisosteres at the sulfur bridging group. 4. Synthesis, tubulin polymerization, cell growth inhibition, and molecular modeling studies.
New arylthioindoles along with the corresponding ketone and methylene compounds were potent tubulin assembly inhibitors. As growth inhibitors of MCF-7 cells, sulfur derivatives were superior or sometimes equivalent to the ketones, while methylene derivatives were substantially less effective. Esters 24, 27-29, 36, 39, and 41 showed approximately 50% of inhibition on human HeLa and HCT116/chr3 cells at 0.5 microM, and these compounds inhibited the growth of HEK, M14, and U937 cells with IC(50)'s in the 78-220 nM range. While murine macrophage J744.1 cell growth was significantly less affected (20% at higher concentrations), four other nontransformed cell lines remained sensitive to these esters. The effect of drug treatment on cell morphology was examined by time-lapse microscopy. In a protocol set up to evaluate toxicity on the Saccharomyces cerevisiae BY4741 wild type strain, compounds 24 and 54 strongly reduced cell growth, and 29, 36, and 39 also showed significant inhibition.


Repair of iatrogenic large colon perforation using laparoscopic methods. Case report and review of the literature.
Iatrogenic perforation of the colon during elective colonoscopy is a serious complication. Surgical treatment remains the standard of care. We report a patient with a large colonic perforation that occurred during a screening colonoscopy, successfully repaired with laparoscopic methods. Although the safety and efficacy of this approach is not entirely established, laparoscopy can be used to treat iatrogenic colonic perforation when the defect is readily recognized, easily accessible for closure and the bowel preparation is excellent. A laparoscopic approach to treat iatrogenic colon perforation results in decreased morbidity and hospital stay, in addition to a shorter incision length compared to an open method. In those cases where it is feasible and the surgical skill exists, a laparoscopic attempt at colon repair should probably be the initial clinical approach..


Microbiological Etiology of Chronic Skin Lesions in Type 2 Diabetic Subjects.
Skin lesions represent lesions that result in loss of tissues and their joints and often this cutaneous process is a primary or secondary consequence of structural changes in the same skin surface. Type 2 diabetic subjects developing chronic skin lesions in the lower limbs in the western world are steadily increasing. We conducted a study on the etiologic incidence of chronic skin lesions in type II diabetic subjects in the lower limbs compared to subjects with chronic skin lesions (controls). Thirty subjects (group "A") with Chronic Skin Lesions (CSL controls) (19 F-11M, mean age 67.5±7.2) in the lower limbs were admitted to our study according to a randomization scheme and compared a thirty (group "B") type II diabetic patients (18F-12M, mean age 73.5±4.9) with chronic skin lesions (CSL). These two groups "A" and "B" have been studied and compared on the basis of infectious etiology responsible for the infectious skin process. In the subjects of the "A" group we found a positive bacteriological colony test of 9 examinations corresponding to the total 30.0%. In the group called "B" we obtained a colony test positive of 12 subjects over 30 corresponding to 40.0% of the examinations. For the number of bacterial species identified in the "A" group we obtained 7 monomicrobial and 2 poly microbial bacteriological tests, while in the "B" group we observed 3 mono microbial and 9 poly microbial tests. All bacteriological isolates showed "in vitro" sensitivity to satisfactory aminoglycosides with MICs range of 0.78- 1.56mg/L. Data from this study show a different etiology among diabetic subjects than nondiabetic subjects. In fact, in the "B" group, more poly microbial bacteriological findings are found in positive culture studies with subjects in group "A". This phenomenon confirms an alteration of the skin microbiome of diabetic subjects with modification of the "opportunistic role" of some species of the skin bacterial flora.


Effect of antipyrine and phenobarbital on renal gamma-glutamyltransferase excretion in human urine.
Serum gamma-glutamyltransferase is used as a marker of hepatic enzyme induction. The kidney contains high activities of gamma-glutamyltransferase in the brush border membrane of the proximal tubule, from which it is released into urine. This study investigated the effect of phenobarbital and antipyrine, two inducers of hepatic monoxygenases and gamma-glutamyltransferase, on the urinary excretion of renal gamma-glutamyltransferase. Three groups (n = 6) of healthy male volunteers received 100 mg phenobarbital for 7 and 14 days and 1200 mg antipyrine for 7 days, respectively. Antipyrine and phenobarbital increased antipyrine elimination, serum gamma-glutamyltransferase, and the urinary excretion of renal gamma-glutamyltransferase, whereas urinary beta-N-acetylglucosaminidase, beta-glucuronidase, and total protein and glucose excretion were unchanged. No correlation was found between serum and urinary gamma-glutamyltransferase or both enzymes and antipyrine elimination. Increases in antipyrine elimination were positively correlated to increases in serum, but not urinary gamma-glutamyltransferase. The findings suggest that antipyrine and phenobarbital increase urinary gamma-glutamyltransferase excretion. However, the increase in urinary gamma-glutamyltransferase does not reflect the magnitude of hepatic enzyme induction.


Lanthanide ion (Ln3+ )-based upconversion sensor for quantification of food contaminants: A review.
The food safety issue has gradually become the focus of attention in modern society. The presence of food contaminants poses a threat to human health and there are a number of interesting researches on the detection of food contaminants. Upconversion nanoparticles (UCNPs) are superior to other fluorescence materials, considering the benefits of large anti-Stokes shifts, high chemical stability, non-autofluorescence, good light penetration ability, and low toxicity. These properties render UCNPs promising candidates as luminescent labels in biodetection, which provides opportunities as a sensitive, accurate, and rapid detection method. This paper intended to review the research progress of food contaminants detection by UCNPs-based sensors. We have proposed the key criteria for UCNPs in the detection of food contaminants. Additionally, it highlighted the construction process of the UCNPs-based sensors, which includes the synthesis and modification of UCNPs, selection of the recognition elements, and consideration of the detection principle. Moreover, six kinds of food contaminants detected by UCNPs technology in the past 5 years have been summarized and discussed fairly. Last but not least, it is outlined that UCNPs have great potential to be applied in food safety detection and threw new insight into the challenges ahead.


Chronic ethanol ingestion potentiates TNF-alpha-mediated oxidative stress and apoptosis in rat type II cells.
In septic patients, chronic alcohol abuse increases the incidence of the acute respiratory distress syndrome (ARDS). Because alveolar type II cell viability is critical for epithelial repair, our objective was to determine if chronic ethanol ingestion increased the sensitivity of type II cells to the inflammatory mediators upregulated during sepsis. In rats chronically fed ethanol, type II cell mitochondrial GSH was depleted, and tumor necrosis factor-alpha (TNF-alpha)-induced generation of mitochondrial reactive oxygen species (ROS) and apoptosis were potentiated. When added to the ethanol diet, the GSH precursor (-)-2-oxo-4-thiazolidinecarboxylic acid (Procysteine; Pro) but not N-acetylcysteine (NAC) normalized type II cell mitochondrial GSH. Likewise, Pro but not NAC normalized TNF-alpha-induced mitochondrial ROS and apoptosis. This suggested that chronic ethanol ingestion potentiated TNF-alpha-induced apoptosis in type II cells via mitochondrial GSH depletion. This may be particularly relevant in ARDS when type II cell viability is critical to repair of the damaged alveolar epithelium and may have important ramifications for the treatment of ARDS patients with a history of alcohol abuse.


Multicentric epitheliotropic T-cell lymphoma in an African hedgehog (Atelerix albiventris).
A 2-year-old female African hedgehog was presented with a 5-month history of pruritus, and diffuse spine and hair loss. A dermatologic examination revealed erythema, excoriation, scales, and crusting affecting the face, flanks, forelimbs, hindlimbs, and dorsal and ventral abdomen. Fine-needle aspiration was performed and skin biopsies were taken from several lesions for cytologic and histologic evaluation. The aspirates yielded smears characterized by a monomorphic population of medium-sized to large lymphocytes with scant to moderate amounts of clear to moderately basophilic cytoplasm and distinct nucleoli along with a low number of cytoplasmic fragments. On histopathologic examination, there were dense dermal lymphoid infiltrates invading the dermis and a monomorphic population of round cells that had infiltrated the overlying epidermis. Epitheliotropic cutaneous lymphoma was diagnosed based on morphologic features. Additional immunochemical analysis using anti-CD3 and anti-CD79a antibodies revealed strong CD3 expression by the tumor cells, which confirmed epitheliotropic cutaneous T-cell lymphoma. This is the first description of a multicentric pattern of epitheliotropic cutaneous T-cell lymphoma in an African hedgehog.


Custom-made free vascularized compound toe transfer for traumatic dorsal loss of the thumb.
Dorsal compound traumatic thumb loss can be reconstructed in selected young and well-motivated patients with a custom-made partial great toe transfer. The transfer, including the nail complex and vascularized piece of bone, can be fashioned by longitudinally cutting the distal phalanx to approach the appearance of the opposite thumb and to allow for more normal nail appearance. Ten patients illustrate this technique and emphasize its reconstructive potential as well as cosmetic acceptance.


Definitive diagnosis of mitochondrial neurogastrointestinal encephalomyopathy by biochemical assays.
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is caused by mutations in the gene encoding thymidine phosphorylase (TP). The clinical manifestations of MNGIE are recognizable and homogeneous, but in the early stages, the disease is often misdiagnosed. This study assesses the reliability of biochemical assays to diagnose MNGIE. We studied 180 patients with clinical features suggestive of MNGIE, 14 asymptomatic TP mutation carriers, and 20 controls. TP enzyme activity in the buffy coat was determined by a fixed-time method, and the plasma nucleosides thymidine (dThd) and deoxyuridine (dUrd) were assessed by a gradient-elution reversed phase HPLC method. TP was sequenced through standard procedures in patients who met the clinical criteria for MNGIE. Twenty-five of the 180 patients fulfilled the clinical criteria for MNGIE and had homozygous or compound heterozygous TP mutations. All had drastically decreased TP activity [mean (SD), 10 (15) nmol thymine formed. h(-1). (mg protein)(-1) vs 634 (217) nmol thymine formed. h(-1). (mg protein)(-1) for the controls]. Relative to the control mean, TP activities were reduced to 35% in mutation carriers and 65% in MNGIE-like patients. All 25 MNGIE patients had detectable plasma dThd [8.6 (3.4) micromol/L] and dUrd [14.2 (4.4) micromol/L]. Controls, carriers, and MNGIE-like patients showed no detectable plasma dThd and dUrd. We propose a diagnostic algorithm based on the determination of plasma dThd and dUrd, TP activity in buffy coat, or both to make a definitive diagnosis of MNGIE. Increased concentrations of dThd (>3 micromol/L) and dUrd (>5 micromol/L) in plasma or a decrease in buffy coat TP activity to </=8% relative to controls is sufficient to diagnose MNGIE.


Intake of Fatty Fish Alters the Size and the Concentration of Lipid Components of HDL Particles and Camelina Sativa Oil Decreases IDL Particle Concentration in Subjects with Impaired Glucose Metabolism.
Intake of long-chain n-3 PUFAs affects the lipoprotein subclass profile, whereas the effect of shorter chain n-3 PUFAs remains unclear. We investigated the effect of fish and camelina sativa oil (CSO) intakes on lipoprotein subclasses. Altogether, 79 volunteers with impaired glucose metabolism were randomly assigned to CSO, fatty fish (FF), lean fish (LF), or control group for 12 weeks. Nuclear magnetic resonance spectroscopy was used to determine lipoprotein subclasses and their lipid components. The average HDL particle size increased in the FF group (overall p = 0.032) as compared with the control group. Serum concentrations of cholesterol in HDL and HDL2 (overall p = 0.024 and p = 0.021, respectively) and total lipids and phospholipids in large HDL particles (overall p = 0.012 and p = 0.019, respectively) increased in the FF group, differing significantly from the LF group. The concentration of intermediate-density lipoprotein (IDL) particles decreased in the CSO group (overall p = 0.033) as compared with the LF group. Our study suggests that FF intake causes a shift toward larger HDL particles and increases the concentration of lipid components in HDL, which may be associated with the antiatherogenic properties of HDL. Furthermore, CSO intake decreases IDL particle concentration. These changes may favorably affect cardiovascular risk.


Mathematical modeling of bacterial track-altering motors: Track cleaving through burnt-bridge ratchets.
The generation of directed movement of cellular components frequently requires the rectification of Brownian motion. Molecular motor enzymes that use ATP to walk on filamentous tracks are typically involved in cell transport, however, a track-altering motor can arise when an enzyme interacts with and alters its track. In Caulobacter crescentus and other bacteria, an active DNA partitioning (Par) apparatus is employed to segregate replicated chromosome regions to specific locations in dividing cells. The Par apparatus is composed of two proteins: ParA, an ATPase that can form polymeric structures on the nucleoid, and ParB, a protein that can bind and destabilize ParA structures. It has been proposed that the ParB-mediated alteration of ParA structures could be responsible for generating the directed movement of DNA during bacterial division. How precisely these actions are coordinated and translated into directed movement is not clear. In this paper we consider the C. crescentus segregation apparatus as an example of a track altering motor that operates using a so-called burnt-bridge mechanism. We develop and analyze mathematical models that examine how diffusion and ATP-hydrolysis-mediated monomer removal (or cleaving) can be combined to generate directed movement. Using a mean first passage approach, we analytically calculate the effective ParA track-cleaving velocities, effective diffusion coefficient, and other higher moments for the movement a ParB protein cluster that breaks monomers away at random locations on a single ParA track. Our model results indicate that cleaving velocities and effective diffusion constants are sensitive to ParB-induced ATP hydrolysis rates. Our analytical results are in excellent agreement with stochastic simulation results.


Exploitation of a non-apoptotic caspase to regulate the abundance of the cdkI p27(KIP1) in transformed lymphoid cells.
Expression of the cyclin dependent kinase inhibitor p27(KIP1) is intimately linked to the control of proliferation, and is itself regulated by transcription, translation, phosphorylation, protein stability or sequestration. p27(KIP1) is also regulated during apoptosis; cleavage occurs at DPSD(139)S and ESQD(108)V, by a sub-set of Z-VAD-fmk-sensitive caspases. We have identified a related but distinct mechanism that regulates p27(KIP1) in proliferating lymphoid cell lines. In a B-lymphoid cell line (BJAB), the abundance of p27(KIP1) oscillates inversely to proliferation; loss of full-length p27(KIP1) correlates with the appearance of a truncated version corresponding to cleavage at DPSD(139)S. A direct correlation exists between the appearance of truncated p27(KIP1) and the presence of an activity able to cleave peptides representing DPSD(139)S and a caspase-8 substrate (Ac-IETD-AMC) in vitro. This activity is inhibited by Ac-IETD-CHO but not Z-VAD-fmk in vitro. Furthermore a requirement for caspase-8 has been excluded. The activity differs from the apoptosis related p27(KIP1)-cleaving activity; indeed few cells undergoing apoptosis are present in the population of proliferating cells. The activity is further distinguished by its inability to cleave a peptide based on ESQD(108)V in vitro, together with the lack of a corresponding cleavage product in vivo. Inhibition of the caspase activity in vivo promotes an accumulation of full length p27(KIP1), as well as a decrease in cell proliferation. Together these studies highlight the importance of non-apoptotic caspases in regulating p27(KIP1) in transformed lymphoid cells.


Ciclosporin and refractory colitis.
Intravenous ciclosporin 4 mg/kg daily is rapidly effective as a salvage therapy for patients with refractory colitis, who would otherwise face colectomy, but its use is controversial because of risk of toxicity, and long-term failure rate. Opportunistic infections remain a serious concern, with a number of reports of death related to ciclosporin. Renal and neurotoxicity are also well-recognized. The drug should not be continued for more than 3-6 months and its main role is as a bridge to azathioprine or 6-mercaptopurine. Risks of toxicity can be reduced by using lower doses (2 mg/kg/day intravenously), by oral microemulsion ciclosporin, or by monotherapy without corticosteroids. Preliminary evidence shows good response rates, but further studies are needed to confirm optimal use of this potent, but hazardous, therapy.


An acceptance-based intervention for children and adolescents with cancer experiencing acute pain - a single-subject study.
Children and adolescents with cancer report pain as one of their most recurrent and troublesome symptoms throughout the cancer trajectory. Pain evokes psychological distress, which in turn has an amplifying effect on the pain experience. Acceptance-based interventions for experimentally induced acute pain predict increased pain tolerance, decreased pain intensity and decreased discomfort of pain. The aim of this study was to preliminarily evaluate an acceptance-based intervention for children and adolescents with cancer experiencing acute pain, with regard to feasibility and effect on pain intensity and discomfort of pain. This is a single-subject study with an AB design with a nonconcurrent multiple baseline. Children and adolescents aged four to 18 years undergoing cancer treatment at the Children's University Hospital, Uppsala, Sweden, reporting sustained acute pain were offered participation. Pain intensity and discomfort of pain were measured during baseline and at post-intervention. The intervention consisted of a pain exposure exercise lasting approximately 15 minutes. Five children participated in the study. All participants completed the intervention and reported that it had helped them to cope with the pain in the moment. All participants reported decreased discomfort of pain at post-measurement, three of whom also reported decreased pain intensity. The results suggest that an acceptance-based intervention may help children and adolescents with cancer to cope with the pain that is often associated with cancer treatment in spite of pharmacological pain management. The results are tentative but promising and warrant further investigation.


EGF receptor activities in mammalian development.
The receptor for epidermal growth factor (EGF) and its analog transforming growth factor alpha (TGF alpha) is ubiquitous, implying quite general roles for EGF/TGF alpha in cell viability and tissue maintenance in adult tissues. There is also evidence that the EGF receptor is active in promoting wound healing and tissue regeneration in adult organs, such as skin, liver, and intestinal epithelium. It is likely that EGF receptors have more specific roles during the gestation period. For example, we have detected EGF receptors on the 3.5-day blastocyst (trophectoderm) surface and since TGF alpha-like mRNA sequences and peptides have been detected at this time (Rappolee et al., Science 241:1823, 1988), there is a strong implication for autocrine stimulation in pre- and peri-implantation stage embryos. Paracrine stimulation between the embryo and maternal tissues is also likely since both receptors and TGF alpha are present in decidual cells. Therefore EGF receptors may take part in growth regulation of the early embryo and in the process of implantation. Other examples where EGF receptors may play specific roles during embryonic development are discussed.


Studies on the interaction of Escherichia coli endotoxin with erythrocyte membranes.
Escherichia coli lipopolysaccharide (endotoxin) alters the stability of erythrocytes to hypotonic lysis although the nature and magnitude of the effect varied with temperature and with the type of red blood cell examined. Evidence has been obtained suggesting a possible modulatory role of membrane lipids in governing the molecular consequences of membrane-endotoxin interaction. The marked effect of temperature on the stabilization of red cells by endotoxin was not attributable to variations in toxin binding and was not observed with more conventional structurally unrelated antihemolytic agents. Although chemical modifications which alter the toxicity of endotoxin in vivo also modify its ability to stabilize erythrocytes in vitro, no simple relationship between in vivo endotoxin toxicity and in vitro effects on erythrocyte stability was apparent. The critical dependence of endotoxin antihemolytic effects in vitro on molecular structure may offer a convenient means of assessing the homogeneity of these preparations before performing experiments in vivo.


Transcatheter closure of patent foramen ovale in patients with migraine headache.
Our objective is to review the epidemiology and pathophysiology of migraine headache, its association with patent foramen ovale (PFO), and the impact of PFO closure on migraine. Upon reviewing English-language publications listed in MEDLINE relating to migraine headache, PFO, and transcatheter closure of PFO, we selected case series, retrospective and prospective studies relevant to the topic. Primarily retrospective case-control studies demonstrate a link between PFO closure and improvement of migraine headache. Few prospective data confirm the initial results. However, the only randomized, controlled trial finished to date analyzing the effect of PFO closure on migraine failed to reach its primary outcome of resolution of migraine following the intervention. The evidence of a benefit on migraine headache following PFO closure is not convincing, but certainly intriguing. With currently ongoing trials, more information related to this topic can be expected.


Management of pulmonary nontuberculous mycobacterial disease.
Nontuberculous mycobacteria are increasingly recognized as causes of chronic pulmonary disease. Treatment decisions are guided by the clinical presentation, microbial isolate, and condition of the patient. Management may include antibiotic therapy, surgical resection, or observation. Definitive trials are lacking, and optimum management remains uncertain.


Expression of the p20 gene from Bacillus thuringiensis H-14 increases Cry11A toxin production and enhances mosquito-larvicidal activity in recombinant gram-negative bacteria.
Experimental analyses with recombinant Escherichia coli and Pseudomonas putida transformed with plasmids bearing genes coding for the Cry11A toxin and P20 protein from Bacillus thuringiensis H-14 showed that cells producing both proteins were more toxic when fed to third-instar Aedes aegypti larvae than were cells expressing cry11A alone; the 50% lethal concentrations were in the range of 10(4) to 10(5) cells/ml. Western blots revealed a higher production of Cry11A when the p20 gene was coexpressed. Cry11A was detected primarily in insoluble form in recombinant cells. Cry11A was not detected in P. putida when P20 was not coproduced, and these recombinants were not toxic to larvae, whereas P. putida recombinants producing both proteins were toxic at concentrations similar to those for E. coli. A coelution experiment was conducted, in which a p20 gene construct producing the P20 protein with an extension of six histidines on the C terminus was mixed with the Cry11A protein. The results showed that Cry11A bound to the P20(His(6)) on a nickel chelating column, whereas Cry11A produced without the P20(His(6)) protein was washed through the column, thus indicating that Cry11A and P20 physically interact. Thus, P20 protein either stabilizes Cry11A or helps it attain the folding important for its toxic activity.


Association of Radial Artery Access with Reduced Incidence of Acute Kidney Injury.
To determine if radial artery (RA) access compared with femoral artery (FA) access for percutaneous coronary intervention (PCI) is associated with a lower incidence of acute kidney injury (AKI). AKI results in substantial morbidity and cost following PCI. Prior studies comparing the occurrence of AKI associated with radial artery (RA) versus femoral artery (FA) access have mixed results. Using a large state-wide database, 14,077 patients (8,539 with RA and 5,538 patents with FA access) were retrospectively compared to assess the occurrence of AKI following PCI. To reduce selection bias and balance clinical data across the two groups, a novel machine learning method called a Generalized Boosted Model was conducted on the arterial access site generating a weighted propensity score for each variable. A logistic regression analysis was then performed on the occurrence of AKI following PCI using the weighted propensity scores from the Generalized Boosted Model. As shown in other studies, multiple variables were associated with an increase in AKI after PCI. Only RA access (OR 0.82; 95% CI 0.74-0.91) and male gender (OR 0.80; 95% CI 0.72-0.89) were associated with a lower occurrence of AKI. Based on the calculated Mehran scores, patients were stratified into groups with an increasing risk of AKI. RA access was consistently found to have a lower risk of AKI compared with FA access across these groups of increasing risk. Compared with FA access, RA access is associated with an 18% lower rate of AKI following PCI. This effect was observed among different levels of risk for developing AKI. Although developed from a retrospective analysis, this study supports the use of RA access when technically possible in a diverse group of patients.


Radial organization of developing preterm human cerebral cortex revealed by non-invasive water diffusion anisotropy MRI.
Cerebral cortical development involves a complex cascade of events which are difficult to visualize in intact, living subjects. In this study, we apply diffusion tensor imaging (DTI) to the evaluation of cortical development in human infants ranging from 26 to 41 weeks gestational age (GA). Apparent diffusion of water in cortex is maximally anisotropic at 26 weeks GA and anisotropy values approach zero by 36 weeks GA. During this period, the major eigenvector of the diffusion tensor in cerebral cortex is oriented radially across the cortical plate, in accord with a predominately radial deployment of its neuronal constituents. Values for the rotationally averaged water diffusion coefficient increase between 26 and 32 weeks GA, then decrease thereafter. These changes in DTI parameters are specific to cerebral cortex and reflect changes in underlying cortical architecture and formation of neuronal connections. Because of its correlation with tissue microstructure and non-invasive nature, DTI offers unique insight into cortical development in preterm human newborns and, potentially, detection of derangements of its basic cytoarchiteture.


Quality of life issues in non-small cell lung cancer.
For most patients with non-small cell lung cancer, maintaining or improving the quality of their remaining life may be as (or more) important than a small extension of survival. Thus, the assessment of quality of life should be a key component of treatment trials to inform future clinical decision-making. However, only a small percentage of randomized trials in non-small cell lung cancer have included quality of life and many of these may be criticized for poor design, inadequate sample size and/or complex analyses. A radical rethink over the way in which quality of life is included in trials is required. Much larger sample sizes, predefined quality of life hypotheses, innovative methods to improve compliance rates and standard methods of analysis are required. Until trialists begin to take note of these messages, information on quality of life from trials will continue to be largely distrusted and disregarded by doctors and patients.


Scaphoid fractures in children: problems and treatment.
From 1984 to 1999, the authors treated 64 cases of fracture of the scaphoid in children. Causes of injury were sports (n = 27), punching game machines or fighting (n = 22), and traffic accident or other trauma (n = 15). Most (46 cases) were nonunion cases. Eighteen cases were acute. Cast immobilization was performed in 10 acute cases and two nonunion cases. Screw fixation was performed in 52 cases, including 35 cases of bone graft. In 10 of these operated cases, freehand screw insertion was used. Ultimately, good bony fusion was achieved in all cases, but in two nonunion cases a secondary bone graft was necessary. Functional results in all cases were acceptable. A major problem is that children are not brought to clinics immediately after injury, so the percentage of nonunion is high.


Supine percutaneous nephrolithotomy: tips and tricks.
This paper aims to give an exhaustive overview of supine percutaneous nephrolithotomy (PCNL) illustrating some tips and tricks in order to optimize its execution in full safety. Critical review of Pros and cons of supine PCNL is accomplished to allow the urologist to experience the beauty of this position while being ready to overcome its minimal shortcomings.


Endolaryngeal extrusion of expanded polytetrafluoroethylene implant after medialization thyroplasty.
Various nonresorbable implants are currently used worldwide for medialization thyroplasty in patients with unilateral vocal cord paralysis. The Gore-Tex (expanded polytetrafluoroethylene) implant was introduced in the late 1990s. At our institution, 27 patients with unilateral laryngeal nerve paralysis had medialization thyroplasty with a Gore-Tex implant during the years 1998 to 2002. The current report documents our first case of endolaryngeal extrusion of a Gore-Tex implant.


Expanding the role of Drosha to the regulation of viral gene expression.
It is well-appreciated that viruses use host effectors for macromolecular synthesis and as regulators of viral gene expression. Viruses can encode their own regulators, but often use host-encoded factors to optimize replication. Here, we show that Drosha, an endoribonuclease best known for its role in the biogenesis of microRNAs (miRNAs), can also function to directly regulate viral gene expression. Kaposi's Sarcoma-associated Herpesvirus (KSHV) is associated with various tumors, and like all herpesviruses, has two modes of infection, latent and lytic, which are characterized by differential expression of viral gene products. Kaposin B (KapB) is a KSHV-encoded protein associated with cytokine production and cytotoxicity. We demonstrate that in addition to previously known transcriptional mechanisms, differences in Drosha levels contribute to low levels of KapB expression in latency and robust increases in expression during lytic replication. Thus, surprisingly, KSHV modulates Drosha activity differentially depending on the mode of replication. This regulation is dependent on Drosha-mediated cleavage, and KapB transcripts lacking the Drosha cleavage sites express higher levels of KapB, resulting in increased cell death. This work increases the known functions of Drosha and implies that tying viral gene expression to Drosha activity is advantageous for viruses.


Oligomer adsorption on dry and wet collagen surfaces.
The development of new biodegradable polymeric tissue adhesives has been almost stagnant for the past 10 years, primarily due to the inability to overcome the problem of inadequate adhesion properties. Efforts at the synthesis and modification of chemical structures by incorporating functional groups have proven futile. This study proposes using simulation as a preliminary move to obtain a better understanding of adsorption behavior on biological tissues. It is hoped that this understanding will subsequently serve as a guide for better polymer design and synthesis. Adsorption under both dry and wet conditions were simulated applying classical molecular mechanics and dynamics (MM/MD) because of their relevancy and efficiency. Twelve types of oligomers and a model collagen surface were constructed, followed by structural optimization and equilibration treatments. The COMPASS force field was used to describe the molecular potential energy surfaces. One strand of the oligomer was then located on top of the collagen surface and their interactions at equilibrium, in terms of van der Waals (vdW) and electrostatic energies, monitored over time. For the wet environment a thick water layer was constructed and placed on top of the oligomer and collagen surface. The results showed that the vdW component dominated physical adsorption for all oligomers, under both dry and wet conditions. This implies that interactions of polymers with tissue surfaces are inherently weak. Functional groups on oligomers could improve adhesion via electrostatic interaction. This interaction is, however, screened off in a wet environment, resulting in a reduction in the adsorption energy for all molecules studied. Of all the oligomers studied, poly(glycine) showed the strongest adsorption to collagen in both dry and wet conditions. Therefore, it is proposed to include the functional groups present in poly(glycine) in future tissue adhesive systems.


Primordial genetics: phenotype of the ribocyte.
The idea that the ancestors of modern cells were RNA cells (ribocytes) can be investigated by asking whether all essential cellular functions might be performed by RNAs. This requires isolating suitable molecules by selection-amplification when the predicted molecules are presently extinct. In fact, RNAs with many properties required during a period in which RNA was the major macromolecular agent in cells (an RNA world) have been selected in modern experiments. There is, accordingly, reason to inquire how such a ribocyte might appear, based on the properties of the RNAs that composed it. Combining the intrinsic qualities of RNA with the fundamental characteristics of selection from randomized sequence pools, one predicts ribocytes with a cell cycle measured (roughly) in weeks. Such cells likely had a rapidly varying genome, composed of many small genetic and catalytic elements made of tens of ribonucleotides. There are substantial arguments that, at the mid-RNA era, a subset of these nucleotides are reproducibly available and resemble the modern four. Such cells are predicted to evolve rapidly. Instead of modifying preexisting genes, ribocytes frequently draw new functions from an internal pool containing zeptomoles (<1 attomole) of predominantly inactive random sequences.


Flexible carbon nanotube sensors for nerve agent simulants.
Chemiresistor-based vapour sensors made from network films of single-walled carbon nanotube (SWNT) bundles on flexible plastic substrates (polyethylene terephthalate, PET) can be used to detect chemical warfare agent simulants for the nerve agents Sarin (diisopropyl methylphosphonate, DIMP) and Soman (dimethyl methylphosphonate, DMMP). Large, reproducible resistance changes (75-150%), are observed upon exposure to DIMP or DMMP vapours, and concentrations as low as 25 ppm can be detected. Robust sensor response to simulant vapours is observed even in the presence of large equilibrium concentrations of interferent vapours commonly found in battle-space environments, such as hexane, xylene and water (10 000 ppm each), suggesting that both DIMP and DMMP vapours are capable of selectively displacing other vapours from the walls of the SWNTs. Response to these interferent vapours can be effectively filtered out by using a 2 µm thick barrier film of the chemoselective polymer polyisobutylene (PIB) on the SWNT surface. These network films are composed of a 1-2 µm thick non-woven mesh of SWNT bundles (15-30 nm diameter), whose sensor response is qualitatively and quantitatively different from previous studies on individual SWNTs, or a network of individual SWNTs, suggesting that vapour sorption at interbundle sites could be playing an important role. This study also shows that the line patterning method used in device fabrication to obtain any desired pattern of films of SWNTs on flexible substrates can be used to rapidly screen simulants at high concentrations before developing more complicated sensor systems.


Collecting and preserving bark and ambrosia beetles (Coleoptera: Curculionidae: Scolytinae & Platypodinae).
This protocol describes the different methods to collect and preserve bark and ambrosia beetles, detailing collecting tools, recording relevant data, and optimizing step-by-step methods to extract beetles from twigs, branches, bark, and trunks. It elaborates on trapping techniques, tools, lures, baits, and beetle preservation. The main rule of manual collecting is to not attempt to pry the insect out of the wood or bark, but instead, remove the wood/bark away from the beetle: gently and systematically. The main rule of trapping is that there is no general attractant; instead, attractants and traps should reflect the ecology of the targeted beetle taxa.


Circulating and Tumor Myeloid-derived Suppressor Cells in Resectable Non-Small Cell Lung Cancer.
Myeloid-derived suppressor cell (MDSC) expansion has been found to play a role in disease progression in patients with cancer. However, the characteristics of MDSCs in lung cancer are poorly understood. We prospectively investigated MDSCs and inflammatory factors in tumor and peripheral blood samples from patients with resectable non-small cell lung cancer and studied their correlations with the disease prognosis. A complex analysis of MDSC subsets and inflammatory mediators was performed using flow cytometry and a Bio-Plex assay. A significant increase in the frequency of circulating monocytic (M)-MDSCs was observed in the patients with non-small cell lung cancer compared with the healthy donors (HDs). Moreover, the frequencies of M- and polymorphonuclear (PMN)-MDSCs were higher in tumors than in the peripheral blood of the same patients. This accumulation was associated with elevated concentrations of inflammatory mediators involved in MDSC migration to and activation in the tumor microenvironment. An analysis of the MDSC immunosuppressive pattern showed increased programmed death-ligand 1 expression on circulating cells from patients compared with HDs. Tumor PMN-MDSCs displayed higher programmed death-ligand 1 expression levels than the same cells in the peripheral blood. The frequency of CCR5 (C-C chemokine receptor 5) expression on circulating M-MDSCs was significantly higher in the patients than in the HDs. Clinical data analysis revealed negative correlations between recurrence-free survival and the frequencies of PMN-MDSCs and CCR5+ M-MDSCs in the circulation but not in tumors. Our findings suggest that the level of MDSCs in the peripheral blood but not in tumor tissues predicts recurrence after surgery.


Fixation location effects on fixation durations during reading: an inverted optimal viewing position effect.
Previous research has found that words are identified most quickly when the eyes are near their center (the Optimal Viewing Position effect). A study was conducted to determine whether this same phenomenon is observed during reading, as revealed by a relationship between fixation position in a word and the duration of the fixation. An analysis of three large existing corpora of eye movement data, two from adults and one from children, showed a surprising inverted Optimal Viewing Position curve: mean fixation duration is greatest, rather than lowest, when the eyes were at the centers of words. From this phenomenon, we suggest an alternative explanation to the fixation duration trade-off effect in word refixations [O'Regan & Lévy-Schoen, Attention and performance XII: the psychology of reading (1987)]; the phenomenon also contradicts expectations of both oculomotor and cognitive theories of eye movement control. Attempts to test alternative explanations led to the discovery of another phenomenon, the Saccade Distance effect: mean fixation durations vary with the distance of the prior fixation from the currently-fixated word, being longer with greater distances. The durations of fixations in reading are complexly determined, with influences both from language and perceptual/oculomotor levels.


Empathy in Human-Robot Interaction: Designing for Social Robots.
For a service robot to serve travelers at an airport or for a social robot to live with a human partner at home, it is vital for robots to possess the ability to empathize with human partners and express congruent emotions accordingly. We conducted a systematic review of the literature regarding empathy in interpersonal, virtual agents, and social robots research with inclusion criteria to analyze empirical studies in a peer-reviewed journal, conference proceeding, or a thesis. Based on the review, we define empathy for human-robot interaction (HRI) as the robot's (observer) capability and process to recognize the human's (target) emotional state, thoughts, and situation, and produce affective or cognitive responses to elicit a positive perception of humans. We reviewed all prominent empathy theories and established a conceptual framework that illuminates critical components to consider when designing an empathic robot, including the empathy process, outcome, and the observer and target characteristics. This model is complemented by empirical research involving empathic virtual agents and social robots. We suggest critical factors such as domain dependency, multi-modality, and empathy modulation to consider when designing, engineering, and researching empathic social robots.


Matching the right dog to the right home.
Many people want to own a dog but – with more than 200 registered breeds with different characteristics and requirements to choose from – they need to find the right one for them. Georgina Mills reports on a discussion of how potential owners can be helped to make the right choices, which took place during the recent BSAVA congress in Birmingham.


Isotopic evidence for pallasite formation by impact mixing of olivine and metal during the first 10 million years of the Solar System.
Pallasites are mixtures of core and mantle material that may have originated from the core-mantle boundary of a differentiated body. However, recent studies have introduced the possibility that they record an impact mix, in which case an isotopic difference between metal and silicates in pallasites may be expected. We report a statistically significant oxygen isotope disequilibrium between olivine and chromite in main group pallasites that implies the silicate and metal portions of these meteorites stem from distinct isotopic reservoirs. This indicates that these meteorites were formed by impact mixing, during which a planetary core was injected into the mantle of another body. The impactor likely differentiated within ∼1-2 Myr of the start of the Solar System based on Hf-W chronology of pallasite metal, and we infer the age of the impact based on Mn-Cr systematics and cooling rates at between ∼1.5 and 9.5 Myr after Ca-Al-rich inclusions (CAIs). When combined with published slow subsolidus cooling rates for these meteorites and considering that several pallasite groups exist, our results indicate that such impacts may be an important stage in the evolution of planetary bodies.