An inhibitor of histamine release from human leukocytes.
Lysates of human leukocytes, prepared by ultrasonic disruption, contained heat-labile histamine-releasing factors. An inhibitor of histamine release was generated from such lysates during thermal inactivation of the histamine-releasing activity. Lysates inactivated at 38 degrees C for 60 min produced up to 90% inhibition of histamine release from human leukocytes. Heated lysates produced significant inhibition (P < 0.001) of leukocyte histamine release induced by goat antihuman IgE (51+/-3% inhibition), compound 48/80 (69+/-7% inhibition), and fresh leukocyte lysate (63+/-6% inhibition). Membrane ultrafiltration and gel-filtration chromatography suggested that the inhibitor was of less than 1,000 molecular weight. The partially purified inhibitor, eluted from Sephadex G-15 and lyophilized, contained no detectable protein or carbohydrate but produced 80-90% inhibition of histamine release at a concentration of only 10 ng/ml. The histamine-releasing factors from lysates of purified suspensions of lymphocytes and granulocytes were fractionated on Sephadex G-25. A single peak of histamine-releasing activity with an estimated molecular weight of 5,000 was detected from each cell type. Incubation of the partially purified histamine-releasing factors at 38 degrees C resulted in generation of an inhibitor of histamine release which was nearly identical to the inhibitor from crude lysates. This natural inhibitor of histamine release, derived from human leukocytes, may provide an endogenous mechanism for the control of histamine release in inflammation.


Lack of adaptation from standing genetic variation despite the presence of putatively adaptive alleles in introduced sweet vernal grass (Anthoxanthum odoratum).
Population genetic theory predicts that the availability of appropriate standing genetic variation should facilitate rapid evolution when species are introduced to new environments. However, few tests of rapid evolution have been paired with empirical surveys for the presence of previously identified adaptive genetic variants in natural populations. In this study, we examined local adaptation to soil Al toxicity in the introduced range of sweet vernal grass (Anthoxanthum odoratum), and we genotyped populations for the presence of Al tolerance alleles previously identified at the long-term ecological Park Grass Experiment (PGE, Harpenden, UK) in the species native range. We found that markers associated with Al tolerance at the PGE were present at appreciable frequency in introduced populations. Despite this, there was no strong evidence of local adaptation to soil Al toxicity among populations. Populations demonstrated significantly different intrinsic root growth rates in the absence of Al. This suggests that selection on correlated root growth traits may constrain the ability of populations to evolve significantly different root growth responses to Al. Our results demonstrate that genotype-phenotype associations may differ substantially between the native and introduced parts of a species range and that adaptive alleles from a native species range may not necessarily promote phenotypic differentiation in the introduced range.


PIWI-interacting RNAs are differentially expressed during cardiac differentiation of human pluripotent stem cells.
PIWI-interacting RNAs (piRNAs) are a class of non-coding RNAs initially thought to be restricted exclusively to germline cells. In recent years, accumulating evidence has demonstrated that piRNAs are actually expressed in pluripotent, neural, cardiac and even cancer cells. However, controversy remains around the existence and function of somatic piRNAs. Using small RNA-seq samples from H9 pluripotent cells differentiated to mesoderm progenitors and cardiomyocytes we identified the expression of 447 piRNA transcripts, of which 241 were detected in pluripotency, 218 in mesoderm and 171 in cardiac cells. The majority of them originated from the sense strand of protein coding and lncRNAs genes in all stages of differentiation, though no evidences of amplification loop (ping-pong) were found. Genes hosting piRNA transcripts in cardiac samples were related to critical biological processes in the heart, like contraction and cardiac muscle development. Our results indicate that these piRNAs might have a role in fine-tuning the expression of genes involved in differentiation of pluripotent cells to cardiomyocytes.


Novel Way to Search for Light Dark Matter in Lepton Beam-Dump Experiments.
A novel mechanism to produce and detect light dark matter in experiments making use of GeV electrons (and positrons) impinging on a thick target (beam dump) is proposed. The positron-rich environment produced by the electromagnetic shower allows us to produce an A^{'} via nonresonant (e^{+}+e^{-}→γ+A^{'}) and resonant (e^{+}+e^{-}→A^{'}) annihilation on atomic electrons. The latter mechanism, for some selected kinematics, results in a larger sensitivity with respect to limits derived by the commonly used A^{'}-strahlung. This idea, applied to beam-dump experiments and active beam-dump experiments, pushes down the current limits by an order of magnitude.


Augmenter of liver regeneration improves therapeutic effect of hepatocyte homotransplantation in acute liver failure rats.
Hepatocyte transplantation (HCT) is an available option on treatment for acute liver failure (ALF). However, short-term survival of engraftment and immunological rejections of recipient are major obstacles. Augmenter of liver regeneration (ALR) has cytoprotective and immunoregulatory effects in liver injury, and has been used in many experimental applications. In the present study, we investigated the potential effect and mechanism of recombinant human ALR (rhALR) on ALF rats treated with intraperitoneal HCT. ALF rats induced by d-galactosamine (GalN) were studied in vivo, and were intraperitoneal injected with or without hepatocytes and rhALR 24h after the induction. Animal survival, serum and ascites liver enzymes, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were assessed. Histological examination was performed, and liver regeneration, apoptosis and immunological responses were identified by immunohistochemistry assay. Our results showed that rhALR promoted hepatocytes regeneration, attenuated liver injury and suppressed immunological responses. The ascites liver enzyme, serum and ascites pro-inflammatory cytokines (TNF-α, IL-1β), liver histological injury, apoptotic hepatocytes and activated immunocytes were significantly reduced in ALF rats treated with rhALR and HCT compared with those without rhALR. The proliferative and mitotic hepatocytes were markedly increased, and overall survival improved with rhALR. The administration of rhALR improved survival and promoted liver recovery in HCT treatment for ALF, which was associated with the role of proliferative promoter and immunosuppressor. This study suggests that co-treated with rhALR and HCT can provide a promising strategy for the treatment of ALF.


Serum Irisin level is associated with fall risk, muscle strength, and cortical porosity in postmenopausal women.
Irisin plays a role in bone-muscle crosstalk, but the relationship between the serum irisin level and bone microarchitecture remains unknown. This study aimed to investigate the relationships between serum irisin level and fall risk, muscle strength, bone mineral density (BMD), and bone microarchitecture among Chinese postmenopausal women. In all 138 postmenopausal women, handgrip strength, short physical performance battery (SPPB), and the timed up-and-go test were performed to evaluate muscle strength, physical performance, and fall risk, respectively. The serum irisin was measured. High-resolution peripheral quantitative computed tomography (HR-pQCT) was performed to acquire volumetric BMD and bone microarchitecture. Bivariate analysis was used to explore relationships between serum irisin level and muscle strength and HR-pQCT parameters. Univariate and multivariate linear regression analyses were performed to determine associations between serum irisin level and vBMD and cortical porosity (Ct.Po). All participants had a median serum irisin level of 3.91 μg/ml. Participants with high fall risk had significantly lower serum irisin levels than those with low fall risk (2.22 μg/ml vs. 4.16 μg/ml, p=0.024). Irisin level was positively related to handgrip strength (rs=0.185, p=0.030) and SPPB performance. In univariate linear regression, serum irisin level was positively associated with cortical volumetric BMD (Ct.vBMD, radius: standardized β=0.184, p=0.031; tibia: standardized β=0.242, p=0.004), but it had no significant associations with Ct.vBMD after multivariate adjustment. After adjusting by age, height, serum sclerostin level, and body fat ratio, only Ct.Po at the distal radius had a significantly negative association with serum irisin level (standardized β=-0.276, p=0.003). Postmenopausal women with lower serum irisin levels have a higher fall risk, weaker muscle strength, and higher cortical porosity. Moreover, serum irisin level has a positive association with Ct.vBMD, but it is affected by factors such as age.


Artificial Ureter in Patients with Extensive Ureteral Damage.
loss of significant lengths of ureter when substitution with bowel or bladder fails is a disaster in urology. This study is conducted to evaluate the results of subcutaneous nephron-vesical bypass (SNVB) in ureteral damage of different etiologies. Seventeen SNVB were employed in patients with ureteral injuries. We employed a device consisted of an internal silicone tube covered by a coiled PTFE tube to replace the ureter. This is called artificial ureter (AU). Proximal end of the AU was introduced in the kidney percutaneously, the tube was passed through a subcutaneous tunnel, while the distal end was inserted in the bladder through a small suprapubic incision. Follow-up ranged from six months to ten years. We removed the prosthetic ureter in one patient due to gross hematuria two months after insertion. One of the patients was reoperated two days after the procedure because of urinary leakage. In all other patients, the procedure was safe and effective. Subcutaneous nephron-vesical bypass is a safe and appealing alternative to a nephrostomy tube. This is a permanent device with no need for exchange. The technique can be applied in ureteral injuries due to various causes.


The use of choline acetyltransferase for measuring the synthesis of acetyl-coenzyme A and its release from brain mitochondria.
1. A method for measuring small amounts of acetyl-CoA synthesized in subcellular fractions of the brain from pyruvate and released from particles into the incubation medium has been developed by using placental choline acetyltransferase and choline in the incubation medium to transform acetyl-CoA into acetylcholine. Acetylcholine is measured by biological assay. Optimum conditions of incubation are described. 2. With fresh mitochondria, a decrease of acetyl-CoA output into the medium is observed in the presence of ATP or ADP, and an increase in the presence of calcium chloride or 2,4-dinitrophenol. Fluorocitrate and malonate have little or no effect. 3. After the mitochondria had been treated with ether, the release of acetyl-CoA into the medium is much larger; presumably, nearly all acetyl-CoA synthesized is then released and transformed into acetylcholine under the conditions used. The release of acetyl-CoA is diminished in the presence of Krebs-cycle intermediates and ADP. 4. Of all subcellular fractions, the highest acetyl-CoA production from pyruvate is found in the crude mitochondria; rates up to 51 mumoles of acetyl-CoA/g. of original tissue/hr. are observed in ether-treated samples. 5. The activities of acetyl-CoA synthetase and ATP citrate lyase found in homogenates and nerve-ending fractions of brain tissue are considerably lower than those of pyruvate oxidase complex and choline acetyltransferase. 6. The bearing of some of the findings on the question of the source of acetyl radicals for the synthesis of acetylcholine in vivo is discussed.


Is crime scene examination science, and does it matter anyway?
This short piece aims to assess the kind of data collected by Crime Scene Examiners (CSEs), and to discuss whether this collection constitutes a scientific process. It also seeks to examine the balance of roles performed by the CSE, between data gatherer and investigator. The piece also aims to conclude on whether a clearer understanding of the structure of data collected by CSEs might be of some practical use in developing a greater understanding of the architecture of knowledge that forensic science as a whole relies upon. As a piece of work it is unapologetically theoretical in its perspective, and seeks to prompt further discussion regarding the structure of scientific knowledge, and any relevance this might have to its application in a forensic context. Ultimately, it seeks the inclusion of the processes of data gathering performed largely by CSEs within the wider processes of forensic science.


Delivery of dsRNA through topical feeding for RNA interference in the citrus sap piercing-sucking hemipteran, Diaphorina citri.
RNA interference (RNAi) is a powerful means to study functional genomics in insects. The delivery of dsRNA is a challenging step in the development of RNAi assay. Here, we describe a new delivery method to increase the effectiveness of RNAi in the Asian citrus psyllid Diaphorina citri. Bromophenol blue droplets were topically applied to fifth instar nymphs and adults on the ventral side of the thorax between the three pairs of legs. In addition to video recordings that showed sucking of the bromophenol blue by the stylets, dissected guts turned blue indicating that the uptake was through feeding. Thus, we called the method topical feeding. We targeted the abnormal wing disc gene (awd), also called nucleoside diphosphate kinase (NDPK), as a reporter gene to prove the uptake of dsRNA via this method of delivery. Our results showed that dsRNA-awd caused reduction of awd expression and nymph mortality. Survival and lifespan of adults emerged from treated nymphs and treated adults were affected. Silencing awd caused wing malformation in the adults emerged from treated nymphs. Topical feeding as a delivery of dsRNA is highly efficient for both nymphs and adults. The described method could be used to increase the efficiency of RNAi in D. citri and other sap piercing-sucking hemipterans.


Injections of AAV Vectors for Optogenetics in Anesthetized and Awake Behaving Non-Human Primate Brain.
Optogenetic techniques have revolutionized neuroscience research and are poised to do the same for neurological gene therapy. The clinical use of optogenetics, however, requires that safety and efficacy be demonstrated in animal models, ideally in non-human primates (NHPs), because of their neurological similarity to humans. The number of candidate vectors that are potentially useful for neuroscience and medicine is vast, and no high-throughput means to test these vectors yet exists. Thus, there is a need for techniques to make multiple spatially and volumetrically accurate injections of viral vectors into NHP brain that can be identified unambiguously through postmortem histology. Described herein is such a method. Injection cannulas are constructed from coupled polytetrafluoroethylene and stainless-steel tubes. These cannulas are autoclavable, disposable, and have low minimal-loading volumes, making them ideal for the injection of expensive, highly concentrated viral vector solutions. An inert, red-dyed mineral oil fills the dead space and forms a visible meniscus with the vector solution, allowing instantaneous and accurate measurement of injection rates and volumes. The oil is loaded into the rear of the cannula, reducing the risk of co-injection with the vector. Cannulas can be loaded in 10 min, and injections can be made in 20 min. This procedure is well suited for injections into awake or anesthetized animals. When used to deliver high-quality viral vectors, this procedure can produce robust expression of optogenetic proteins, allowing optical control of neural activity and behavior in NHPs.


Faster phonological processing and right occipito-temporal coupling in deaf adults signal poor cochlear implant outcome.
The outcome of adult cochlear implantation is predicted positively by the involvement of visual cortex in speech processing, and negatively by the cross-modal recruitment of the right temporal cortex during and after deafness. How these two neurofunctional predictors concur to modulate cochlear implant (CI) performance remains unclear. In this fMRI study, we explore the joint involvement of occipital and right hemisphere regions in a visual-based phonological task in post-lingual deafness. Intriguingly, we show that some deaf subjects perform faster than controls. This behavioural effect is associated with reorganized connectivity across bilateral visual, right temporal and left inferior frontal cortices, but with poor CI outcome. Conversely, preserved normal-range reaction times are associated with left-lateralized phonological processing and good CI outcome. These results suggest that following deafness, involvement of visual cortex in the context of reorganized right-lateralized phonological processing compromises its availability for audio-visual synergy during adaptation to CI.


Development of the life skills for promotion of health with art-therapy.
Individuals, who work in an organization, develop a shared perception that influences their behavior and emotions. This perception guides operators in the interpretation of the main business processes and in the modes of decision-making. The Italian Ministry of Public Administration in 2004 issued a directive to improve the organizational well-being and the emotional state of the environment in the workplace. This law identifies the necessity of an organizational climate that fosters creativity at the workplace, for the development and the efficiency of public administration. Several studies have shown that the development of creativity in the operators becomes a resource for the organization to facilitate the adaptation to change and to the solution of problems. So the techniques of creativity can be used as a training strategy for the quality management and human resources, optimizing services. The following pilot study evaluates the effectiveness of a training course for veterinary staff of ASL Napoli 1 Centre The aim of the course has been promoting the well-being, the development of life skills and the resilience of the learners using techniques of creativity and art therapy.


BNIP3L-dependent mitophagy accounts for mitochondrial clearance during 3 factors-induced somatic cell reprogramming.
Induced pluripotent stem cells (iPSCs) have fewer and immature mitochondria than somatic cells and mainly rely on glycolysis for energy source. During somatic cell reprogramming, somatic mitochondria and other organelles get remodeled. However, events of organelle remodeling and interaction during somatic cell reprogramming have not been extensively explored. We show that both SKP/SKO (Sox2, Klf4, Pou5f1/Oct4) and SKPM/SKOM (SKP/SKO plus Myc/c-Myc) reprogramming lead to decreased mitochondrial mass but with different kinetics and by divergent pathways. Rapid, MYC/c-MYC-induced cell proliferation may function as the main driver of mitochondrial decrease in SKPM/SKOM reprogramming. In SKP/SKO reprogramming, however, mitochondrial mass initially increases and subsequently decreases via mitophagy. This mitophagy is dependent on the mitochondrial outer membrane receptor BNIP3L/NIX but not on mitochondrial membrane potential (ΔΨm) dissipation, and this SKP/SKO-induced mitophagy functions in an important role during the reprogramming process. Furthermore, endosome-related RAB5 is involved in mitophagosome formation in SKP/SKO reprogramming. These results reveal a novel role of mitophagy in reprogramming that entails the interaction between mitochondria, macroautophagy/autophagy and endosomes.


Alteration of renal blood flow during epidural anesthesia in normal subjects.
The cardiovascular consequences of epidural anesthesia secondary to sympathetic blockade are well documented; however, their repercussions on renal hemodynamics in humans have not been reported. We investigated the effect of epidural anesthesia on renal blood flow (RBF) in 13 healthy volunteers 18-45 yr of age. RBF was measured using paraaminohippurate clearance before and after bilateral T6 epidural sensory block (to ensure adequate sympathetic renal nerve blockade). Epidural anesthesia was established using 22 +/- 3 mL of 2% plain lidocaine (without epinephrine) via L1-L2 epidural catheter; urine output was measured using a three-way Foley catheter. Mean arterial pressure remained > or = 70 mm Hg in all subjects without any pharmacologic intervention. Mean RBF before epidural anesthesia was 16.1 +/- 6.8 mL.kg-1.min-1 and 14.3 +/- 2.9 mL.kg-1.min-1 after bilateral T6 epidural blockade. We conclude that the institution of epidural anesthesia in healthy subjects does not result in a significant change in RBF (P > 0.25).


[Identification of sodium channels in vitro].
The membrane fraction isolated from cattle brain and vagal nerve was treated by ultrasonic irradiation in the presence of 22Na. It was shown that 22Na was trapped in vesicles formed from sonicated membranes in an osmotically active forms and slowly released into a nonradioactive solution. The efflux of 22Na from vesicles was studied in the presence and in the absence of substances which change the sodium conductance of excitable membranes. The local anesthetics (procaine, dibucaine) and tetrodotoxin at concentrations blocking electrical excitation in vivo decreased the sodium efflux from the vesicles. Veratrine, an activator of sodium channels, increased this efflux. The results are interpretated as an indication of the presence of functionally active sodium channels in the isolated membrane fragments.


Aquaporin 11 is related to cryotolerance and fertilising ability of frozen-thawed bull spermatozoa.
Aquaporins (AQPs) are channel proteins involved in the transport of water and solutes across biological membranes. In the present study we identified and localised aquaporin 11 (AQP11) in bull spermatozoa and investigated the relationship between the relative AQP11 content, sperm cryotolerance and the fertilising ability of frozen-thawed semen. Bull ejaculates were classified into two groups of good and poor freezability and assessed through immunofluorescence and immunoblotting analyses before and after cryopreservation. AQP11 was localised throughout the entire tail and along the sperm head. These findings were confirmed through immunoblotting, which showed a specific band of approximately 50 kDa corresponding to AQP11. The relative amount of AQP11 was significantly (P<0.05) higher in both fresh and frozen-thawed spermatozoa from bull ejaculates with good freezability compared with those with poorer freezability. In addition, in vitro oocyte penetration rates and non-return rates 56 days after AI were correlated with the relative AQP11 content in fresh spermatozoa. In conclusion, AQP11 is present in the head and tail of bull spermatozoa and its relative amount in fresh and frozen-thawed spermatozoa is related to the resilience of the spermatozoa to withstand cryopreservation and the fertilising ability of frozen-thawed spermatozoa. Further research is needed to elucidate the actual role of sperm AQP11 in bovine fertility.


Effects of the chymase inhibitor fulacimstat on adverse cardiac remodeling after acute myocardial infarction-Results of the Chymase Inhibitor in Adverse Remodeling after Myocardial Infarction (CHIARA MIA) 2 trial.
Adverse cardiac remodeling is a major risk factor for the development of post myocardial infarction (MI) heart failure (HF). This study investigates the effects of the chymase inhibitor fulacimstat on adverse cardiac remodeling after acute ST-segment-elevation myocardial infarction (STEMI). In this double-blind, randomized, placebo-controlled trial patients with first STEMI were eligible. To preferentially enrich patients at high risk of adverse remodeling, main inclusion criteria were a left-ventricular ejection fraction (LVEF) ≤45% and an infarct size >10% on day 5 to 9 post MI as measured by cardiac MRI. Patients were then randomized to 6 months treatment with either 25 mg fulacimstat (n = 54) or placebo (n = 53) twice daily on top of standard of care starting day 6 to 12 post MI. The changes in LVEF, LV end-diastolic volume index (LVEDVI), and LV end-systolic volume index (LVESVI) from baseline to 6 months were analyzed by a central blinded cardiac MRI core laboratory. Fulacimstat was safe and well tolerated and achieved mean total trough concentrations that were approximately tenfold higher than those predicted to be required for minimal therapeutic activity. Comparable changes in LVEF (fulacimstat: 3.5% ± 5.4%, placebo: 4.0% ± 5.0%, P = .69), LVEDVI (fulacimstat: 7.3 ± 13.3 mL/m2, placebo: 5.1 ± 18.9 mL/m2, P = .54), and LVESVI (fulacimstat: 2.3 ± 11.2 mL/m2, placebo: 0.6 ± 14.8 mL/m2, P = .56) were observed in both treatment arms. Fulacimstat was safe and well tolerated in patients with left-ventricular dysfunction (LVD) after first STEMI but had no effect on cardiac remodeling.


Altered editing of serotonin 2C receptor pre-mRNA in the prefrontal cortex of depressed suicide victims.
Five adenosines within the coding sequence of the serotonin 2C receptor (5-HT2C) pre-mRNA are converted to inosines by RNA editing (named A, B, C' (E), C, and D sites). In human prefrontal cortex (PFC), the most abundant 5-HT2C mRNA sequences result from editing at the A site, or from the editing combinations AC'C, ABCD, and ABD. In suicide victims with a history of major depression, C' site editing is significantly increased, D site editing is significantly decreased, and the C site shows a trend toward increased editing. Treatment of mice with the antidepressant drug fluoxetine (Prozac) causes changes in C', C, and D site editing that are exactly opposite to those seen in suicide victims. Thus, one outcome of fluoxetine treatment may be to reverse the abnormalities in 5-HT2C pre-mRNA editing seen in depressed suicide victims.


The resilience of the pork supply chain to a food safety outbreak: The case of dioxins.
Food supply chains are constantly challenged by food safety hazards entering the chain. The ability of the supply chain to provide safe food within a reasonable time after such a food safety threat or shock can be investigated with the concept of resilience using food safety as an indicator. Resilience is then defined as the food safety performance deviation due to the shock and takes both the severity of the shock as well as the time to fully recover or reach a new equilibrium into account. This study developed a stochastic simulation model to evaluate the resilience of the Dutch pork supply chain to dioxin contamination in the feed. The resilience of the supply chain as well as the potential costs associated with the contamination are compared between several monitoring strategies with the aim to determine the optimal control points for dioxin monitoring. Model results show that collecting and analyzing samples at more than one control point along the pork supply chain, in particular at feed mills and fat melting facilities, resulted in the highest resilience and the lowest costs after a shock. This model and these results can be used by public and private decision makers to make proactive and informed decisions on the monitoring strategies to control dioxins in the pork supply chain that result in optimal resilience to a dioxin crises.


Chemical bonding and aromaticity in furan, pyrrole, and thiophene: a magnetic shielding study.
Aromaticity and bonding in furan, pyrrole, and thiophene are investigated through the behavior of the isotropic shielding σiso(r) within the regions of space surrounding these molecules. HF-GIAO/6-311++G(d,p) and MP2-GIAO/6-311++G(d,p) (Hartree-Fock and second-order Møller-Plesset perturbation theory utilizing gauge-including atomic orbitals) σiso(r) contour plots are constructed using regular two-dimensional 0.05 Å grids in the molecular plane, in horizontal planes 0.5 and 1 Å above it, and in a vertical plane through the heteroatom. The nucleus-independent chemical shifts (NICS) calculated at the ring centers and at 0.5 Å and 1 Å above these centers, NICS(0), NICS(0.5), and NICS(1), respectively, support the widely accepted order of aromaticities thiophene > pyrrole > furan. The results suggest that accurate NICS calculations benefit more from the use of an extended basis set than from the inclusion of dynamical electron correlation effects. The different extents of σiso(r) delocalization observed in the horizontal contour plots and other features of σiso(r) are also consistent with an aromaticity reduction of the order thiophene > pyrrole > furan. It is suggested that the extent of σiso(r) delocalization in σiso(r) contour plots in planes 1 Å above the molecular plane could be used for comparing the relative aromaticities of a wide range of aromatic systems.


[Knockdown of SIRT1 enhances the sensitivity to cisplatin by inhibiting autophagy in A549 cells].
Objective To inhibit cisplatin-induced autophagy and improve the cisplatin sensitivity of A549 cells by knockdown the silent information regulator of transcription 1 (SIRT1). Methods Both mRNA and protein levels of SIRT1 in BEAS-2B, A549 and A549/DDP cells were detected by real-time quantitative PCR and Western blotting. After cisplatin treatment, the protein levels of SIRT1, LC3, P62 and beclin-1 in A549 cells were detected by Western blotting. A549 cells were transfected by siRNA to silence SIRT1 expression. Then, the apoptotic morphology was observed by fluorescence microscopy with Hoechst33258 staining. The apoptotic rate was analyzed by flow cytometry. The expressions of SIRT1, LC3, P62, cleaved caspase-3 and poly(ADP-ribose)polymerase (PARP) were measured by Western blotting. Results Both mRNA and protein levels of SIRT1 in A549 cells and A549/DDP cells were significantly higher than those in BEAS-2B cells, and they were higher in A549/DDP cells than in A549 cells. After cisplatin treatment, the protein levels of SIRT1, LC3 and beclin-1 in A549 cells increased, while P62 decreased. After transfected with SIRT1-siRNA, the expression of SIRT1 in A549 cells decreased. Compared with cisplatin group, the number of the apoptotic cells increased with the obvious occurrence of pyknosis and nuclear fragmentation in cisplatin plus SIRT1-siRNA group. Moreover, the expressions of P62, cleaved caspase-3 and PARP were up-regulated accompanied with LC3 decrease. Conclusion SIRT1 is highly expressed in A549 cells. The sensitivity of A549 cells to cisplatin can be improved by inhibiting the cisplatin-induced autophagy through knockdown of SIRT1.


Temporal Facelift: A New Method for Temporal and Mid-face Lifting.
Lifting the temporal and mid-face areas creates a very dynamic change in the facial appearance and different planes of dissection were described before. In this article, a new plane of dissection is described which allows the surgeon to perform a very quick and safe dissection in both the temporal and mid-face regions. Patients were operated on using the presented technique and brow lift, cantopexy, and mid-facelift were performed. The outcome of the surgery was analyzed by the authors from standardized photos before and 6 months after the surgery with measurements of the brow and lateral canthus. The plane of dissection is just over the subgaleal fascia which is actually the sub-superficial musculoaponeurotic system layer in the mid-face. This plane of dissection is easy and quick and creates a very mobile mid-face and temporal flap. Forty female patients were operated using the presented technique with a mean follow-up period of 15 months, the longest follow-up was 26 months. No major complication was encountered in these patients. In 5 patients, transient unilateral frontal branch palsy was encountered. In 1 patient, bilateral temporal area depression was observed 8 months after the surgery and treated with a fat injection under local anesthesia. One patient had alopecia in the temporal suture line which can be covered with hair. Temporal facelift is a versatile method with long-lasting results due to its important features; creating a very mobile flap for suspension dissection area, a large surface for adherence, and numerous sutures sharing the tension on the key sutures. Despite its slightly difficult early healing period, the technique should be kept in mind for the rejuvenation of the periorbital area and mid-face. Level of Evidence: Level I.


Manganese Privation-Induced Transcriptional Upregulation of the Class IIa Bacteriocin Plantaricin 423 in Lactobacillus plantarum Strain 423.
Plantaricin 423 is produced by Lactobacillus plantarum 423 using the pla biosynthetic operon located on the 8,188-bp plasmid pPLA4. As with many class IIa bacteriocin operons, the pla operon carries biosynthetic genes (plaA, precursor peptide; plaB, immunity; plaC, accessory; and plaD, ABC transporter) but does not carry local regulatory genes. Little is known about the regulatory mechanisms involved in the expression of the apparently regulationless class IIa bacteriocins, such as plantaricin 423. In this study, phylogenetic analysis of class IIa immunity proteins indicated that at least three distinct clades exist, which were then used to subgroup the class IIa operons. It became evident that the absence of classical quorum-sensing genes on mobile bacteriocin-encoding elements is a predisposition of the subgroup that includes plantaricin 423, pediocin AcH/PA-1, divercin V41, enterocin A, leucocin-A and -B, mesentericin Y105, and sakacin G. Further analysis of the subgroup suggested that the regulation of these class IIa operons is linked to transition metal homeostasis in the host. By using a fluorescent promoter-reporter system in Lactobacillus plantarum 423, transcriptional regulation of plantaricin 423 was shown to be upregulated in response to manganese privation. IMPORTANCE Lactic acid bacteria hold huge industrial application and economic value, especially bacteriocinogenic strains, which further aids in the exclusion of specific foodborne pathogens. Since bacteriocinogenic strains are sought after, it is equally important to understand the mechanism of bacteriocin regulation. This is currently an understudied aspect of class IIa operons. Our research suggests the existence of a previously undescribed mode of class IIa bacteriocin regulation, whereby bacteriocin expression is linked to management of the producer's transition metal homeostasis. This delocalized metalloregulatory model may fundamentally affect the selection of culture conditions for bacteriocin expression and change our understanding of class IIa bacteriocin gene transfer dynamics in a given microbiome.


Higher serum leptin level in women than in men with type 1 diabetes.
Leptin is the protein product of the obese (ob) gene, a lipostatic hormone that contributes to body weight regulation through suppressing appetite and/or stimulating energy expenditure in humans and/or rodents. In humans, serum leptin concentrations are increased in relation to increased body fat content. Studies have shown a higher leptin level in women compared with men. However, the gender influence on serum leptin concentrations has never been evaluated in patients with type 1 diabetes. In this study, serum leptin levels and percentage body fat mass were measured in men and women with type 1 diabetes. Fasting serum leptin levels were higher in women (16.7 + 11.6 ng/mL) than in men (3.0 +/- 1.5 ng/mL; P < 0.05) and were independent of exogenous insulin intake and of glucose control. Percentage body fat and fat mass were significant determinants of leptin concentration, whereas age and duration of diabetes were not related to leptin concentration. Subgroups of men (n = 12) and women (n = 11) with total body fat between 20 and 30% were compared. Leptin levels were also higher in women compared with men (13.5 +/- 8.3 ng/mL versus 3.2 +/- 1.7 ng/mL; P < 0.05, respectively). In conclusion, our findings indicate that gender is an important determinant of serum leptin concentration in type 1 diabetics, this gender difference is partly explained by body fat distribution and that type 1 diabetic women may be more resistant than type 1 diabetic men to leptin's alleged lipostatic actions.


Differences between prescribed daily doses and defined daily doses of antiepileptics--therapeutic drug monitoring as a marker of the quality of the treatment.
Prescribed daily doses (PDDs) of antiepileptics (N03A ATC group) were recorded for drugs used in monotherapy or in combination therapy in the University Hospital in Ostrava, Czechia. Plasma levels were used as an indicator of the quality of treatment. Request and reply forms for therapeutic drug monitoring (TDM) were used as a source of PDDs and plasma levels. The study included 1,144 in-patients examined in the period 1993 - 2004. The differences in PDD were tested by Mann-Whitney-U-test. ATC/DDD index 2005 was used. Doses given in mono- and polytherapy were compared. Median PDDs in samples within the therapeutic range (in mg) in mono-/polytherapy were as follows (DDDs in parenthesis): carbamazepine 600/800 (1,000), clonazepam 2.0/2.0 (8), phenytoin 300/300 (300), ethosuximide -/1000 (1,250), lamotrigine 250/200 (300), phenobarbital -/200 (100), primidone 500/625 (1,250), topiramate -/300 (300), valproic acid 750/1,000 (1,500). Median PDDs in polytherapy with antiepileptics not analyzed for TDM were: gabapentin 900 (1,800), levetiracetam 1,500 (1,500), vigabatrin 1,500 (2,000). PDDs in monotherapy were similar or slightly lower than in combination therapy with an exception for lamotrigine, NS. The differences were significant in carbamazepine, p < 0.0001, and valproic acid, p < 0.001. Patients with plasma levels within the therapeutic range were usually treated with similar or slightly higher doses than the remainder. In polytherapy the PDDs were similar to DDDs in carbamazepine, ethosuximide, phenytoin, and topiramate in samples within the therapeutic range when difference +/- 20 per cent was considered as acceptable PDD of levetiracetam was also similar to actual DDD. In general plasma levels tended to be below the therapeutic range. The differences between PDD and DDD of antiepileptics have to be taken into account especially when utilization of different drugs is compared.


Severe Pediatric Acute Respiratory Distress Syndrome Due to Scrub Typhus: Successful Ventilation with Airway Pressure Release Ventilation Mode after Becoming Refractory to Protective Ventilation.
Scrub typhus can affect lungs from mild illness like pneumonitis to a severe illness like acute respiratory distress syndrome (ARDS). Such patients may be very challenging to treat when their hypoxemia becomes severe and refractory to treatment. Main treatment is supportive in terms of mechanical ventilation. In adult ARDS, low tidal volume (TV) ventilation has been recommended, but there is no consensus on most effective ventilation mode in children. We present a case of a 12-year-old girl who developed severe ARDS (PO2/FiO2 ratio - 58), refractory to low TV ventilation. There was a rapid improvement in oxygenation on the application of airway pressure release ventilation (APRV) mode within ½ h. She was successfully ventilated and weaned off the ventilator over 5 days. This case highlights the utility of APRV mode of ventilation as a rescue therapy for severe refractory ARDS in children.


Domain Evolution and Piezoelectric Response across Thermotropic Phase Boundary in (K,Na)NbO3-Based Epitaxial Thin Films.
Recent research progress in (K,Na)NbO3 (KNN)-based lead-free piezoelectric ceramics has attracted increasing attention for their applications to microsystems or microelectromechanical systems (MEMS) in the form of thin films. This work demonstrates that high-quality KNN-based epitaxial films can be synthesized by a conventional sol-gel method, whose phase structure and domain characteristics have been investigated with emphasis on the temperature effect. A monoclinic MC structure is observed at room temperature in KNN-based epitaxial films, which is close to but different from the orthorhombic phase in bulk counterparts. Piezoresponse force microscopy (PFM) at elevated temperatures reveals continuous changes of ferroelectric domains in KNN films during heating and cooling cycles between room temperature and 190 °C. A distinct change in domain morphology is observed upon heating to 110 °C, accompanied by a clear variation of dielectric permittivity suggesting a thermotropic phase transition, which is revealed to belong to a MC-MA phase transition on the basis of structural and PFM analysis on local ferroelectric and piezoelectric behaviors. Enhanced piezoelectric response at the thermotropic phase boundary is observed, which is attributed to active domains and/or nanodomains formed across the boundary. Domain engineering by utilizing the phase transition should be important and effective in KNN-based films not only for property enhancement but also for its textured ceramics.


Fusion of nacre, mussel, and lotus leaf: bio-inspired graphene composite paper with multifunctional integration.
Multifunctional integration is an inherent characteristic for biological materials with multiscale structures. Learning from nature is an effective approach for scientists and engineers to construct multifunctional materials. In nature, mollusks (abalone), mussels, and the lotus have evolved different and optimized solutions to survive. Here, bio-inspired multifunctional graphene composite paper was fabricated in situ through the fusion of the different biological solutions from nacre (brick-and-mortar structure), mussel adhesive protein (adhesive property and reducing character), and the lotus leaf (self-cleaning effect). Owing to the special properties (self-polymerization, reduction, and adhesion), dopamine could be simultaneously used as a reducing agent for graphene oxide and as an adhesive, similar to the mortar in nacre, to crosslink the adjacent graphene. The resultant nacre-like graphene paper exhibited stable superhydrophobicity, self-cleaning, anti-corrosion, and remarkable mechanical properties underwater.


Characterization of the Burkholderia thailandensis SOS response by using whole-transcriptome shotgun sequencing.
The bacterial SOS response is a well-characterized regulatory network encoded by most prokaryotic bacterial species and is involved in DNA repair. In addition to nucleic acid repair, the SOS response is involved in pathogenicity, stress-induced mutagenesis, and the emergence and dissemination of antibiotic resistance. Using high-throughput sequencing technology (SOLiD RNA-Seq), we analyzed the Burkholderia thailandensis global SOS response to the fluoroquinolone antibiotic, ciprofloxacin (CIP), and the DNA-damaging chemical, mitomycin C (MMC). We demonstrate that a B. thailandensis recA mutant (RU0643) is ∼4-fold more sensitive to CIP in contrast to the parental strain B. thailandensis DW503. Our RNA-Seq results show that CIP and MMC treatment (P < 0.01) resulted in the differential expression of 344 genes in B. thailandensis and 210 genes in RU0643. Several genes associated with the SOS response were induced and include lexA, uvrA, dnaE, dinB, recX, and recA. At the genome-wide level, we found an overall decrease in gene expression, especially for genes involved in amino acid and carbohydrate transport and metabolism, following both CIP and MMC exposure. Interestingly, we observed the upregulation of several genes involved in bacterial motility and enhanced transcription of a B. thailandensis genomic island encoding a Siphoviridae bacteriophage designated E264. Using B. thailandensis plaque assays and PCR with B. mallei ATCC 23344 as the host, we demonstrate that CIP and MMC exposure in B. thailandensis DW503 induces the transcription and translation of viable bacteriophage in a RecA-dependent manner. This is the first report of the SOS response in Burkholderia spp. to DNA-damaging agents. We have identified both common and unique adaptive responses of B. thailandensis to chemical stress and DNA damage.


[Bipolar wet-field diathermy in microsurgery].
The author describes a miniature bipolar diathermy unit which can be used for several microsurgical purposes. It was developed from a standard endodiathermy instrument which has been in use for pars plana vitrectomy since 1973. It features bipolar forceps which can be used for welding conjunctival flaps and macrohemostasis in strabismus, orbital and lid surgery; bipolar electrodes with and without infusion, for extraocular hemostasis and intraocular microhemostasis in the anterior and posterior segments; bipolar electrodes with infusion for special purposes (still at the experimental stage), for capsulotomy of the anterior lens capsule for extracapsular cataract extraction, section of intraocular strands and membranes and sector iridectomy for tumors or rubeosis of the iris.


Development and Application of Cyclodextrin Hydrolyzing Mutant Enzyme Which Hydrolyzes β- and γ-CD Selectively.
Cyclodextrins (CDs) are produced from starch by cyclodextrin glucanotransferase (CGTase), which has cyclization activity. Specifically, α-CD is an important biomolecule, as it is a molecular carrier and soluble dietary fiber used in the food industry. Upon inspection of the conserved regions of the glycoside hydrolase (GH) 13 family amylases, the amino acids K232 and H233 of CGTase were identified as playing an important role in enzyme reaction specificity. A novel CD hydrolyzing enzyme, cyclodextrin glycosyl transferase (CGTase)-alpha, was developed using site-directed mutagenesis at these positions. Action pattern analysis using various substrates revealed that CGTase-alpha was able to hydrolyze β- and γ-CD, but not α-CD. This selective CD hydrolyzing property was employed to purify α-CD from a CD mixture solution. The α-CD that remained after treatment with CGTase-alpha and exotype glucoamylase was purified using hydrophobic interaction chromatography with 99% purity.


Stimulus context affects the phonemic categorization of temporally based word contrasts in adult cochlear-implant users.
Cochlear-implant (CI) users rely heavily on temporal envelope cues for speech understanding. This study examined whether their sensitivity to temporal cues in word segments is affected when the words are preceded by non-informative carrier sentences. Thirteen adult CI users performed phonemic categorization tasks that present primarily temporally based word contrasts: Buy-Pie contrast with word-initial stop of varying voice-onset time (VOT), and Dish-Ditch contrast with varying silent intervals preceding the word-final fricative. These words were presented in isolation or were preceded by carrier stimuli including a sentence, a sentence-envelope-modulated noise, or an unmodulated speech-shaped noise. While participants were able to categorize both word contrasts, stimulus context effects were observed primarily for the Buy-Pie contrast, such that participants reported more "Buy" responses for words with longer VOTs in conditions with carrier stimuli than in isolation. The two non-speech carrier stimuli yielded similar or even greater context effects than sentences. The context effects disappeared when target words were delayed from the carrier stimuli for ≥75 ms. These results suggest that stimulus contexts affect auditory temporal processing in CI users but the context effects appear to be cue-specific. The context effects may be governed by general auditory processes, not those specific to speech processing.


Clinical assessment of assays for diagnosis of herpes simplex infection.
It is becoming increasingly clear that the herpes simplex viruses (HSVs) 1 and 2 constitute a major, global, public health problem, particularly as genital herpes is implicated in the causation of a significant percentage of onwards transmission of the HIV virus. A major factor in the transmission of HSV is that most carriers are unaware of their diagnosis. In the last few years, the development of nucleic acid amplification technology and type-specific antibody serology to test for HSV-1 and -2 has contributed significantly to the accurate diagnosis of these infections. Despite guidance to the contrary, there is still much use of less sensitive tests such as viral culture and antibody testing based on crude antigen. It is essential that we use the most sensitive and specific diagnostic tests if we are to curb this epidemic.


[Treatment of Petrochemical Treatment Plant Secondary Effluent by Fenton Oxidation].
Fenton oxidation was applied to treat the petrochemical treatment plant secondary effluent by the continuous flow configuration. The effect of Fenton agent dosage on the COD and phosphorus removal and the variation of the dissolved organic matter characteristics during the treatment process were investigated. The results showed the average COD and PO(4)3- -P concentrations were 64.8 mg.L-1 and 0. 79 mg.L-1, respectively. When the dosage of H2O (30%), FeSO4.7H2O and PAM were 0. 4 mL.L-1, 0. 8 mg.L-1 and 0. 9 mg.L-1 and the residence time was 30 min, the average removal rate of COD and PO(4)3- -P were 24. 3% and 95. 5% respectively. The effluent COD was lower than 50 mg.L-1. The percentage of dissolved organic matters with molecular weight less than 1 x 10(3) was 80. 4% in the raw wastewater, however, the percentage increased to 95. 6% when treated by Fenton oxidation. Three-dimensional fluorescence analysis showed that the Fenton oxidation can effectively remove protein and phenols. GC-MS results showed that there were about 117 kinds of organic matters detected in the secondary effluent, while the number reduced to 27 after oxidation by Fenton. The organics containing unsaturated bond had a better removal than those of other types of organics. Fenton oxidation can be used in the advanced treatment of petrochemical secondary effluent.


Short-form versions of the Parental-Caregivers Perceptions Questionnaire and the Family Impact Scale.
To develop short-form versions of the Parental-Caregivers Perceptions Questionnaire (P-CPQ) and Family Impact Scale (FIS). Pretest/post-test clinical studies involved parent-completed questionnaires (the P-CPQ and the FIS) before and some weeks after dental care (under general anaesthesia) for early childhood caries (ECCs) in consecutive clinical samples from Wellington and Auckland. Deriving the short-form versions used only the baseline data from the Wellington sample (N = 195), whereas their evaluation used both baseline and follow-up data from the Auckland sample (N = 144 followed up). Item impact analysis was used to identify the 8 and 16 items with the greatest impact. An eight-item short-form FIS version was obtained in the same way. In the Wellington sample, Cronbach's α for the full, 16- and 8-item P-CPQ scales was 0.92, 0.89 and 0.82, respectively, and it was 0.88 and 0.85 for the full and eight-item FIS. Cross-sectional concurrent validity in the Wellington sample was acceptable for all short forms. Examining their responsiveness in the Auckland sample, large decreases post-treatment were observed in the short-form P-CPQ scores which were similar in relative magnitude to those seen with the full version. The full and short-form FIS scale scores showed moderate decreases. The reliability, validity and responsiveness of the short-form versions were acceptable in these settings with children suffering from severe ECC; however, before they can be treated as definitive measures for use in health services research to determine the effects of clinical interventions for ECC, their test-retest reliability should be examined and further validation undertaken.


Pharmacological analysis of the inhibition produced by moxonidine and agmatine on the vasodepressor sensory CGRPergic outflow in pithed rats.
Calcitonin gene-related peptide (CGRP) plays a role in several (patho)physiological functions, and modulation of its release is considered a therapeutic target. In this respect, electrical spinal (T9--T12) stimulation of the perivascular sensory outflow in pithed rats produces vasodepressor responses mediated by CGRP release. This study investigated the role of imidazoline I1 and I2 receptors in the inhibition by moxonidine and agmatine of these vasodepressor responses. Male Wistar pithed rats (pretreated i.v. with 25mg/kg gallamine and 2mg/kg⋅min hexamethonium) received i.v. continuous infusions of methoxamine (20μg/kg⋅min) followed by physiological saline (0.02ml/min), moxonidine (1, 3, 10 or 30μg/kg⋅min) or agmatine (1000 or 3000μg/kg⋅min). Under these conditions, electrical stimulation (0.56-5.6Hz; 50V; 2ms) of the spinal cord (T9-T12) produced frequency-dependent vasodepressor responses which were: (i) unchanged during saline infusion; and (ii) inhibited during the above infusions of moxonidine or agmatine. Moreover, using i.v. administrations, the inhibition by 3μg/kg⋅min moxonidine or 3000μg/kg⋅min agmatine (which failed to inhibit the vasodepressor responses by α-CGRP; 0.1-1µg/kg) was: (i) unaltered after saline (1ml/kg), rauwolscine (300μg/kg; α2-adrenoceptor antagonist) or BU224 (300μg/kg; imidazoline I2 receptor antagonist); and (ii) reversed after AGN 192403 (3000μg/kg; imidazoline I1 receptor antagonist). This reversion was relatively more pronounced after AGN 192403 plus rauwolscine. These blocking doses of antagonists lacked any effects on the electrically-induced vasodepressor responses. Therefore, the inhibition of the vasodepressor sensory CGRPergic outflow by moxonidine and agmatine is mainly mediated by prejunctional imidazoline I1 receptors on perivascular sensory nerves.


Stimulation of flux through hepatic pyruvate dehydrogenase by 3-mercaptopicolinate.
Isolated hepatocytes from 24-h-starved rats were used to assess the possible effect of the hypoglycaemic agent 3-mercaptopicolinate on flux through the hepatic pyruvate dehydrogenase complex. Increasing the extracellular pyruvate concentration from 1 mM to 2 mM or 5 mM resulted in an increase in flux through pyruvate dehydrogenase and the tricarboxylic acid cycle as measured by 14CO2 evolution from [1-14C]pyruvate and [3-14C]pyruvate. Gluconeogenesis was inhibited by 3-mercaptopicolinate from both 1 mM and 2 mM pyruvate, but significant increases in malate and citrate concentrations only occurred in cells incubated with 1 mM pyruvate. Flux through pyruvate dehydrogenase was stimulated by 3-mercaptopicolinate with 1 mM pyruvate but was unaltered with 2 mM pyruvate. Dichloroacetate stimulated flux through pyruvate dehydrogenase with no effect on gluconeogenesis in the presence of 1 mM pyruvate. There was no effect of 3-mercaptopicolinate, administered in vivo, to 24-h-starved rats on the activity of pyruvate dehydrogenase in freeze-clamped heart or liver tissue, although the drug did decrease blood glucose concentration and increase the blood concentrations of lactate and alanine. Dichloroacetate, administered in vivo to 24-h-starved rats, increased the activity of pyruvate dehydrogenase in freeze-clamped heart and liver, and caused decreases in the blood concentrations of glucose, lactate, and alanine. The results suggest that 3-mercaptopicolinate increases flux through hepatocyte pyruvate dehydrogenase by an indirect mechanism.


[Psychiatric and neurological complications associated with cardiac surgery (author's transl)].
The following problems are discussed as the result of an own investigation done with 150 patients after cardiac surgery: 1. the differences in incidence of cerebral complications understood as 2. a probleme of qualitatively different psychopathological and neurological syndromes. 3. Causes and relationship between the clinical stages of heart-disease and neuropsychiatric complications with special regard to the question 4. congenital heart-disease versus aquired heart-disease. 5. The role of extracorporeal circulation. 6. Remarks on the role of microembolism associated with open cardiac surgery. 7. Hereditary factors as the cause for specific psychopathological reactions.


Blockade of Deubiquitylating Enzyme USP1 Inhibits DNA Repair and Triggers Apoptosis in Multiple Myeloma Cells.
Purpose: The ubiquitin proteasome pathway is a validated therapeutic target in multiple myeloma. Deubiquitylating enzyme USP1 participates in DNA damage response and cellular differentiation pathways. To date, the role of USP1 in multiple myeloma biology is not defined. In the present study, we investigated the functional significance of USP1 in multiple myeloma using genetic and biochemical approaches.Experimental Design: To investigate the role of USP1 in myeloma, we utilized USP1 inhibitor SJB3-019A (SJB) for studies in myeloma cell lines and patient multiple myeloma cells.Results: USP1-siRNA knockdown decreases multiple myeloma cell viability. USP1 inhibitor SJB selectively blocks USP1 enzymatic activity without blocking other DUBs. SJB also decreases the viability of multiple myeloma cell lines and patient tumor cells, inhibits bone marrow plasmacytoid dendritic cell-induced multiple myeloma cell growth, and overcomes bortezomib resistance. SJB triggers apoptosis in multiple myeloma cells via activation of caspase-3, caspase-8, and caspase-9. Moreover, SJB degrades USP1 and downstream inhibitor of DNA-binding proteins as well as inhibits DNA repair via blockade of Fanconi anemia pathway and homologous recombination. SJB also downregulates multiple myeloma stem cell renewal/survival-associated proteins Notch-1, Notch-2, SOX-4, and SOX-2. Moreover, SJB induced generation of more mature and differentiated plasma cells. Combination of SJB and HDACi ACY-1215, bortezomib, lenalidomide, or pomalidomide triggers synergistic cytotoxicity.Conclusions: Our preclinical studies provide the framework for clinical evaluation of USP1 inhibitors, alone or in combination, as a potential novel multiple myeloma therapy. Clin Cancer Res; 23(15); 4280-9. ©2017 AACR.


Shoulder impingement syndrome: a systematic review of clinical trial participant selection criteria.
Shoulder impingement syndrome (SIS) is a common diagnosis for patients with pain and dysfunction of the shoulder. Variations in the signs and symptoms might lead to uncertainty regarding the definition of SIS. The aim of this review is to explore the participant selection criteria used in the literature when investigating SIS and to assess differences in criteria among treating professions. This is a PRISMA systematic review of publications from 2009 to 2014 from MEDLINE, PubMed, The Cochrane Library, Embase, Scopus and CINAHL. Ninety-seven articles met inclusion criteria for this review. Twenty-five different surgical and nonsurgical treatments were investigated. Impingement-specific index tests were used in all studies. Exclusion index tests were used in 62% of studies. Twenty index tests were identified. Radiological investigations were reported in 53% of all studies, of which a further 53% reported using two or more radiological investigations. This systematic review has illustrated that studies investigating SIS test for various signs and symptoms, which is in keeping with describing the condition as a 'syndrome'. However, there are inconsistencies in participant selection criteria between health disciplines, highlighting a need for harmonization of the selection criteria in the form of an international editorial consensus.


Central organization of wave localization in the clawed frog, Xenopus laevis. I. Involvement and bilateral organization of the midbrain.
The central nervous organization of water wave localization in the clawed frog Xenopus laevis was investigated by performing behavioral tests on frogs that had various brain ablations. The criterion of localization was the orientation of response turns toward the origin of stimulus waves. After complete midbrain ablation, Xenopus still detected impinging waves but could not localize them. After thalamopretectal ablation, however, Xenopus localized waves with normal accuracy. Thus, wave localization can be accomplished in the brainstem, and the midbrain is necessary for it. After forebrain ablation, the frogs no longer responded to water waves, which shows that higher brain centers modulate localization. Tectal lesions that spared the ventrolateral tectum did not abolish localization. After unilateral extirpation of tectum and torus, all ipsilateral waves were localized, but contralateral waves were not. This indicates a functional chiasm for the determination of wave directions in the midbrain. Total localization failure after unilateral midbrain destruction demonstrates that wave localization also requires the ipsilateral motorial tegmentum. When wave localization was abolished, a residual correlation between stimulus directions and response angles remained.


Effect of thermal annealing in vacuum and in air on nanograin sizes in hard and superhard coatings Zr-Ti-Si-N.
Zr-Ti-Si-N coating had high thermal stability of phase composition and remained structure state under thermal annealing temperatures reached 1180 degrees C in vacuum and 830 degrees C in air. Effect of isochronous annealing on phase composition, structure, and stress state of Zr-Ti-Si-N-ion-plasma deposited coatings (nanocomposite coatings) was reported. Below 1000 degrees C annealing temperature in vacuum, changing of phase composition is determined by appearing of siliconitride crystallites (beta-Si3N4) with hexagonal crystalline lattice and by formation of ZrO2 oxide crystallites. Formation of the latter did not result in decay of solid solution (Zr, Ti)N but increased in it a specific content of Ti-component. Vacuum annealing increased sizes of solid solution nanocrystallites from (12 to 15) in as-deposited coatings to 25 nm after annealing temperature reached 1180 degrees C. One could also find macro- and microrelaxations, which were accompanied by formation of deformation defects, which values reached 15.5 vol.%. Under 530 degrees C annealing in vacuum or in air, nanocomposite coating hardness increased. When Ti and Si concentration increased and three phases nc-ZrN, (Zr, Ti)N-nc, and alpha-Si3N4 were formed, average hardness increased to 40.8 +/- 4 GPa. Annealing to 500 degrees C increased hardness and demonstrated lower spread in values H = 48 +/- 6 GPa and E = (456 +/- 78) GPa. Zr-Ti-Si-N coatings has high wear resistance and low friction coefficient in comparison at a temperature of 500 degrees C possess with coatings TiN, Ti-Si-N.


Effect of losartan on vascular function in fructose-fed rats: the role of perivascular adipose tissue.
Recent studies have shown the effect of perivascular adipose tissue (PVAT) on the regulation of vascular function; however, its role in the model of metabolic syndrome remains unclear. The aim of this study was to examine the effect of losartan on PVAT-derived vascular dysfunction in fructose-induced hypertensive rats. Rats were fed with either water, 10% fructose, or 10% fructose with 10mg/kg losartan for 8 weeks. In the isolated aorta with PVAT and endothelium, contraction induced by norepinephrine (NE) was more potent in fructose-fed rats compared to control rats. Losartan normalized blood pressure, insulin resistance, and NE-induced vasoconstriction in fructose-fed rats. In the aortic rings with/without endothelium and with/without PVAT, losartan could not improve the acetylcholine-induced relaxation in fructose-fed rats. The observation suggested that losartan partly improved the PVAT-associated vascular regulation in fructose-induced hypertensive rats.


A randomized clinical trial of a gamified app for the treatment of perfectionism.
Perfectionism is a common transdiagnostic problem that may lead to substantial distress and functional impairments. Cognitive behavioural therapy (CBT) is an effective treatment for perfectionism. However, the existing significant barriers to access and utilization of mental health services, including among college students, demand the development of low-intensity accessible interventions. The aim of the present study was to evaluate the effectiveness of a low-intensity CBT-based self-help gamified app developed specifically for perfectionism in a sample of college students. Participants completed assessments of perfectionism, related symptoms, emotional burden and functional impairments at pretreatment, posttreatment and at one-month follow-up. Compared with the waitlist condition (n = 35), the app condition (n = 35) demonstrated a significant and greater reduction in perfectionism, obsessive-compulsive symptoms, functional impairments and subjective ratings of emotional burden. Results suggest that a brief, daily app-based game-like intervention targeting maladaptive perfectionistic beliefs may be a viable, low-cost alternative to traditional CBT treatments for vulnerable populations on college campuses.


The role of CD40/CD40L and interferon regulatory factor 4 in Hodgkin lymphoma microenvironment.
Inflammation and cancer are two independent biological events that can play an interdependent role. The model of such interaction is represented by Hodgkin lymphoma (HL), where the microenvironment is dominated by an extensive mixed, potentially cellular inflammatory infiltrate that plays a decisive role in the pathobiology of HL. In this review we summarize updated information on the complex interactions between Hodgkin Reed-Sternberg (HRS) cells and their tissue microenvironment, highlighting the functional role of CD40/CD40L and interferon regulatory factor 4 (IRF4).


Growth patterns and the risk of breast cancer in women.
Adult height and body mass index (BMI) influence the risk of breast cancer in women. Whether these associations reflect growth patterns of the fetus or growth during childhood and adolescence is unknown. We investigated the association between growth during childhood and the risk of breast cancer in a cohort of 117,415 Danish women. Birth weight, age at menarche, and annual measurements of height and weight were obtained from school health records. We used the data to model individual growth curves. Information on vital status, age at first childbirth, parity, and diagnosis of breast cancer was obtained through linkages to national registries. During 3,333,359 person-years of follow-up, 3340 cases of breast cancer were diagnosed. High birth weight, high stature at 14 years of age, low BMI at 14 years of age, and peak growth at an early age were independent risk factors for breast cancer. Height at 8 years of age and the increase in height during puberty (8-14 years of age) were also associated with breast cancer. The attributable risks of birth weight, height at 14 years of age, BMI at 14 years of age, and age at peak growth were 7%, 15%, 15%, and 9%, respectively. No effect of adjusting for age at menarche, age at first childbirth, and parity was observed. Birth weight and growth during childhood and adolescence influence the risk of breast cancer.


Ultrasensitive immunoassay based on electrochemical measurement of enzymatically produced polyaniline.
A novel ultrasensitive immunoassay method was developed based on the electrochemical measurement of polyaniline, which was catalytically produced by horseradish peroxidase-functionalized gold nanoparticle (HRP-Au NP) probe at an immunosensor. The immunosensor was prepared step-wise by first modifying the electrode with reduced graphene oxide (rGO)/Au NPs nanocomposite followed by the immobilization of capture antibodies on its surface. After performing a sandwich immunoreaction, the quantitatively captured HRP-Au NP nanoprobes could catalyze oxidation of aniline to produce electroactive polyaniline on the immunosensor surface. The electrochemical measurement of polyaniline enabled a novel detection strategy for HRP-based immunoassay. Both the signal amplification of the HRP-Au NP nanoprobe and the electron transfer acceleration of rGO/Au NPs on the immunosensor surface greatly improved the detection sensitivity of the immunoassay method. With the use of human IgG as a model analyte, this method showed a wide linear range over 4 orders of magnitude with a detection limit of 9.7 pg/mL. In addition, the immunosensor had low cost, satisfactory reproducibility and stability, and acceptable reliability. The relatively positive potential range for the polyaniline measurement completely excluded the conventional interference from dissolved oxygen. Thus, this method provides a promising potential for practical applications.


Synthesis, structure and magnetic properties of a decametallic Ni single-molecule magnet.
Ferromagnetic exchange between the ten Ni2+ ions in the complex [Ni10(tmp)2(N3)8(acac)6(MeOH)6] leads to a spin ground state of S = 10; single crystal M vs. H studies reveal the temperature and sweep rate dependent hysteresis loops expected for a single-molecule magnet.


Microbial degradation of chlorinated benzenes.
Chlorinated benzenes are important industrial intermediates and solvents. Their widespread use has resulted in broad distribution of these compounds in the environment. Chlorobenzenes (CBs) are subject to both aerobic and anaerobic metabolism. Under aerobic conditions, CBs with four or less chlorine groups are susceptible to oxidation by aerobic bacteria, including bacteria (Burkholderia, Pseudomonas, etc.) that grow on such compounds as the sole source of carbon and energy. Sound evidence for the mineralization of CBs has been provided based on stoichiometric release of chloride or mineralization of (14)C-labeled CBs to (14)CO(2). The degradative attack of CBs by these strains is initiated with dioxygenases eventually yielding chlorocatechols as intermediates in a pathway leading to CO(2) and chloride. Higher CBs are readily reductively dehalogenated to lower chlorinated benzenes in anaerobic environments. Halorespiring bacteria from the genus Dehalococcoides are implicated in this conversion. Lower chlorinated benzenes are less readily converted, and mono-chlorinated benzene is recalcitrant to biotransformation under anaerobic conditions.


VGGIN-Net: Deep Transfer Network for Imbalanced Breast Cancer Dataset.
In this paper, we have presented a novel deep neural network architecture involving transfer learning approach, formed by freezing and concatenating all the layers till block4 pool layer of VGG16 pre-trained model (at the lower level) with the layers of a randomly initialized naïve Inception block module (at the higher level). Further, we have added the batch normalization, flatten, dropout and dense layers in the proposed architecture. Our transfer network, called VGGIN-Net, facilitates the transfer of domain knowledge from the larger ImageNet object dataset to the smaller imbalanced breast cancer dataset. To improve the performance of the proposed model, regularization was used in the form of dropout and data augmentation. A detailed block-wise fine tuning has been conducted on the proposed deep transfer network for images of different magnification factors. The results of extensive experiments indicate a significant improvement of classification performance after the application of fine-tuning. The proposed deep learning architecture with transfer learning and fine-tuning yields the highest accuracies in comparison to other state-of-the-art approaches for the classification of BreakHis breast cancer dataset. The articulated architecture is designed in a way that it can be effectively transfer learned on other breast cancer datasets.


MESA is a Plasmodium falciparum phosphoprotein associated with the erythrocyte membrane skeleton.
The mature-parasite-infected erythrocyte surface antigen (MESA) of Plasmodium falciparum is an antigenically variable, high molecular weight protein of trophozoites and schizonts that is located at the erythrocyte surface membrane. It is first synthesized at the late ring stage and continues to be synthesized until late schizogony. MESA cannot be detected on the external surface of erythrocytes infected by trophozoites and early schizonts but is located at the internal surface in association with the erythrocyte membrane skeleton. The degree of association with the membrane skeleton varies among parasite lines, being greater in knobby parasite lines. MESA is phosphorylated and is present in a similar location to another phosphoprotein, the ring-infected erythrocyte surface antigen (RESA). However, it differs from RESA in being detected at a later stage of asexual development of the parasite.


Insulin-like growth factor-1 (IGF-1) specifically binds to bovine lens epithelial cells and increases the number of fibronectin receptor sites.
The purpose of the study was to determine the quantitative characteristics of IGF-1 binding sites in lens cells and to investigate its ability to modulate cell growth, in particular by inducing integrin expression. Studies were carried out in bovine lens epithelial cells in culture. IGF-1 receptor binding parameters were measured from saturation experiments with 125I-IGF-1. Scatchard plot indicates one class of high affinity sites (Kd = 2.5 +/- 1.5 nM). In addition, we showed that this growth factor was synthesized and released by lens cells. The characteristics of the receptor sites are in accordance with the effects of the growth factor (e.g. stimulation of DNA synthesis) in the range of nM concentrations. Moreover, by incubating cells with IGF-1 (12 nM) for 40 hr we demonstrated that the expression of integrin, the fibronectin receptor, was activated (N = 885 +/- 169 x 10(3) sites/cell vs N = 453 +/- 105 x 10(3) sites/cell in control cultures) without modification of its affinity (Kd congruent to 16 x 10(-8) M). These new data emphasize the role of IGF-1 in the regulation of migration, proliferation and differentiation of mature lens cells.


Generation of cytolytic T lymphocytes in vitro. XI. Accessory cell requirement in secondary responses to particulate alloantigen.
The non-T accessory cell requirement for cytolytic T lymphocyte (CTL) generation in vitro was studied in a system which makes use of particulate membrane preparations as a source of alloantigen, and spleen cells from alloimmune mice as a source of responding cells. It is shown that removal of nylon-adherent cells from the responding cell population strongly reduced CTL generation, whereas direct removal of Ig+, phagocytic or plastic-adherent cells had no effect. The CTL response of the nylon-nonadherent cell population could be reconstituted by the addition of normal spleen cells, which by themselves do not generate CTL in response to particulate alloantigen. The accessory cell function of normal spleen cells was not affected by depletion of T cells or of phagocytic cells, but was sensitive to gamma-irradiation (1000 rd). The system thus demonstrates the requirement for a nylon-adherent accessory cell population in the secondary CTL response to particulate alloantigens which does not exhibit the typical characteristics of T cells, B cells or macrophages.


Assembly of the intrinsic factor domains and oligomerization of the protein in the presence of cobalamin.
Human intrinsic factor (IF) was purified from the recombinant plant Arabidopsis thaliana by affinity chromatography. Cobalamin (Cbl) saturated protein was separated by gel filtration into peaks I and II, which contained according to SDS electrophoresis the 50 kDa full-length protein IF(50) and a mixture of two fragments, respectively. Two components of peak II were identified as the 30 kDa N-terminal peptide IF(30) and the 20 kDa C-terminal glycopeptide IF(20). Measurements of M(w) under the nondenaturing conditions were conducted by static light scattering. They revealed 100 kDa IF dimers in peak I, whereas 50 kDa cleaved monomers were found in peak II. The protein devoid of Cbl dissociated to the elementary units incapable of association in the absence of Cbl. The individual proteolytic fragments bound Cbl at high concentration of the ligand; however, neither IF(30).Cbl nor IF(20).Cbl oligomerized. A mixture of two fragments IF(30) + IF(20) and Cbl produced a firm complex, IF(30+20).Cbl, which could not associate to dimers. In contrast to IF(30+20).Cbl, the saturated full-length monomers IF(50).Cbl dimerized with K(d) approximately 1 microM. We suggest a two-domain organization of the full-length protein, where two distant units, IF(30) and IF(20), can be assembled only by Cbl. They are connected by a protease-sensitive link, whose native structure is likely to be important for dimerization. However, linkage between two domains is not compulsory for Cbl binding. Advantages of the two-domain structure of IF are discussed.


Many-body interaction in glycine-(water)3 complex using density functional theory method.
Various configurations were investigated to find the most stable structures of glycine-(water)3 complex. Five different optimized conformers of glycine-(water)3 complex are obtained from density functional theory calculations using 6-311++G* basis set. Relaxation energy and many body interaction energies (two, three, and four body) are also calculated for these conformers. Out of the five conformers, the most stable conformer has the BSSE corrected total energy -513.917 967 7 Hartree and binding energy -27.28 Kcal/mol. It has been found that the relaxation energies, two body energies and three body energies have significant contribution to the total binding energy whereas four body energies are very small. The chemical hardness and chemical potential also confirmed the stability of the conformer having lowest total energy.


What to do if you're exposed to a bloodborne pathogen.
What happens when the healthcare worker is the one needing care? Occupational exposure to a bloodborne pathogen is a known risk for healthcare workers but one that we are often ill prepared to handle. Each healthcare worker must know what the risks are and how to immediately access specialized care. This article will outline what you should expect and do if you are exposed.


Biobanking sustainability--experiences of the Australian Breast Cancer Tissue Bank (ABCTB).
Sustainability of biorepositories is a key issue globally. This article is a description of the different strategies and mechanisms used by the Australian Breast Cancer Tissue Bank (ABCTB) in developing and operating the resource since its inception in 2005. ABCTB operates according to a hub and spoke model, with a central management hub that is responsible for overall management of the resource including financial, ethical, and legal processes, researcher applications for material, clinical follow-up, information/database activities, and security. A centralized processing laboratory also operates from the hub site where DNA and RNA extractions are performed, digital imaging of stained tumor sections occurs, and specimens are assembled for dispatch for research projects. ABCTB collection sites where donors are identified, consent obtained, and specimens collected and processed for initial storage are located across Australia. Each of the activities of the resource requires financial support and different sources of revenue, some of which are allocated to a specific function of the ABCTB. Different models are in use at different collection centers where local variations may exist and local financial support may sometimes be obtained. There is also significant in-kind support by clinics and diagnostic and research facilities that house the various activities of the resource. However, long-term financial commitment to ensure the survival of the resource is not in place, and forward planning of operations remains challenging under these circumstances.


Too harts, won sole: Using dysgraphia treatment to address homophone representation.
Previous spoken homophone treatment in aphasia found generalization to untreated homophones and interpreted this as evidence for shared phonological word form representations. Previous written treatment of non-homophones has attributed generalization to orthographic neighbours of treated items to feedback from graphemes to similarly spelled orthographic word forms. This feedback mechanism offers an alternative explanation for generalization found in treatment of spoken homophones. The aim of this study was to investigate the mechanism underpinning generalization (if any) from treatment of written homophones. To investigate this question a participant with acquired dysgraphia and impaired access to orthographic output representations undertook written spelling treatment. Generalization to untreated items with varying degrees of orthographic overlap was investigated. Three experimental sets included homographs (e.g., bank-bank), heterographs (e.g., sail-sale), and direct orthographic neighbours (e.g., bath-path). Treatment improved written picture naming of treated items. Generalization was limited to direct neighbours. Further investigation of generalization found that items with a greater number of close neighbours in the treated set showed greater generalization. This suggests that feedback from graphemes to orthographic word forms is the driving force of generalization. The lack of homograph generalization suggests homographs do not share a representation in the orthographic lexicon.


Advantageous metabolic effects of pulsatile insulin delivery in noninsulin-dependent diabetic patients.
This study was done to compare the actions of pulsatile and continuous insulin administration in eight noninsulin-dependent diabetic patients. Human insulin was delivered in a pulsatile manner (1.3 mU/kg.min for 2 min, followed by 11 min during which no insulin was infused) or continuously (0.2 mU/kg.min) for 325 min. Endogenous hormone secretion was inhibited by somatostatin (125 micrograms/h), and glucagon was replaced at rate of 3.5 micrograms/h. Under these conditions plasma C-peptide levels fell progressively to extremely low values at the end of the experiment. Continuous insulin infusion resulted in steady plasma insulin levels, averaging 86 pmol/L, while during intermittent insulin administration plasma insulin levels were 5.7 and 158 pmol/L before and 3 min after the start of the insulin injection, respectively. Basal plasma glucagon [mean 158 +/- 11 (+/- SE) vs. 163 +/- 21 ng/L; P = NS] levels were similar on both occasions. During replacement peripheral plasma glucagon levels were no different whatever the mode of insulin administration, nor did they differ from the basal values. The mean plasma glucose concentrations were similar before both studies and rose to 9.5 and 8.6 mmol/L in the first 65 min during continuous and pulsatile insulin administration, respectively. In contrast, during the last 65 min, plasma glucose averaged 6.2 mmol/L during both studies. The glucose infusion rate initially increased, but then rapidly fell to values close to zero at the end of the first 65 min during the continuous insulin infusion, whereas during this time it averaged 0.59 +/- 0.10 mg/kg.min (32.5 +/- 5.5 mumol/kg.min) during pulsatile insulin administration. In the last 65 min the glucose infusion rate was significantly higher during pulsatile than during continuous insulin delivery. Furthermore, pulsatile rather than continuous insulin administration significantly reduced plasma triglyceride, very low density lipoprotein triglyceride, and FFA levels and increased high density lipoprotein cholesterol and apolipoprotein-B levels. We conclude that pulsatile insulin delivery has advantageous metabolic effects compared to continuous hormone administration in patients with noninsulin-dependent diabetes mellitus.


Neuronal Migration and Lamination in the Vertebrate Retina.
In the retina, like in most other brain regions, developing neurons are arranged into distinct layers giving the mature tissue its stratified appearance. This process needs to be highly controlled and orchestrated, as neuronal layering defects lead to impaired retinal function. To achieve successful neuronal layering and lamination in the retina and beyond, three main developmental steps need to be executed: First, the correct type of neuron has to be generated at a precise developmental time. Second, as most retinal neurons are born away from the position at which they later function, newborn neurons have to move to their final layer within the developing tissue, a process also termed neuronal lamination. Third, these neurons need to connect to their correct synaptic partners. Here, we discuss neuronal migration and lamination in the vertebrate retina and summarize our knowledge on these aspects of retinal development. We give an overview of how lamination emerges and discuss the different modes of neuronal translocation that occur during retinogenesis and what we know about the cell biological machineries driving them. In addition, retinal mosaics and their importance for correct retinal function are examined. We close by stating the open questions and future directions in this exciting field.


Family Group Decision Making (FGDM) with Lakota families in two tribal communities: tools to facilitate FGDM implementation and evaluation.
This article describes an adapted Family Group Decision Making (FGDM) practice model for Native American communities, the FGDM family and community engagement process, and FGDM evaluation tools as one example for other native communities. Challenges and successes associated with the implementation and evaluation of these meetings are also described in the context of key historical and cultural factors, such as intergenerational grief and trauma, as well as past misuse of data in native communities.


Endoplasmic reticulum stress causes thyroglobulin retention in this organelle and triggers activation of nuclear factor-kappa B via tumor necrosis factor receptor-associated factor 2.
Perturbing the endoplasmic reticulum homeostasis of thyroid cell lines with thapsigargin, a specific inhibitor of the sarcoendoplasmic reticulum Ca(2+) adenosine triphosphatases, and tunicamycin, an inhibitor of the N-linked glycosylation, blocked Tg in the endoplasmic reticulum. This event was signaled outside the endoplasmic reticulum and resulted in activation of the c-Jun N-terminal kinase (JNK)/stress-activated protein kinase and nuclear factor-kappa B (NF-kappa B) stress response pathways. Activation of the JNK/stress-activated protein kinase signaling pathway was assessed by measuring the amount of phospho-JNK and the activity of JNK by kinase assays. Activation of the NF-kappa B signaling pathway was assessed by measuring the level of inhibitory subunit I kappa B alpha, DNA binding, and transcriptional activity of NF-kappa B. Cycloheximide treatment, at a dose able to profoundly inhibit protein synthesis in FRTL-5 cells, obliterated the decrease in the level of the inhibitory subunit I kappa B alpha produced by thapsigargin and tunicamycin. Therefore, protein synthesis was required to generate a signal from stressed endoplasmic reticulum. This substantiates the hypothesis that endoplasmic reticulum retention of newly synthesized Tg and other cargo (secretory and membrane) proteins functions upstream of signal activation. Dominant negative TNF receptor-associated factor 2 (TRAF2) inhibited activation of NF-kappa B, which was also inhibited in embryonic fibroblasts derived from TRAF2(-/-) mice, respect to their normal counterpart. These data extend the recent demonstration that TRAF2 mediated JNK activation in response to endoplasmic reticulum stress and strongly strengthened the idea that endogenous stress signals initiated in the endoplasmic reticulum proceed by a pathway similar to that initiated by plasma membrane receptors in response to extracellular signals.


Physical family violence and externalizing and internalizing behaviors among children and adolescents.
Family violence has been associated with various negative outcomes among children and adolescents. Yet, less is known about how unique forms of physical family violence contribute to externalizing and internalizing behaviors based on a child's developmental stage. Using data from the Illinois Families Study and administrative Child Protective Services data, we explored the relation between 3 types of physical family violence victimization and externalizing and internalizing behaviors among a sample of 2,402 children and adolescents. After including parent and family level covariates in Poisson regressions, we found that a unique form of family violence victimization was associated with increased externalizing behaviors among children at each age group: exposure to physical intimate partner violence (IPV) among children ages 3-5, exposure to the physical abuse of a sibling among children ages 6-12, and child physical abuse among adolescents ages 13-18. No form of physical family violence was significantly associated with internalizing behaviors for children in any age group. Including exposure to the child maltreatment of a sibling is crucial when attempting to contextualize children's responses to family violence and providing comprehensive services in an effort to enhance the well-being of all children in a family. (PsycINFO Database Record


Heat transfer in the Knudsen layer.
A concept of the surface heat conductivity determining a heat transfer in the Knudsen layer was introduced. It has the same order with respect to the Knudsen number as the bulk heat transfer and must be taken into account in practical calculations. Using the Onsager principle the coefficient of the surface heat conductivity was related to the thermal slip coefficient.


Tumour of great occipital foramen.
We present the case of tumour of the great occipital foramen in a patient who was having headaches and significant mobility restriction of the cervical spine. Attention is called to diagnostic and surgical difficulties related to this location of neoplasm.


[In vitro effect of combinations of netilmicin and amikacin with fosfomycin and pefloxacin on 31 strains of heterogeneous methicillin- resistant Staphylococcus aureus].
The Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) of 31 strains of Staphylococcus aureus resistant to methicillin and gentamicin were determined towards aminoglycosides: netilmicin (N) and amikacin (A). The results of the study showed a large discordance between the technic using dilution in Mueller-Hinton broth and the technic using agar diffusion with antibiotic discs. The level of sensitivity appears to decrease by dilution. The problem of using these aminoglycosides in combination with other antibiotics as fosfomycin (F) and pefloxacin (P) was faced. In vitro, antibacterial activity of combinations [N-F], [N-P] and [A-F], [A-P], was studied by microtiter checkerboard method. The antibacterial effects of these combinations were evaluated by determination of Fractional Bactericidal Indices (FBC-indices). The combination netilmicin or amikacin with pefloxacin has an additive bactericidal effect in most cases, without discrimination between the different aminoglycosides (FBC #0.82). Netilmicin or amikacin in combination with fosfomycin are found to be additive or moderately synergistic (FBC #0.53). No occurrence of antagonism was observed.


Effect of Staphylococcus epidermidis on U(VI) sequestration by Al-goethite.
Effect of Staphylococcus epidermidis (S. epidermidis) on U(VI) sequestration by Al-goethite were conducted under different geologic conditions. The batch experiments showed that S. epidermidis significantly enhanced the adsorption rates of U(VI) at pH < 9.0 due to the additional metal binding sites. The maximum adsorption capacities of U(VI) on Al-goethite and Al-goethite +S. epidermidis at pH 4.0 and 310 K were calculated from Langmuir equation to be 13.16 and 47.86 mg/g, respectively. The decreased adsorption of U(VI) on Al-goethite+ S. epidermidis at high carbonate and pH conditions were primarily driven by the electrostatic repulsion between negatively charged U(VI)-carbonate complexes and the negatively charged adsorbents. According to XPS analysis, the adsorbed U(VI) can be reduced to U(IV) by S. epidermidis, whereas inhibited reduction of U(VI) on Al-goethite + S. epidermidis at high pH could be attributed to the complexation of structural Fe(III) with the oxygen-containing functional groups of S. epidermidis. FT-IR analysis further demonstrated that the bonding of structural Fe(III) with functional groups (e.g., carboxyl and phosphate groups) of S. epidermidis. These results herein are important to understand the fate and transport of U(VI) on the mineral-bacteria ternary systems in the near-surface environment.


A case of combined small cell lung carcinoma with unique morphology: Investigation of tumorigenesis.
Small cell lung carcinoma (SCLC) usually grows in a pure form with no other associated histological components. However, combined small cell lung carcinoma (cSCLC), which is accompanied by other histological components (cSCLCs) may sometimes occur. Herein, we analyzed the tumorigenesis of cSCLC containing a demarcated area of pure SCLC. A 76-year-old man had a 25-mm mass in the perihilar portion of his right upper lung. Histologically, the cSCLC contained two relatively demarcated areas: one area composed of pure SCLC cells and another area of SCLC, squamous-like component (SLC), and spindle cell carcinoma (SpCC) cells. Loss of heterozygosity (LOH) was observed at allele 3p in all tumor components and at 22q in the pure SCLC component. Histological and immunohistochemical analysis and LOH study suggested that all components were likely to be monoclonal in origin and revealed that the pure SCLC component was not the precursor of the cSCLC. In the tumorigenesis of this case, the pure SCLC and the cSCLC may have originated from a common pluripotent tumor cell and then diverged, although we cannot state this conclusively. Further studies with more cases are necessary to test this theory.


Hierarchical patch-based sparse representation--a new approach for resolution enhancement of 4D-CT lung data.
4D-CT plays an important role in lung cancer treatment because of its capability in providing a comprehensive characterization of respiratory motion for high-precision radiation therapy. However, due to the inherent high-dose exposure associated with CT, dense sampling along superior-inferior direction is often not practical, thus resulting in an inter-slice thickness that is much greater than in-plane voxel resolutions. As a consequence, artifacts such as lung vessel discontinuity and partial volume effects are often observed in 4D-CT images, which may mislead dose administration in radiation therapy. In this paper, we present a novel patch-based technique for resolution enhancement of 4D-CT images along the superior-inferior direction. Our working premise is that anatomical information that is missing in one particular phase can be recovered from other phases. Based on this assumption, we employ a hierarchical patch-based sparse representation mechanism to enhance the superior-inferior resolution of 4D-CT by reconstructing additional intermediate CT slices. Specifically, for each spatial location on an intermediate CT slice that we intend to reconstruct, we first agglomerate a dictionary of patches from images of all other phases in the 4D-CT. We then employ a sparse combination of patches from this dictionary, with guidance from neighboring (upper and lower) slices, to reconstruct a series of patches, which we progressively refine in a hierarchical fashion to reconstruct the final intermediate slices with significantly enhanced anatomical details. Our method was extensively evaluated using a public dataset. In all experiments, our method outperforms the conventional linear and cubic-spline interpolation methods in preserving image details and also in suppressing misleading artifacts, indicating that our proposed method can potentially be applied to better image-guided radiation therapy of lung cancer in the future.


[Uptake and incorporation of 3H-orotic acid in isolated perfused rat liver].
3H-orotic acid incorporation into RNA and the level of RNA polymerase activity in isolated rat liver perfused for 5 hrs were investigated. In spite of a dramatic decrease in 3H-orotic acid uptake by liver cells during perfusion, a constant rate of RNA synthesis was observed. Moreover, RNA polymerase I and II activities were not affected by a 5-hr perfusion. It is suggested that isolated perfused rat liver can be used to study direct effects of hormones and drugs on RNA synthesis.


Ontogeny and potential function of poacher armor (Actinopterygii: Agonidae).
Many vertebrates are armored over all or part of their body. The armor may serve several functional roles including defense, offense, visual display, and signal of experience/capability. Different roles imply different tradeoffs; for example, defensive armor usually trades resistance to attack for maneuverability. The poachers (Agonidae), 47 species of scorpaeniform fishes, are a useful system for understanding the evolution and function of armor due to their variety and extent of armoring. Using publically available CT-scan data from 27 species in 16 of 21 genera of poachers we compared the armor to axial skeletal in the mid body region. The ratio of average armor density to average skeleton density ranged from 0.77 to 1.17. From a defensive point of view, the total investment in mineralization (volume * average density) is more interesting. There was 10 times the material invested in the armor as in the endoskeleton in some small, smooth plated species, like Aspidophoroides olrikii. At the low end, some visually arresting species like Percis japonica, had ratios as low as 2:1. We categorized the extent and type (impact vs. abrasion) in 34 Agonopsis vulsa across all 35+ plates in the eight rows along the body. The ventral rows show abrasive damage along the entire length of the fish that gets worse with age. Impact damage to head and tail plates gets more severe and occurs at higher rates with age. The observed damage rates and the large investment in mineralization of the armor suggest that it is not just for show, but is a functional defensive structure. We cannot say what the armor is defense against, but the abrasive damage on the ventrum implies their benthic lifestyle involves rubbing on the substrate. The impact damage could result from predatory attacks or from intraspecific combat.