Precession electron diffraction tomography for solving complex modulated structures: the case of Bi5Nb3O15.
The crystal structure of the 1D incommensurately modulated phase Bi5Nb3O15 [superspace group X2mb(0b0)000, a = 5.46781(7) Å, b = 5.47381(8) Å, c = 41.9005(5) Å, and q = 0.17588(8)b*] is solved by electron diffraction using a tomography technique combined with precession of the electron beam. The (3 + 1)D structure is further validated by a refinement against powder X-ray diffraction (PXRD). A coherent picture of the true nature of this compound is obtained, conciliating experimental observations made by different groups using transmission electron microscopy and PXRD. Bi5Nb3O15 does not have a mixed-layer Aurivillius-type structure but does contain structural elements, [Bi2O2](2+) slabs, and perovskite-like blocks, characteristic of Aurivillius phases. The presence of aperiodic crystallographic shear planes (CSPs) along the modulated direction b leads to the formation of an original layered structure containing both continuous and discontinuous [Bi2O2](2+) and perovskite-like octahedral layers. Between CSPs, the stacking of these two structural elements exhibits an unprecedented nonuniform sequence referring to Aurivillius phases.


Identification of miR-758-3p as Potential Modulator of CBX5 Expression in Gastric Cancer.
Gastric cancer is one of the most frequently diagnosed cancer types in China and also the leading causes of cancer-related death. Previous study showed chromobox 5 expression was elevated in gastric cancer, but little is known regarding the precise molecular mechanisms by which chromobox 5 expression was modulated. In this study, we revealed that chromobox 5 could promote gastric cancer cell proliferation, migration, and invasion in vitro. We screened and identified microRNA-758-3p, whose expression was downregulated in gastric cancer tissues and cell lines, which was a potential upstream molecule of chromobox 5. Upregulation of microRNA-758-3p could markedly downregulate the expression of chromobox 5. Additionally, expression of microRNA-758-3p and chromobox 5 was inversely correlated in gastric cancer tissues. Moreover, microRNA-758-3p overexpression suppressed gastric cancer cell proliferation, migration, and invasion, but these effects can be partially reversed by chromobox 5 overexpression. Collectively, our results indicate that microRNA-758-3p serves as a tumor suppressor and plays a crucial role in inhibiting the proliferation, migration, and invasion of gastric cancer via targeting chromobox 5 and implicate its potential application in cancer therapy.


Rice OsLHT1 Functions in Leaf-to-Panicle Nitrogen Allocation for Grain Yield and Quality.
Proper allocation of nitrogen (N) from source leaves to grains is essential step for high crop grain yield and N use efficiency. In rice (Oryza sativa) grown in flooding paddy field, amino acids are the major N compounds for N distribution and re-allocation. We have recently identified that Lysine-Histidine-type Transporter 1 (OsLHT1) is the major transporter for root uptake and root-to-shoot allocation of amino acids in rice. In this study, we planted knockout mutant lines of OsLHT1 together wild-type (WT) in paddy field for evaluating OsLHT1 function in N redistribution and grain production. OsLHT1 is expressed in vascular bundles of leaves, rachis, and flowering organs. Oslht1 plants showed lower panicle length and seed setting rate, especially lower grain number per panicle and total grain weight. The concentrations of both total N and free amino acids in the flag leaf were similar at anthesis between Oslht1 lines and WT while significantly higher in the mutants than WT at maturation. The Oslht1 seeds contained higher proteins and most of the essential free amino acids, similar total starch but less amylose with lower paste viscosity than WT seeds. The mutant seeds showed lower germination rate than WT. Knockout of OsLHT1 decreased N uptake efficiency and physiological utilization efficiency (kg-grains/kg-N) by about 55% and 72%, respectively. Taken together, we conclude that OsLHT1 plays critical role in the translocation of amino acids from vegetative to reproductive organs for grain yield and quality of nutrition and functionality.


Picosecond transient photoconductivity in functionalized pentacene molecular crystals probed by terahertz pulse spectroscopy.
We have measured transient photoconductivity in functionalized pentacene molecular crystals using ultrafast optical pump-terahertz probe techniques. The single crystal samples were excited using 800 nm, 100 fs pulses, and the change in transmission of time-delayed, subpicosecond terahertz pulses was used to probe the photoconducting state over a temperature range from 10 to 300 K. A subpicosecond rise in photoconductivity is observed, suggesting that mobile carriers are a primary photoexcitation. At times longer than 4 ps, a power-law decay is observed consistent with dispersive transport.


HMGI-C, a member of the high mobility group family of proteins, is expressed in hematopoietic stem cells and in leukemic cells.
The human HMGI-C gene encoding a member of the high mobility group protein family normally is expressed only during embryonic/fetal development but in none of the adult tissues tested so far. Recently, the HMGI-C gene has attracted a lot of interest since its rearrangements seem to underlie the development of frequent benign mesenchymal tumors. We have therefore checked CD34 positive hematopoietic stem cells and their normal and malignant descendants for HMGI-C expression. CD34 positive stem cells from healthy donors and the leukemia samples tested were positive while all peripheral blood samples from healthy volunteers were negative. We have concluded that the expression of the HMGI-C gene in leukemia seems to be a secondary effect due to abnormal stem cell proliferation and might be a sensitive tumor marker for particular types of leukemia.


Unintended drug exposure during pregnancy in clinical trials - a survey in early drug development.
To collect information on unintended drug exposure during pregnancy in early clinical drug development. Questionnaire mailed in autumn 2015 to members of human pharmacology societies in Europe for anonymous responses via the online tool SurveyMonkey. 53 of the ~ 700 addressees participated in the survey. 23 female trial participants and 11 female partners of male trial participants were exposed to investigational medicinal products during unintended pregnancies in a clinical trial. Most survey respondents confirmed adequate contraceptive methods by in/exclusion criteria and the use of pregnancy tests in female trial participants at screening and before the first dose. The last menstrual period was documented less frequently (at screening: 28 of 44, before first dose: 5 of 44 respondents). A considerable proportion of respondents denied the routine use of compliance checks about the appropriate use of contraceptive methods, had no procedures in place if contraceptive methods failed, and did not train physicians in instructing trial participants about the appropriate use of contraceptive methods. The methods to avoid unintended pregnancies during participation in a clinical trial need improvement and should include (i) pregnancy tests, (ii) documentation of last menstrual period before the first dose, (iii) compliance checks of the appropriate use of contraceptive methods, and (iv) training of trial physicians. Procedures should be in place for what to do if contraceptive methods fail.


Effect of imidazoline drugs on human blood platelet aggregation.
The effect of seven commonly used in therapy imidazoline derivatives on human blood platelet aggregation was studied. Three of the agents, i.e. clonidine, antazoline and tetryzoline were classified as partial agonists of the receptor responsible for aggregation. Two other drugs, i.e. phentolamine and tolazoline act as competitive antagonists of relatively high receptor affinity. The remaining imidazolines: xylometazoline and naphazoline effectively inhibit the platelet receptor in a non-competitive manner. The last two compounds seem to be selective alpha 2-adrenoceptor antagonists.


Modified apparatus for low temperature/high pressure Mossbauer absorber studies.
A method is described in which a system designed to study Mossbauer sources as a function of pressure and temperature is modified to include absorbers as well. This is accomplished by coupling the Mossbauer source, mounted inside a cryostat, to an external transducer by means of a bellows. In addition, a simple modification has converted an existing helium Dewar to a dynamic gas flow cryostat. Temperature can be continuously varied from 300 to 20 K at pressures up to 200 kilobars.


Isosteric replacement of amide by ester function. Synthesis and benzodiazepine receptor affinity of indol-3-ylglyoxylyl ester derivatives.
A number of benzyl and phenylethyl esters of indol-3-ylglyoxylic acid were synthesized and tested for their ability to displace [3H]Ro 15-1788 binding from bovine brain membranes. In these new compounds the oxygen atom of the ester function replaced the amide NH group of a class of previously described indolylglyoxylylamides, since it is reported in literature that in the beta-carboline series an ester function is more favourable to the activity than an amide group. However, none of the compounds showed an affinity at the Benzodiazepine receptor higher than that of the corresponding amides, demonstrating that the presence of the amide NH group is favourable to the interaction of ligands with the receptor site.


Does the Owl Fly out of the Tree or Does the Owl Exit the Tree Flying? How L2 Learners Overcome Their L1 Lexicalization Biases.
Learning a language is more than learning its vocabulary and grammar. For example, compared to English, Spanish uses many more path verbs such as ascender ('to move upward') and salir ('to go out'), and expresses manner of motion optionally. English, in contrast, has many manner verbs (e.g., run, jog) and expresses path in prepositional phrases (e.g., out of the barn). The way in which a language encodes an event is known as its lexicalization pattern or bias. Using a written sentence elicitation task, we asked whether adult Spanish learners whose L1 was English adopted Spanish lexicalization biases, and what types of L2 exposure facilitated the learning of lexicalization biases. Results showed that advanced, but not intermediate, adult Spanish learners showed a path bias comparable to that found in native speakers of Spanish. Furthermore, study abroad experience is associated with better acquisition of L2 lexicalization biases when describing certain types of events.


Glyoxal-methylglyoxal cross-reactions in secondary organic aerosol formation.
Glyoxal (G) and methylglyoxal (MG) are potentially important secondary organic aerosol (SOA) precursors. Previous studies of SOA formation by G and MG have focused on either species separately; however, G and MG typically coexist in the atmosphere. We studied the formation of secondary organic material in aqueous aerosol mimic mixtures containing G and MG with ammonium sulfate. We characterized the formation of light-absorbing products using UV-vis spectrophotometry. We found that absorption at 280 nm can be described well using models for the formation of light-absorbing products by G and MG in parallel. Pendant drop tensiometry measurements showed that surface tension depression by G and MG in these solutions can be modeled as a linear combination of the effects of G and MG alone. Product species were identified using chemical ionization mass spectrometry with a volatilization flow tube inlet (Aerosol CIMS). Peaks consistent with G-MG cross-reaction products were observed, accounting for a significant fraction of detected product mass, but most peaks could be attributed to self-reaction. We conclude that cross-reactions contribute to SOA mass from uptake of G and MG, but they are not required to accurately model the effects of this process on aerosol surface tension or light absorption.


Proinflammatory cytokine profile in Vibrio vulnificus septicemic patients' sera.
Vibrio vulnificus causes a fulminant and frequently fatal septicemia in susceptible hosts. The present study was designed to evaluate the proinflammatory cytokine profile in V. vulnificus septicemia patients' sera and the effect of doxycycline therapy on the levels of proinflammatory cytokines. Levels of proinflammatory cytokines, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6, were measured in the sera of V. vulnificus septicemic patients and normal healthy volunteers using colorimetric sandwich ELISA. The mean values of TNF-alpha, IL-1beta and IL-6 in the sera of V. vulnificus patients (n=33) increased by 210-, 232- and 40-fold in comparison with those of normal healthy volunteers (n=5), but only the IL-6 level showed a statistically significant difference (P<0.05) between the two groups. Sera from the cases for which doxycycline treatment histories were obvious were designated 'before-treatment' (TX). All the others were included in the after-TX group. In the before-TX group (n=5), the levels of TNF-alpha and IL-1beta significantly increased (P<0.05) in comparison with the after-TX group (n=5). IL-6 levels in the two groups showed no difference. In conclusion, the levels of the well known proinflammatory cytokines TNF-alpha, IL-1beta and IL-6 increased in the V. vulnificus septicemic patients' sera, and the levels of TNF-alpha and IL-1beta decreased significantly after doxycycline treatment. These data indicate that proinflammatory cytokines might play a critical role in V. vulnificus septicemia like in other endotoxemic shocks. The use of doxycycline as an effective bactericidal agent and as an effective modulator of proinflammatory cytokines is supported.


Neuronal mechanisms underlying the laryngeal adductor reflex.
Electromyographic studies of the laryngeal adductor reflex, glottal closure occurring in response to laryngeal stimulation, have demonstrated an early ipsilateral response (R1) and a late bilateral response (R2). To better define the physiologic properties of these responses, we recorded responses from expiratory laryngeal motoneurons (ELMs) in rats during stimulation of the superior laryngeal nerve (SLN). Single unit extracellular recordings were obtained from 5 ELMs, identified by their antidromic responses to recurrent laryngeal nerve stimulation and postinspiratory firing pattern, in 4 Sprague-Dawley rats. Unilateral stimulation of the SLN (at 20 Hz) stopped both phrenic nerve inspiratory activity and ELM postinspiratory activity. However, the ELMs displayed robust tonic firing, consisting of non-respiratory burst activity and single action potentials. The single action potentials were identified as short-latency ones (5 to 10 ms) activated by ipsilateral SLN stimulation, with an occurrence rate of 90%, and long-latency ones (20 to 50 ms) activated by bilateral SLN stimulation, with occurrence rates of 47% on the ipsilateral side and 58% on the contralateral side. The R1 response appears to be the result of the short-latency action potentials, orthodromically activated by ipsilateral stimulation of the SLN. The R2 response is likely to be a result of the long-latency action potentials that can be recorded from ELMs on both sides.


Macroalgae Extracts From Antarctica Have Antimicrobial and Anticancer Potential.
Background: Macroalgae are sources of bioactive compounds due to the large number of secondary metabolites they synthesize. The Antarctica region is characterized by extreme weather conditions and abundant aggregations of macroalgae. However, current knowledge on their biodiversity and their potential for bio-prospecting is still fledging. This study evaluates the antimicrobial and cytotoxic activity of different extracts of four macroalgae (Cystosphaera jacquinotii, Iridaea cordata, Himantothallus grandifolius, and Pyropia endiviifolia) from the Antarctic region against cancer and non-cancer cell lines. Methods: The antimicrobial activity of macroalgae was evaluated by the broth microdilution method. Extracts were assessed against Staphylococcus aureus ATCC 19095, Enterococcus faecalis ATCC 4083, Escherichia coli ATCC29214, Pseudomonas aeruginosa ATCC 9027, Candida albicans ATCC 62342, and the clinical isolates from the human oral cavity, namely, C. albicans (3), C. parapsilosis, C. glabrata, C. lipolytica, and C. famata. Cytotoxicity against human epidermoid carcinoma (A-431) and mouse embryonic fibroblast (NIH/3T3) cell lines was evaluated with MTT colorimetric assay. Results: An ethyl acetate extract of H. grandifolius showed noticeable antifungal activity against all fungal strains tested, including fluconazole-resistant samples. Cytotoxicity investigation with a cancer cell line revealed that the ethyl acetate extract of I. cordata was highly cytotoxic against A-431 cancer cell line, increasing the inhibitory ratio to 91.1 and 95.6% after 24 and 48 h exposure, respectively, for a concentration of 500 μg mL-1. Most of the algal extracts tested showed little or no cytotoxicity against fibroblasts. Conclusion: Data suggest that macroalgae extracts from Antarctica may represent a source of therapeutic agents. HIGHLIGHTS Different macroalgae samples from Antarctica were collected and the lyophilized biomass of each macroalgae was extracted sequentially with different solventsThe antimicrobial and anticancer potential of macroalgae extracts were evaluatedEthyl acetate extract of H. grandifolius showed noticeable antifungal activity against all the fungal strains tested, including fluconazole-resistant samplesEthyl acetate extract of I. cordata was highly cytotoxic against the A-431 cancer cell lineMost of the algal extracts tested showed little or no cytotoxicity against normal cell lines.


[Surgical treatment of temporal lobe epilepsy: reality and prospectives].
This chapter provides a synthetic overview of the topics treated in this issue. Presurgical diagnostic procedures are schematically described and an analysis of surgical results is made in comparison with those obtained from other epilepsy surgery groups. Surgical complications linked both to invasive presurgical diagnostic procedures and therapeutic surgical acts are described. Finally, the creation of new epilepsy surgery centres is suggested on the basis of epidemiological data, which demonstrate the discrepancy among the patients operated on at present and those who could benefit from the surgical treatment.


Full 360° Terahertz Dynamic Phase Modulation Based on Doubly Resonant Graphene-Metal Hybrid Metasurfaces.
Dynamic phase modulation is vital for tuneable focusing, beaming, polarisation conversion and holography. However, it remains challenging to achieve full 360° dynamic phase modulation while maintaining high reflectance or transmittance based on metamaterials or metasurfaces in the terahertz regime. Here, we propose a doubly resonant graphene-metal hybrid metasurface to address this challenge. Simulation results show that by varying the graphene Fermi energy, the proposed metasurface with two shifting resonances is capable of providing dynamic phase modulation covering a range of 361° while maintaining relatively high reflectance above 20% at 1.05 THz. Based on the phase profile design, dynamically tuneable beam steering and focusing were numerically demonstrated. We expect that this work will advance the engineering of graphene metasurfaces for the dynamic manipulation of terahertz waves.


The development and use of vaccine adjuvants.
Interest in vaccine adjuvants is intense and growing, because many of the new subunit vaccine candidates lack sufficient immunogenicity to be clinically useful. In this review, I have emphasized modern vaccine adjuvants injected parenterally, or administered orally, intranasally, or transcutaneously with licensed or experimental vaccines in humans. Every adjuvant has a complex and often multi-factorial immunological mechanism, usually poorly understood in vivo. Many determinants of adjuvanticity exist, and each adjuvanted vaccine is unique. Adjuvant safety is critical and can enhance, retard, or stop development of an adjuvanted vaccine. The choice of an adjuvant often depends upon expensive experimental trial and error, upon cost, and upon commercial availability. Extensive regulatory and administrative support is required to conduct clinical trials of adjuvanted vaccines. Finally, comparative adjuvant trials where one antigen is formulated with different adjuvants and administered by a common protocol to animals and humans can accelerate vaccine development.


Imaging via complete cantilever dynamic detection: general dynamic mode imaging and spectroscopy in scanning probe microscopy.
We develop and implement a multifrequency spectroscopy and spectroscopic imaging mode, referred to as general dynamic mode (GDM), that captures the complete spatially- and stimulus dependent information on nonlinear cantilever dynamics in scanning probe microscopy (SPM). GDM acquires the cantilever response including harmonics and mode mixing products across the entire broadband cantilever spectrum as a function of excitation frequency. GDM spectra substitute the classical measurements in SPM, e.g. amplitude and phase in lock-in detection. Here, GDM is used to investigate the response of a purely capacitively driven cantilever. We use information theory techniques to mine the data and verify the findings with governing equations and classical lock-in based approaches. We explore the dependence of the cantilever dynamics on the tip-sample distance, AC and DC driving bias. This approach can be applied to investigate the dynamic behavior of other systems within and beyond dynamic SPM. GDM is expected to be useful for separating the contribution of different physical phenomena in the cantilever response and understanding the role of cantilever dynamics in dynamic AFM techniques.


Circulating antigens, immune complexes and C3d levels in human schistosomiasis: relationship with Schistosoma mansoni egg output.
Circulating schistosome antigens (CSA), circulating immune complexes (CIC) and C3 breakdown product - C3d - were investigated in human schistosomiasis in comparison to the S. mansoni egg count. A close relationship was observed between the mean number of eggs/g of stool and the detection of CSA (evaluated by the radioimmunoprecipitation-PEG assay - Ripega), CIC (Clq-binding test) and C3d levels (quantitated by radial immunodiffusion). All the patients with more than 500 S. mansoni eggs/g of stool also presented antigen '4', specific of the genus Schistosoma, in the serum. A significant correlation was noticed between levels of CSA and CIC. This suggests the involvement of several schistosome antigens in the detected CIC. No relationship was noted between CIC and C3d levels. In contrast, there was a highly significant correlation between levels of CSA and C3d. The interaction between certain schistosome antigens and the complement system is discussed.


Adolescents' Perceptions of Family Belonging in Stepfamilies.
Prior research has established that adolescents' perceptions of family belonging are associated with a range of well-being indicators and that adolescents in stepfamilies report lower levels of family belonging than adolescents in two-biological-parent families. Yet, we know little regarding what factors are associated with adolescents' perceptions of family belonging in stepfamilies. Guided by family systems theory, the authors addressed this issue by using nationally representative data (Add Health) to examine the associations between family characteristics and adolescents' perceptions of family belonging in stepfather families (N = 2,085). Results from structural equation models revealed that both the perceived quality of the stepfather-adolescent relationship, and in particular the perceived quality of the mother-adolescent relationship, were the factors most strongly associated with feelings of family belonging.


Comparison of procedural complications with versus without interventional cardiology fellows-in-training during contemporary percutaneous coronary intervention.
Despite increasing complexity of contemporary procedures at tertiary care hospitals, the relationship between interventional cardiology fellows-in-training (ICFITs) and complications of percutaneous coronary intervention (PCI) has not been reported. We compiled logbooks of 6 ICFITs at an academic hospital and evaluated patient and procedural characteristics of PCIs performed with and without presence of an ICFIT. The primary end point was the composite of all in-hospital PCI complications defined by the American College of Cardiology's National Cardiovascular Data Registry: (1) catheterization laboratory events such as no-reflow and dissection/perforation, (2) general clinical events such as stroke or cardiogenic shock, (3) vascular and bleeding complications, and (4) miscellaneous complications such as peak troponin or creatinine levels. Logistic regression adjusted for differences in measured confounders between patients treated with and without presence of an ICFIT. All analyses were repeated after excluding PCI for ST-elevation myocardial infarction. Of 2,605 PCI procedures at the academic hospital between July 2007 and April 2010, an ICFIT was present for 1,638 procedures (63%). Despite having worse clinical and procedural characteristics, patients in the ICFIT group experienced similar rates of the composite end point (12.9% vs 14.5% without ICFIT, p = 0.27). Longer mean fluoroscopy times and greater number of stents were noted in the ICFIT group; however, hospital length of stay was shorter and no individual adverse events were increased in the ICFIT procedures. Presence of an ICFIT remained unrelated to the composite end point after multivariable adjustment (odds ratio 0.92, 95% confidence interval 0.71 to 1.20; p = 0.53), and findings were similar after excluding PCI for ST-elevation myocardial infarction. In conclusion, in contemporary practice at a large academic medical center, PCI complication rates were not adversely affected by the presence of an ICFIT.


MicroRNA-223-3p inhibits oxidized low-density lipoprotein-mediated NLRP3 inflammasome activation via directly targeting NLRP3 and FOXO3.
MicroRNAs (miRNAs) have emerged as crucial players in the initiation and development of atherosclerosis (AS), and the low miR-223-3p level is observed in AS patients. However, the function and mechanism behind miR-223-3p in AS progression have not been fully elucidated. In the present study, THP-1 cells treated with oxidized low-density lipoprotein (ox-LDL) were employed as the cell model of AS. The expression levels of miR-223-3p, NLR family pyrin domain containing 3 (NLRP3), caspase-1, pro-caspase-1, cleaved interleukin 18 (IL-18), cleaved IL-1β, and forkhead box O3 (FOXO3) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot (WB) analyses. The relationship between miR-223-3p and FOXO3 or NLRP3 was determined using a dual-luciferase reporter assay. The production of IL-1β, IL-18, IL-6, and TNF-α was examined by Enzyme-linked immunosorbent assay (ELISA). MiR-223-3p was decreased in AS patients and ox-LDL-induced THP-1 cells, and its upregulation downregulated the abundance of NLRP3, caspase-1, cleaved IL-18, cleaved IL-1β, IL-1β, IL-6, and TNF-α in THP-1 cells treated with ox-LDL or not, and the depletion of miR-223-3p revealed an opposite phenomenon. NLPR3 and FOXO3 were identified as two authentic targets of miR-223-3p. Knockdown of NLRP3 or FOXO3 reversed the stimulatory effect of the miR-223-3p inhibitor on the inflammatory responses of THP-1 cells. Our data indicate that miR-223-3p inhibited ox-LDL-mediated NLRP3 inflammasome activation via directly targeting NLRP3 and FOXO3 in THP-1 cells, which offered a prospective therapeutic target for AS therapy.


Update on kidney transplantation: increasing clinical success, expanding waiting lists.
Short-term and long-term renal allograft survivals have improved in recent years for several reasons. Improvements in immunosuppression have reduced acute cellular rejections to about 15% to 25%. The use of erythropoietin to treat anemia allows patients to avoid transfusions, thereby reducing sensitization and hyperacute rejections. Advances in the management of cardiovascular disease and infection have also been significant factors in improved patient and allograft survival. Although living donations are helping to increase the number of transplants, their effect on rapidly growing waiting lists is relatively small.


Hepatocellular carcinoma and the underlying mechanisms.
The incidence of hepatocellular carcinoma is increasing worldwide as well as the associated risk factors, some of which include exposure to aflatoxin B1, Hepatitis B (HBV) virus and hepatitis C (HCV) virus. Mutation of tumour suppressor gene p53 at codon 249(ser) at exon 7 has been found to contribute significantly to replication of damaged DNA and subsequent tumour progression. The x gene of HBV (HBx) is the most common open reading frame integrated into the host genome in hepatocellular carcinoma and the integrated HBx is frequently mutated in hepatocellular carcinoma. Mutant HBx proteins still retain their ability to bind to p53 thereby attenuating DNA repair and p53-mediated apoptosis.


Stomatal responses to carbon dioxide and light require abscisic acid catabolism in Arabidopsis.
In plants, stomata control water loss and CO2 uptake. The aperture and density of stomatal pores, and hence the exchange of gases between the plant and the atmosphere, are controlled by internal factors such as the plant hormone abscisic acid (ABA) and external signals including light and CO2. In this study, we examine the importance of ABA catabolism in the stomatal responses to CO2 and light. By using the ABA 8'-hydroxylase-deficient Arabidopsis thaliana double mutant cyp707a1 cyp707a3, which is unable to break down and instead accumulates high levels of ABA, we reveal the importance of the control of ABA concentration in mediating stomatal responses to CO2 and light. Intriguingly, our experiments suggest that endogenously produced ABA is unable to close stomata in the absence of CO2. Furthermore, we show that when plants are grown in short day conditions ABA breakdown is required for the modulation of both elevated [CO2]-induced stomatal closure and elevated [CO2]-induced reductions in leaf stomatal density. ABA catabolism is also required for the stomatal density response to light intensity, and for the full range of light-induced stomatal opening, suggesting that ABA catabolism is critical for the integration of stomatal responses to a range of environmental stimuli.


Nuclear Quantum Dynamics of Three-Dimensional Condensed-Phase Systems by Constant Uncertainty Molecular Dynamics.
Constant uncertainty molecular dynamics (CUMD), which was developed to include nuclear quantum effects (NQEs) in molecular dynamics (MD) simulations, is extended to three-dimensional condensed-phase systems. Its applicability was verified via CUMD simulations of bulk water and ice Ih with the q-TIP4P/F potential model. The simulated radial distribution functions, proton momentum distributions, and infrared spectra were compared with those of previous studies in which the simulations were carried out on the basis of the imaginary-time path-integral formalism. We found that CUMD can function as an alternative trajectory-based simulation method for including static and dynamic NQEs in MD simulations of three-dimensional condensed-phase systems.


Fluorous iminoalditols: a new family of glycosidase inhibitors and pharmacological chaperones.
A collection of new reversible glycosidase inhibitors of the iminoalditol type featuring N-substituents containing perfluorinated regions has been prepared for evaluation of physicochemical, biochemical and diagnostic properties. The vast variety of feasible oligofluoro moieties allows for modular approaches to customised structures according to the intended applications, which are influenced by the fluorine content as well as the distance of the fluorous moiety from the ring nitrogen. The first examples, in particular in the D-galacto series, exhibited excellent inhibitory activities. A preliminary screen with two human cell lines showed that, at subinhibitory concentrations, they are powerful pharmacological chaperones enhancing the activities of the catalytically handicapped lysosomal D-galactosidase mutants associated with GM1 gangliosidosis and Morquio B disease.


Hepcidin as a predictor of response to epoetin therapy in anemic cancer patients.
Hepcidin is thought to be the central regulator of iron metabolism. Iron deficiency is associated with low hepcidin concentrations, and anemia in patients with cancer is associated with high concentrations of hepcidin. Our main objective was to assess the potential role of hepcidin for predicting response to epoetin therapy in anemic cancer patients. We also aimed to identify a cutoff value for hepcidin as a potential predictive marker for response to epoetin therapy. Using data from 525 anemic cancer patients enrolled in 5 studies, we assessed serum hepcidin concentrations in 408 of these patients at baseline and analyzed pooled data from the 408 patients. The analysis population was separated into 2 categories using a threshold hepcidin concentration of 13 nmol/L: low hepcidin (< 13 nmol/L) and high hepcidin (> or = 13 nmol/L). A significantly higher percentage of responders (defined as hemoglobin increase > or = 10 g/L or > or = 20 g/L from baseline) was observed in the low hepcidin group compared with the high hepcidin group (P = 0.04 for > or = 10 g/L increase and P = 0.009 for > or = 20 g/L from baseline). There was also a statistically significant difference between the 2 groups for hematopoietic response (hemoglobin rise at least once > or = 20 g/L from baseline or at least once > or = 120 g/L) to epoetin therapy (P = 0.0004). The results of this analysis suggest a potential role of hepcidin serum concentrations in predicting the response to epoetin therapy.


Guidelines on the care of diabetic nephropathy, retinopathy and foot disease.
Diabetes mellitus is a common disease frequently managed by family physicians. Because of its high prevalence and associated comorbidity, diabetes mellitus has received a great deal of attention from several specialty organizations. The American Diabetes Association, the American Board of Family Practice and the Centers for Disease Control and Prevention have published specific practice guidelines and recommendations for the care of diabetic patients. These recommendations include annual comprehensive foot examinations, yearly ophthalmologic screening for retinopathy, and urinalysis for microalbuminuria. The use of angiotensin converting enzyme inhibitors is advocated for the majority of diabetic patients with proteinuria or hypertension. Based on recent evidence, improved glycemic control is also increasingly advocated. Compliance with practice guidelines by primary care physicians has historically been poor. Mechanisms such as the use of patient problem lists and diabetic flow sheets can serve as reminders to physicians and can facilitate closer adherence to practice guidelines.


Preparation and Characterization of Regenerated Cellulose Film from a Solution in Lithium Bromide Molten Salt Hydrate.
In this study, the molten salt hydrate of lithium bromide (LiBr) was utilized as a non-derivatizing cellulose dissolution solvent to prepare regenerated cellulose films for kraft pulp. The effects of LiBr concentrations (60, 62, and 65 wt %) and dissolving time (from 5 to 40 min with the interval of 5 min) on the structures and the properties of the films were investigated. Fourier transform infrared (FT-IR) and cross-polarization magic-angle spinning carbon-13 nuclear magnetic resonance (CP/MAS 13C NMR) characterizations verified the breakage of inter- and intra-cellulose hydrogen bonds during the regeneration, resulting in the disruption of the crystalline structure of cellulose. X-ray diffraction (XRD) data indicated that the regeneration converted the polymorphism of cellulose from I to II as well as decreased its crystallinity. Ultraviolet-visible spectra (UV-Vis) and scanning electron microscopy (SEM) analyses revealed the excellent optical transparency of the films to visible light due to the complete dissolution of cellulose fibers as well as the sufficient breaking of the inter- and intra-cellulose hydrogen bonds. In terms of tensile testing, tuning LiBr concentrations and dissolving time could increase the elongation at break and tensile strength of the films. The maximum elongation at break of 26% and tensile strength of 67 MPa were achieved when the films prepared in 65 wt % LiBr for 10 and 15 min, respectively. These results indicated the great potential of the cellulose films for packaging use.


[Two patients who recovered fully from profound circulatory and respiratory failure after cardiac arrest].
Two patients who were both 62-year-old males, also with various complications fully recovered from profound circulatory and respiratory failure. Both patients had experienced cardiac arrest one week or three months previously. Ischemic insult of brain produced from the prior cardiac arrest may be related to these excellent outcomes, because induction of tolerance to brain ischemia was demonstrated in animals which had undergone prior sublethal brain ischemia.


Cortisol binding in uremic plasma. II. Decreased cortisol binding to albumin.
We measured cortisol binding to albumin in uremic plasma during a study to see if increased morning plasma free cortisol values, reported previously in chronic renal failure patients, could be explained by binding abnormalities of plasma proteins. Cortisol binding was measured in plasma from chronic renal failure patients and compared to values in normal controls. The unbound and albumin-bound fractions of plasma cortisol were determined using an isocolloidosmolar equilibrium dialysis method and heat inactivation of corticosteroid-binding globulin. A lower ratio of albumin-bound cortisol to unbound cortisol was seen in uremic than in nonuremic plasma (p less than 0.05). This difference was eliminated when uremic plasma was treated with dextran-activated charcoal. These studies suggest that cortisol binding to albumin is decreased in uremic plasma because of a heat-stable substance which is removed from plasma by charcoal treatment.


The prospective payment system: information for the medical librarian and a selected annotated bibliography.
The implementation of the prospective payment system for inpatient Medicare services and the usage of Diagnosis Related Groups as a vehicle for allocation of monies to providers has impacted significantly the health care industry as a whole. Librarians are instrumental in providing information to key health care personnel to meet the strategic challenge of prospective payment. This article reviews the evolution of prospective payment by DRG and provides selected sources of information as a beginning in developing a knowledge of the facets of prospective payment and the health care environment.


The reproducibility of temporomandibular joint vibrations over time in the human.
The aim of the study was to assess the reproducibility of vibrations recorded from the temporomandibular joint (TMJ) in a group of healthy subjects. The vibrations from TMJ were recorded bilaterally from 34 healthy subjects by electrovibratography in three sessions at intervals of 3 min and again after 1 week. The total integral of the vibration energy, the ratio of the integral between frequencies above 300 Hz and below 300 Hz (ratio of >300 Hz/<300 Hz), peak frequency, median frequency, peak amplitude and distance to centric occlusion position were calculated. Data were analysed with intraclass correlation coefficients (ICC) and two-way anova for repeated measures. All variables showed good to excellent reliability across different sessions (ICCday1 : 0·935-0·987; ICCday2 : 0·910-0·992) and across different days (ICC: 0·738-0·907). According to anova for repeated measures, all variables showed good reproducibility (P > 0·05) between sessions at the same day. There was no significant difference between the 2 days for the frequency-related variables including peak frequency (P = 0·083), median frequency (P = 0·188) and ratio of >300 Hz/<300 Hz (P = 0·26). There was a statistical difference between the 2 days for the intensity-related vibration variables including total integral (P = 0·045) and peak amplitude (P = 0·026). The wave patterns of the power-frequency spectra were qualitatively similar over both the sessions and days. Joint vibration analysis could provide a fast, non-invasive, and repeatable method to record the status of TMJ. Further studies are needed to identify the characteristic waveforms for different subgroups of temporomandibular disorders and to evaluate the possibility of diagnostic value.


[Hospitalization of peritoneal dialysis patients: the impact of peritonitis episodes on the hospitalization rate].
Peritonitis is still a frequent complication in peritoneal dialysis patients. Medical guidelines have been established to manage this infection. These guidelines do not provide any information regarding the requirement for hospitalization. The main objective of this study was to evaluate the impact of peritonitis episode on the hospitalization rate and on the hospitalization duration in a centre where peritoneal dialysis patients were hospitalized in case of peritonitis. This was a retrospective study of incident peritoneal patients over a six years period. Among 101 peritoneal dialysis patients 65% were hospitalized. Two hundred and twenty hospital stays were registered. The total duration of hospital stays was 2091 days. The hospitalization rate was 2 per patient and per year, the hospital duration was 19 days per patient per year. Of the 220 hospital stays, 67 (30%) were due to a peritoneal infection. Peritonitis episodes represent 581/2091 (28%) days of hospitalization. The mean duration of hospitalization for peritonitis was 8.7+/-7 days. Among the patients hospitalized for a peritonitis episode, 57% were assisted by a nurse at home to perform their peritoneal dialysis exchanges. Of the 67 peritonitis episodes, 91% were discharged from the hospital without any complication. This study emphases the fact that peritonitis has an important impact on the hospitalization rate and on the hospitalization duration in peritoneal dialysis patients. In an attempt to decrease the rate of hospitalization, educational programs are clearly needed in order to treat more peritonitis without any hospitalization requirement.


Inclusion of Respiratory Frequency Information in Heart Rate Variability Analysis for Stress Assessment.
Respiratory rate and heart rate variability (HRV) are studied as stress markers in a database of young healthy volunteers subjected to acute emotional stress, induced by a modification of the Trier Social Stress Test. First, instantaneous frequency domain HRV parameters are computed using time-frequency analysis in the classical bands. Then, the respiratory rate is estimated and this information is included in HRV analysis in two ways: 1) redefining the high-frequency (HF) band to be centered at respiratory frequency; 2) excluding from the analysis those instants where respiratory frequency falls within the low-frequency (LF) band. Classical frequency domain HRV indices scarcely show statistical differences during stress. However, when including respiratory frequency information in HRV analysis, the normalized LF power as well as the LF/HF ratio significantly increase during stress ( p-value 0.05 according to the Wilcoxon test), revealing higher sympathetic dominance. The LF power increases during stress, only being significantly different in a stress anticipation stage, while the HF power decreases during stress, only being significantly different during the stress task demanding attention. Our results support that joint analysis of respiration and HRV obtains a more reliable characterization of autonomic nervous response to stress. In addition, the respiratory rate is observed to be higher and less stable during stress than during relax ( p-value 0.05 according to the Wilcoxon test) being the most discriminative index for stress stratification (AUC = 88.2 % ).


The in vitro anti-osteoporotic activity of some diarylheptanoids and lignans from the rhizomes of Dioscorea spongiosa.
Three diarylheptanoids and three lignans from the 90 % ethanol fraction of the rhizomes of DIOSCOREA SPONGIOSA were isolated and subjected to IN VITRO experiments to investigate their activity on osteoblasts and osteoclasts. Diarylheptanoid 1 and furofuran lignan 6 were found to significantly stimulate the proliferation of primary osteoblasts and 6 also mildly stimulated osteoblast mineralization by mouse calvaria osteoblastic cells. All diarylheptanoids and lignans at a concentration of 200 muM completely inhibited the formation of osteoclast-like cells. These results demonstrate that the isolated diarylheptanoids and lignans in the 90 % ethanol fraction have significant anti-osteoporotic activities.


Determinants of public T cell responses.
Historically, sharing T cell receptors (TCRs) between individuals has been speculated to be impossible, considering the dramatic discrepancy between the potential enormity of the TCR repertoire and the limited number of T cells generated in each individual. However, public T cell response, in which multiple individuals share identical TCRs in responding to a same antigenic epitope, has been extensively observed in a variety of immune responses across many species. Public T cell responses enable individuals within a population to generate similar antigen-specific TCRs against certain ubiquitous pathogens, leading to favorable biological outcomes. However, the relatively concentrated feature of TCR repertoire may limit T cell response in a population to some other pathogens. It could be a great benefit for human health if public T cell responses can be manipulated. Therefore, the mechanistic insight of public TCR generation is important to know. Recently, high-throughput DNA sequencing has revolutionized the study of immune receptor repertoires, which allows a much better understanding of the factors that determine the overlap of TCR repertoire among individuals. Here, we summarize the current knowledge on public T-cell response and discuss future challenges in this field.


Simple innovative adaptor to improve genome walking with convenient PCR.
Various polymerase chain reaction (PCR)-based methods have been applied for the development of genome walking (GW) technique. These methods which could be based on the application of restriction enzymes or primers have various efficiencies to identify the unknown nucleotide sequences. The present study was conducted to design a new innovative double-strand adaptor using MAP30 gene sequence of Momordica charantia plant as a model to improve genome walking with convenient PCR. The adaptor was designed using multiple restriction sites of Hind III, BamH I, EcoR I, and Bgl II enzymes with no restriction site in a known sequence of the MAP30 gene. In addition, no modification was required to add phosphate, amine, or other groups to the adaptor, since restriction enzyme digestion of double-strand adaptor provided the 5' phosphate group. Here, preparation of the phosphate group in the genomic DNA of the plant digestion with restriction enzymes was performed followed by ligation with digested adaptor containing 5' phosphate group. PCR was done to amplify the unknown sequence using MAP30 gene-specific primer and adaptor primer. Results confirmed the ability of the technique for successful identification of the sequence. Consequently, a newly designed adaptor in the developed technique reduced the time and cost of the method compared to the conventional genome walking; also, cloning and culturing of bacterial steps could be eliminated.


Beyond CNNs: Exploiting Further Inherent Symmetries in Medical Image Segmentation.
Automatic tumor or lesion segmentation is a crucial step in medical image analysis for computer-aided diagnosis. Although the existing methods based on convolutional neural networks (CNNs) have achieved the state-of-the-art performance, many challenges still remain in medical tumor segmentation. This is because, although the human visual system can detect symmetries in 2-D images effectively, regular CNNs can only exploit translation invariance, overlooking further inherent symmetries existing in medical images, such as rotations and reflections. To solve this problem, we propose a novel group equivariant segmentation framework by encoding those inherent symmetries for learning more precise representations. First, kernel-based equivariant operations are devised on each orientation, which allows it to effectively address the gaps of learning symmetries in existing approaches. Then, to keep segmentation networks globally equivariant, we design distinctive group layers with layer-wise symmetry constraints. Finally, based on our novel framework, extensive experiments conducted on real-world clinical data demonstrate that a group equivariant Res-UNet (called GER-UNet) outperforms its regular CNN-based counterpart and the state-of-the-art segmentation methods in the tasks of hepatic tumor segmentation, COVID-19 lung infection segmentation, and retinal vessel detection. More importantly, the newly built GER-UNet also shows potential in reducing the sample complexity and the redundancy of filters, upgrading current segmentation CNNs, and delineating organs on other medical imaging modalities.


[Research into the psychosocial aspects of ENT tumor surgery (excluding laryngectomy). 4: Status of research and future research goals].
The literature on the psychosocial aspects of head and neck cancer surgery from 1950 to 1995 was reviewed in four parts. In the present Part 4 ten possibly useful targets for future research are formulated: 1. An increase in the comparability of research data; 2. Comparisons of therapeutic alternatives; 3. Identification of psychosocial high-risk patients; 4. Studies on psychotherapeutic interventions; 5. Expanded of the knowledge about preventive work; 6. Searches for new possibilities for widening communication by the treating team; 7. Better understanding of ethical restrictions to surgery; 8. Exploration of psychosocial factors with potentially etiologic importance; 9. Methods for using qualitative approaches to research; 10. Creation of a community of researchers.


Chitinase gene expression during mycoparasitic interaction of Trichoderma harzianum with its host.
For monitoring chitinase expression during mycoparasitism of Trichoderma harzianum in situ, we constructed strains containing fusions of green fluorescent protein (GFP) to the 5'-regulatory sequences of the T. harzianum nag1 (N-acetyl-beta-d-glucosaminidase-encoding) and ech42 (42-kDa endochitinase-encoding) genes. Confronting these strains with Rhizoctonia solani led to induction of gene expression before (ech42) or after (nag1) physical contact. A 12-kDa cut-off membrane separating the two fungi abolished ech42 expression, indicating that macromolecules are involved in its precontact activation. No ech42 expression was triggered by culture filtrates of R. solani or by placing T. harzianum onto plates previously colonized by R. solani. Instead, high expression occurred upon incubation of T. harzianum with the supernatant of R. solani cell walls digested with culture filtrates or purified endochitinase 42 (CHIT42, encoded by ech42) from T. harzianum. The chitinase inhibitor allosamidin blocked ech42 expression and reduced inhibition of R. solani growth during confrontation. The results indicate that ech42 is expressed before contact of T. harzianum with R. solani and its induction is triggered by soluble chitooligosaccharides produced by constitutive activity of CHIT42 and/or other chitinolytic enzymes.


Deploying Machine Learning Techniques for Human Emotion Detection.
Emotion recognition is one of the trending research fields. It is involved in several applications. Its most interesting applications include robotic vision and interactive robotic communication. Human emotions can be detected using both speech and visual modalities. Facial expressions can be considered as ideal means for detecting the persons' emotions. This paper presents a real-time approach for implementing emotion detection and deploying it in the robotic vision applications. The proposed approach consists of four phases: preprocessing, key point generation, key point selection and angular encoding, and classification. The main idea is to generate key points using MediaPipe face mesh algorithm, which is based on real-time deep learning. In addition, the generated key points are encoded using a sequence of carefully designed mesh generator and angular encoding modules. Furthermore, feature decomposition is performed using Principal Component Analysis (PCA). This phase is deployed to enhance the accuracy of emotion detection. Finally, the decomposed features are enrolled into a Machine Learning (ML) technique that depends on a Support Vector Machine (SVM), k-Nearest Neighbor (KNN), Naïve Bayes (NB), Logistic Regression (LR), or Random Forest (RF) classifier. Moreover, we deploy a Multilayer Perceptron (MLP) as an efficient deep neural network technique. The presented techniques are evaluated on different datasets with different evaluation metrics. The simulation results reveal that they achieve a superior performance with a human emotion detection accuracy of 97%, which ensures superiority among the efforts in this field.


Interesting Patchy Alopecia.
Patchy alopecias of the scalp are frequently seen in clinical practice. We report a young man who presented with progressive patchy alopecia of the scalp, which was finally diagnosed to be due to tuberculoid leprosy. Progression of alopecia was stopped after anti-leprosy treatment was instituted. Despite high prevalence of leprosy in our country, scalp affection due to leprosy is extremely rare but important to recognize.


Carrot AOX2a Transcript Profile Responds to Growth and Chilling Exposure.
Alternative oxidase (AOX) is a key enzyme of the alternative respiration, known to be involved in plant development and in response to various stresses. To verify the role of DcAOX1 and DcAOX2a genes in carrot tap root growth and in response to cold stress, their expression was analyzed in two experiments: during root growth for 13 weeks and in response to a cold challenge trial of 7 days, in both cases using different carrot cultivars. Carrot root growth is initially characterized by an increase in length, followed by a strong increase in weight. DcAOX2a presented the highest expression levels during the initial stages of root growth for all cultivars, but DcAOX1 showed no particular trend in expression. Cold stress had a negative impact on root growth, and generally up-regulated DcAOX2a with no consistent effect on DcAOX1. The identification of cis-acting regulatory elements (CAREs) located at the promoters of both genes showed putative sequences involved in cold stress responsiveness, as well as growth. However, DcAOX2a promoter presented more CAREs related to hormonal pathways, including abscisic acid and gibberellins synthesis, than DcAOX1. These results point to a dual role of DcAOX2a on carrot tap root secondary growth and cold stress response.


Radiographic signs in the temporomandibular joint in Reiter's disease.
To investigate whether involvement of the temporomandibular joint (TMJ) can occur in men with Reiter's disease (RD). Forty-nine men with RD and 49 individually matched (gender, age and dentition type) controls with no known general joint disease were screened for findings in the TMJ by panoramic tomography. Duration of subjective symptoms (e.g., pain) in the masticatory system correlated with duration of RD (P = .05). In the RD group, severity of clinical signs of symptoms correlated with the progressive form of RD (P = .01), number of affected joints (P = .0001), and involvement of the cervical (P = .0001) and lumbar spine (P = .05). Patients with RD more frequently had radiographic findings (33%) in the condyle of the TMJ than did controls (10%) (P = .002). The most characteristic radiographic sign in the condyle in the RD group was unilateral erosion (12%). Patients with RD often have erosion causing pain and dysfunction in the TMJ. Potential masticatory system problems for such patients should be brought to the attention of dentists and physicians.


Three mixed venous saturation catheters in patients with circulatory shock and respiratory failure.
Thirty-one critically ill patients with acute respiratory failure and circulatory shock were divided into three groups. Group 1 included 11 patients with an inserted mixed venous saturation (SvO2) catheter using three-reference wavelengths and characterized by one transmitting and one detecting fiberoptic filament (Oximetrix opticath catheter); group 2 included eight patients with an inserted SvO2 catheter using two-reference wavelengths and characterized by one transmitting and one detecting fiberoptic filament; (Edwards sat-one catheter); group 3 included 12 patients with an inserted SvO2 catheter using two-reference wavelengths and characterized by one transmitting and two detecting fiberoptic filaments. Once calibration procedures were performed, SvO2 measured by the catheter and by an hemoximeter OSM 3 (reference value) were compared following each therapeutic intervention. Over a period of 1.5 to 6 hours during which the hematocrit value remained unchanged, 119 measurements were obtained in group 1, 91 in group 2 and 181 in group 3. The dispersion of SvO2 values was much more pronounced with the two-reference wavelength systems using either one or two detecting fiber optic filaments, and the correlation coefficient was significantly higher with the three-reference wavelength system (r = 0.970 for the Oximetrix catheter vs r = 0.855 for the Edwards catheter and r = 0.826 for the Spectramed catheter, p less than 0.001). After 24 hours, the spontaneous drifts in the two-reference wavelength systems, using either one or two detecting fiber optic filaments (expressed as the SvO2 value measured by the catheter minus the reference SvO2 value) were significantly higher than the spontaneous drift in the three-reference wavelength system (9.3 +/- 7 percent for the Edwards catheter and +/- 6 +/- 4.1 percent for the Spectramed catheter vs 3.3 +/- 3.1 percent for the Oximetrix catheter, p less than 0.05). This study shows that a three-wavelength system is more accurate than a two-wavelength system for measuring acute changes in SvO2. The addition of a second detecting fiber optic filament does not seem to improve the accuracy of the system when SvO2 changes occur in conditions of stable hematocrit.


Intrabodies: Turning the immune system inside out for new discovery tools and therapeutics.
Extract: The human immune system has evolved over millennia to effectively deal with a huge diversity of threats to the integrity of the body. Antibodies, which are the principal agents of the humoral immune system, are masterpieces of evolutionary engineering, combining precise discrimination of target molecules or structures with potent binding capacities. The function of an alien molecule can either be blocked directly by an antibody binding it, or the antibody can recruit effector functions from the immune system to bring about the neutralization, destruction, or removal of the molecule. The potential value of antibodies is nowhere more evident than in the production of new medicines. Technological developments have allowed for the isolation and large scale production of single antibody molecules that can target disease-relevant molecules or structures either in the body fluids or on the surface of cells, resulting in highly precise and potent therapeutic outcomes and, as a result, antibodies currently form the fastest growing group of new drugs being developed and brought to market.


Pediatric visceral leishmaniasis in Western Sicily, Italy: a retrospective analysis of 111 cases.
The clinical and epidemiological characteristics of 111 consecutive cases of visceral leishmaniasis identified from 1980 to 2000 in a Sicilian pediatric hospital were analyzed retrospectively. The mean age of the patients was 1.7 years. All children were HIV negative, but 15% were severely malnourished. Fever and splenomegaly were present in all cases and hepatomegaly in 101 (90.1%) cases. Thrombocytopenia and anemia were both observed in 78 (70.2%) cases and leukopenia in 47 (42.3%) cases. A bone marrow aspirate was obtained in all cases; Leishmania amastigotes were detected in 89 (80.2%) cases. Initial treatment consisted of meglumine antimoniate in 99 (89.2%) patients and amphotericin B in 12 (10.8%) patients. Only two children treated with meglumine antimoniate relapsed. The findings highlight the differences between the cases of visceral leishmaniasis observed in the Mediterranean basin and those observed in other regions. The use of the term "Mediterranean visceral leishmaniasis", rather than the term "kala-azar", is proposed for cases observed in the Mediterranean area.


Performance evaluation of the Precision PCx point-of-care blood glucose analyzer using discriminant ratio methodology.
Point-of-care glucose testing needs to be integrated into a laboratory information system to provide continuous care. Selecting a particular glucose monitoring system is based on both analytical performance and on user's preference. We evaluated accuracy, performance and regulatory compliance of the Precision PCx glucose analyzer (Abbott), with automatic download into a central station, for remote quality control (QC) management and automatic upgrading. We used the discriminant ratio (DR) methodology, which determines the DR of a test (e.g. the ratio between the underlying SD and the within-subject SD), and compares it to that of another test allegedly measuring the same parameter. Accuracy was evaluated by Clarke's error grid method. Seven hundred and ninety four blood samples were taken from 22 diabetic patients, combined with two capillary blood samples: one for analysis by reference method and the second for PCx analysis. Linear regression analysis revealed, over a 2.1 to 26.9 mmol/l glucose concentration range, a correlation coefficient of 0.963, an intercept of 0.7 mmol/l and a slope of 0.851. Mean difference between meter-generated results and the reference method was -7.1+/-10.8%. Between-run imprecision for PCx using Abbott's controls at low and mid-low concentrations was 5.4 and 3.8%, respectively. Clarke's error grid did not show any clinical impact related to difference between methods. DRs were of similar magnitude using both methods. Nursing staff found PCx easy for everyday use. Our data show that PCx results agree with those obtained with the reference method, as shown by lack of significant difference in DRs, and by excellent correlation.


Metabolites of organophosphorous insecticides in urine specimens from inhabitants of a residential area.
The most frequently used pesticide in U.S. homes, as well as in schools and day care centers, is chlorpyrifos. In 1998, this insecticide was detected in household dust from the former U.S. Forces housing estates in Frankfurt am Main, Germany, resulting from its earlier use up to 1993, i.e., at least 4 years ago. This led to great concern in the new inhabitants. To investigate their internal exposure to the substance, they were offered the opportunity of taking part in biomonitoring examinations. Children playing on the floor were assumed to be especially at risk due to increased exposure to chlorpyrifos via oral or dermal intake. A total of 1146 inhabitants took part in this voluntary investigation. All of them stated that they had never used chlorpyrifos in their homes. Spot urine samples of the study participants were analyzed for six metabolites of organophosphorous insecticides [dimethylphosphate (DMP), diethylphosphate (DEP), dimethylthiophosphate (DMTP), diethylthiophosphate (DETP), dimethyldithiophosphate (DMDTP), and diethyldithiophosphate (DEDTP)] using a very sensitive gas chromatographic method with mass-selective detection and a limit of detection of 1 microg/L. No evidence was found of increased internal exposure due to former chlorpyrifos application in these homes (>4 years ago), either in children or in adults. The median values and 95th percentiles of the urinary metabolite concentrations in 484 adults were (microg/g creatinine): DMP, 15.5 and 102.5; DMTP, 13.5 and 125.8; DMDTP, <1 and 13.1; DEP, 2.1 and 11.6; DETP, <1 and 6.4; DEDTP, both <1. The urinary metabolite concentrations in children <6 years of age were higher; this was caused mainly by lower creatinine concentrations. To conclude, no increase in internal exposure due to former indoor application of chlorpyrifos could be found, and the reference values published for internal organophosphate exposure in adults in Germany were confirmed. However, as shown in other environmental studies, the urinary excretion of organophosphorous metabolites exceeds dietary intake several fold; this has been estimated from the data in various duplicate dietary studies. This observation calls for further investigation.


[Prevention of prematurity].
Premature delivery is defined as birth between 22 and 37 weeks of pregnancy. Perinatal mortality and morbidity and their sequellae are strongly linked to gestational age. Minimum prematurity is around 3% of births. Medical risks of premature birth should be detected outside of pregnancy (uterine) or during pregnancy, at the first outpatient visit, the critical moment for establishing factors of risk. Preventive measures include awakening women to their responsibility, before and during pregnancy, and suppressing toxic agents (tobacco and alcohol). Treatment of medical causes of preterm birth is more effective if accompanied by measures acting on the environment, such as rest adapted to fatigue, improved environmental conditions, decentralisation and local situation of medical follow-up and social assistance, hospitalisation at home, telesurveillance and, in severe cases, total hospital rest (for which alternatives such as family hotels should be sought). Every element of the existing structures should be used complementarily.


What to do with screening for distress scores? Integrating descriptive data into clinical practice.
Implementation of routine Screening for Distress constitutes a major change in cancer care, with the aim of achieving person-centered care. Using a cross-sectional descriptive design within a University Tertiary Care Hospital setting, 911 patients from all cancer sites were screened at the time of their first meeting with a nurse navigator who administered a paper questionnaire that included: the Distress Thermometer (DT), the Canadian Problem Checklist (CPC), and the Edmonton Symptom Assessment System (ESAS). Results showed a mean score of 3.9 on the DT. Fears/worries, coping with the disease, and sleep were the most common problems reported on the CPC. Tiredness was the most prevalent symptom on the ESAS. A final regression model that included anxiety, the total number of problems on the CPC, well-being, and tiredness accounted for almost 50% of the variance of distress. A cutoff score of 5 on the DT together with a cutoff of 5 on the ESAS items represents the best combination of specificity and sensitivity to orient patients on the basis of their reported distress. These descriptive data will provide valuable feedback to answer practical questions for the purpose of effectively implementing and managing routine screening in cancer care.


Assessing muscle compliance in stroke with the Myotonometer.
This study explores changes of the intrinsic biomechanical property in the biceps brachii muscle after a hemispheric stroke using the Myotonometry technique. Nineteen subjects with chronic hemiplegia participated in the study. Myotonometer was used to measure tissue displacement when compression force was applied at 8 levels from 2.45N to 19.6N. Muscle displacement and compliance were determined and averaged over multiple trials. Statistical analysis indicated a significant decrease in muscle displacement and compliance in the spastic muscles compared with the contralateral side (muscle displacements: spastic: 4.51 (0.31) mm, contralateral: 5.74 (0.37) mm, p<0.005; compliance: spastic: 0.17 (0.011) mm/N, contralateral: 0.22 (0.014) mm/N, p<0.005). Correlation analysis, however, did not show any association between clinical assessments and myotonometric measurement (p>0.1). Alterations of muscle compliance in the spastic side reflect changes in the contractile or intrinsic mechanical properties after a stroke. Findings of the study have demonstrated high sensitivity and effectiveness of the Myotonometer in assessing muscle compliance changes.


Local Application of Isogenic Adipose-Derived Stem Cells Restores Bone Healing Capacity in a Type 2 Diabetes Model.
Bone regeneration is typically a reliable process without scar formation. The endocrine disease type 2 diabetes prolongs and impairs this healing process. In a previous work, we showed that angiogenesis and osteogenesis-essential steps of bone regeneration-are deteriorated, accompanied by reduced proliferation in type 2 diabetic bone regeneration. The aim of the study was to improve these mechanisms by local application of adipose-derived stem cells (ASCs) and facilitate bone regeneration in impaired diabetic bone regeneration. The availability of ASCs in great numbers and the relative ease of harvest offers unique advantages over other mesenchymal stem cell entities. A previously described unicortical tibial defect model was utilized in diabetic mice (Lepr(db-/-)). Isogenic mouse adipose-derived stem cells (mASCs)(db-/db-) were harvested, transfected with a green fluorescent protein vector, and isografted into tibial defects (150,000 living cells per defect). Alternatively, control groups were treated with Dulbecco's modified Eagle's medium or mASCs(WT). In addition, wild-type mice were identically treated. By means of immunohistochemistry, proteins specific for angiogenesis, cell proliferation, cell differentiation, and bone formation were analyzed at early (3 days) and late (7 days) stages of bone regeneration. Additionally, histomorphometry was performed to examine bone formation rate and remodeling. Histomorphometry revealed significantly increased bone formation in mASC(db-/db-)-treated diabetic mice as compared with the respective control groups. Furthermore, locally applied mASCs(db-/db-) significantly enhanced neovascularization and osteogenic differentiation. Moreover, bone remodeling was upregulated in stem cell treatment groups. Local application of mACSs can restore impaired diabetic bone regeneration and may represent a therapeutic option for the future. This study showed that stem cells obtained from fat pads of type 2 diabetic mice are capable of reconstituting impaired bone regeneration in type 2 diabetes. These multipotent stem cells promote both angiogenesis and osteogenesis in type 2 diabetic bony defects. These data might prove to have great clinical implications for bony defects in the ever-increasing type 2 diabetic patient population.


Mitochondrial genome sequences and molecular evolution of the Irish potato famine pathogen, Phytophthora infestans.
The mitochondrial genomes of haplotypes of the Irish potato famine pathogen, Phytophthora infestans, were sequenced. The genome sizes were 37,922, 39,870 and 39,840 bp for the type Ia, IIa and IIb mitochondrial DNA (mtDNA) haplotypes, respectively. The mitochondrial genome size for the type Ib haplotype, previously sequenced by others, was 37,957 bp. More than 90% of the genome contained coding regions. The GC content was 22.3%. A total of 18 genes involved in electron transport, 2 RNA-encoding genes, 16 ribosomal protein genes and 25 transfer RNA genes were coded on both strands with a conserved arrangement among the haplotypes. The type I haplotypes contained six unique open reading frames (ORFs) of unknown function while the type II haplotypes contained 13 ORFs of unknown function. Polymorphisms were observed in both coding and non-coding regions although the highest variation was in non-coding regions. The type I haplotypes (Ia and Ib) differed by only 14 polymorphic sites, whereas the type II haplotypes (IIa and IIb) differed by 50 polymorphic sites. The largest number (152) of polymorphic sites was found between the type IIb and Ia haplotypes. A large spacer flanked by the genes coding for tRNA-Tyr (trnY) and the small subunit RNA (rns) contained the largest number of polymorphic sites and corresponds to the region where a large indel that differentiates type II from type I haplotypes is located. The size of this region was 785, 2,666 and 2,670 bp in type Ia, IIa and IIb haplotypes, respectively. Among the four haplotypes, 81 mutations were identified. Phylogenetic and coalescent analysis revealed that although the type I and II haplotypes shared a common ancestor, they clearly formed two independent lineages that evolved independently. The type II haplotypes diverged earlier than the type I haplotypes. Thus our data do not support the previous hypothesis that the type II lineages evolved from the type I lineages. The type I haplotypes diverged more recently and the mutations associated with the evolution of the Ia and Ib types were identified.


Laparoscopic ovariectomy in two horses with granulosa cell tumors.
Two mares were admitted for ovariectomy of unilateral granulosa cell tumors. Both mares were ovariectomized (1 unilateral and 1 bilateral) by use of a ventral abdominal laparoscopic technique. This approach required tilting the operative table 30 degrees to elevate the pelvis and to allow observation of the ovaries. Using a single laparoscopic portal and 3 to 4 instrument portals, a triangulation technique was used. The ovarian pedicles were isolated and secured via loop ligation. The ovaries then were divided from the ligated pedicle and placed within specimen bags for extraction. The specimen bags then were removed through a ventral midline celiotomy. Using this technique, it was determined that granulosa cell tumors or ovaries of up to 20 cm in diameter can be removed. Laparoscopic ovariectomy provided a means to provide tension-free dissection and ligation of the ovarian pedicle. In comparison to conventional techniques, this may improve suture security and reduce complications related to excessive pedicle tension. Improved observation during surgery, less pedicle tension, and minimal invasiveness made laparoscopic ovariectomy of these 2 mares advantageous.


Consistency, comprehensiveness, and compatibility of pathway databases.
It is necessary to analyze microarray experiments together with biological information to make better biological inferences. We investigate the adequacy of current biological databases to address this need. Our results show a low level of consistency, comprehensiveness and compatibility among three popular pathway databases (KEGG, Ingenuity and Wikipathways). The level of consistency for genes in similar pathways across databases ranges from 0% to 88%. The corresponding level of consistency for interacting genes pairs is 0%-61%. These three original sources can be assumed to be reliable in the sense that the interacting gene pairs reported in them are correct because they are curated. However, the lack of concordance between these databases suggests each source has missed out many genes and interacting gene pairs. Researchers will hence find it challenging to obtain consistent pathway information out of these diverse data sources. It is therefore critical to enable them to access these sources via a consistent, comprehensive and unified pathway API. We accumulated sufficient data to create such an aggregated resource with the convenience of an API to access its information. This unified resource can be accessed at http://www.pathwayapi.com.


Comparative lateralisation patterns in the language area of human, chimpanzee, and rhesus monkey brains.
Lateralised architectural differences in radial cell column structure were detected in the planum temporale of humans but were not found in homologous regions of ape or monkey brains. This study used a new computer imaging method to quantify the architecture of thousands of cortical minicolumns. A study of Lamina III in the left hemisphere of human brains revealed a wider separation between cell columns and more non-neuronal (empty) space within cell columns compared to the right hemisphere. This asymmetry was absent in the chimpanzee brains and weakly reversed in the rhesus monkey brains. The results imply an evolution towards more clearly defined columnar structures in the left hemisphere of human brains compared to those of monkeys.


Aperture superposition dose model versus pencil beam superposition dose model for a finite size Cobalt-60 source for tomotherapy deliveries.
The finite size pencil beam (FSPB) superposition method is a commonly used dose calculation method in intensity modulated radiation therapy (IMRT). The FSPB model assumes that dose for a broad intensity modulated beam can be calculated by superposition of dose from small, pencil-like beams. However, this model is limited to point-like radiation sources and is not valid for finite size sources, such as a Cobalt-60 (Co-60) source of 2 cm diameter. In this paper, the authors present results that show the limitation of this model and propose an alternative model, namely the aperture superposition (AS) model, to calculate photon dose for intensity modulated beams arising from finite size radiation sources. The AS model is based on adding beam apertures rather than pencil beams. Each aperture is defined as a series of adjacently opened leaves of a multileaf collimator with no closed leaves in between them. The apertures are calculated using the EGSnrc Monte Carlo program. The accuracy of the AS model was tested for dose calculations of fan beams, as encountered in tomotherapy treatment plans. The results were compared with the FSPB model and GafChromic film measurements. The measurements and simulations were performed for a clinical Theratronics T780C Co-60 unit with MIMiC binary multileaf collimator mounted on it. The comparisons between the AS model and film measurements show agreement better than 1.5% in the high dose regions and 3.7% in the low dose regions. On the contrary, film measurement comparisons to the FSPB model show that the FSPB model underestimates the dose by up to 7% for small field sizes such as 2 × 2 cm(2) and 20% for larger field sizes such as 20 × 2 cm(2). The results presented in this paper indicate that the AS model provides better accuracy than the FSPB model when calculating dose for fan beams from large radiation sources. The implementation of this model to the current treatment planning systems has the scope of advancing Co-60 based IMRT and tomotherapy.


Precocious puberty and decreased melatonin secretion due to a hypothalamic hamartoma.
Hypothalamic hamartomata are benign malformations of the brain consisting of heterotopic nervous tissue, and are often associated with precocious puberty and gelastic seizures in early childhood. We report for the first time the melatonin plasma values of a girl with central precocious puberty and gelastic seizures due to a hypothalamic hamartoma. The melatonin plasma levels were low for the chronological age but appropriate for the pubertal status, making a causal relationship between lowered melatonin plasma levels and precocious puberty possible.


Fructan synthesis is inhibited by phosphate in warm-grown, but not in cold-treated, excised barley leaves.
The inhibition of fructan accumulation by phosphate was investigated in warm-grown and cold-treated barley (Hordeum vulgare) plants. Detached leaves were incubated in water or phosphate for 24 h under lighting or in darkness. Fructosyltransferase, sucrose phosphate synthase (SPS) and cytosolic fructose-1,6-bisphosphatase (FBPase) activities were subsequently analysed, as well as the content of carbohydrates, hexose-phosphates, phosphate, amino acids and protein. In warm-grown leaves, phosphate decreased fructan accumulation and total carbon in carbohydrates and did not affect protein content. Phosphate increased hexose-phosphates, phosphate and amino acids. Fructosyltransferase and FBPase activities were not affected by phosphate feeding, while SPS activity was inhibited by phosphate in incubations in both light and darkness. In cold-treated leaves, which before incubation had higher SPS activities than warm-grown leaves, phosphate had no inhibitory effect on fructan accumulation, carbohydrate content or total C in carbohydrates. The activities of SPS and FBPase were unaffected by phosphate. The results indicate that phosphate decreases fructan accumulation through an inhibition of SPS whenever this activity is not high before a rise in phosphate content.


A pharmacokinetic model of drug-drug interaction between clopidogrel and omeprazole at CYP2C19 in humans.
Clopidogrel is a thienopryridine antiplatelet agent commonly used in the management of cardiovascular diseases. Clopidogrel is metabolized by hepatic CYP2C19 and CYP2B6, therefore, co-administration of clopidogrel and CYP2C19 inhibitors can alter pharmacokinetics of clopidogrel. Omeprazole is a proton pump inhibitor used for decreasing gastric acid production. Omeprazole is known to be a potent inhibitor of CYP2C19. Thus when the drugs are simultaneously administered, clopidogrel plasma concentration levels can be increased. However, plasma levels of the active metabolite of clopidogrel can be significantly decreased, thereby, its antiplatelet activity is reduced. We aimed to develop a mathematical model describing a drug-drug interaction between clopidogrel and omeprazole in humans. Searching for pharmacokinetic interaction studies between clopidogrel and omeprazole in humans was performed in PubMed. Six studies were selected into our modeling purposes to develop 3 mathematical models (i.e. 4 studies for clopidogrel alone, 1 study for omeprazole alone and 1 study for clopidogrel-omeprazole interaction). Subsequently, concentration-time course data from the selected studies were extracted. Computer codes and simulations were performed using the Advanced Continuous Simulating Language Extreme (ACSLX) program. We successfully developed 3 mathematical models which are able to describe all of the datasets. Our clopidogrel-omeprazole pharmacokinetic interaction model with a description of competitive inhibition at CYP2C19 could successfully describe concentration-time courses from the selected datasets. Our interaction model may be useful in predicting plasma levels of clopidogrel and its active metabolite.


[Diagnosis in infants with hearing loss using auditory steady-state evoked potentials].
To investigate the correlation between the auditory steady-state response (ASSR) thresholds and the vision reinforcement audiometry (VRA) thresholds in infants with auditory neuropathy. Ten cases in control group were measured by the ASSR and VRA. Based upon the ABR, DPOAE, and impedance data, as well as the aetiology (infection of the early pregnancy, defect of oxygen in birth and jaundice after birth), the 16 cases with hearing losses were divided into three groups (I , II and III). ASSR and VRA were examined. From the analysis of ABR, DPOAE, and impedance data, the patients with the infection of early pregnancy in group I (5 cases/8 ears) had that the DPOAE were absent (5 cases/8 ears), the latency of wave I of ABR was delay and the interpeak latency of wave I - V of ABR was short (4 cases/6 ears), as well as the acoustic reflect thresholds in 500 Hz and 1000 Hz were normal (3 cases/6 ears) and high (2 cases/2 ears). They were deduced in cochlear lesion. The patients of group II with defect of oxygen in birth (5 cases/10 ears) showed that the DPOAEs were absent, the wave I of ABR was absent (3 cases/5 ears), and the interpeak latency of wave I - III of ABR was delay (2 cases/3 ears) They were deduced in auditory neuropathy (lesion from the cochlea to the brain-stem). The patients of group III had that the DPOAEs were present (6 cases/8 ears), the wave I/III/V of ABR and acoustic reflect were absent(4 cases/5 ears), and the interpeak latency of wave I -V of ABR was delay (2 cases/3 ears) who were deduced in auditory neuropathy(from the brain-stem to the subcortical lesion). Our results showed that the correlation coefficient-ranges between the ASSR thresholds and the VRA thresholds were the 0. 95 - 0. 98 in group I, the 0. 72 - 0. 84 in group II, and the 0.43 - 0.64 in group III. Comparison of the mean threshold-differences between the ASSR VRA thresholds for group I, group II, and group III for each frequency revealed significant difference (F test, P < 0.05, P < 0.01, P < 0.01, P < 0.05, P < 0.05). The correlation technique between the ASSR thresholds and the VRA thresholds could provide the auditory neuropathy diagnosis and differential diagnosis in infants.


K+ extraction induced phase evolution of KFeO2.
Orthorhombic KFeO2 has a unique structure where K+ cations can migrate inside the Fe-O skeleton, thus making it a promising material for heterogeneous catalysis and electrochemical energy storage devices. However, KFeO2 is sensitive to conditions such as moisture and carbon dioxide, which would trigger severe phase evolution and consequently deteriorate the performance. In this work, we investigated the phase evolution using freshly prepared KFeO2 and KFeO2 after exposure to ambient air and after immersion in water, respectively. We found that the phase evolution of KFeO2 was composed of K-redistribution and phase transition, both of which originated from K+ extraction. We observed that K+ cations were extracted after exposing KFeO2 to ambient air, resulting in the formation of K2CO3·1.5 H2O outside KFeO2 and lattice expansion inside KFeO2. We also observed that water molecules were crucial to K+ extraction when calculating the function between potassium and the adjacent oxygen atoms via ab initio molecular dynamics simulations. Moreover, we successfully reinserted K+ cations into lattice expanded KFeO2 by high-temperature calcination at 900 °C; such a reversible extraction-insertion process would have great potential for application in catalyst reactivation and rechargeable high-temperature batteries.


Endoscopic surgery combining chemotherapy for vaginal yolk-sac tumor: a case report.
To report and explore the effectiveness of the endoscopic surgery combining cisplatin, etoposide, and bleomycin (PEB) chemotherapy in treating vaginal yolk-sac tumor. The clinical case of vaginal yolk-sac tumor in a young girl was analyzed. Hysteroscopy equipment was used to inspect and remove the majority of the tumor tissue, followed by six cycles of PEB chemotherapy. Hysteroscopy equipment was used again to exam the vagina and remove of the tumor pedicle for biopsy, which revealed no tumor cells after two cycles of chemotherapy. The patient remained disease free on follow up for a year. The use hysteroscopy equipment to exam vagina can diagnose early vaginal yolk-sac tumor and cytoreductive surgery which can preserve fertility can then be performed. Cytoreductive surgery may also be able to reduce the cycles of the chemotherapy to reduce the side effects and the risks of chemotherapy.


Photoinduced processes in hydrogen bonded system: photodissociation of imidazole clusters.
The photodissociation of imidazole in hydrogen bonded clusters has been studied at photodissociation wavelengths 243 and 193 nm. Imidazole clusters of different mean cluster sizes n approximately 3 and 6 have been produced in expansions with He and Ar carrier gases, and the mean cluster sizes were determined by mass spectrometric and crossed beam scattering experiments. Simultaneously, the (C(3)N(2)H(4))(n) clusters were studied by ab initio calculations for n up to 4 molecules, confirming the hydrogen bond N-H...N motif in the clusters. The measured H-fragment kinetic energy distribution spectra exhibit a bimodal character similar to the KEDs found for the bare molecule. (1) At 243 nm the fast H-atoms originate from the direct dissociation process on the repulsive pi sigma* state, and the slow component results from the dynamics populating the vibrationally hot ground state via an S(1)/S(0) conical intersection. In the clusters the contribution of the slow component increases with the cluster size. The slow component is also dominant at the shorter wavelength of 193 nm, where the dynamics starts with the excitation of pi pi* state. It is shown that the slow component in our experiment is a product of subsequent two-photon absorption. We have proposed different mechanisms how the observed enhanced internal conversion can be rationalized. The increased stability with respect to the H-fragment dissociation in clusters can be caused either by hydrogen transfer in the N-H...N bond or by closing the pi sigma* dissociation channel as in the case of pyrrole clusters.


Extrafoveal vitreous traction associated with branch retinal vein occlusion.
To present patients with extrafoveal vitreous traction associated with diffuse macular edema secondary to branch retinal vein occlusion (BRVO). A retrospective study on consecutive patients with BRVO using optical coherence tomography (OCT)-2000 is reported. Excluded were patients with eyes with other retinopathies that could affect analysis and eyes following pars plana vitrectomy (PPV). A control group of 30 age-matched patients allowed for normal OCT 6-mm macular maps. Vitreous traction was detected in 4 of 17 eyes (17 patients, 23.5%). The traction was located extrafoveally in each of the 4 eyes. In one eye there was a simultaneous central macular traction. Only the manually controlled OCT-Line group program, but not the central automatic 6-radial lines program, confirmed vitreous traction in each case. Retinal edema (n = 4) and serous retinal detachment (n = 2) underlining the traction sites were in continuum with the central macula in 3 eyes, presenting either as diffuse macular edema or combined with serous macular detachment, respectively. In one eye the edema subsided after PPV, and visual acuity stabilized during 7 postoperative months of follow-up. Macular thickness and visual acuity of another eye improved temporarily in repeated conventional treatments after PPV was discarded, but its fovea markedly atrophied 12 months later. Extrafoveal vitreous traction may be apparent following BRVO. Further studies are required to assess whether such traction membranes may play a role in the persistence of diffuse macular edema.


Faulty old ideas about translational regulation paved the way for current confusion about how microRNAs function.
Despite a recent surge of reports about how microRNAs might regulate translation, the question has not been answered. The proposed mechanisms contradict one another, and none is supported by strong evidence. This review explains some deficiencies in the experiments with microRNAs. Some of the problems are traceable to bad habits carried over from older studies of translational regulation, here illustrated by discussing two models involving mRNA binding proteins. One widely-accepted model, called into doubt by recent findings, is the maskin hypothesis for translational repression of cyclin B1 in Xenopus oocytes. The second dubious model postulates repression of translation of ceruloplasmin by mRNA binding proteins. A big fault in the latter case is reconstructing the imagined mechanism before looking carefully at the real thing--a criticism that applies also to studies with microRNAs. Experiments with microRNAs often employ internal ribosome entry sequences (IRESs) as tools, necessitating brief discussion of that topic. A sensitive new assay reveals that many putative IRESs promote expression of downstream cistrons via splicing rather than internal initiation of translation. Recent claims about the biological importance of IRES-binding proteins--including suggestions that these proteins might serve as targets for cancer therapy--are not supported by any meaningful evidence. The bottom line is that older studies of mRNA binding proteins and putative IRESs have created a confusing picture of translational regulation which is not helpful when trying to understand how microRNAs might work. The obvious biological importance of microRNAs makes it essential to understand how they do what they do. Fresh ways of thinking and looking are needed.


Breadth and Specificity in Pleiotropic Protein Kinase A Activity and Environmental Responses.
Protein Kinase A (PKA) is an essential kinase that is conserved across eukaryotes and plays fundamental roles in a wide range of organismal processes, including growth control, learning and memory, cardiovascular health, and development. PKA mediates these responses through the direct phosphorylation of hundreds of proteins-however, which proteins are phosphorylated can vary widely across cell types and environmental cues, even within the same organism. A major question is how cells enact specificity and precision in PKA activity to mount the proper response, especially during environmental changes in which only a subset of PKA-controlled processes must respond. Research over the years has uncovered multiple strategies that cells use to modulate PKA activity and specificity. This review highlights recent advances in our understanding of PKA signaling control including subcellular targeting, phase separation, feedback control, and standing waves of allosteric regulation. We discuss how the complex inputs and outputs to the PKA network simultaneously pose challenges and solutions in signaling integration and insulation. PKA serves as a model for how the same regulatory factors can serve broad pleiotropic functions but maintain specificity in localized control.


Combining enhanced biomass density with reduced lignin level for improved forage quality.
To generate a forage crop with increased biomass density that retains forage quality, we have genetically transformed lines of alfalfa (Medicago sativa L.) expressing antisense constructs targeting two different lignin pathway biosynthetic genes with a construct for down-regulation of a WRKY family transcription factor that acts as a repressor of secondary cell wall formation in pith tissues. Plants with low-level expression of the WRKY dominant repressor construct produced lignified cell walls in pith tissues and exhibited enhanced biomass and biomass density, with an increase in total sugars in the cell wall fraction; however, lines with high expression of the WRKY dominant repressor construct exhibited a very different phenotype, with loss of interfascicular fibres associated with repression of the NST1 transcription factor. This latter phenotype was not observed in transgenic lines in which the WRKY transcription factor was down-regulated by RNA interference. Enhanced and/or ectopic deposition of secondary cell walls was also seen in corn and switchgrass expressing WRKY dominant repressor constructs, with enhanced biomass in corn but reduced biomass in switchgrass. Neutral detergent fibre digestibility was not impacted by WRKY expression in corn. Cell walls from WRKY-DR-expressing alfalfa plants with enhanced secondary cell wall formation exhibited increased sugar release efficiency, and WRKY dominant repressor expression further increased sugar release in alfalfa down-regulated in the COMT, but not the HCT, genes of lignin biosynthesis. These results suggest that significant enhancements in forage biomass and quality can be achieved through engineering WRKY transcription factors in both monocots and dicots.


Comparison of the effect of propofol and N-acetyl cysteine in preventing ischaemia-reperfusion injury.
The aim of this study was to compare the effects of propofol and N-acetyl cysteine (NAC) on tourniquet-induced ischaemia-reperfusion injury by determining malonyldialdehyde, ischaemia-modified albumin, lactate, blood gas and haemodynamic levels in arthroscopic knee surgery. Sixty ASA I or II patients were randomized into three groups. Intrathecal anaesthesia was administered using 0.5% heavy bupivacaine in all patients. In group P, propofol was administered in a 0.2 mg kg(-1) bolus, followed by infusion at a rate of 2 mg kg(-1) h(-1); in group NAC, NAC was administered as an infusion at a rate of 5 mg kg(-1) h(-1), and, in group C (the control group), an equal volume of isotonic saline was administered to patients until 30 min after reperfusion. Blood samplings were obtained immediately before intrathecal anaesthesia (t1), 1 min before tourniquet release (t2), 5 min after tourniquet release (t3) and 30 min after tourniquet release (t4). Plasma malonyldialdehyde, ischaemia-modified albumin and lactate levels increased significantly in group C at t3 and t4 compared with the baseline values. Plasma concentrations of malonyldialdehyde, ischaemia-modified albumin and lactate in groups P and NAC were significantly lower than those in group C at t3 and t4. In blood gas analyses, pH, HCO3 and base excess were found to be significantly lower at t3 and t4 compared with t1 and t2 in group C. Comparisons between groups P and NAC revealed no significant differences. Small-dose infusions of both propofol and NAC appear to provide similar protection against ischaemia-reperfusion injury in arthroscopic knee surgery.