Effects of alcohol on risk-seeking behavior: a group-level analysis.
Although much drinking occurs in social settings, there has been little testing of alcohol in groups. The authors examined the effects of alcohol on performance on a group decision-making task. Fifty-four unacquainted male social drinkers were randomly assigned to 3-person groups that consumed either alcohol (0.82 g/kg) or a placebo. After drinking, participants decided whether to complete a 30-min questionnaire battery or toss a coin and, pending the outcome of that toss, complete either no questionnaires or a 60-min battery. Alcohol groups were significantly more likely than placebo groups to choose the coin toss. Results highlight the potent effects of alcohol on group decision making and suggest that application of social psychological theory and methods to the study of alcohol is warranted.


[Psychotic manifestations complicating surgical operation in the ocular region].
The authors report ten observations as well as the results of an investigation conducted by ophtalmologists and psychiatrists with intention of better understanding clinical, physiological and psychological problems, provoked by occurance of complications stemming from psychoses which are the result of ophtamological complications. They conclude that it is necessary to form accurate distinctions with regard to the total manifestations of the malady "black patch delirium". They emphasize the fact that its manifestations are not an appanage of the aged ; they especially insist upon not only the role of visual disorientation but also of the social factors which are united with restrictions, beyond those of motor, control and biological imvalances. With regard to etiopathology they acknowledge a need for a combination of organogenic and psychodynamic models to account for each case ; a certain number of communal points can be found : subjects (declined in physical and metal capacities), there is a rapid weaking of the external comportment, resulting in an imptiness, which must be compensated for by a fantasy life or some other physiopathological mecanisms.


[Influence of adefovir dipivoxil or telbivudine monotherapy on renal function of patients with chronic hepatitis B].
To evaluate the changes in the renal function of patients with chronic hepatitis B (CHB) receiving adefovir dipivoxil (ADV) or telbivudine (L-DT) monotherapy. This retrospective analysis involved 101 patients with CHB and liver cirrhosis receiving either ADV or L-DT monotherapy for 52 weeks. Serum creatinine, estimates of glomerular filtration rate (eGFR), and the percentage of patients with eGFR≥90 ml·min(-1)·1.73 m(-2) at week 52 were compared with the baseline data between the two groups. The mean changes of CR at week 52 from baseline were +0.05 mg/dl in ADV group and -0.12 mg/dl in L-DT group, showing a significant difference between the two groups (P=0.000). No patient was found to have an elevation of creatinine over 0.50 mg/dl. The median change of eGFR at week 52 from baseline differed significantly between ADV and L-DT groups (-4.09 vs+18.32 ml·min(-1)·1.73 m(-2), P=0.000). Ninety-two percent (12/13) of the patients with baseline eGFR<90 ml·min(-1)·1.73 m(-2) shifted to eGFR ≥90 ml·min(-1)·1.73 m(-2) after 52 weeks of L-DT treatment, as compared to 38% (3/8) in ADV group. The proportion of patients with eGFR≥90 ml·min(-1)·1.73 m(-2) in L-DT group increased from 76.36% (42/55) at baseline to 94.55% (52/55) at week 52, while that in ADV group decreased from 82.61% (38/46) at baseline to 78.26% (36/46). The constituent ratios of eGFR at different levels were similar at baseline (P=0.443) but significantly different at week 52 between the two groups (P=0.015). L-DT treatment is associated with a renoprotective effect in patients with CHB, but the mechanism remains unclear.


Conductivity Classification of Non-Magnetic Tilting Metals by Eddy Current Sensors.
Metallic waste classification benefits the environment, resource reuse and industrial economy. This paper provides a fast, non-contact and convenient method based on eddy current to classify metals. The characteristic phase to characterize different conductivity is introduced and extracted from mutual inductance in the form of amplitude and phase. This characteristic phase could offer great separation for non-tilting metals. Although it is hard to classify tilting metals by only using the characteristic phase, we propose the technique of phase compensation utilizing photoelectric sensors to obtain the rectified phase corresponding to the non-tilting situation. Finally, we construct a classification algorithm involving phase compensation. By conducting a test, a 95 % classification rate is achieved.


A novel actin barbed-end-capping activity in EPS-8 regulates apical morphogenesis in intestinal cells of Caenorhabditis elegans.
Redundant gene function frequently hampers investigations of the physiological roles of mammalian proteins. This is the case for Eps8, a receptor tyrosine kinase (RTK) substrate that participates in the activation of the Rac-specific guanine nucleotide-exchange function of Sos1 (refs 2-5), thereby regulating actin remodelling by RTKs. EPS8-knockout mice, however, exhibit no evident phenotype, owing to the redundant function of three other EPS8-related genes. Here we show that in the nematode Caenorhabditis elegans, only one orthologue of the EPS8 gene exists, which gives rise to two alternatively spliced isoforms, EPS-8A and EPS-8B, differing at their carboxyl termini. In the nematode, eps-8 is essential for embryonic development. Furthermore, EPS-8A, but not EPS-8B, is specifically required for proper apical morphogenesis in the intestinal cells. This latter phenotype could be precisely correlated with a previously unknown actin barbed-end-capping activity, which is present in the C terminus of the EPS-8A isoform. Therefore, nematode genetics allowed not only the unmasking of distinct EPS-8-linked phenotypes, but also the definition of a novel function for this molecule in actin dynamics.


Anti-mycobacterial activity of marine fungus-derived 4-deoxybostrycin and nigrosporin.
4-Deoxybostrycin is a natural anthraquinone compound isolated from the Mangrove endophytic fungus Nigrospora sp. collected from the South China Sea. Nigrosporin is the deoxy-derivative of 4-deoxybostrycin. They were tested against mycobacteria, especially Mycobacterium tuberculosis. In the Kirby-Bauer disk diffusion susceptibility test, they both had inhibition zone sizes of over 25 mm. The results of the absolute concentration susceptibility test suggested that they had inhibitory effects against mycobacteria. Moreover, 4-deoxybostrycin exhibited good inhibition which was even better than that of first line anti-tuberculosis (TB) drugs against some clinical multidrug-resistant (MDR) M. tuberculosis strains. The gene expression profile of M. tuberculosis H37Rv after treatment with 4-deoxybostrycin was compared with untreated bacteria. One hundred and nineteen out of 3,875 genes were significantly different in M. tuberculosis exposed to 4-deoxybostrycin from control. There were 46 functionally known genes which are involved in metabolism, information storage and processing and cellular processes. The differential expressions of six genes were further confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). The present study provides a useful experiment basis for exploitation of correlative new drugs against TB and for finding out new targets of anti-mycobacterial therapy.


Dutch population specific sex estimation formulae using the proximal femur.
Sex estimation techniques are frequently applied in forensic anthropological analyses of unidentified human skeletal remains. While morphological sex estimation methods are able to endure population differences, the classification accuracy of metric sex estimation methods are population-specific. No metric sex estimation method currently exists for the Dutch population. The purpose of this study is to create Dutch population specific sex estimation formulae by means of osteometric analyses of the proximal femur. Since the Netherlands lacks a representative contemporary skeletal reference population, 2D plane reconstructions, derived from clinical computed tomography (CT) data, were used as an alternative source for a representative reference sample. The first part of this study assesses the intra- and inter-observer error, or reliability, of twelve measurements of the proximal femur. The technical error of measurement (TEM) and relative TEM (%TEM) were calculated using 26 dry adult femora. In addition, the agreement, or accuracy, between the dry bone and CT-based measurements was determined by percent agreement. Only reliable and accurate measurements were retained for the logistic regression sex estimation formulae; a training set (n=86) was used to create the models while an independent testing set (n=28) was used to validate the models. Due to high levels of multicollinearity, only single variable models were created. Cross-validated classification accuracies ranged from 86% to 92%. The high cross-validated classification accuracies indicate that the developed formulae can contribute to the biological profile and specifically in sex estimation of unidentified human skeletal remains in the Netherlands. Furthermore, the results indicate that clinical CT data can be a valuable alternative source of data when representative skeletal collections are unavailable.


High performance top-gated multilayer WSe2 field effect transistors.
In this paper, high performance top-gated WSe2 field effect transistor (FET) devices are demonstrated via a two-step remote plasma assisted ALD process. High-quality, low-leakage aluminum oxide (Al2O3) gate dielectric layers are deposited onto the WSe2 channel using a remote plasma assisted ALD process with an ultrathin (∼1 nm) titanium buffer layer. The first few nanometers (∼2 nm) of the Al2O3 dielectric film is deposited at relatively low temperature (i.e. 50 °C) and remainder of the film is deposited at 150 °C to ensure the conformal coating of Al2O3 on the WSe2 surface. Additionally, an ultra-thin titanium buffer layer is introduced at the WSe2 channel surface prior to ALD process to mitigate oxygen plasma induced doping effects. Excellent device characteristics with current on-off ratio in excess of 106 and a field effect mobility as high as 70.1 cm2 V-1 s-1 are achieved in a few-layer WSe2 FET device with a 30 nm Al2O3 top-gate dielectric. With further investigation and careful optimization, this method can play an important role for the realization of high performance top gated FETs for future optoelectronic device applications.


On the ionic chemistry in DC cold plasmas of H2 with Ar.
An experimental diagnosis and kinetic modeling of the ionic chemistry in low pressure DC plasmas of H(2)/Ar has been carried out. The studies were performed at pressures of 2 Pa and 0.7 Pa, in a hollow-cathode discharge reactor, using as plasma precursor a H(2)/Ar mixture with 15% Ar content. Experimental measurements include distributions of ion fluxes to the cathode, as well as electronic temperatures and densities in the plasma glow. Besides the species resulting directly from electron impact ionization (H(+), H(2)(+), Ar(+) and Ar(2+)), the ions H(3)(+) and ArH(+) were found to be formed in large amounts through protonation reactions in the glow. In spite of the not too large variation in the pressure of the two plasmas, the differences in the ion distributions are worth mentioning. In the 2 Pa discharge (but not in the 0.7 Pa), H(3)(+) was the dominant ion and ArH(+) exceeded markedly the Ar(+) signal. On the other hand, the appearance of Ar(2+) in the two plasmas points at the relevance of high energy electrons. The experimental results can be accounted for by a simple kinetic model, after including corrections for the presence of a small fraction (<3%) of high energy (>50 eV) electrons and for the attenuation of the Ar(+) ions in the sheath through asymmetric charge exchange with H(2).


Gene-flow patterns in Atlantic and Mediterranean populations of the Lusitanian sea star Asterina gibbosa.
In this study, the population structure of the Lusitanian sea star Asterina gibbosa was assessed using amplified fragment length polymorphism (AFLP). One hundred and twenty-two AFLP loci were analysed in 159 individuals from eight populations from across the species' range and revealed high levels of genetic diversity, with all individuals but two harbouring a unique banding pattern. As reported for other marine invertebrates, we found high levels of genetic differentiation between the Atlantic and Mediterranean basins, suggesting that the Strait of Gibraltar represents a major barrier to dispersal for this sea star. Our assignment studies suggest that, in the Atlantic, a measurable degree of gene flow occurs between populations, which could result in the isolation-by-distance pattern of differentiation observed in this basin. In contrast, no evidence of contemporary gene flow was found in the Mediterranean, suggesting contrasting patterns of dispersal of Asterina gibbosa in the Atlantic and Mediterranean basins.


Low-volume resuscitation using polyethylene glycol-20k in a preclinical porcine model of hemorrhagic shock.
Polyethylene glycol-20k (PEG-20k) is highly effective for low-volume resuscitation (LVR) by increasing tolerance to the low-volume state. In our rodent shock model, PEG-20k increased survival and expanded the "golden hour" 16-fold compared to saline. The molecular mechanism is largely attributed to normalizations in cell and tissue fluid shifts after low-flow ischemia resulting in efficient microvascular exchange. The objective of this study was to evaluate PEG-20k as an LVR solution for hemorrhagic shock in a preclinical model. Anesthetized male Yorkshire pigs (30-40 kg) were hemorrhaged to a mean arterial pressure (MAP) of 35 to 40 mm Hg. Once lactate reached 7 mmol/L, either saline (n = 5) or 10% PEG-20k (n = 5) was rapidly infused at 10% calculated blood volume. The primary outcome was LVR time, defined by the time from LVR administration to the time when lactate again reached 7 mmol/L. Other outcomes measured included MAP, heart rate, cardiac output, mixed venous oxygen saturation, splanchnic blood flow, and hemoglobin. Relative to saline, PEG-20k given after controlled hemorrhage increased LVR time by 16-fold, a conservative estimate given that the lactate never rose after LVR in the PEG-20k group. Survival was 80% for PEG-20k LVR compared to 0% for the saline controls (p < 0.05). Polyethylene glycol-20k also significantly decreased heart rate after hemorrhage and increased cardiac output, MAP, splanchnic flow, and mixed venous oxygen saturation. Falling hemoglobin concentrations suggested sizable hemodilution from fluid shifts into the intravascular compartment. In a preclinical model of controlled hemorrhagic shock, PEG-20k-based LVR solution increased tolerance to the shock state 16-fold compared to saline. Polyethylene glycol-20k is a superior crystalloid for LVR that may increase safe transport times in the prehospital setting and find use in hospital emergency departments and operating rooms for patients awaiting volume replacement or normalization of cell, tissue, and compartment fluid volumes.


Characterizing Sorption and Permeation Properties of Membrane Filters Used for Aquatic Integrative Passive Samplers.
Aquatic integrative passive sampling is a promising approach to measure the time-weighted average concentration, yet our understanding for the sampling mechanisms of polar organic contaminants should be further advanced to fully exploit the potential of the method for real-world applications. This study aimed to characterize the sorption and permeation properties of poly(ether sulfone) (PES) and poly(tetrafluoroethylene) (PTFE) membrane filters (MFs) used for passive samplers. Batch sorption experiments with 14 probe chemicals showed that the sorption by PES was generally strong, with the respective sorption coefficients greater than the octanol-water partition coefficients by 2-3 log units. In contrast, the PTFE filter exhibited no significant sorption for all tested chemicals, representing a promising candidate MF that avoids lag-times and slow responses to fluctuating concentrations. Permeation experiments in a glass cell system and successive modeling demonstrated that, if no sorption to the MF occurs, the MF permeation of a chemical can be fully described with a first-order model that considers the transfer through the aqueous boundary layers and the diffusion in water-filled MF pores. Significant sorption to the MF coincided with substantial delay of permeation, which was successfully modeled with the local sorption equilibrium assumption. These findings have implications for improved sampler configurations and successful models for the chemical uptake.


[Application of tissue flaps in repair of limbs injuries].
To summarize and analyze the main point on the reconstruction of traumatic tissue defects of limbs with vascularized skin and multi-tissue flaps. Sixty-seven cases of traumatic tissue defects of limbs were reconstructed with 14 kinds of skin or multi-tissue flaps. The operative methods included local transposition, cross-transposition with vessel pedicles and vessel anastomosed free transplantation. Forty cases with vessel anastomosed free transplantation and 26 cases with local or cross-transposition of vessel pedicled flaps were survived. In the followed up cases, 53 cases were satisfied with the outward appearance of the skin flaps. All the cases with bone flap or skin-bone flap resulted in union. And the cases with motor nerve anastomosed myocutaneous flap transplantation had recovered to 2-3 grade muscle contraction ability. It is important that the appropriate flaps and operative methods should be chosen according to the size, location, depth and structure of the tissue defects. To raise the success rate and to gain better operation effect, the correct manipulation in operation and the rational postoperative treatment are necessary.


Reliability and Criterion-Related Validity of the Seated Posture Scale.
Earlier, we reported development and initial testing of a rapid, low burden measure of wheelchair seated posture (the Seated Posture Scale [SPS]) for research and clinical use. The purpose of this study was to test the intrarater reliability, interrater reliability, and criterion related validity of the SPS. We used a descriptive design to test and develop the instrument. We used the method described by Walter, Donner, and Eliasziw to determine 46 participants were needed, from two Veterans Administration nursing homes or CLCs (community living centers). Using a digital goniometer to score rapidly and with two trained raters, we scored individual participants simultaneously and again in succession. For criterion related concurrent validity, we also scored each participant with Section 2 of the Seated Postural Control Measure for Adults. Intrarater reliability, interrater reliability, and criterion related, concurrent validity were assessed using kappa statistics for individual instrument items (and corresponding 95% confidence intervals where appropriate) and intraclass correlation coefficients (ICC) for total scores. The intrarater intraclass correlation coefficient (ICC) was .995; interrater ICC was .80; interrater reliability kappas ranged from -.03 to .80. Criterion-related, concurrent validity kappas ranged from .13 to .91. ICC for total scores was .85. The SPS has sufficient preliminary validity and reliability to support measurement of wheelchair-seated posture in outcomes research and clinical use. In the future, rehabilitation nurses may use the SPS to improve management of wheelchair seated posture, to improve clinical outcomes, particularly for those who do not reposition themselves.


Highly Polarized Single Photons from Strain-Induced Quasi-1D Localized Excitons in WSe2.
Single photon emission from localized excitons in two-dimensional (2D) materials has been extensively investigated because of its relevance for quantum information applications. Prerequisites are the availability of photons with high purity polarization and controllable polarization orientation that can be integrated with optical cavities. Here, deformation strain along edges of prepatterned square-shaped substrate protrusions is exploited to induce quasi-one-dimensional (1D) localized excitons in WSe2 monolayers as an elegant way to get photons that fulfill these requirements. At zero magnetic field, the emission is linearly polarized with 95% purity because exciton states are valley hybridized with equal shares of both valleys and predominant emission from excitons with a dipole moment along the elongated direction. In a strong field, one valley is favored and the linear polarization is converted to high-purity circular polarization. This deterministic control over polarization purity and orientation is a valuable asset in the context of integrated quantum photonics.


Human cord blood T-cell receptor alpha beta cell responses to protein antigens of Paracoccidioides brasiliensis yeast forms.
Paracoccidioides brasiliensis causes a chronic granulomatous mycosis, prevalent in South America, and cell-mediated immunity represents the principal mode of protection against this fungal infection. We investigated the response of naive cord blood T cells to P. brasiliensis lysates. Our results show: (1) P. brasiliensis stimulates T-cell expansion, interleukin-2 (IL-2) production and differentiation into cytotoxic T cells; (2) T-cell stimulation depends on P. brasiliensis processing and major histocompatibility complex (MHC) class II expression; (3) the responsive T-cell population expresses alpha beta T-cell receptors (TCR) with different V beta gene products, CD4 and CD45RO; (4) the P. brasiliensis components involved in T-cell expansion primarily reside in a high molecular weight (100,000 MW) and a low molecular weight (< 1000 MW) protein fraction. These results indicate that protein antigens of P. brasiliensis stimulate cord blood CD4 alpha beta T cells, independent from in vivo presensitization, and thus question direct correlation of positive in vitro responses with protective immunity in vivo.


Laryngotracheal separation for intractable aspiration.
Intractable aspiration may be a life-threatening problem for patients with altered laryngeal function secondary to neurologic disorders or abnormal laryngeal anatomy. Multiple surgical procedures have been devised to deal with this problem. An effective technique involves the creation of a tracheostoma and closure of the larynx at the first or second tracheal ring. Laryngotracheal separation is relatively easy to perform and potentially reversible. Experience with this technique in six patients who required laryngeal separation for intractable aspiration is described. The procedure was successful in preventing aspiration and recurrent pneumonia associated with neurologic dysfunction, unresectable neoplasm, and conservation laryngeal surgery. One patient of one has had a successful reconstruction.


Modulation of vascular gene expression by hypoxia.
Angiogenesis and inflammation are important features in atherosclerotic plaque destabilization. The transcription factors hypoxia-inducible factor-1alpha and Notch are key regulators of angiogenesis. In addition, hypoxia-inducible factor-1alpha has been linked to regulation of inflammatory processes and innate immunity. This review will document how hypoxia-inducible factor-mediated signaling pathways are initiated in hypoxic cells, and how the hypoxia-inducible factor and Notch-dependent signaling pathways are functionally integrated. Activation of the hypoxia-inducible factor-mediated signaling events by hypoxia is complex and regulated by a cascade of molecular events that will be reviewed in detail. The activated form of hypoxia-inducible factor enhances Notch-dependent activation of Notch target genes, thereby providing a mechanism by which hypoxia can regulate the differentiation status of a cell. Recent observations implicate the Notch signaling pathway in proper specification of cell identity, position and behavior in a developing blood vessel sprout, and the hypoxia-inducible factor-mediated signaling pathway is critical for induction of expression of vascular endothelial growth factor. Hypoxia-inducible factor and Notch transcription factors represent potentially attractive targets for regulation of angiogenesis and possibly inflammation. In view of the pleiotropic effects of these transcription factors, however, successful targeting of these signaling pathways will require the development of gene specific (and possibly tissue-specific) modulators and extensive validation in relevant model systems.


Understanding how mammalian scavengers use information from avian scavengers: cue from above.
Interspecific social information transfer can play a key role in many aspects of animal ecology from foraging to habitat selection to predator avoidance. Within scavenging communities, avian scavengers often act as producers and mammalian scavengers act as scroungers, but we predict that species-specific cueing will allow for mammalian scavengers to utilize particular avian scavenger species using preferred food sources similar to their own preferences. We use empirical and theoretic approaches to assess interactions between mammalian and avian scavengers in one of the most diverse scavenging guilds in Masai Mara National Reserve, Kenya. Using a spatially explicit model and data from experimental carcasses, we found evidence that mammals benefit from local enhancement provided by vultures and that mammalian-avian following patterns are consistent with the idea that species-specific cueing is occurring. Results suggest that ongoing population declines in avian scavengers may have significant impacts on mammalian scavengers and potentially create trophic cascades.


Newly synthesized noradrenaline mediates the alpha 2-adrenoceptor inhibition of [3H]5-hydroxytryptamine release induced by beta-phenylethylamine in rat hippocampal slices.
In slices of the rat hippocampus, alpha 2-adrenoceptors located presynaptically on serotonergic nerve terminals modulate the electrically evoked calcium-dependent release of [3H]serotonin [( 3H]5HT). We have investigated the effects of a naturally occurring trace amine, beta-phenylethylamine (beta-PEA), on noradrenergic transmission in the rat hippocampus. Under experimental conditions in which MAO of type B is inhibited by deprenyl-exposure to beta-PEA (0.1-10 microM) facilitates the spontaneous outflow of [3H]noradrenaline and inhibits the electrically evoked release of [3H]5HT. The inhibitory effect of beta-PEA (3 microM) on the evoked release of [3H]5HT was antagonized by the alpha 2-adrenoceptor antagonist idazoxan at 1 microM, and by pretreatment with alpha-methyl-p-tyrosine (alpha-MpT, 300 mg/kg i.p., 2 h). The inhibition of tyrosine hydroxylase activity by alpha-MpT does not modify the inhibition of the evoked release of [3H]5HT by the alpha 2-adrenoceptor agonist, 6-fluoronoradrenaline, or the serotonin receptor agonist, 5-methoxytryptamine. Pretreatment with the neurotoxin DSP4 (50 mg/kg i.p., 10 days) markedly antagonized the inhibitory action of beta-PEA on [3H]5HT release. These results indicate that the noradrenaline-releasing action of beta-PEA inhibits the electrically evoked release of [3H]5HT through the activation of alpha 2-adrenoceptors. This inhibitory effect appears to be mediated exclusively through the release of newly synthesized noradrenaline, and does not involve the direct activation by beta-PEA of the inhibitory 5HT autoreceptors which modulate [3H]5HT release in the rat hippocampus.


Suppression of aortic atherosclerosis in cholesterol-fed rabbits by purified rabbit interferon.
The effectiveness of rabbit interferon in suppressing atherosclerosis was evaluated in rabbits fed a diet containing 1% cholesterol. Ten male New Zealand White rabbits received intramuscular injections of 1 million units of interferon twice a week, while a control group of 10 rabbits received injections of buffer. Both groups had average serum cholesterol levels of over 2000 mg/dl during the 8-week experimental period. Interferon treatment resulted in no significant hypolipidemic effect or changes in lipoprotein composition. Atherosclerotic lesions in aortas were quantified both macroscopically and microscopically. Interferon treatment decreased the grossly visible lesion area significantly from 25 +/- 4% to 8 +/- 1% (mean +/- SEM, p less than 0.005) compared to the untreated group. Microscopic analysis of serial cross-sections of aortic segments revealed significant (p less than 0.01) reductions in both lesion size and frequency in the interferon-treated group. Electron microscopy also showed that interferon treatment reduced the pathological effects of cholesterol feeding. Tissue analysis showed that total aortic cholesterol was reduced by 28% by interferon treatment, while the aortic phospholipid concentration was increased by 25%. The possibility exists that the interferon preparation used contained other biological response modifiers and that the observed effects may be totally unrelated with interferon. These results suggest that the mechanism of atherosclerosis suppression in these cholesterol-fed rabbits is not related to the lowering of serum cholesterol but may be associated with inhibition of lesion initiation.


Intelligent Diagnostics of Radial Internal Clearance in Ball Bearings with Machine Learning Methods.
This article classifies the dynamic response of rolling bearings in terms of radial internal clearance values. The value of the radial internal clearance in rolling-element bearings cannot be described in a deterministic manner, which shows the challenge of its detection through the analysis of the bearing's dynamics. In this article, we show the original approach to its intelligent detection through the analysis of short-time intervals and the calculation of chosen indicators, which can be assigned to the specific clearance class. The tests were carried out on a set of 10 brand new bearings of the same type (double row self-aligning ball bearing NTN 2309SK) with different radial internal clearances corresponding to individual classes of the ISO-1132 standard. The classification was carried out based on the time series of vibrations recorded by the accelerometer and then digitally processed. Window statistical indicators widely used in the diagnosis of rolling bearings, which served as features for the machine learning models, were calculated. The accuracy of the classification turned out to be unsatisfactory; therefore, it was decided to use a more advanced method of time series processing, which allows for the extraction of subsequent dominant frequencies into experimental modes (Variational Mode Decomposition (VMD)). Applying the same statistical indicators to the modes allowed for an increase in classification accuracy to over 90%.


Cultivation of Isochrysis galbana in phototrophic, heterotrophic, and mixotrophic conditions.
This study compared the growth and biomass production of Isochrysis galbana under hetero-, mixo-, and phototrophic conditions using different organic carbon sources. The growth of I. galbana was inhibited in heterotrophy but was enhanced in mixotrophy compared to that in phototrophy. Subsequently, the influences of organic carbon and environmental factors (light and salinity) on the growth of I. galbana were further investigated. Algal dry weight increased as glycerol concentrations increased from 0 to 200 mmol and the highest algal production occurred at 50 mmol glycerol. At a range of light intensities of 25-200 μ mol photons m(-2) s(-2), the highest algal growth rate occurred at 100 photons μ mol m(-2) s(-2). The growth of I. galbana was significantly affected by photoperiod, and the maximal dry weight was obtained at 12 h light and 12 h dark. In the salinity test, I. galbana could grow in a wide range of salinities from 10 to 65 ‰, but the 35 ‰ salinity was optimal. This study suggests that the growth and production of I. galbana can be improved using mixotrophic culture at 50 mmol glycerol in 35 ‰ salinity.


Developmental potential of bovine oocytes following IVM in the presence of glutathione ethyl ester.
Glutathione (GSH) is synthesised during oocyte maturation and represents the oocyte's main non-enzymatic defence against oxidative stress. Inadequate defence against oxidative stress may be related to poor embryo quality and viability. In the present study, bovine oocytes were matured in vitro in the presence of GSH ethyl ester (GSH-OEt), a cell permeable GSH donor, and its effects on subsequent fertilisation and embryo development were assessed. GSH-OEt significantly increased the GSH content of IVM oocytes without affecting fertilisation or Day 3 cleavage rates. Maturation in the presence of GSH-OEt did not significantly increase the blastocyst rate compared with control oocytes. However, 5 mM GSH-OEt treatment resulted in significantly higher blastocyst total cell number. The GSH level of IVM oocytes was significantly decreased in the absence of cumulus cells and when cumulus-oocyte complexes were cultured in the presence of buthionine sulfoximine (BSO), an inhibitor of GSH synthesis. The addition of GSH-OEt to cumulus-denuded or BSO-treated oocytes increased the GSH content of bovine oocytes and restored the rate of normal fertilisation, but not embryo development, to levels seen in control oocytes. Thus, GSH-OEt represents a novel approach for effective in vitro elevation of bovine oocyte GSH and improvement in blastocyst cell number.


The novel in vitro reanimation of isolated human and large mammalian heart-lung blocs.
In vitro isolated heart preparations are valuable tools for the study of cardiac anatomy and physiology, as well as for preclinical device testing. Such preparations afford investigators a high level of hemodynamic control, independent of host or systemic interactions. Here we hypothesize that recovered human and swine heart-lung blocs can be reanimated using a clear perfusate and elicit viable cardiodynamic and pulmonic function. Further, this approach will facilitate multimodal imaging, which is particularly valuable for the study of both functional anatomy and device-tissue interactions. Five human and 18 swine heart-lung preparations were procured using techniques analogous to those for cardiac transplant. Specimens were then rewarmed and reperfused using modifications of a closed circuit, isolated, beating and ventilated heart-lung preparation. Positive pressure mechanical ventilation was also employed, and epicardial defibrillation was applied to elicit native cardiac sinus rhythm. Videoscopy, fluoroscopy, ultrasound, and infrared imaging were performed for anatomical and experimental study. Systolic and diastolic left ventricular pressures observed for human and swine specimens were 68/2 ± 11/7 and 74/3 ± 17/5 mmHg, respectively, with associated native heart rates of 80 ± 7 and 96 ± 16 beats per minute. High-resolution imaging within functioning human pulmonary vasculature was obtained among other anatomies of interest. Note that one human specimen elicited poor cardiac performance post defibrillation. We report the first dynamic videoscopic images of the pulmonary vasculature during viable cardiopulmonary function in isolated reanimated heart-lung blocs. This experimental approach provides unique in vitro opportunities for the study of novel medical therapeutics applied to large mammalian, including human, heart-lung specimens.


Identification of the ligand-binding regions in the macrophage colony-stimulating factor receptor extracellular domain.
The c-fms gene encodes the receptor for the macrophage colony-stimulating factor (M-CSF), and its extracellular domain consists of five immunoglobulin-like subdomains. To identify which of the five immunoglobulin-like regions are involved in ligand binding, we polymerase chain reaction-cloned five segments of the extracellular domain of the murine c-fms gene, each starting with the normal initiation codon and containing successive additions of the immunoglobulin-like subdomains. These protein segments are designated A, B, C, D, and E and contain, from the N-terminal end, either one, two, three, four, or all five immunoglobulin-like subdomains, respectively. Each segment was expressed as a secreted soluble protein from a baculovirus expression vector in Sf9 insect cells. In addition, segments A, B, C, and E were produced as soluble alkaline phosphatase fusion proteins, as was a segment containing only the fourth and fifth immunoglobulin domains. These segments of the Fms extracellular domain were used to assess M-CSF binding by competition radioimmunoassays, plate binding immunoassays, and immunoprecipitation analyses. The results indicated that the first two N-terminal immunoglobulin-like domains did not interact with M-CSF but, in combination with the third immunoglobulin-like domain, provided high-affinity M-CSF binding. The fourth and fifth immunoglobulin-like domains near the cell membrane did not exhibit M-CSF binding and may inhibit interaction of M-CSF with the first three immunoglobulin domains. These results suggest that the three N-terminal immunoglobulin-like domains constitute the high-affinity M-CSF binding region and that the fourth and fifth immunoglobulin-like domains may perform functions other than ligand binding.


Psoriasis associated with vulval scarring.
Psoriasis is a chronic inflammatory skin disorder which is generally not associated with scarring. We report two patients with long-standing severe anogenital psoriasis, that was associated with loss of the labia minora, thus clinically mimicking the scarring associated with lichen sclerosus. Histopathological finding were however, consistent with psoriasis with no evidence of lichen sclerosus. Elastic fibres were present and there was no evidence of abnormal collagen or fibrous tissue. The association of vulval psoriasis with scarring has not been reported previously.


Bacterial protoplast-derived nanovesicles as vaccine delivery system against bacterial infection.
The notion that widespread infectious diseases could be best managed by developing potent, adjuvant-free vaccines has resulted in the use of various biological immune-stimulating components as new vaccine candidates. Recently, extracellular vesicles, also known as exosomes and microvesicles in mammalian cells and outer membrane vesicles in Gram-negative bacteria, have gained attention for the next generation vaccine. However, the more invasive and effective the vaccine is in delivery, the more risk it holds for severe immune toxicity. Here, in optimizing the current vaccine delivery system, we designed bacterial protoplast-derived nanovesicles (PDNVs), depleted of toxic outer membrane components to generate a universal adjuvant-free vaccine delivery system. These PDNVs exhibited significantly higher productivity and safety than the currently used vaccine delivery vehicles and induced strong antigen-specific humoral and cellular immune responses. Moreover, immunization with PDNVs loaded with bacterial antigens conferred effective protection against bacterial sepsis in mice. These nonliving nanovesicles derived from bacterial protoplast open up a new avenue for the creation of next generation, adjuvant-free, less toxic vaccines to be used to prevent infectious diseases.


The Use of T1 Sagittal Angle in Predicting Cervical Disc Degeneration.
Retrospective evaluation. To analyze the effect of T1 slope on degree of degeneration in patients with cervical disc degeneration. The T1 slope is well known parameter that may be very useful in evaluating sagittal balance. There are no reports on the analysis of the relationship between T1 slope and cervical disc degeneration. We hypothesized that T1 slope has an effect on the degree of cervical degeneration. Sixty patients who had cervical spine magnetic resonance imaging (MRI) in our orthopedic clinic were enrolled. Patients were divided into two groups according to T1 slope. Radiologic parameters obtained from radiography and cervical spine MRI were compared between low T1 slope group (≤25) and high T1 slope group (>25). Among low T1 slope group, average degeneration grade of each cervical segment was 2.65 in C2-3, 2.50 in C3-4, 2.62 in C4-5, 3.23 in C5-6, and 2.81 in C6-7. And that of high T1 group was 2.35 in C2-3, 2.32 in C3-4, 2.59 in C4-5, 2.79 in C5-6, and 2.32 in C6-7. Grade of degeneration of low T1 group was significantly higher, as compared with high T1 group in C5-6 (p=0.028) and C6-7 (p=0.009). Percentage of high grade degeneration of more than grand III was 65.4% in low T1 group and 32.4% in high T1 group (p=0.018). Risk of high grade degeneration of C6-7 was significantly higher in low T1 group (odds ratio, 5.63; 95% confidence interval, 1.665-19.057; p=0.005). Patients with low T1 slope had higher grade of degeneration regardless of age and gender. Low T1 slope is a potential risk factor of cervical spondylosis especially in the C6-7 cervical segment.


Technical overview of the millimeter-wave imaging reflectometer on the DIII-D tokamak (invited).
The two-dimensional mm-wave imaging reflectometer (MIR) on DIII-D is a multi-faceted device for diagnosing electron density fluctuations in fusion plasmas. Its multi-channel, multi-frequency capabilities and high sensitivity permit visualization and quantitative diagnosis of density perturbations, including correlation length, wavenumber, mode propagation velocity, and dispersion. The two-dimensional capabilities of MIR are made possible with 12 vertically separated sightlines and four-frequency operation (corresponding to four radial channels). The 48-channel DIII-D MIR system has a tunable source that can be stepped in 500 μs increments over a range of 56 to 74 GHz. An innovative optical design keeps both on-axis and off-axis channels focused at the cutoff surface, permitting imaging over an extended poloidal region. The integrity of the MIR optical design is confirmed by comparing Gaussian beam calculations to laboratory measurements of the transmitter beam pattern and receiver antenna patterns. Measurements are presented during the density ramp of a plasma discharge to demonstrate unfocused and focused MIR signals.


Corneal melting and scleromalacia perforans in a patient with pyoderma gangrenosum and acute myeloid leukemia.
Postoperative endophthalmitis may present in an atypical fashion (absent or minimal anterior chamber reaction) in the presence of underlying immunosuppressive disorder. The authors describe an apparently healthy 58-year-old man who displayed endophthalmitis with minimal anterior chamber reaction following penetrating keratoplasty for granular corneal dystrophy with underlying acute myeloid leukemia. Scleromalacia perforans in association with pyoderma gangrenosum subsequently developed, leading to ciliary staphyloma and corneal melting. Pyoderma gangrenosum is an uncommon, idiopathic skin disease that may also have ocular manifestations.


Scutellaria baicalensis Georgi and Their Natural Flavonoid Compounds in the Treatment of Ovarian Cancer: A Review.
Ovarian cancer (OC) is one of the most common types of cancer in women with a high mortality rate, and the treatment of OC is prone to high recurrence rates and side effects. Scutellaria baicalensis (SB) is a herbal medicine with good anti-cancer activity, and several studies have shown that SB and its flavonoids have some anti-OC properties. This paper elucidated the common pathogenesis of OC, including cell proliferation and cell cycle regulation, cell invasion and metastasis, apoptosis and autophagy, drug resistance and angiogenesis. The mechanisms of SB and its flavonoids, wogonin, baicalein, baicalin, Oroxylin A, and scutellarein, in the treatment of OC, are revealed, such as wogonin inhibits proliferation, induces apoptosis, inhibits invasion and metastasis, and increases the cytotoxicity of the drug. Baicalein also inhibits vascular endothelial growth factor (VEGF) expression etc. Analyzing their advantages and disadvantages in treating OC provides a new perspective on the role of SB and its flavonoids in OC treatment. It serves as a resource for future OC research and development.


Multifunctional elastin-like polypeptide renders β-glucosidase enzyme phase transition and high stability.
In the enzymatic conversion of biomass, it becomes an important issue to efficiently and cost-effectively degrade cellulose into fermentable glucose. β-Glucosidase (Bgluc), an essential member of cellulases, plays a critical role in cellulosic biomass degradation. The difficulty in improving the stability of Bgluc has been a bottleneck in the enzyme-dependent cellulose degradation. The traditional method of protein purification, however, leads to higher production cost and a decrease in activity. To simplify and efficiently purify Bgluc with modified special properties, Bgluc-tagged ELP and His with defined phase transitions was designed to facilitate the process. Here, a novel binary ELP and His tag was fused with Bgluc from termite Coptotermes formosanus to construct a Bgluc-linker-ELP-His recombinant fusion protein (BglucLEH). The recombinant plasmid Bgluc expressing a His tag (BglucH) was also constructed. The BglucLEH and BglucH were expressed in E. coli BL21 and purified using inverse transition cycling (ITC) or Ni-NTA resin. The optimum salt concentration for the ITC purification of BglucLEH was 0.5 M (NH4)2SO4 and the specific activity of BglucLEH purified by ITC was 75.5 U/mg for substrate p-NPG, which was slightly higher than that of BglucLEH purified by Ni-NTA (68.2 U/mg). The recovery rate and purification fold of BglucLEH purified by ITC and Ni-NTA were 77.8%, 79.1% and 12.60, 11.60, respectively. The results indicated that purification with ITC was superior to the traditional Ni-NTA. The K m of BglucLEH and BglucH for p-NPG was 5.27 and 5.73 mM, respectively. The K ca t/K m (14.79 S-1 mM-1) of BglucLEH was higher than that of BglucH (12.10 S-1 mM-1). The effects of ELP tag on the enzyme activity, secondary structure and protein stability were also studied. The results showed that ELP tag did not affect the secondary structure or enzyme activity of Bgluc. More importantly, ELP improved the protein stability in harsh conditions such as heating and exposure to denaturant. The Bgluc-linker-ELP-His system shows wide application prospect in maintaining the activity, efficient purification and improving the stability of Bgluc. These properties of BglucLEH make it an interesting tool to reduce cost, to improve the efficiency of biocatalyst and potentially to enhance the degradation of lignocellulosic biomass.


Distribution of B-lymphocytes in the areas of bursal and cloacal lymphoid infiltration.
The present study was carried out on the Diffusely Infiltrated Area of the bursa of Fabricius (DIA) and the area of lymphoid infiltration of the dorsal wall of the cloaca, using immunoperoxidase and electron transmission microscopy, in order to verify the behaviour of antibody-producing cells and their distribution in the two organs. An anti-chicken Ig antiserum was used for this purpose, and the results obtained show that there is a progressive increase in the antibody-producing cells in the DIA, and subsequently also in the cloaca, during the first few weeks of life; the percentage values remain constantly higher in the DIA compared with the cloaca. Electron microscopy made it possible to detect numerous lymphocytes and some plasma cells in the epithelium. Many of the intra-epithelial lymphocytes were immunoperoxidase-positive. The possible role played by the B-lymphocytes found in both organs is discussed.


Simultaneous biplane first-pass radionuclide angiocardiography using a scintillation camera with two perpendicular detectors.
Generally performed in a single anterior or right anterior oblique (RAO) view, first-pass radionuclide angiocardiography (RNA) is limited due to its inability to evaluate septal and posterior wall motion. Thirty-five patients undergoing stress/rest sestamibi SPECT (22 mCi/22 mCi 2-day protocol) underwent biplane RNA at the time of resting injection. The stress SPECT images (acquired with the patient at rest) were ECG-gated to evaluate resting regional myocardial wall thickening. By this means wall motion assessed by RNA was compared to the presence of a resting SPECT perfusion defect accompanied by a localized decrease in wall thickening. In 16 patients in whom both resting perfusion and wall thickening were normal one demonstrated apical hypokinesis by RNA in the RAO view. In the other 29 patients, a total of 58 resting segmental perfusion defects with abnormal wall thickening were present (12 anterior, 13 inferior, 14 apical, 11 septal and 8 posterolateral). Wall motion abnormalities were detected in all these patients and in 57/58 segments (98%) by biplane RNA. Septal and posterolateral wall motion abnormalities were detected in only the LAO RNA study. In three patients, wall motion abnormalities were detected by LAO imaging only. Of the remaining 87 normally perfused segments in these 29 patients, RNA wall motion was normal in 85. Two posterolateral segments demonstrated apparent hypokinesis, probably due to left atrial overlap in the LAO projection. Simultaneous biplane RNA accurately detects wall motion abnormalities frequently missed by single-plane RAO imaging.


Predictors of stroke in high-risk patients after acute myocardial infarction: insights from the VALIANT Trial.
We sought to determine risk models for predicting early and late stroke in a large cohort of high-risk post-myocardial infarction (MI) patients. We prospectively analysed data from 14 703 patients in the VALIANT trial with acute MI complicated by heart failure, left ventricular (LV) systolic dysfunction, or both. Patients were randomized 0.5-10 days after acute MI to valsartan, captopril, or their combination. We evaluated risk factors for early (<45 days) and late (>45 days) stroke by using multivariable Cox proportional hazards regression analyses with stepwise variable selection techniques applied to 92 pre-specified potential predictor variables. After randomization, 463 (3.2%) patients had fatal (n = 124) or non-fatal (n = 339) strokes, with 134 strokes occurring in the first 45 days. The strokes were classified as ischaemic (348), haemorrhagic (40), or of indeterminate cause (75). Estimated glomerular filtration rate and heart rate when in sinus rhythm were the most powerful predictors of early stroke (<45 days after MI), whereas diastolic blood pressure (DBP) >90 mmHg, prior stroke, and atrial fibrillation (AF) were the most powerful predictors of stroke overall. Ejection fraction and sex were not predictive of stroke in this cohort. Among high-risk patients presenting with MI but without initial neurological symptoms, the risk of stroke 6 weeks thereafter is 0.94% (95% CI 0.78-1.09). Of the most powerful baseline predictors of stroke, DBP and AF are amenable to therapeutic interventions and thus merit special attention in these patients.


Potential Link Between Proprotein Convertase Subtilisin/Kexin Type 9 and Alzheimer's Disease.
Alzheimer's disease [AD] is not only the most common neurodegenerative disease but is also currently incurable. Proprotein convertase subtilisin/kexin-9 [PCSK9] is an indirect regulator of plasma low density lipoprotein [LDL] levels controlling LDL receptor expression at the plasma membrane. PCSK9 also appears to regulate the development of glucose intolerance, insulin resistance, abdominal obesity, inflammation, and hypertension, conditions that have been identified as risk factors for AD. PCSK9 levels also depend on age, sex, and ethnic background, factors associated with AD. Herein, we will review indirect evidence that suggests a link between PCSK9 levels and AD.


From Halogen to Superhalogen Behavior of Organic Molecules Created by Functionalizing Benzene.
Benzene, the classic organic molecule obeying Hückel's rule of aromaticity, has negative electron affinity (EA), namely -1.15 eV. By using density functional theory with hybrid functional for exchange and correlation potential, we show that a series of organic molecules created by changing either the benzene core or the ligands, or both, result in species with EAs that range from 2.15 to 5.37 eV. This shows that ligand substitution is more effective than aromaticity in increasing the EA of organic molecules. The ability to create highly electronegative organic molecules by functionalizing benzene may provide new opportunities for synthesizing organic oxidizing agents with potential new applications.


The genetic basis of rapidly evolving male genital morphology in Drosophila.
The external genitalia are some of the most rapidly evolving morphological structures in insects. The posterior lobe of the male genital arch shows striking differences in both size and shape among closely related species of the Drosophila melanogaster species subgroup. Here, we dissect the genetic basis of posterior lobe morphology between D. mauritiana and D. sechellia, two island endemic species that last shared a common ancestor ∼300,000 years ago. We test a large collection of genome-wide homozygous D. mauritiana genetic introgressions, which collectively cover ∼50% of the genome, for their morphological effects when placed in a D. sechellia genetic background. We find several introgressions that have large effects on posterior lobe morphology and that posterior lobe size and posterior lobe shape can be separated genetically for some of the loci that specify morphology. Using next generation sequencing technology, we perform whole transcriptome gene expression analyses of the larval genital imaginal disc of D. mauritiana, D. sechellia, and two D. mauritiana-D. sechellia hybrid introgression genotypes that each have large effects on either posterior lobe size or posterior lobe shape. Many of the genes we identify as differentially expressed are expressed at levels similar to D. mauritiana in one introgression hybrid, but are expressed at levels similar to D. sechellia in the other introgression hybrid. However, we also find that both introgression hybrids express some of the same genes at levels similar to D. mauritiana, and notably, that both introgression hybrids possess genes in the insulin receptor signaling pathway, which are expressed at D. mauritiana expression levels. These results suggest the possibility that the insulin signaling pathway might integrate size and shape genetic inputs to establish differences in overall posterior lobe morphology between D. mauritiana and D. sechellia.


The speed of sound in a gas-vapour bubbly liquid.
In addition to the vapour of the liquid, bubbles in cavitating flows usually contain also a certain amount of permanent gas that diffuses out of the liquid as they grow. This paper presents a simplified linear model for the propagation of monochromatic pressure waves in a bubbly liquid with these characteristics. Phase change effects are included in detail, while the gas is assumed to follow a polytropic law. It is shown that even a small amount of permanent gas can have a major effect on the behaviour of the system. Particular attention is paid to the low-frequency range, which is of special concern in flow cavitation. Numerical results for water and liquid oxygen illustrate the implications of the model.


Tumor detection with some 99mTc-labeled S-containing amino acids.
99mTc-labeled L-cysteine, DL-homocysteine, and S-carbamyl-L-cysteine were prepared and tested for effectiveness in gamma camera imaging and for bioradiodistribution in mice bearing Ehrlich solid tumors. Among these labeled compounds, 99mTc-DL-homocysteine seems most promising for the nuclear medical imaging of tumors.


Preservation of beluga (Delphinapterus leucas) spermatozoa using a trehalose-based cryodiluent and directional freezing technology.
A beluga (Delphinapterus leucas) sperm preservation method was developed for use in genome banking and AI. In Study 1, glycerol-based cryodiluents (modified BF5F and modified Platz Diluent Variant (PDV)) were unable to maintain adequate progressive motility using straws (fast and slow freezing rate (FR)) or pellets (slow FR). Neither freezing method nor FR affected in vitro sperm characteristics (P > 0.05), but retention of prefreeze progressive motility following thawing was greater (P < 0.05) for BF5F (21%) than PDV (15%). In Study 2, examining the effects of straw freeze-thawing using BF5F with glycerol (1 and 3%, v/v) or trehalose (46 and 91 mM) on sperm characteristics, samples cryopreserved in trehalose exhibited superior (P < 0.05) in vitro parameters compared with their glycerol-treated counterparts. In Study 3, compared with a straw method, directional freezing using 91 mM trehalose enhanced (P < 0.05) sperm characteristics, with samples retaining 38%, 75% and 61% of their prefreeze progressive motility, curvilinear velocity and viability, respectively. A higher (P < 0.05) proportion of motile spermatozoa displayed rapid velocity after directional (21 +/- 1%) compared with straw (12 +/- 3%) freezing. Systematic development of a cryodiluent and the use of directional freezing resulted in beluga spermatozoa exhibiting adequate post-thaw quality for genome banking and use in AI.


The Role of Specificity Protein 1 (SP1) in Bladder Cancer Progression through PTEN-Mediated AKT/mTOR Pathway.
The aim of the study was to investigate the potential mechanism of specificity protein 1 (SP1) in bladder cancer progression through the PTEN-mediated AKT/mTOR pathway. Human bladder cancer cell lines (HT-1197, HT-1376, and T24) and normal ureteral epithelial cell line SV-HUC-1 were used. SP1 expression was detected via quantitative real-time PCR and Western blotting. Cell viability, migration, invasion, and apoptosis were assessed using CCK-8, transwell, and flow cytometry assays, respectively. The involvement of the PTEN-mediated AKT/mTOR pathway was evaluated by Western blot. A mouse xenograft model was built, and immunohistochemical staining was applied to visualize SP1 and Ki67 expression in tumor tissues. SP1 was overexpressed in bladder cancer cells. SP1 knockdown inhibited viability, migration, and invasion and promoted apoptosis in bladder cancer cells. PTEN intervention increased cell viability, migration, and invasion and decreased apoptosis, which was reversed by SP1 knockdown. The activation of the AKT/mTOR pathway resulting from PTEN knockdown was attenuated by SP1 knockdown. In vivo results showed that SP1 knockdown suppressed tumor growth, increased PTEN expression, and decreased AKT/mTOR pathway-related protein levels. SP1 promotes bladder cancer progression by inhibiting the PTEN-mediated AKT/mTOR pathway. Targeting SP1 may be a potential therapeutic strategy for treating bladder cancer.


Why and when the treatment of acne fails. What to do.
The majority of acne patients show a good response to the proper acne treatment. However, a small percentage not exceeding 10-15% do not respond as satisfactorily as expected. The main reason for the treatment failure is the poor patient compliance. In order to improve the patient compliance the strategy for the treatment of acne has to be carefully planned and includes the following: discussion before treatment; give clear instructions; explain the rhythm of improvement; explain the role of cosmetics; explain the role of sunbathing; explain the expected side effects. It has to be emphasized that all acne cases can be adequately controlled if the relationship between doctor and patient has been built on trust and confidence, maximizing the patient compliance.


Prediagnosis ultra-processed food consumption and prognosis of patients with colorectal, lung, prostate, or breast cancer: a large prospective multicenter study.
Whether ultra-processed food consumption is associated with cancer prognosis remains unknown. We aimed to test whether prediagnosis ultra-processed food consumption is positively associated with all-cause and cancer-specific mortality in patients with colorectal, lung, prostate, or breast cancer. This study included 1,100 colorectal cancer patients, 1750 lung cancer patients, 4,336 prostate cancer patients, and 2,443 breast cancer patients. Ultra-processed foods were assessed using the NOVA classification before the diagnosis of the first cancer. Multivariable Cox regression was used to calculate hazard ratio (HR) and 95% confidence interval (CI) for all-cause and cancer-specific mortality. High ultra-processed food consumption before cancer diagnosis was significantly associated with an increased risk of all-cause mortality in lung (HRquartile 4 vs. 1: 1.18; 95% CI: 0.98, 1.40; Ptrend = 0.021) and prostate (HRquartile 4 vs. 1: 1.18; 95% CI: 1.00, 1.39; Ptrend = 0.017) cancer patients in a nonlinear dose-response manner (all Pnonlinearity < 0.05), whereas no significant results were found for other associations of interest. Subgroup analyses additionally revealed a significantly positive association with colorectal cancer-specific mortality among colorectal cancer patients in stages I and II but not among those in stages III and IV (Pinteraction = 0.006), and with prostate cancer-specific mortality among prostate cancer patients with body mass index <25 but not among those with body mass index ≥25 (Pinteraction = 0.001). Our study suggests that reducing ultra-processed food consumption before cancer diagnosis may improve the overall survival of patients with lung or prostate cancer, and the cancer-specific survival of certain subgroups of patients with colorectal or prostate cancer.


Exceptionally mild, high-yield synthesis of alpha-fluoro acrylates.
Novel achiral and chiral alkyl alpha-(1,3-benzothiazol-2-ylsulfonyl)-alpha-fluoroacetates can be readily synthesized by metalation-fluorination of (1,3-benzothiazol-2-ylsulfonyl)acetates. DBU-mediated condensations of these fluorinated synthons with aldehydes proceed in a facile manner at 0 degrees C or at room temperature giving high yields of alpha-fluoro acrylates. Ketones are unreactive under these conditions. The presence of fluorine renders the synthon substantially more reactive compared to the unfluorinated analogue. Reactivity of alpha-(1,3-benzothiazol-2-ylsulfonyl)-alpha-fluoroacetate and the Horner-Wadsworth-Emmons reagent (EtO)2P(O)CHFCOOEt has also been compared.


Placement and Loading Protocols for Single Implants in Different Locations: A Systematic Review.
To analyze the effect of implant placement and loading protocols (protocol types) on the survival of single implant tooth replacements in different locations. An electronic search was conducted to identify clinical trials regarding outcomes of single implants subjected to different treatment protocols. A weighted mean survival rate for each protocol type in the anterior maxilla, anterior mandible, posterior maxilla, and posterior mandible was calculated. Study design, sample size, and outcome homogeneity were used to evaluate the validation of each protocol type in different locations. A total of 45 publications (13 RCTs, 21 prospective studies, and 11 retrospective studies) were included. The anterior maxilla was the most reported site (35 studies, 1,391 implants, weighted survival rate: 97.5% to 99.6%). Immediate placement + conventional loading (Type 1C) and late placement + immediate restoration/loading (Type 4A) were scientifically and clinically validated (SCV). For the posterior maxilla (19 studies, 567 implants, weighted survival rate: 85.7% to 100%), Type 1C was SCV. The anterior mandible was the least-reported site (three studies, 42 implants, weighted survival rate: 98.5% to 100%). For the posterior mandible (13 studies, 447 implants, weighted survival rate: 95.0% to 100%), late placement + conventional loading (Type 4C) was SCV. It was not possible to perform a metaanalysis due to the limited number of controlled studies that had the same comparison and considerable heterogeneity in study design. Differences were found in the level of scientific evidence between the anterior and posterior and the maxilla and mandible, indicating that location is a consideration when selecting treatment protocol for a single implant.


Control of the molecular alignment inside liquid-crystal droplets by use of laser tweezers.
Here, we demonstrate how the light-induced birefringence due to the dipole molecular realignment and anisotropic polarizability of a nematic liquid crystal inside a droplet changes the droplet's radial (and thus optically isotropic) structure into a birefringent one. This intensity-dependent change of birefringence can be understood in terms of the anisotropic polarizability and orientational optical nonlinear effect. Birefringence induced by laser tweezers changes the momentum of the passing light. In turn, for the circularly polarized tweezers, this change generates an angular momentum change large enough to spin micrometer-sized droplets. For the linearly polarized tweezers, the molecular ordering generates momentum, which laterally displaces the droplet. It is shown that the optical nonlinearity can be "large" enough to have mechanical (ponderomotive) implications, that is, it allows control of the movement and position of micro-objects with submicrometer resolution. The optically induced molecular alignment controlled by the polarization and power of the laser tweezers allows one to actuate, rotate, and translate objects which are up to 10(3)-10(4) times larger than the constituent molecules themselves.


[Not Available].
The present work is based on the lecture notes from the year 1812/1813 of the medical student Johann Baptist Huber. The lectures on ophthalmology, otology, and dentistry were given by the zurich hospital physician Johann Ludwig Meyer at the Institute of Medicine and Surgery in Zurich. The main part of this dissertation contains the exact transcription of Huber's lecture notes, where only orthography and punctuation have been changed; these changes were made according to the present German grammar. Short biographies of the student Huber and the lecturer Meyer are also given. A brief overview on the history of ophthalmology, otology, and dentistry is given separately. The didactical and medical aspects of Meyer's lecture are discussed. Important medical methods of the time have been highlighted and compared with modern mainstream medicine.


Facilitating Factors and Barriers to the Implementation of the Icelandic Prevention Model of Adolescent Substance Use in Chile: A Focus Group Study.
The use of alcohol and other drugs is a major public health problem in adolescence. The implementation of evidence-based prevention strategies is still scarce in the global south. This study aimed to evaluate facilitators and barriers to the implementation of the Icelandic prevention model of adolescent substance use (IPM) in Chile. We conducted a qualitative study of stakeholders during the implementation process of the IPM in six municipalities of the Metropolitan Region of Santiago, Chile. We convened six focus groups with parents and professionals from schools and municipal prevention teams (38 participants). Recordings were transcribed and submitted to a six-step thematic analysis. The following facilitators emerged: Participants valued the contribution of the IPM to articulate existing programs and teams, its community focus, and the local data obtained through the survey. There were also several barriers: Those included resistance to adopting a foreign model, the tension between generating local strategies and looking for measures to ensure the fidelity of the implementation, socioeconomic differences between and within municipalities, low-risk perception and supervision of parents in Chile, and a culture that generally does not discourage adolescent substance use. Implementation of the IPM was largely accepted by the stakeholders who agreed with the community approach of the model. The main barriers to consider were related to cultural and socioeconomic factors that need to be addressed in further research and may limit the effects of the model in Chile.


Adjuvant chemotherapy in clinical stage M0 sarcoma of soft tissue.
The clinical course of 117 patients who were treated for Stages IIB-IIIC sarcoma of soft tissues by the combined approach of radiation and surgery at MGH during the period 1971-1984 have been analyzed for an effect of adjuvant chemotherapy to improve clinical results. Thirty-two patients received adjuvant chemotherapy and 85 were treated by local methods alone. The chemotherapy protocols featured doxorubicin (25 patients) or VAC (seven patients). The no chemotherapy patients were controls matched for tumor grade and size and were treated over approximately the same period. The two groups were not well matched for age: median age of 38.5 and 54 years for the treated and control groups, respectively. There was no significant difference in survival. However, the time to first metastasis was longer in the treated group, P = 0.04. Furthermore, the local failure rate appeared to be lower in the treated group, P = 0.06.


Lupus Damage and Waist Circumference as the Independent Risk Factors for Cardiovascular Disease in SLE Patients from Phramongkutklao Hospital.
Cardiovascular disease (CVD) has been reported to be a major cause of both morbidity and premature mortality in systemic lupus erythematosus (SLE) patients. To determine the prevalence of cardiovascular disease and associated risk factors in Thai SLE patients from Phramongkutklao Hospital, Thailand. A retrospective cross-sectional study was performed to investigate the frequency of CVD in SLE patients in Phramongkutklao Hospital on the basis of medical record documentation. CVD was defined as coronary heart disease, congestive heart failure, cerebrovascular disease (stroke), transient ischemic attack, and peripheral arterial disease (PAD). The associated risk factors of CVD were examined by univariate and multivariate logistic regression analyses. One hundred fifty nine SLE patients were enrolled in the present study. Nine female and one male SLE patients had CVD (prevalence 6.3%). SLE patients with CVD had higher Systemic Lupus International Collaborating Clinics Damage Index (SDI) score (p-value = 0.025) and received higher average dose of corticosteroid (p-value = 0.034) than SLE patients without CVD. Patients with CVD were more likely to present with malar rash (p-value = 0.054), discoid rash (p-value = 0.047), and more likely to used cyclophosphamide (p-value = 0.045) than patients without CVD. SLE patients with CVD were more likely to have diabetes mellitus (p-value = 0.037), antiphospholipid syndrome (p-value = 0.055), and had higher proportion of patients whose waist circumference more than 90 centimeters in male or more than 80 centimeters in female (p-value = 0.06) than SLE patients without CVD. The presence of antiphospholipid antibodies was higher in SLE patients with CVD than SLE patients without CVD (p-value = 0.076). The multivariate regression analysis identified that SDI score (odds ratio (OR) = 1.74 with 95% confidence interval (CI) 1.12-2.69, p-value = 0.013), and waist circumference more than 90 centimeters in male or more than 80 centimeters in female (OR = 6.9 with 95% CI 1.20-38.46, p-value = 0.031) were independently associated risk factors for the occurrence of CVD in SLE patients. The presence of antiphospholipid antibodies also had a trend toward increased risk of CVD in SLE patients (OR = 4.1 with 95% CI 0.96-17.8, p-value = 0.057). Lupus damage, waist circumference more than 90 centimeters in male or more than 80 centimeters in female were the independent risk factors for CVD in SLE patients.


Phosphoprotein particles: calcium and inorganic phosphate binding structures.
Phosphoprotein particles were isolated in their native state from the physiological fluid of the estuarine clam Rangia cuneata , and the characteristics of the mineral ion-protein complex which constitutes the native particle were investigated by using mineral ion binding and mineral ion exchange techniques. The particles are aspartic acid rich, highly phosphorylated proteins containing calcium, magnesium, and inorganic phosphate ions and covalently cross-linked via histidinoalanine residues. Twenty-nine percent of the amino acid residues are phosphorylated. In their native state, the particles contain a protected pool of calcium and inorganic phosphate ions and an exchangeable pool of calcium and magnesium ions. The Ca/PO4 ratio in the protected pool is about 2.5. The number of binding sites for the protected mineral is unknown, but on the average, the native particles contain about 0.2 inorganic phosphate ion per organic phosphate residue. There is 1.0 exchangeable metal ion binding site per organic phosphate residue, and there is probably a phosphoserine residue at each site. These sites bind calcium with an apparent binding constant (KCa) of 4 X 10(3) M-1 at 50% saturation under physiological conditions, and KCa/ KMg is about 1.6. In vivo, about 85% of the exchangeable sites are occupied. The total number of calcium ion binding sites (N) in the phosphoprotein particles is related to the number of organic phosphate residues (Po) and the number of bound inorganic phosphate ions (Pi) by the equation N = Po + 2. 5Pi . The phosphoprotein particles probably serve as both the transporter and reserve source of calcium ions for shell development.


Breast arterial calcifications (BACs) found on screening mammography and their association with cardiovascular disease.
Breast arterial calcifications (BACs) are common but unreported findings on screening mammograms. This study correlated mammographically detected BACs with coronary artery disease (CAD) risk factors and a history of atherosclerotic cardiovascular disease (ASCVD), estimating the relative risk of ASCVD in patients with BACs. Women arriving for breast cancer screening mammography gave their consent to complete a questionnaire and to allow their mammograms to be analyzed independently for the presence of BACs by certified radiologists, who were blinded to the results of the questionnaire. The questionnaire assessed major risk factors for CAD and gathered information on hormone therapy use. Of the 1,919 women with results, 268 were BAC positive, giving a BAC prevalence of 14%. Five cardiovascular risk factors (age, hypertension, hypercholesteremia, diabetes mellitus, and menopause) were significantly more prevalent in the BAC-positive population (P < 0.001). The BAC-positive group also had a significantly higher (P < 0.001) occurrence of ASCVD events (angina, previous myocardial infarction, previous abnormal angiography, previous stroke, and previous coronary artery bypass graft). Multiple logistic regression analysis found BACs to be strongly associated with ASCVD events (odds ratio = 2.29, 95% CI: 1.40-3.74) as compared with other CAD risk factors (including hypertension, cigarette smoking, diabetes mellitus, age, and family history of ASCVD). The association of BAC with ASCVD was present even after accounting for age. BACs are associated with an increased prevalence of both cardiovascular risk factors and cardiovascular morbidity. BACs may be a practical tool to use as a risk indicator for CAD in women.


Novel B-cell subsets in atherosclerosis.
The number of deaths associated with cardiovascular disease remains high, despite great advances in treating the associated high levels of cholesterol. The main underlying pathology of cardiovascular disease is atherosclerosis, which is recognized as a chronic autoimmune-like inflammatory disease. Hence, there is a pressing need to shed light on the immune pathways associated with atherosclerosis. B cells have long been thought to have a general protective effect in atherosclerosis. However, findings in the last decade have challenged this paradigm, showing that it is crucial to differentiate between the various B-cell subsets when assessing their role/effect on atherosclerosis. It has become increasingly recognized lately that B cells can have significant effects on the immune system independent of antibody production. The understanding that B cells form a major source of cytokines and can directly influence T-cell responses via surface markers, have led to the identification of novel B-cell subsets. These subsets are important modulators of autoimmune disorders but have not yet been fully investigated in atherosclerosis. Here we review the current known roles of B-cell subsets and the putative effects of recently identified B cells on atherosclerosis.


An Intraoral Appliance to Retract the Protrusive Premaxilla in Bilateral Cleft Lip Patients Presenting Late for Primary Lip Repair.
The protruding and deviated premaxilla in bilateral complete cleft lip and palate (BCL/P) patients causes a perplexing problem in achieving a tension-free primary lip closure. An innovative noninvasive active intraoral Fixed Pre-Surgical Cleft Orthopedic (FPSCO) appliance is presented that has enabled to successfully reposition the premaxillary segment to a more favorable position prior to the surgical repair in 4 BCL/P patients, who reported late for treatment with a mean age of 18 ± 3 months. All the patients had at least 1 deciduous tooth erupted in 3 cleft segments, 1 premaxilla (PM), and 2 lateral maxillary (LM) segments. This innovative approach is a noninvasive method of getting the cleft segments closer prior to chelioplasty, where conventional presurgical nasoalveolar molding (PNAM) is not possible, which needs to be done early in life as it requires circulating maternal estrogen levels to achieve results preferably possible in patients younger than 3 to 6 months. Bonding to erupted teeth with glass ionomer cement was implemented to secure the appliance. Nickel-titanium (Ni-Ti) closed-coil springs were used that delivered continuous forces of 150 g/5 oz per side to retract the premaxillary segment. The mean active period of treatment time was 3.5 ± 1.6 months and the retention period was 1.2 ± 0.6 months, following which cheiloplasty was performed.


Feeding the hypotensive patient: does enteral feeding precipitate or protect against ischemic bowel?
Although the enteral route of enteral feeding is the preferred method of nutrition support for critically ill patients, this important therapeutic strategy is not without risk. In human subjects, the digestion and absorption of nutrients induce typical hemodynamic changes, consisting of an increase in mesenteric blood flow at the expense of reduced systemic blood pressure. On rare occasion when providing aggressive enteral nutrition to critically ill patients, common symptoms of gastrointestinal intolerance may progress to a syndrome of abdominal distention, hypotension, and shock, with the development of small bowel ischemia or necrosis. Although the incidence of small bowel ischemia secondary to enteral feeding is low, the overall clinical outcome is still poor and carries a high mortality rate. Enteral feeding is well tolerated and is probably beneficial in most critically ill patients before and after a period of hypotension. Although enteral nutrition may be used with caution during the period of hypotension, evidence of poor gastrointestinal function (increased nasogastric tube output, unexplained abdominal pain, and abdominal distention), or development of dilated loops of bowel or intramural gas (pneumatosis intestinalis) on radiographic studies should be interpreted as potential indicators of gut ischemia. With progress in our understanding of the pathophysiology, diagnosis, and prevention of ischemic injury to the intestinal mucosa, the strategy of aggressive enteral feeding for critically ill patients may result in a reduction in this major complication and enhanced functional recovery from severe illness.


Vaginal treatment of vaginal cuff dehiscence with visceral loop prolapse: a new challenge in reparative vaginal surgery?
Vaginal cuff dehiscence is a rare, but potentially morbid, complication of total hysterectomy and refers to separation of the vaginal cuff closure. The term vaginal cuff dehiscence is frequently interchanged with the terms of cuff separation or cuff rupture. All denote the separation of a vaginal incision that was previously closed at time of total hysterectomy. After dehiscence of the vaginal cuff, abdominal or pelvic contents may prolapse through the vaginal opening. Bowel evisceration, outside the vulvar introitus, can lead to serious sequelae, including peritonitis, bowel injury and necrosis, or sepsis. Therefore, although prompt surgical and medical intervention is required to replace prolapsed structures, the main problem remains the reconstruction of vaginal vault. In case of recent hysterectomy, vaginal reparation only requires the approximation of vaginal walls, including their fascia, while if dehiscence occurs after a long time from hysterectomy, the adequate suspension of the vaginal vault has to be taken into consideration. In this report we describe the case of a postmenopausal patient, undergoing surgical emergency because of the evisceration of an intestinal loop through a dehiscence of vaginal vault, after numerous reconstructive vaginal surgeries for vaginal prolapse. This paper analyzes clinical circumstances, risk factors, comorbidity, and clinical and surgical management of this complication.


Mitochondrial oxidative damage by co-exposure to bisphenol A and acetaminophen in rat testes and its amelioration by melatonin.
Human exposure to multiple xenobiotics, over various developmental windows, results in adverse health effects arising from these concomitant exposures. Humans are widely exposed to bisphenol A, and acetaminophen is the most commonly used over-the-counter drug worldwide. Bisphenol A is a well-recognized male reproductive toxicant, and increasing evidence suggests that acetaminophen is also detrimental to the male reproductive system. The recent recognition of male reproductive system dysfunction in conditions of suboptimal reproductive outcomes makes it crucial to investigate the contributions of toxicant exposures to infertility and sub-fertility. We aimed to identify toxicity in the male reproductive system at the mitochondrial level in response to co-exposure to bisphenol A and acetaminophen, and we investigated whether melatonin ameliorated this toxicity. Male Wistar rats were divided into six groups (n=10 each): a control group and groups that received melatonin, bisphenol A, acetaminophen, bisphenol A and acetaminophen, and bisphenol A and acetaminophen with melatonin treatment. Significantly higher lipid peroxidation was observed in the testicular mitochondria and sperm in the treatment groups than in the control group. Levels of glutathione and the activities of catalase, glutathione peroxidase, glutathione reductase, and manganese superoxide dismutase decreased significantly in response to the toxicant treatments. Likewise, the toxicant treatments significantly decreased the sperm count and motility, while significantly increasing sperm mortality. Melatonin mitigated the adverse effects of bisphenol A and acetaminophen. Co-exposure to bisphenol A and acetaminophen elevated oxidative stress in the testicular mitochondria, and this effect was alleviated by melatonin.


Mortality in rheumatoid arthritis: 2008 update.
Mortality rates in patients with rheumatoid arthritis (RA) are 1.5-1.6 fold higher than in the general population, with similar patterns over 60 years. The acute attributed causes of death appear overall similar to the general population, with cardiovascular disease the most common attributed cause of death, and with more infection, pulmonary and renal disease in RA than in the general population. All clinical measures indicating more severe clinical status appear prognostic of premature mortality, with rheumatoid factor and the shared epitope significant for progressive RA. Functional and global measures as well as comorbidities generally are the most significant predictors of premature death.


Training the next generation of psychotraumatologists: COllaborative Network for Training and EXcellence in psychoTraumatology (CONTEXT).
In this paper we present a description of the Horizon2020, Marie Skłodowska-Curie Action funded, research and training programme CONTEXT: COllaborative Network for Training and EXcellence in psychoTraumatology. The three objectives of the programme are put forward, each of which refers to a key component of the CONTEXT programme. First, we summarize the 12 individual research projects that will take place across three priority populations: (i) refugees and asylum seekers, (ii) first responders, and (iii) perpetrators and survivors of childhood and gender-based violence. Second, we detail the mentoring and training programme central to CONTEXT. Finally, we describe how the research, together with the training, will contribute towards better policy, guidelines, and practice within the field of psychotraumatology.


New prospective 4D-CT for mitigating the effects of irregular respiratory motion.
Artifact caused by irregular respiration is a major source of error in 4D-CT imaging. We propose a new prospective 4D-CT to mitigate this source of error without new hardware, software or off-line data-processing on the GE CT scanner. We utilize the cine CT scan in the design of the new prospective 4D-CT. The cine CT scan at each position can be stopped by the operator when an irregular respiration occurs, and resumed when the respiration becomes regular. This process can be repeated at one or multiple scan positions. After the scan, a retrospective reconstruction is initiated on the CT console to reconstruct only the images corresponding to the regular respiratory cycles. The end result is a 4D-CT free of irregular respiration. To prove feasibility, we conducted a phantom and six patient studies. The artifacts associated with the irregular respiratory cycles could be removed from both the phantom and patient studies. A new prospective 4D-CT scanning and processing technique to mitigate the impact of irregular respiration in 4D-CT has been demonstrated. This technique can save radiation dose because the repeat scans are only at the scan positions where an irregular respiration occurs. Current practice is to repeat the scans at all positions. There is no cost to apply this technique because it is applicable on the GE CT scanner without new hardware, software or off-line data-processing.


Osteoblastoma of the coracoid process: an unusual location.
Bone tumours arising from the coracoid process of the scapula are very rare. We present a case of a 19-year-old man with left shoulder pain for 1 year, with associated infraclavicular swelling for 8 months. Examination revealed a tender, bony, hard swelling measuring 3×4 cm. Imaging revealed an expansile osteolytic lesion arising from the coracoid process with loss of corticomedullary differentiation. MRI showed altered signal in the adjacent soft tissues. The patient underwent en bloc resection of the lesion. Histology was suggestive of osteoblastoma. At the end of 2 years follow-up, the patient had no pain or recurrence of the lesion. We present this case for its rare location and have briefly discussed the difficulties in diagnosis of this condition.


The Divergence of Flowering Time Modulated by FT/TFL1 Is Independent to Their Interaction and Binding Activities.
FLOWERING LOCUS T (FT) and TERMINAL FLOWER1 (TFL1) proteins share highly conserved amino acid residues but they play opposite regulatory roles in promoting and repressing the flowering response, respectively. Previous substitution models and functional analysis have identified several key amino acid residues which are critical for the promotion of flowering. However, the precise relationship between naturally occurring FT/TFL1 homologs and the mechanism of their role in flowering is still unclear. In this study, FT/TFL1 homologs from eight Rosaceae species, namely, Spiraea cantoniensis, Pyracantha fortuneana, Photinia serrulata, Fragaria ananassa, Rosa hybrida, Prunus mume, Prunus persica and Prunus yedoensis, were isolated. Three of these homologs were further characterized by functional analyses involving site-directed mutagenesis. The results showed that these FT/TFL1 homologs might have diverse functions despite sharing a high similarity of sequences or crystal structures. Functional analyses were conducted for the key FT amino acids, Tyr-85 and Gln-140. It revealed that TFL1 homologs cannot promote flowering simply by substitution with key FT amino acid residues. Mutations of the IYN triplet motif within segment C of exon 4 can prevent the FT homolog from promoting the flowering. Furthermore, physical interaction of FT homologous or mutated proteins with the transcription factor FD, together with their lipid-binding properties analysis, showed that it was not sufficient to trigger flowering. Thus, our findings revealed that the divergence of flowering time modulating by FT/TFL1 homologs is independent to interaction and binding activities.


[EFFECT OF RECOMBINANT ADENOVIRUS-BONE MORPHOGENETIC PROTEIN 12 TRANSFECTION ON DIFFERENTIATION OF PERIPHERAL BLOOD MESENCHYMAL STEM CELLS INTO TENDON/LIGAMENT CELLS].
To research the effect of recombinant adenovirus-bone morphogenetic protein 12 (Ad-BMP-12) transfection on the differentiation of peripheral blood mesenchymal stem cells (MSCs) into tendon/ligament cells. Peripheral blood MSCs were isolated from New Zealand rabbits (3-4 months old) and cultured in vitro until passage 3. The recombinant adenoviral vector system was prepared using AdEasy system, then transfected into MSCs at passage 3 (transfected group); untransfected MSCs served as control (untransfected group). The morphological characteristics and growth of transfected cells were observed under inverted phase contrast microscope. The transfection efficiency and green fluorescent protein (GFP) expression were detected by flow cytometry (FCM) and fluorescence microscopy. After cultured for 14 days in vitro, the expressions of tendon/ligament-specific markers were determined by immunohistochemistry and real-time fluorescent quantitative PCR. GFP expression could be observed in peripheral blood MSCs at 8 hours after transfection. At 24 hours after transfection, the cells had clear morphology and grew slowly under inverted phase contrast microscope and almost all expressed GFP at the same field under fluorescence microscopy. FCM analysis showed that the transfection efficiency of the transfected group was 99.57%, while it was 2.46% in the untransfected group. The immunohistochemistry showed that the expression of collagen type I gradually increased with culture time in vitro. Real-time fluorescent quantitative PCR results showed that the mRNA expressions of the tendon/ligament-specific genes (Tenomodulin, Tenascin-C, and Decorin) in the transfected group were significantly higher than those in untransfected group (0.061+/- 0.013 vs. 0.004 +/- 0.002, t = -7.700, P=0.031; 0.029 +/- 0.008 vs. 0.003 +/- 0.001, t = -5.741, P=0.020; 0.679 +/- 0.067 vs. 0.142 +/- 0.024, t = -12.998, P=0.000). Ad-BMP-12 can significantly promote differentiation of peripheral blood MSCs into tendon/ligament fibroblasts and enhance the expressions of tendon/ligament-specific phenotypic differentiation, which would provide the evidence for peripheral blood MSCs applied for tendon/ligament regeneration.


Targeted absolute quantification of intact proteins by reversed phase liquid chromatography-mass spectrometry, charge reduced electrospray, and condensation particle counting.
A novel approach involving the use of reversed phase liquid chromatography-mass spectrometry (RPLC-MS), charge reduced electrospray (CRES), and condensation particle counting (CPC) for the absolute quantification of intact proteins in liquid solutions is introduced. Under analysis conditions optimized for the quantification of select proteins within their predetermined linear ranges, a set of at least five protein standards with molecular weights (MW) spanning the dynamic ranges of both a quadrupole time-of-flight (QTOF) MS and a suitably selected RPLC column is used to generate a calibration curve of CPC detection efficiency (DE) as a function of the square root of MW. Next, the sample of interest is analyzed, and from the MS-generated MW data, the DE of each target protein is determined from the calibration curve. On the basis of MW, DE, and number concentration (molecules/unit volume), absolute quantification is achieved for each protein of interest. Application of this approach to the absolute quantification of cytochrome C (as target compound) in a commercial protein mixture is demonstrated with a deviation of 8%, a coefficient of variation (CV) of 5%, and a quantification limit of 432 fmol. For nontarget components of the mixture (ribonuclease A, holotransferrin, and apomyoglobin), the percent deviation from the stated concentrations and the CV varied from 0.20 to 23 and from 4.1 to 18, respectively. Performance of the method was further assessed by analyzing a laboratory quality control mixture comprising 0.33 μM of cytochrome C. The calculated value was 0.34 (CV: 5.1%). Universal in essence, the new technique holds strong promise for the absolute quantification of select proteins in liquid samples under conditions of good peak resolution and stable baseline.


Glucose challenge test does not predict gestational diabetes mellitus.
It is widely acknowledged that identification and treatment of gestational diabetes mellitus (GDM) results in better maternal and neonatal outcomes. However, the utility of the glucose challenge test (GCT) remains controversial regarding the diagnostic approach and decision making. We performed a retrospective analysis on the database of our Laboratory Information System to retrieve results of GCT and oral glucose tolerance test (OGTT), which were performed on consecutive female outpatients referred by the gynecologists over the last 3 years. Cumulative results for GCT and OGTT were retrieved for 724 female outpatients and screening test was abnormal in 114 of them. This group was classified in terms of normal glucose tolerance (NGT), one abnormal value for the 100-g-3h OGTT (OAV) and GDM. GDM was diagnosed only in 34 subjects (4.7%). No statistically significant differences were observed in the basal plasma glucose and 1-h GCT values among groups. Multivariable logistic regression analysis demonstrated that age, OGTT values >or=180 mg/dL at 1 hour and OGTT values >or=155 mg/dL at 2 hours, but not GCT values, were independent predictors for GDM (p=0.048, p=0.012 and p<0.001, respectively). Results of our retrospective analysis on an unselected population are consistent with the hypothesis that GCT is not predictive of GDM and its diagnostic significance remains questionable.


The associations between five polymorphisms of vascular endothelial growth factor and renal cell carcinoma risk: an updated meta-analysis.
Vascular endothelial growth factor (VEGF) is a key mediator that plays an important role in angiogenesis, tumor growth, and tumor metastasis. The associations between five polymorphisms of VEGF (rs3025039, rs699947, rs10434, rs1570360, and rs2010963) and renal cell carcinoma (RCC) risk have been extensively investigated, but the currently available results are inconsistent and inconclusive. To obtain a more accurate assessment of the associations, we conducted a meta-analysis in this study. Relevant studies were collected systemically from the following three electronic databases: MEDLINE, Web of Science, and CNKI (Chinese National Knowledge Infrastructure). Statistical analyses were performed using Review Manager 5.2 in a fixed- or random-effects model. Pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to establish the strength of associations. A total of eight case-control studies with 1,936 RCC cases and 2,770 controls fulfilling the inclusion criteria were selected for this meta-analysis. The pooled OR indicated that rs699947 polymorphism was significantly associated with RCC risk in all genetic models. A significant association was also found between the rs3025039 polymorphism and RCC risk in a homozygous model (TT vs CC: OR =1.38, 95% CI =1.11-1.72, P=0.004), a dominant model (CT+TT vs CC: OR =1.21, 95% CI =1.05-1.39, P=0.01), and a recessive model (TT vs CC+CT: OR =1.28, 95% CI =1.04-1.57, P=0.02). After a subgroup analysis of ethnicity in the allele contrast model of rs3025039 polymorphism, we found a significant relationship in the allele contrast model (T vs C: OR =1.21, 95% CI =1.05-1.40, P=0.007) in the Asian population. With regard to rs10434 polymorphism, significant association was observed only in a homozygous model (GG vs AA: OR =0.75, 95% CI =0.57-0.98, P=0.03). As to rs1570360 or rs2010963, we did not observe any relationship between the two polymorphisms and RCC risk in our study. Our meta-analysis confirmed the fact that rs699947, rs3025039, and rs10434 polymorphisms were significantly relevant to elevated RCC risk. In the meanwhile, this study also demonstrated that the allele contrast model of rs3025039 polymorphism was likely to be associated with risk of RCC in the Asian population.