Right ventricular outflow tract landing zone perimeter / circularised diameter - new imaging standards in pulmonary valve replacement reporting.
Right ventricular outflow tract intervention spans transcatheter, surgical, or hybrid pulmonary valve replacement methodologies. Standardised pre-procedure workup includes cardiac MRI to identify an intended valve site (landing zone). Our institutional practice includes measurement of the right ventricular outflow tract perimeter (circumference) of this site in end-systole. Our primary aim was to compare patients by their perimeter values to the palliative interventions performed (transcatheter versus surgical/hybrid methodologies). Retrospective review of patients undergoing pulmonary valve replacement from January 2017 to 2021. We performed perimeter measurements at the intended valve site on advanced imaging; the outcomes of interventions were outlined via descriptive and statistical analyses. A total of 37 patients underwent pulmonary valve replacement that met study criteria - 21 transcatheter, 7 surgical, and 9 hybrid. Median age at intervention was 26 years (range 8-70). The mean end-systolic perimeter of the transcatheter cohort was 88.9 ± 8.7 mm and in the surgical/hybrid cohort measured 106.6 ± 7.5 mm. For the transcatheter cohort, the median "circularised" diameter derived from the perimeter measurement (divided by π) was 27.7 mm (range 24.3-32.4). Notably, this correlated (r = 0.93, p < 0.01) with the median diameter of the narrowest region during actual transcatheter right ventricular outflow tract balloon sizing (lateral imaging) of 27.1 mm (range 23.2-30.1). Right ventricular outflow tract perimeter measurement to determine circularised diameter is useful in planning pulmonary valve replacement in terms of candidacy of transcatheter versus the need for a surgical/hybrid approach. The circularised diameter correlates with transcatheter right ventricular outflow tract balloon sizing.


Security enhanced EMV-based mobile payment protocol.
Near field communication has enabled customers to put their credit cards into a smartphone and use the phone for credit card transaction. But EMV contactless payment allows unauthorized readers to access credit cards. Besides, in offline transaction, a merchant's reader cannot verify whether a card has been revoked. Therefore, we propose an EMV-compatible payment protocol to mitigate the transaction risk. And our modifications to the EMV standard are transparent to merchants and users. We also encrypt the communications between a card and a reader to prevent eavesdropping on sensitive data. The protocol is able to resist impersonation attacks and to avoid the security threats in EMV. In offline transactions, our scheme requires a user to apply for a temporary offline certificate in advance. With the certificate, banks no longer need to lower customer's credits for risk control, and users can have online-equivalent credits in offline transactions.


Evaluation of serological tests using A60 antigen for diagnosis of tuberculosis.
Identification of acid-fast bacilli (AFB) in sputum or tissue samples is among definite diagnostic methods of tuberculosis. However, this method of diagnosis is restricted by certain limitations. Serologic diagnosis of tuberculosis (TB) has been used for a long time. The aim of this study was to determine the sensitivity and, specificity of Antigen 60 (A60) IgG, IgA, IgM test results in TB diagnosis. Mycobacterial A60-based ELISA was used to measure specific IgA, IgM and IgG antibodies in the sera of 127 adult TB patients (consisted of 74 pulmonary and 53 extra-pulmonary cases), and 95 controls (46 healthy volunteers and 49 patients with various acute or chronic diseases other than tuberculosis). Data from A60 IgG-based ELISA, chest radiography, AFB culture and pathologic evaluation for AFB were obtained .The cutoff value of A60 IgG, IgA and IgM were chosen according to a receiver operating characteristic (ROC) analysis. The sensitivity, specificity and positive likelihood ratio were determined. The mean levels of IgG, IgA and IgM were significantly higher in patients with pulmonary tuberculosis when compared with control groups. Sensitivity of IgG test was 54.3 %, while the specificity was 84.2%. The IgA test showed a sensitivity of 70.1% with a specificity of 80 %. Combination of the IgG and IgA tests showed a total sensitivity of 45.7 % and a specificity of 94.7% and the positive likelihood ratio of 8.62. Chosen cutoff values of IgG, IgA, and IgM sets were 285,265 and 0.9 ELISA units respectively. Our study results showed a good specificity (94.7%) and a reasonable positive likelihood ratio (8.62) of the test when combined IgA and IgG with new cutoff points were considered on diagnosis of tuberculosis in adult patients. Combined use of both IgG and IgA tests results allows an increased accuracy in diagnostic of tuberculosis.


Selenoether macrocyclic chemistry--syntheses and properties of new potentially tridentate and hexadentate Se/O-donor macrocycles.
Treatment of O(CH2CH2SeCN)2 with Na in NH3(l), followed by dropwise addition of a thf solution of o-C6H4(CH2Br)2 at -40 degrees C leads to formation of three mixed Se/O-donor macrocycles which are separable by column chromatography, the [1 + 1] species L1, the [2 + 2] ring L2 and the [3 + 3] ring L3, of which L2 is by far the major species. Using the same starting materials, but in a high dilution cyclisation at room temperature with NaBH4 in thf/EtOH gives exclusively the [1 + 1] ring, L1. The saturated ring Se/O-donor macrocycles, L4 and L5 are obtained by simultaneous dropwise addition of solutions of O(CH2CH2SeCN)2 and Br(CH2)3Br to NaBH4 suspended in thf/EtOH. The small tridentate Se2O-donor ring, L4, is again the dominant product under these conditions (71%), although the more flexible precursors in this reaction also give rise to the larger Se4O2-donor ring, L5, as a by-product in 8% yield. These compounds are readily separated and purified by column chromatography (ethyl acetate:hexane, 1:19). The new macrocycles have been characterised by 1H, (13)C{1H} and (77)Se{1H} NMR spectroscopy and mass spectrometry, together with crystal structures of L1 and L2. Complexes of L1 and L2 with late transition metals (Pd(II), Pt(II), Cu(I) and Ag(I)) are also described.


Association of selected variants in genes involved in cell cycle and apoptosis with bladder cancer risk in North Indian population.
Perturbations in the cell cycle and apoptotic genes have been implicated in human malignancies. Cell cycle (MDM2 and Cyclin D1) and apoptotic (Fas) genes that are differentially expressed in urinary bladder cancer (UBC) were investigated with the susceptibility to UBC in northern India. A total of 212 UBC patients and age- and sex-matched 250 controls were investigated for MDM2 G309T, Cyclin D1 G870A, and Fas A670G polymorphisms by polymerase chain reaction and restriction fragment length polymorphism. MDM2 309GG was at reduced risk for developing UBC when compared with TT genotype (p = 0.027; odds ratio, 0.55). GG genotype was also associated with reduced risk in nonmuscle invasive bladder cancer (NMIBC) and muscle invasive BC (p = 0.006 and p = 0.049). Cyclin D1 AA genotype was associated with high risk in NMIBC (intermediate risk) stage (p = 0.015; odds ratio, 4.55). MDM2-Cyclin D1 interaction revealed overall protective effect. The GG genotype of MDM2 also showed a protective effect and high recurrence-free survival in Bacillus Calmette-Guerin-treated NMIBC patients (log rank p = 0.008). MDM2 GG genotype had protective effect and MDM2T309G polymorphism had profound influence in Bacillus Calmette-Guerin-treated UBC patients in the North Indian population.


Investigation of Efficacy of Lidocaine Spray for Sedated Esophagogastroduodenoscopy in Children.
Our aim in this study is to investigate efficacy of topical lidocaine spray for sedated esophagogastroduodenoscopy (EGD) in children. The endoscopy of children aged between 3-18 years who underwent EGD in our endoscopy unit. Intravenous (IV) midazolam and ketamine were used for sedation. Prior to sedation, endoscopy nurse applied topical lidocaine 10% with pump spray at 1 mg/kg dose in group 1, and distilled water via identically scaled pump spray in group 2, in a double blinded fashion. Sedation was not applied in 24.1% of the cases in topical lidocaine spray group (LS group) and in 5.7% of the cases in distilled water spray group (DS group). Gag reflex was observed in 6.5% of cases in LS group and 33.3% of cases in DS group (p=0.024), increased oral secretion was observed in 9.3% of cases in LS group and 51.7% of cases in DS group (p=0.038), sore throat was observed in 3.7% of cases in LS group and 35.6% of cases in DS group (p=0.019) and the difference was statistically significant. The study showed that topical pharyngeal lidocaine reduces both requirement and amount of IV sedation before EGD in children and sore throat, gag reflex and decreased oral secretion increase.


Green analyzer for the measurement of total arsenic in drinking water: electrochemical reduction of arsenate to arsine and gas phase chemiluminescence with ozone.
We describe matrix-isolated, reaction chemistry based measurement of arsenic in water down to submicrograms per liter levels in a system that requires only air, water, electricity, and dilute sulfuric acid, the bulk of the latter being recycled. Gas phase chemiluminescence (GPCL) measurement of arsenic is made in an automated batch system with arsenic in situ electroreduced to arsine that is reacted with ozone to emit light. The ozone is generated from oxygen that is simultaneously anodically produced. Of 22 different electrode materials studied, graphite was chosen as the cathode. As(V) is reduced much less efficiently to AsH(3) than As(III). Prereducing all As to As(III) is difficult in the field and tedious. Oxidizing all As to As(V) is simple (e.g., with NaOCl) but greatly reduces subsequent conversion to AsH(3) and hence sensitivity. The rate of the AsH(3)-O(3) GPCL reaction and hence signal intensity increases with [O(3)]. Using oxygen to feed the ozonizer produces higher [O(3)] and substantial signal enhancement. This makes it practical to measure all arsenic as As(V). The system exhibits an LOD (S/N = 3) for total arsenic as As(V) of 0.36 microg/L (5 mL sample). Comparison of total As results in native and spiked water samples with those from inductively coupled plasma mass spectrometry (ICPMS) and other techniques show high correlation (r(2) = 0.9999) and near unity slopes.


Believing Jeny About Her Pain.
A 19-year-old woman with cancer and excruciating pain was not easily responding to morphine. Some of the staff suspected that this pain was not physical, that it was all emotional. But when the palliative care team believed the young woman's report of her pain, they were able to arrive at the right combination of medicines to treat her pain, and to relieve her intolerable suffering.


[Gene editing].
Development of the gene engineering techniques has raised worries that they will be used for construction of organism endangering humans and environment. In 1975 at the Asilomar conference, geneticists from many countries decided that genetic engineering brings more benefits than threats. In last years a new CRISPR-Cas technique emerged . It allows to make the precise changes in genomes, e.g. to inactivate particular genes or to replace mutated genes by their wild-type alleles. Inactivation in mice of genes corresponding to those whose mutations cause the genetic diseases in man allows to get model organisms for studying the etiology of given disease and for working out the methods of its curing. This technique can be applied for repairing genes whose mutations result in metabolic diseases and cancer. Some voices were raised that the technique can be potentially used for the "improvement" of man, what would create many ethical and social problems. Geneticists, ethicists and lawyers gathered in 2015 at the Washington conference, discussed these problems and proposed rules for their solving.


Spanish validation endorsement of SDM-Q-9, a new approach.
The Shared Decision Making (SDM) model allows the patient to be part of their own disease treatment and control. The translation to Spanish of a questionnaire that measures the patient perception of SDM will allow enlarging the range of its application. However, the essence of the questionnaire can be altered during its translation, which could curb the appreciation of the question and what the question originally asked for. The objective of this study is to evaluate the application of SDM-Q-9 in its psychometric properties, to a Spanish speaking population after its translation process. The questionnaire was given to 76 outpatients who attended a medical control at the hospital. The informed consent process was developed before the patient underwent the physician's evaluation, and the SDM-Q-9 was applied when the patient finished the medical evaluation. The reliability of the questionnaire was evaluated and its structural validity was verified by the exploratory factor analysis (EFA) and the confirmatory factor analysis (CFA). The SDM-Q-9 presented reliability and validity according to the following indicators. The internal consistency, measured by Cronbach's alpha, was 0.839 for the whole scale. The EFA showed a bi-dimensional solution, but the CFA indicated that the model with best indices of fit was the one-dimensional solution, excluding the first item. The indices used where: CFI 0.953, RMSEA (IC) 0.076 (0.000-0.134) for model 2, and CFI 0.961, RMSEA 0.071 (0.000-0.132) for model 5 are better. The questionnaire adaptation to the Latin American Spanish language has displayed reliability and validity according to the Cronbach's alpha indicators.


Effect of intestinal microflora on 2,2'-dimethyl-4-aminobiphenyl-induced carcinogenesis in F344 rats.
The effect of intestinal microflora on colon and breast carcinogenesis induced by 3,2'-dimethyl-4-aminobiphenyl (DMAB) was studied with the use of germfree and conventional F344 rats of both sexes. At 7 weeks of age, all animals except controls were given 20 weekly sc injections of DMAB in corn oil (100 mg/kg body wt/wk). Male animals were autopsied 15 weeks after the last injection, whereas female animals were autopsied 10 weeks after the last injection. Tumors were induced in the colons, duodena, breasts, ear ducts, salivary glands, and skin of conventional rats, and in the colons, breasts, ear ducts, salivary glands, and skin of germfree rats. No consistent difference was found in the incidence of tumors in the ear ducts, salivary glands, and skin between the germfree and conventional rats. None of the germfree rats showed duodenal tumors, whereas 13% of the female and 53% of the male conventional rats developed duodenal tumors. The incidence of intestinal tumors was lower in the germfree rats than in conventional animals. The mammary tumor incidence was lower in germfree female rats than in the conventional female rats than in the conventional females. DMAB induced fewer intestinal and breast tumors in germfree rats than in conventional rats.


Paraparesis associated with mild congenital kyphoscoliosis in an adult.
A 48-year-old man suffering from paraparesis had congenital kyphoscoliosis due to fused wedged vertebrae between T2 and T4. The kyphoscoliosis consisted of left convex scoliosis measuring 26 degrees and kyphosis measuring 27 degrees. On CT-myelograms and axial MR images, the dura and spinal cord were deviated anterolaterally to the concave side of the curve around its apex. The spinal cord was stuck and flattened against the posterolateral margin of the vertebral body to the base of the pedicle with the posterior subarachnoid space preserved. Anterior decompression from the concave side through a transthoracic approach resulted in a remarkable neurological improvement. The paraparesis may have been caused by compression of the spinal cord through a tethering effect due to its developmental tightness around the apical vertebra and the additional tension created by motions of the neck.


Presumed glial retinal hamartomas in Usher's syndrome.
The presence of glial hamartomas of the retina and the optic disc in retinitis pigmentosa is discussed. This association is described in a 26 year old white male with Usher's syndrome who had at the posterior pole of each eye a mass which closely resembled the mulberry-like lesions of tuberose sclerosis. Several fine blood vessels were seen on the surface of these masses. The significance of the association of these presumed hamartomas with retinitis pigmentosa is not clear. They might be the result of a focal reactive hyperplasia of the glial cells of the retina.


Overweight and obesity: a review of their relationship to metabolic syndrome, cardiovascular disease, and cancer in South America.
Socioeconomic and demographic transformations are occurring very rapidly in some areas of the world, especially in South America, and are accompanied by changes in lifestyle, dietary patterns, and the epidemiological profile of prevalent diseases. This review examines whether obesity and overweight are related to metabolic syndrome, cardiovascular disease, and cancer in South America. Research carried out in more than 6,000 cases and controls was evaluated, along with most of the available publications related to South America. In South America, obesity and risk factors for cardiovascular disease are related mainly to aging, ethnicity effects, and preventable risky lifestyle conditions. Most of the studies that found an association between cancer and obesity are from the Southern Cone, the geographic area most affected by this pathology. Overall, the prevalence of metabolic syndrome was highest in Chile, followed in decreasing order by Colombia, Peru, Argentina, and Ecuador, with differences noted between urban and rural areas or between urban and periurban areas. Obesity and cancer may be preventable, at least in part, by healthy behavior; hence, exercise, weight control, and healthy dietary habits are important to reduce the risk of these major chronic diseases.


A "new" primed lymphocyte typing (PLT) defined DP-antigen associated with a private HLA--DR antigen.
We have recently described a "new" private HLA-DR antigen, DR"LTM", which has a frequency of approximately 0.6% in Danes. Primed Lymphocyte Typing (PLT) cells directed towards DR"LTM"-associated determinants were generated in vitro by haplotype primings in two unrelated families with DR"LTM" positive individuals. Both PLT-cells reacted in parallel and gave positive reactions with (i) two unrelated and (ii) eight related individuals, all of whom were DR"LTM"-positive. Both PLT-cells gave negative reactions with (i) 38 unrelated and (ii) 15 related DR"LTM"-negative individuals. Thus, there was total agreement between the results obtained by HLA-DR typing with the antiserum "LTM" and by PLT-typing with these two haplotype primed PLT-cells. None of the DP"LTM"-positive individuals carried more than one of the antigens HLA-Dw/-DRw/DP1-8 and the local specificity D/DP"H". Accordingly, this "new" PLT-defined antigen, DP"LTM", most probably belongs to the series of HLA-D/DR-associated DP-antigens previously described.


Evolution of the antimicrobial resistance of Pseudomonas aeruginosa in Spain: second national study (2003).
The second national prevalence study of Pseudomonas aeruginosa has been carried out in Spain. A total of 1250 clinical isolates of P. aeruginosa were collected from 127 hospitals in 1 week in 2003 and the resistance data gathered from the isolates was compared with those of the first study in 1998 (1014 isolates from 136 hospitals). Antimicrobial susceptibility testing was performed in both studies in the same laboratory. The most active antimicrobials were piperacillin, piperacillin-tazobactam, and amikacin (< or =10% resistant) and resistance to these antimicrobials did not change over the time. The least active were ofloxacin and gentamicin (> or =30% resistant). From 1998 to 2003, resistance increased significantly to ciprofloxacin (23% vs. 28%, respectively, p=0.015); ofloxacin (30% vs. 37%, p=0.002); imipenem (14% vs. 18%, p=0.017) and meropenem (8% vs. 13%, p <0.001). Resistance to aztreonam (23%), ceftazidime (16%), cefepime (20%), ticarcillin (13%) and tobramycin (11%) remained stable. Isolates from inpatients were significantly more resistant than those from outpatients to all antimicrobials, with the exception of fluoroquinolones and aminoglycosides (p <0.01). Isolates from outpatients were significantly more resistant to these two groups (p <0.05) than to other antimicrobials. In Spain, from 1998 to 2003, the susceptibility pattern of P. aeruginosa to antimicrobial agents has changed. Isolates have become significantly more resistant to fluoroquinolones and carbapenems. However, resistance to beta-lactams and aminoglycosides remains stable.


[The interrelation of chemical structure and inhibiting action of the stericly hindered phenols of ichfan groups].
Inhibitory action of spatially hindered phenol antioxidants (AO) of ICHFAN groups, phenosan derivatives, containing ethanolamine, substituted by N- alkyl substituents R3 containing various carbon chains (from C2 to C 16) was investigated using two models, initiated oxidation of the homogenous methyl oleate (MO) solution in chlorbenzene, and a water-emulsive medium containing sodium dodecyl sulphate. ICHFANs act via two mechanisms: they react with peroxide radicals with the reaction rate constant of k7 = (0.59-1.06) x 10(4) (Mxc)(-1) and destroy hydroperoxides with formation of molecular products. The action of ICHFANs substantially depends on their chemical structure and oxidation conditions. In the lipidic solution, the ICHFANs effectively reduce MO oxidation; in comparable concentrations they exceed the action of the alpha-tocopherol, dibunol, phenosan K and its ether. The most effective AO is ICHFAN-10, which has the shortest substituent R3 (CH3). Elongation of R3 significantly reduced antioxidant activity. Behavior of the oxidation kinetics may be attributed to formation of micro-heterogeneous systems, with the participation of AO, in which OH phenol groups are oriented towards the nuclear of the micelle, limiting the possibility for their interaction with RO2* radicals. In the ICHFAN group, with the length of the R3 chain from C8H17 to C16H33, the periods of inhibition are increased proportionally to R3. The is explained by the insertion of such AO in the bilayer with internal orientation within hydrophobic radicals R3, and exposure of phenol OH groups to the external and internal micelle surfaces allowing them to destroy effectively RO2* radicals. During the oxidation in the water-emulsive medium, the inhibiting action of the corresponding ICHFAN is lower than in the homogenous solution, at that, the difference in the effectiveness of AO with different structures is reduced. This phenomenon is determined by the formation and stabilization with the presence of PAF micelles, in which the active OH-groups are located inside supramolecular structure.


Time-dependent changes in drug sensitivity expressed by mammalian cells after exposure to trypsin.
Immediately after a 5-minute exposure to 0.025% trypsin, Chinese hamster ovary cells treated with anticancer drugs exhibited changes in drug sensitivity. Depending on the drug, cells immediately became more sensitive, less sensitive, or showed no change in sensitivity at all. The deviation from normally expected survival values ranged from fourfold to fifty-fold and varied with time (of drug treatment) after trypsinization. By the 12th hour post trypsinization, the drug survival responses had returned to values obtained with untrypsinized cells.


Dynamic pay strategies for the changing health care environment.
In the rush to adapt to the rapidly shifting health care environment, organizations have spent thousands of hours and dollars changing structures, processes, and jobs. Largely overlooked have been compensation strategies, which if used effectively are critical drivers of the change process. This article details the following issues: the evolution of new health care work cultures and the need for compensation strategies that are aligned with these new cultures; dynamic reward and recognition strategies, including team- and competency-based pay, and their application in the health care environment; and the changing role of the nurse manager in developing, implementing, and administering dynamic reward programs.


Effect of Atomic Layer Coating on the Stability of Solid Myoglobin Formulations.
The effects of atomic layer (ALC) coating on physical properties and storage stability were examined in solid powders containing myoglobin, a model protein. Powders containing myoglobin and mannitol (1:1 w/w) were prepared by lyophilization or spray drying and subjected to aluminum oxide or silicon oxide ALC coating. Uncoated samples of these powders as well as coated and uncoated samples of myoglobin as received served as controls. After preparation (t0), samples were analyzed for moisture content, reconstitution time, myoglobin secondary structure, crystallinity, and protein aggregate content. Samples were stored for 3 months (t3) under controlled conditions (53% RH, 40 °C) in both open and closed vials and then analyzed as above. At t3, the recovery of soluble native (i.e., monomeric) protein depended on formulation, coating type, and drying method and was up to 2-fold greater in coated samples than in uncoated controls. Promisingly, some samples with high recovery also showed low soluble aggregate content (<10%) at t3 and low total monomer loss; the latter was correlated to sample moisture content. Overall, the results demonstrate that ALC coatings can stabilize solid protein formulations during storage, providing benefits over uncoated controls.


Mechanochemistry for Energy Materials: Impact of High-Energy Milling on Chemical, Electric and Thermal Transport Properties of Chalcopyrite CuFeS2 Nanoparticles.
Chalcopyrite CuFeS2 , a semiconductor with applications in chemical sector and energy conversion engineering, was synthetized in a planetary mill from elemental precursors. The synthesis is environmentally friendly, waste-free and inexpensive. The synthesized nano-powders were characterized by XRD, SEM, EDX, BET and UV/Vis techniques, tests of chemical reactivity and, namely, thermoelectric performance of sintered ceramics followed. The crystallite size of ∼13 nm and the strain of ∼17 were calculated for CuFeS2 powders milled for 60, 120, 180 and 240 min, respectively. The evolution of characteristic band gaps, Eg, and the rate constant of leaching, k, of nano-powders are corroborated by the universal evolution of the parameter SBET /X (SBET -specific surface area, X-crystallinity) introduced for complex characterization of mechanochemically activated solids in various fields such as chemical engineering and/or energy conversion. The focus on non-doped semiconducting CuFeS2 enabled to assess the role of impurities, which critically and often negatively influence the thermoelectric properties.


[Molecular imprinting technology and its application in terpenoids].
Molecular imprinting technology is widely used in the separation and analysis of compounds such as flavonoids, alkaloids and polyphenols, due to its high selectivity and specific recognition and so on. However, no much of attention has been paid to the terpenoids. This paper is aimed to not only review the effects of common synthetic elements such as functional monomers, cross-linking agents and porogens on the polymer properties, but also highlight the application of terpene molecular imprinting in solid phase extraction, sensor, membrane separation and chromatographic separation by means of statistical analysis of literature. Furthermore, the shortcomings and improvement directions are discussed.We believed that this paper could provide references for better applications of molecular imprinting techniques to the analysis of terpenoid compounds.


Integrated photonic reservoir computing with an all-optical readout.
Integrated photonic reservoir computing has been demonstrated to be able to tackle different problems because of its neural network nature. A key advantage of photonic reservoir computing over other neuromorphic paradigms is its straightforward readout system, which facilitates both rapid training and robust, fabrication variation-insensitive photonic integrated hardware implementation for real-time processing. We present our recent development of a fully-optical, coherent photonic reservoir chip integrated with an optical readout system, capitalizing on these benefits. Alongside the integrated system, we also demonstrate a weight update strategy that is suitable for the integrated optical readout hardware. Using this online training scheme, we successfully solved 3-bit header recognition and delayed XOR tasks at 20 Gbps in real-time, all within the optical domain without excess delays.


Pain and pain mechanisms in patients with inflammatory arthritis: A Danish nationwide cross-sectional DANBIO registry survey.
Central pain mechanisms may be prominent in subsets of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and other spondyloarthritis (SpA). The painDETECT questionnaire (PDQ) identifies neuropathic pain features, which may act as a proxy for centrally mediated pain. The objectives were to quantify and characterize pain phenotypes (non-neuropathic vs. neuropathic features) among Danish arthritis patients using the PDQ, and to assess the association with on-going inflammation. The PDQ was included onto the DANBIO touch screens at 22 departments of Rheumatology in Denmark for six months. Clinical data and patient reported outcomes were obtained from DANBIO. A PDQ-score >18 indicated neuropathic pain features, 13-18 unclear pain mechanism and <13 non-neuropathic pain. Pain data (visual analogue scale, VAS) was available for 15,978 patients. 7,054 patients completed the PDQ (RA: 3,826, PsA: 1,180, SpA: 1,093). 52% of all patients and 63% of PDQ-completers had VAS pain score ≥ 30 mm. The distribution of the PDQ classification-groups (<13/ 13-18/ >18) were; RA: 56%/24%/20%. PsA: 45%/ 27%/ 28%. SpA: 55% / 24%/ 21%. More patients with PsA had PDQ score >18 compared to RA and SpA (p<0.001). For PDQ > 18 significantly higher scores were found for all patient reported outcomes and disease activity scores. No clinical difference in CRP or swollen joint count was found. Logistic regression showed increased odds for having VAS pain ≥39 mm (the median) for a PDQ-score >18 compared to <13 (OR = 10.4; 95%CI 8.6-12.5). More than 50% of the Danish arthritis patients reported clinically significant pain. More than 20% of the PDQ-completers had indication of neuropathic pain features, which was related to a high pain-level. PDQ-score was associated with DAS28-CRP and VAS pain but not with indicators of peripheral inflammation (CRP and SJC). Thus, pain classification by PDQ may assist in mechanism-based pain treatment.


Uranium(III)/(IV) nitrile adducts including UI4(N[triple bond]CPh)4, a synthetically useful uranium(IV) complex.
The synthesis of complexes used to elucidate an understanding of fundamental An(III) and An(IV) coordination chemistry requires the development of suitable organic-soluble precursors. The reaction of oxide-free uranium metal turnings with 1.3 equivalents of elemental iodine in acetonitrile provided the U(III)/U(IV) complex salt, [U(N[triple bond]CMe)9][UI6][I] (1), in which the U(III) cation is surrounded by nine acetonitrile molecules in a tricapped trigonal prismatic arrangement, a [UI6]2- counterion, and a noncoordinating iodide. The U-N distances for the prismatic and capping nitrogens are 2.55(3) and 2.71(5) A, respectively. The same reaction performed in benzonitrile afforded crystalline UI4(N[triple bond]CPh)4 (3) in 78% isolated yield. In the solid state, 3 shows an eight-coordinate U(IV) atom in a "puckered" square antiprismatic geometry with U-N and U-I distances of 2.56(1) and 3.027(1) A, respectively. This benzonitrile UI4 adduct is a versatile U(IV) synthon that is soluble in methylene chloride, benzonitrile, and tetrahydrofuran, and moderately soluble in toluene and benzene, but decomposes in benzonitrile at 198 degrees C to [UI(N[triple bond]CPh)8][UI]6 (4), a U(III)/U(IV) salt analogous to 1. A toluene slurry of 3 treated with 2.2 equiv of Cp*MgCl.THF (Cp* = pentamethylcyclopentadienide) provided Cp*2UI2(N[triple bond]CPh) (5) in low yields. Single-crystal X-ray structure determination shows that the iodide ligands in 5 are in a rare cis configuration with an acute I-U-I angle of 83.16(7) degrees . Treatment of a methylene chloride solution of 3 with KTp* (Tp* = hydridotris(3,5-dimethylpyrazolylborate)) formed green TpUI3 (6) which was converted to yellow Tp*UI3(N[triple bond]CMe) (7) by rinsing with acetonitrile. Addition of 2.2 equiv of KTp* to a toluene solution of 3 followed by heating at 95 degrees C, filtration, and crystallization led to the isolation of the dinuclear species [Tp*UI(dmpz)]2[mu-O] (9) (dmpz = 3,5-dimethylpyrazolide), presumably formed by hydrolytic cleavage of excess KTp* by adventitious water. The Tp* complexes 6, 7, and 9 were characterized by single-crystal X-ray diffraction, NMR, FT-IR, and optical absorbance spectroscopies.


InCl3/I2-catalyzed cross-coupling of alkyl trimethylsilyl ethers and allylsilanes via an in situ derived combined Lewis acid of InCl3 and Me3SiI.
Direct Csp3-Csp3 coupling of various aliphatic trimethylsilyl ethers and allylsilanes is effectively catalyzed by InCl3 and I2. The transformation is thought to involve an in situ-derived combined Lewis acid of InCl3 and Me3SiI. The reaction can be used for the construction of quaternary-quaternary and quaternary-tertiary carbon-carbon bonds. This system enabled a highly chemoselective coupling to be conducted with a trimethylsilyl ether including an aryl halide moiety. Furthermore, couplings were possible using an alkynyltrimethylsilane and a trimethylsilyl ketene acetal.


NXP-2 Positive Dermatomyositis: A Unique Clinical Presentation.
Dermatomyositis (DM), a myopathy associated with inflammation and muscle weakness, has historically been difficult to diagnose. Recently, nuclear matrix protein (NXP-2) antibodies have been described as a myositis-specific antibody that may aid in the diagnostic evaluation. We present the case of a 21-year-old, previously healthy, African American male with DM. He presented to our outpatient clinic with periorbital swelling and a rash, for which he was started on prednisone by an ophthalmologist. Towards the end of the prednisone taper, he began to experience muscle weakness, a worsening rash, and dysphagia to solids with a resultant loss of 60 pounds within a month. He was transferred to a tertiary care hospital where he was further evaluated and ultimately diagnosed with dermatomyositis, supported by skin and muscle biopsies, and was found to be positive for NXP-2. He was given intravenous immunoglobulin (IVIG) and high-dose steroids with improvement.


Inhibitory effect of enalapril on the constriction of the ductus arteriosus in newborn rats.
Caesarean newborn rats were given subcutaneously enalapril maleate (EM), an angiotensin-converting enzyme inhibitor, (1) immediately or (2) 180 min after delivery. The ductus arteriosus (DA) in these newborn pups was calibrated 30, 60 and 90 min after the EM-treatment. The results were as follows: (1) DA calibers of the pups given 10 or 50 mg/kg EM just at caesarean delivery remained significantly larger than those of the controls thereafter until 90 min. (2) The DA was completely closed 180 min after caesarean delivery. However, with 50 mg/kg EM given at this time, the DA was temporarily re-opened and then constricted. It is concluded that, in newborn rats, EM has the direct inhibitory action on the constriction of the DA, and that it also has the re-opening action on the once-constricted DA.


Clinicopathologic Characteristics and Clinical Outcome of Localized Liposarcoma: A Single-Center Experience over 25 Years and Evaluation of PD-L1 Expression.
For liposarcoma (LPS), clinical course and proper treatment strategies have not been well-established. Recently, immune-checkpoint inhibitors have shown potential efficacy in LPS. We aimed to describe the clinical course of LPS and evaluate the clinical impact of programmed death-ligand 1 (PD-L1). We reviewed all consecutive patients (n=332) who underwent curative-intent surgery for localized LPS at Asan Medical Center between 1989 and 2017. PD-L1 testing was performed in well-differentiated and dedifferentiated LPS. The median age was 56 years with males comprising 60.8%. Abdomen-pelvis (47.6%) and well-differentiated (37.7%) were the most frequent primary site and histologic subtype, respectively. During a median follow-up of 81.2 months, recurrence was observed in 135 (40.7%), and 86.7% (117/135) were loco-regional. Well-differentiated subtype (hazard ratio [HR], 0.38), abdomen-pelvis origin (HR, 2.43), tumor size larger than 5 cm (HR, 1.83), positive resection margin (HR, 2.58), and postoperative radiotherapy (HR, 0.36) were significantly related with recurrence-free survival as well as visceral involvement (HR, 1.84) and multifocality (HR, 3.79) in abdomen-pelvis LPS. PD-L1 was positive in 31.5% (23/73) and 51.3% (39/76) of well-differentiated and dedifferentiated LPS, respectively, but had no impact on survival outcomes. Clinical course of LPS was heterogeneous according to histology and anatomic location. Clear resection margin was important to lower recurrence and postoperative radiotherapy might have additional benefit. A decent portion of well-differentiated and dedifferentiated LPS were positive for PD-L1, but its prognostic role was unclear. Further research is needed to determine clinical implications of PD-L1, especially for advanced-stage LPS with unmet needs for effective systemic treatment.


The miR-29 transcriptome in endocrine-sensitive and resistant breast cancer cells.
Aberrant microRNA expression contributes to breast cancer progression and endocrine resistance. We reported that although tamoxifen stimulated miR-29b-1/a transcription in tamoxifen (TAM)-resistant breast cancer cells, ectopic expression of miR-29b-1/a did not drive TAM-resistance in MCF-7 breast cancer cells. However, miR-29b-1/a overexpression significantly repressed TAM-resistant LCC9 cell proliferation, suggesting that miR-29b-1/a is not mediating TAM resistance but acts as a tumor suppressor in TAM-resistant cells. The target genes mediating this tumor suppressor activity were unknown. Here, we identify miR-29b-1 and miR-29a target transcripts in both MCF-7 and LCC9 cells. We find that miR-29b-1 and miR-29a regulate common and unique transcripts in each cell line. The cell-specific and common downregulated genes were characterized using the MetaCore Gene Ontology (GO) enrichment analysis algorithm. LCC9-sepecific miR-29b-1/a-regulated GO processes include oxidative phosphorylation, ATP metabolism, and apoptosis. Extracellular flux analysis of cells transfected with anti- or pre- miR-29a confirmed that miR-29a inhibits mitochondrial bioenergetics in LCC9 cells. qPCR,luciferase reporter assays, and western blot also verified the ATP synthase subunit genes ATP5G1 and ATPIF1 as bone fide miR29b-1/a targets. Our results suggest that miR-29 repression of TAM-resistant breast cancer cell proliferation is mediated in part through repression of genes important in mitochondrial bioenergetics.


The genome sequence of the Lunar Hornet, Sesia bembeciformis (Hübner 1806).
We present a genome assembly from an individual male Sesia bembeciformis (the Lunar Hornet; Arthropoda; Insecta; Lepidoptera; Sesiidae). The genome sequence is 477.1 megabases in span. Most of the assembly is scaffolded into 31 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 16.1 kilobases in length. Gene annotation of this assembly on Ensembl has identified 15,843 protein coding genes.


Hybrid Areal Interpolation of Census Counts from 2000 Blocks to 2010 Geographies.
To measure population changes in areas where census unit boundaries do not align across time, a common approach is to interpolate data from one census's units to another's. This article presents a broad assessment of areal interpolation models for estimating counts of 2000 characteristics in 2010 census units throughout the United States. We interpolate from 2000 census block data using 4 types of ancillary data to guide interpolation: 2010 block densities, imperviousness data, road buffers, and water body polygons. We test 8 binary dasymetric (BD) models and 8 target-density weighting (TDW) models, each using a unique combination of the 4 ancillary data types, and derive 2 hybrid models that blend the best-performing BD and TDW models. The most accurate model is a hybrid that generally gives high weight to TDW (allocating 2000 data in proportion to 2010 densities) but gives increasing weight to a BD model (allocating data uniformly within developed land near roads) in proportion to the estimated 2000-2010 rate of change within each block. Although for most 2010 census units, this hybrid model's estimates differ little from the simplest model's estimates, there are still many areas where the estimates differ considerably. Estimates from the final model, along with lower and upper bounds for each estimate, are publicly available for over 1,000 population and housing characteristics at 10 geographic levels via the National Historical Geographic Information System (NHGIS - http://nhgis.org).


Molecular theory of hydrodynamic boundary conditions in nanofluidics.
Motivated by the fundamental questions raised by the most recent experimental achievements in nanofluidics, we propose the first-ever derivation and calculation of the hydrodynamic slip length from the first principles of statistical mechanics, namely, a combination of linear response theory and equilibrium molecular theory of solvation. The slip length derived is related to the fluid organization near the solid surface, as governed by the solid-liquid interaction. In the wide range of shear rates and surface-liquid interactions, the slip length is expressed in terms of the Green-Kubo-Nakano relations as a function of the anisotropic inhomogeneous time-correlation function of density fluctuations of the liquid in contact with the surface. The time dependence of the correlation function is factored out by treating it in the hydrodynamic limit. The spatially inhomogeneous two-body correlation function is represented in the Kirkwood-type approximation as a product of the three-dimensional density distributions of interaction sites of the liquid near the surface and the site-site pair correlations of the bulk liquid. The presented treatment generalizes the phenomenological definition of the friction coefficient (as well as the slip length) to a tensor quantity, which reflects an anisotropic nature of an ordered crystalline or nanopatterned surface. This enables theoretical prediction of friction forces acting aslant to the liquid flow direction for such surfaces. We derive generic analytical expressions for the liquid-surface friction coefficient (and slip length) for an arbitrary surface-liquid interaction potential. We further illustrate it by numerical calculations for a laminar flow of nine different molecular liquids, including water, at ambient conditions in contact with the (100) face-centered cubic cell surface of gold, copper, and nickel modeled by using optimized potential for liquid simulation models for liquids and the Steele potential for crystalline surfaces. The obtained values for slip length range from few to hundreds of nanometers and microns and are consistent with experimental measurements.


Sensitivity of locally naturalized Panicum species to HPPD- and ALS-inhibiting herbicides in maize.
Until recently the Panicum species Panicum schinzii Hack. (Transvaal millet), Panicum dichotomiflorum Michx. (Fall panicum) and Panicum capillare L. (Witchgrass) were completely overlooked in Belgium. Since 1970, these species have gradually spread and are now locally naturalized and abundant in and along maize fields. One of the possible raisons for their expansion in maize fields might be a lower sensitivity to postemergence herbicides acting against panicoid grasses, in particular those inhibiting 4-hydroxyphenyl pyruvate dioxygenase (HPPD) and acetolactate synthase (ALS). A dose-response pot experiment was conducted in the greenhouse to evaluate the effectiveness of five HPPD-inhibiting herbicides (sulcotrione, mesotrione, isoxaflutole, topramezone, tembotrione) and two ALS-inhibiting herbicides (nicosulfuron, foramsulfuron) for controlling Belgian populations of P. schinzii, P. dichotomiflorum and P. capillare. Shortly after sowing, half of all pots were covered with a film of activated charcoal to evaluate foliar activity of the applied herbicides. In another dose-response pot experiment, sensitivity of five local P. dichotomiflorum populations to HPPD-inhibitors and nicosulfuron was investigated. Finally, the influence of leaf stage at time of herbicide application on efficacy of topramezone and nicosulfuron for Panicum control was evaluated. Large interspecific differences in sensitivity to HPPD-inhibiting herbicides were observed. Panicum schinzii was sensitive (i.e., required a dose lower than the maximum authorized field dose to achieve 90% reduction in biomass) to tembotrione but moderately sensitive (i.e. required maximum field dose) to topramezone and poorly sensitive (i.e. required three-fold higher dose than maximum field dose) to mesotrione and sulcotrione. However, P. dichotomiflorum, a species that morphologically closely resembles P. schinzii, was sensitive to mesotrione and topramezone but moderately sensitive to tembotrione. All Panicum species were sensitive to low doses of nicosulfuron and foramsulfuron. The relative contribution from soil activity to weed control resulting from postemergence applications was important for isoxaflutole, sulcotrione, tembotrione and mesotrione but not for topramezone, nicosulfuron and foramsulfuron. Naturalized Panicum dichotomiflorum populations exhibited differential herbicide sensitivity profiles. Panicum schinzii, P. capillare and P.dichotomiflorum showed a progressive decrease in sensitivity to topramezone and nicosulfuron during seedling development. A satisfactory postemergence control of Panicum species in the field will require appropriate choice of herbicide and dose, as well as a more timely application (i.e. before weeds reach the four leaves stage).


Diet-Related Colorectal Cancer Prevention Beliefs and Dietary Intakes in an Urban Minority Population.
In the United States, colorectal cancer (CRC) is the third leading cause of cancer-related death and third most commonly diagnosed cancer among adults. This study is the first to examine the relationship between diet-related beliefs for colorectal cancer prevention and dietary intake among an urban, predominantly Black population (n = 169). More than two-thirds reported diet-related CRC prevention beliefs. Those with diet-related CRC prevention beliefs had healthier intakes for dietary fiber (p = .005), fruit, vegetable, bean (p = .027), red meat (p = .032), vitamin C (p = .039), and cholesterol (p = .045). Most people may already have diet-related CRC prevention beliefs and having them is associated with a more healthful dietary intake.


Transcriptome sequences spanning key developmental states as a resource for the study of the cestode Schistocephalus solidus, a threespine stickleback parasite.
Schistocephalus solidus is a well-established model organism for studying the complex life cycle of cestodes and the mechanisms underlying host-parasite interactions. However, very few large-scale genetic resources for this species are available. We have sequenced and de novo-assembled the transcriptome of S. solidus using tissues from whole worms at three key developmental states - non-infective plerocercoid, infective plerocercoid and adult plerocercoid - to provide a resource for studying the evolution of complex life cycles and, more specifically, how parasites modulate their interactions with their hosts during development. The de novo transcriptome assembly reconstructed the coding sequence of 10,285 high-confidence unigenes from which 24,765 non-redundant transcripts were derived. 7,920 (77 %) of these unigenes were annotated with a protein name and 7,323 (71 %) were assigned at least one Gene Ontology term. Our raw transcriptome assembly (unfiltered transcripts) covers 92 % of the predicted transcriptome derived from the S. solidus draft genome assembly currently available on WormBase. It also provides new ecological information and orthology relationships to further annotate the current WormBase transcriptome and genome. This large-scale transcriptomic dataset provides a foundation for studies on how parasitic species with complex life cycles modulate their response to changes in biotic and abiotic conditions experienced inside their various hosts, which is a fundamental objective of parasitology. Furthermore, this resource will help in the validation of the S solidus gene features that have been predicted based on genomic sequence.


[Validation of the Kit for Detecting Mycoplasma Genitalium from the Male Urethritis].
Mycoplasma genitalium is one of the pathogenic microorganisms in male urethritis as a sexually transmitted infection (STI). M.genitalium is detected in the urine specimens of 15-25% male patients with urethritis. The emergence of macrolide- or fluoroquinolone-resistant M.genitalium has become a serious problem in the treatment of male urethritis worldwide, but there is no commercial-based detecting kits accepted by the national insurance in Japan. In this study, we tested the validity of a molecular kit for detecting seven microorganisms related to STI (Anyplex™ II STI-7 Detection which detects Neisseria gonorrhoeae, Chlamydia trachomatis, M.genitalium, Mycoplasma hominis, Ureaplasma urealyticum, Ureaplasma parvum, Trichomonas vaginalis) produced by Seegene company in Korea. Seventeen M.genitalium strains were used to determine the detection limit of M.genitalium. M.genitalium DNA samples were extracted from M.genitalium strains and the diluted DNA samples were reacted to detect M.genitalium by the Anyplex™ II STI-7 Detection. The detection limit was determined as the maximum dilution of DNA samples and the number of M.genitalium DNA copies calculated. In this study, the minimum DNA copies to detect M.genitalium by the Anyplex™ II STI-7 Detection was determined to be around 50 per reaction. The detection rates of M.genitalium in urine specimens were compared between MgPa gene PCR and the Anyplex™ II STI-7 Detection. The positive and negative concordant rates were high as 96.4% (27/28) and 98.6% (71/72), respectively. The validity of the kit for detecting seven microorganisms related to STI (Anyplex™ II STI-7 Detection) was high and thought to be useful for clinical uses.


Urgency in the Treatment of Sudden Sensorineural Hearing Loss.
Sudden sensorineural hearing loss (SSNHL) is considered an otolaryngologic emergency that must be treated within 72 hours. Failure to treat within that time frame typically results in permanent hearing loss. Here, we present a case of SSNHL confirmed by an audiogram that was treated as eustachian tube dysfunction. Aggressive management measures started at follow-up failed to improve the hearing loss. This case demonstrates the need for early recognition and ENT referral for SSNHL.


Interactive video conferencing: a means of providing interim care to Parkinson's disease patients.
Inequity in health care delivery is attributable to a variety of factors including geographic isolation. Patients living far from major urban centers have limited access to medical specialists. In the instance of Parkinson's disease (PD), optimal assessment and care may depend upon availability of specialty health care providers. In order to broaden health care access, interactive video conference (IVC) units are being developed for medical use. IVC allows a patient at a distant site to be "seen and heard" by a hospital-based physician; simultaneously, the patient can "see and hear" the doctor. To establish the validity of this technology in the evaluation of PD, nine patients were independently examined and scored (UPDRS) by two movement disorder specialists. One examination was performed in-person by the usual physician. The other examination was performed on the same day via IVC over a distance of 350 miles by an examiner previously unfamiliar with the patients. Individual patient scores did not differ based on examiner (Spearman Rho Correlation Coefficients: UPDRS total scores r = 0.933, p < 0.0002; Hoehn and Yahr Scale r = 0.883, p < 0.001). A standardized exit interview was conducted to assess patients' perceptions of this application of video technology. Responses were favorable and virtually all patients viewed this as a means of accessing better health care. We conclude that valid motor assessments of PD patients can be made via IVC.


Shelf Life Potential and the Fruit Cuticle: The Unexpected Player.
The plant cuticle is an extracellular barrier that protects the aerial, non-lignified parts of plants from the surrounding environment, and furthermore plays important functions in organ growth and development. The role of the cuticle in post-harvest quality of fruits is a topic currently driving a lot of interest since an increasing bulk of research data show its modulating influence on a number of important traits determining shelf life and storage potential, including water transpiration and fruit dehydration, susceptibility to rots, pests and disorders, and even firmness. Moreover, the properties of fruit cuticles keep evolving after harvest, and have also been shown to be highly responsive to the external conditions surrounding the fruit. Indeed, common post-harvest treatments will have an impact on cuticle integrity and performance that needs to be evaluated for a deeper understanding of changes in post-harvest quality. In this review, chemical and biophysical properties of fruit cuticles are summarized. An overview is also provided of post-harvest changes in cuticles and the effects thereupon of some post-harvest procedures, with the purpose of offering a comprehensive summary of currently available information. Identification of natural sources of variability in relevant quality traits would allow breeding for the improvement of post-harvest life of fruit commodities.


Effect of pancreatic biliary reflux as a cofactor in cholecystitis.
This study assessed the effect of pancreatico-biliary reflux (PBR) as co-factor in the process of chronic cholecystitis by measurement of the levels of active pancreatic enzyme amylase in gallbladder bile and serum of patients undergoing cholecystectomy. Pancreatic Amylase levels in bile from the gallbladder and serum were measured during surgery in 68 patients with chronic calcular cholecystitis subjected to elective open or laparoscopic cholecystectomy in the National Hepatology and Tropical Medicine Research Institution and Theodore Bilharz Research Institute. Bile amylase was detected in 64 patients (94.1%) indicating pancreatico-biliary reflux. Biliary amylase level ranged from 20-50 IU/L in 42 patients (61.76%), below 20 IU/l in 14 patients (20.59%), over 50 IU/L in 8 patients (11.76%) and undetectable in two patients. According to gallbladder bile amylase, the incidence of Occult PBR in patients operated upon for chronic calcular cholecystitis was 94.1%. The reason should be clarified by further research and wider scale study. Routinely investigating biliary amylase in every patient having cholecystitis can be a method for early detection of precancerous lesions.


Who is calling? Optimizing source identification from marmoset vocalizations with hierarchical machine learning classifiers.
With their highly social nature and complex vocal communication system, marmosets are important models for comparative studies of vocal communication and, eventually, language evolution. However, our knowledge about marmoset vocalizations predominantly originates from playback studies or vocal interactions between dyads, and there is a need to move towards studying group-level communication dynamics. Efficient source identification from marmoset vocalizations is essential for this challenge, and machine learning algorithms (MLAs) can aid it. Here we built a pipeline capable of plentiful feature extraction, meaningful feature selection, and supervised classification of vocalizations of up to 18 marmosets. We optimized the classifier by building a hierarchical MLA that first learned to determine the sex of the source, narrowed down the possible source individuals based on their sex and then determined the source identity. We were able to correctly identify the source individual with high precisions (87.21%-94.42%, depending on call type, and up to 97.79% after the removal of twins from the dataset). We also examine the robustness of identification across varying sample sizes. Our pipeline is a promising tool not only for source identification from marmoset vocalizations but also for analysing vocalizations of other species.


1-Thiopsoralen, a new photobiologically active heteropsoralen. Photophysical, photochemical and computer aided studies.
1-Thiopsoralen (7H-thieno[3,2-g]benzofuran-7-one) 1, a lead compound of a series of heteropsoralens, was investigated. The electronic transitions involved were studied. Fluorescence quantum yield is very low, while laser flash photolysis showed that the triplet state is practically the sole transient of 1. Fluorescence quantum yield (phi F) and triplet lifetime (tau F) as well as triplet quantum yield (phi T) and lifetime (tau T) were determined. The production of singlet oxygen was also evaluated by photophysical measurements. Photophysical data suggest that DNA photobinding of 1, owing to short fluorescence lifetime value and high triplet quantum yield, occurs likely through triplet mechanism. Interactions between 1 and DNA were studied both in the ground and the excited state. In the ground state 1 undergoes intercalation inside duplex DNA. This fact is also supported by molecular modeling studies. By UVA-light activation 1 photobinds covalently to DNA forming mono and diadducts. The furan side 1-thymine monoadduct, isolated from DNA photomodified by thiopsoralen, shows a cis-syn stereochemistry, in agreement with quantum mechanics studies. Compound 1 photobinds also with linolenic acid, component of lecithins, giving a C4-cycloaddition, and supporting that this compound also induces photolesions at the level of cell membrane, like psoralen. Compound 1 exhibits strong skin-phototoxicity.


Biglycan regulates the expression of EGF receptors through EGF signaling pathways in human articular chondrocytes.
Biglycan is a member of the family of small leucine-rich proteoglycans. It is an important structural component of articular cartilage and participates in the assembly of the chondrocyte extracellular matrix through formation of protein interactions with collagen type VI and large proteoglycan aggregates. Biglycan also possesses signaling properties. In articular chondrocytes, short-term activation of epidermal growth factor receptors (EGFR) with biglycan initiated mitogen-activated protein kinase and phosphatidylinositol 3-kinase (PI3K) signaling events, similar to the effect of epidermal growth factor (EGF) observed in other cell types. The extent and duration of intracellular signaling resolves biological effects initiated by EGFR stimulation, thus, establishing cell fate. In this study, we elucidate a novel regulatory mechanism of EGFR expression in human articular chondrocytes that is modulated by prolonged biglycan treatment and is in contrast to changes detected in the expression of EGFR following EGF stimulation. Treatment of chondrocytes for 24 hr with biglycan upregulated EGFR mRNA and protein expression, whereas treatment with EGF downregulated EGFR message and protein levels. Biglycan and EGF treatment protracted extracellular signal-regulated kinases (ERK1/2) and Akt phosphorylation, albeit to different extents. Mechanistic studies with mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathway-specific inhibitors revealed that biglycan and EGF distinctly modulate the expression of EGFR in chondrocytes. Biglycan promoted the coactivation of ERK1/2 and Akt, however, phosphorylated Akt induced a prolonged inhibition of ERK1/2. Consequently, total EGFR mRNA and protein expression was increased. This regulatory mechanism contrasts the modulation of EGFR expression by exogenous EGF, which strongly protracts ERK1/2 activation, therefore, inducing a decrease of EGFR message and protein levels. Thus, biglycan might impinge on the expression of total EGFR and possibly, on the cell-surface expression of the receptors. These observations suggest that biglycan might play a critical role in the regulation of chondrocyte and pericellular matrix homeostasis.


Clinical utility of the relationship between fetal femur length and biparietal diameter.
The relationship between fetal femur length and biparietal diameter on ultrasound examination was evaluated in a large, unselected obstetric population of 12-40 weeks' gestational age. The derived ratio of fetal femur length to biparietal diameter was evaluated retrospectively as a tool for examining the technical reliability of fetal measurements obtained and as a screening mechanism for detecting asymmetric fetal development. The ratio of femur length to biparietal diameter is of value as an aid to the detection of fetal developmental anomalies and should be a routine parameter considered in the performance of an obstetric ultrasound examination.


[Releasing anterior part of spine under video-assisted thoracoscope for treatment of adolescent idiopathic scoliosis].
To evaluate the safety and efficacy of the operation performed under the video-assisted thoracoscope to release the anterior part of the spine of the patient with severe adolescent idiopathic scoliosis (AIS). From April 2004 to July 2006, 24 patients with AIS (Illness course, 1.5-9 years; Lenke I in 17 patients, Lenke II in 7; right scoliosis in 22, left scoliosis in 2), among whom there were 9 males and 15 females, with an average age of 14.7 years (range, 11-21 years) at the time of the operation. Before operation, the thoracic vertebral Cobb anger at the coronal plane was averaged 78.3 degrees (range, 65-125 degrees). All the patients had normal muscle strength and muscle tension in their lower limbs, but 5 of the patients had a decrease of the superficial sensation in their lower limbs. All the patients had a moderately or severely decreased lung reserve function. Under general anesthesia, the patient was placed in the lateral position to set up a work channel for thoracoscopy. The releasing of the thoracic intervertebral space and the confluence of the bone grafts were performed. During Stage I or Stage II , the orthopedic procedures for the posterior part of the scoliosis spine, the internal fixation, and the confluence of the bone grafts were completed. All the patients survived the period of perioperation. During operation, there was a hemorrhage of 50-200 ml, averaged 100 ml, with a postoperative thoracic closely-drained fluid of 100-150 ml. The incision was healed by the first intention. Each patient underwent the release of 4-6 intervertebral spaces, with an average of 5.5 spaces released. The average coronal Cobb angle was 45.6 degrees (range, 25- 75 degrees). The physiological curvature at the sagittal plane was normal, with an improved shape of the spine. The follow-up for 3-18 months averaged 9.3 months revealed that the bilateral pulmonary markings were clear, with confluence of the orthopedic segment of the spine. The patients could live and work normally, and had a significantly-improved psychological condition and an active social participation because of their improved appearance. The releasing of the anterior part of the spine under the video-assisted thoracoscope can effectively release the adolescent idiopathic scoliosis and improve the flexibility of the spine, with a smaller degree of the surgical wound and a faster and clearer exposure of the spinal column during operation.


Angiographic screening and elective surgery of familial cerebral aneurysms: a decision analysis.
Up to 6% of cerebral aneurysms may be familial. Because the pattern of inheritance and the prevalence of aneurysms within families are unknown, the management of family members at risk of harboring a cerebral aneurysm is currently empirical. We established the prevalence of aneurysms in the second generation of individuals with familial cerebral aneurysms and determined the possible benefit of angiographic screening and elective surgery of such individuals by using a simple decision analysis model. Four consecutive families were identified in whom the mother and a child had a ruptured cerebral aneurysm. A total of 19 siblings at risk in the second generation were identified. Fifteen underwent elective cerebral angiography: one had a cerebral aneurysm and two had an infundibulum at the origin of the posterior communicating artery. Including the previously known aneurysms, the prevalence of aneurysms in the second generation was thus established at 29.4%. A decision analysis was performed with 2% as the annual risk of rupture, 72.7% as the risk of death or disability with rupture, 0.1% as the risk of angiography, and 6.5% as the risk of surgery. The benefit in years of survival free of sequelae resulting from angiographic screening and elective surgery (intervention) over natural history was computed for life expectancy corresponding to each quinquennial age group from age 15 to 100 years. Intervention equaled natural history, in terms of years of survival expected with each choice, at a life expectancy of 10.6 years, corresponding to age 76.5 years for men and 80 years for women, and produced a net gain of at least 1 year for patients whose life expectancy was 32 years or more, corresponding to age 53.5 years for women and 49 years for men. Greater benefit was achieved with increasing life expectancy (younger age). The prevalence of aneurysms in the second generation when a mother and child have an aneurysm is 29.4%. Intervention produces a benefit of at least 1 year of survival free of sequelae over natural history in such individuals if their life expectancy is 32 years or more.


NHC-Catalyzed Enantioselective Synthesis of Tetracyclic δ-Lactones by (4 + 2) Annulation of ortho-Quinodimethanes with Activated Ketones.
The N-heterocyclic carbene (NHC)-catalyzed generation of ortho-quinodimethanes (o-QDMs) from 9H-fluorene-1-carbaldehydes followed by the interception with activated ketones resulting in the enantioselective synthesis of tetracyclic δ-lactones is presented. High diastereoselectivity of products, remote C(sp3)-H functionalization, broad substrate scope, and mild reaction conditions are the notable features of the present (4 + 2) annulation.


Seropositivity and higher immunoglobulin g antibody levels against cytomegalovirus are associated with mortality in the population-based European prospective investigation of Cancer-Norfolk cohort.
The relationship between cytomegalovirus (CMV) infection and mortality among immunocompetent individuals is uncertain. We aimed to examine whether seropositivity for CMV and the level of CMV immunoglobulin G (IgG) antibody are associated with all-cause and cause-specific mortality. We used data from a random sample of 13 090 participants aged 40-79 years at recruitment in 1993-1997 to the European Prospective Investigation of Cancer-Norfolk population-based cohort study. We measured baseline IgG antibody levels against CMV. Death certificates were obtained for all participants who died before 31 March 2011. Codes for the underlying cause of death were used to investigate cause-specific mortality. A total of 2514 deaths occurred during a mean follow-up of 14.3 years (SD, 3.3 years). Compared to seronegative participants (age- and sex-adjusted mortality rate, 12.4 [95% confidence interval {CI}, 11.3-13.2] per 1000 person-years at risk), rates increased across thirds of IgG antibody levels (score test of trend P < .0001). CMV seropositivity (prevalence 59%) was associated with increased all-cause mortality (age- and sex-adjusted hazard ratio [HR], 1.16 [95% CI, 1.07-1.26]), similarly in men and women (P for interaction = .52). The association persisted after additionally adjusting for measures of socioeconomic status and possible confounders. Cause-specific analyses suggested that increased mortality from cardiovascular disease (HR, 1.06 [95% CI, .91-1.24]), cancer (HR, 1.13 [95% CI, .98-1.31]), and other causes (HR, 1.23 [95% CI, 1.04-1.47) all appeared to contribute to the overall associations. Seropositivity and higher IgG antibody levels against CMV are associated with increased mortality and after adjustment for a range of potential confounders in the general population.


Communication between S1N330 and a region in S2 of murine coronavirus spike protein is important for virus entry into cells expressing CEACAM1b receptor.
The soluble receptor-resistant (srr) mutants, srr7 and srr11, isolated from a murine coronavirus, mouse hepatitis virus (MHV) JHMV, have an amino acid mutation at positions 1114 (Leu to Phe) and 65 (Leu to His), respectively, in the spike (S) protein. These mutants failed to efficiently infect BHK cells expressing CEACAM1b (BHK-R2), due to their low entry into this cell line, although they infected cells expressing CEACAM1a (BHK-R1) in a manner similar to that of wild-type (wt) JHMV cl-2 (Matsuyama and Taguchi, Virology 273, 80-89, 2000). Following the repeated passage of these mutants through BHK-R2 cells, viruses were no longer isolated from srr11-infected cells, while two distinct mutants, srr7A and srr7B, were obtained from srr7-infected cells. Srr7A and srr7B grew 2 log10 higher than srr7 and induced fusion in BHK-R2 cells, being similar to wt virus. In addition to the amino acid change at position 1114 that stemmed from parental srr7, srr7A and srr7B had mutations around position 280, corresponding to the third region of the S1N330 receptor-binding site (S1N330-III) common to all MHV strains examined thus far. Srr7A and srr7B S proteins showed high fusogenicity in both BHK-R1 and BHK-R2 cells, like the wt virus, while srr7Aa and srr7Ba S proteins, which had mutations in S1N330-III but not at amino acid 1114, exhibited profoundly reduced fusion activity in these cell lines. These findings suggest that communication between S1N330-III and the amino acid at position 1114 is important for efficient fusion activity in BHK-R2 cells. S1N330-III is a possible region in the S1 involved in viral entry into cells.


Renoprotective Effects of a New Free Radical Scavenger, XH-003, against Cisplatin-Induced Nephrotoxicity.
Acute renal injury has an incidence of 25%-30% in patients with tumors who are treated with cisplatin and in patients for whom no specific drugs are available for treatment. Amifostine is the only FDA-approved chemoprotective drug; however, its clinical application is limited because of side effects. The small-molecule antioxidant XH-003, an acute radiation syndrome- (ARS-) protective drug independently developed in our laboratory, with 100% intellectual property rights, overcomes the side effects of amifostine but retains its high efficacy. In this study, XH-003 showed a chemoprotective effect similar to that of amifostine. A mechanistic study showed that XH-003 could significantly reduce cisplatin-induced increases in serum creatinine and urea nitrogen, increase the activity of antioxidant enzymes (SOD, CAT, and GSH-Px), reduce oxidative stress and tissue inflammation, and alleviate renal tissue damage by blocking the activity of the mitochondrial apoptosis pathway. Most importantly, XH-003 could reduce the accumulation of cisplatin in renal tissue by regulating the expression of proteins involved in cisplatin uptake and excretion, such as organic cation transporter 2 and MRP2. Moreover, in an in vivo xenotransplantation model, XH-003 did not interfere with the antitumor effect of cisplatin. These data provide strong evidence that the ARS-protective agent has a great potential for protecting against chemotherapy-induced toxicity. Thus, XH-003 can be considered in antitumor therapy.


A Bacterial mRNA-Lysis-Mediated Cargo Release Vaccine System for Regulated Cytosolic Surveillance and Optimized Antigen Delivery.
Engineered vector-based in vivo protein delivery platforms have made significant progress for both prophylactic and therapeutic applications. However, the lack of effective release strategies results in foreign cargo being trapped within the vector, restricting the provision of significant performance benefits and enhanced therapeutic results compared to traditional vaccines. Herein, the development of a Salmonella mRNA interferase regulation vector (SIRV) system is reported to overcome this challenge. The genetic circuits are engineered that (1) induce self-lysis to release foreign antigens into target cells and (2) activate the cytosolic surveillance cGAS-STING axis by releasing DNA into the cytoplasm. Delayed synthesis of the MazF interferase regulates differential mRNA cleavage, resulting in a 36-fold increase in the delivery of foreign antigens and modest activation of the inflammasome, which collectively contribute to the marked maturation of antigen-presenting cells (APCs). Bacteria delivering the protective antigen SaoA exhibits excellent immunogenicity and safety in mouse and pig models, significantly improving the survival rate of animals challenged with multiple serotypes of Streptococcus suis. Thus, the SIRV system enables the effective integration of various modular components and antigen cargos, allowing for the generation of an extensive range of intracellular protein delivery systems using multiple bacterial species in a highly efficient manner.


One-pot synthesis of substituted 2,2'-bipyrroles. A straightforward route to aryl porphycenes.
A one-pot reaction for the synthesis of 4,4'-diaryl- and 4,4'-diheteroaryl-substituted 2,2'-bipyrroles is described. The new methodology is based on the oxidative coupling of a 2-trimethylstannylated pyrrole and does not require chromatography. These 2,2'-bipyrroles can be used as precursors in a expeditious synthesis of 2,7,12,17-tetraaryl-porphycenes.


Paradoxical effect of isoprenaline infusion.
Isoprenaline (isoproterenol) is a beta-adrenergic drug, used to increase the heart rate and, during electrophysiological study, to facilitate the induction of supraventricular (SVT) and ventricular tachycardias (VT). Decrease in heart rate during isoprenaline infusion is a rare phenomenon. The purpose of the study was to evaluate the incidence, the possible mechanisms, and the significance of a paradoxical bradycardia induced by isoprenaline infusion. Electrophysiological study was performed for the evaluation of tachycardias (n = 551) or dizziness/syncope (n = 214) in 765 patients aged from 15 to 85 years. The study was negative in the basal state, and was repeated after isoprenaline infusion (2-4 microg/min). In 714 patients, this perfusion increased the heart rate to 100-140 bpm. A bradycardia was noted in 51 patients (7%). Two bradyarrhythmias were noted: (1) sinus or junctional bradycardia (cycle length - 10%) occurred in 43 patients, aged 15-70 years, generally studied for unexplained syncope (n = 37); a young age (40+/-16 years), syncope (n = 37) and absence of heart disease (n = 27) were more frequent than that in patients without isoprenaline-induced sinus or junctional bradycardia; another arrhythmia (SVT or VT) was induced in seven patients with syncope, five with heart disease and two without; six young patients (<50 years) had no syncope and were studied for SVT or VT; (2) eight patients, aged 65+/-11 years, developed second-degree atrioventricular (AV) block which was supraHisian (n = 4) or infraHisian (n = 4); they were studied for exercise-related syncope; they had no signs of myocardial ischaemia and AV block was reproduced by ajmaline testing: isoprenaline revealed organic conduction disturbance. The occurrence of paradoxical bradycardia was a rare finding during isoprenaline infusion (7%); sinus or junctional bradycardia was a sign of hypervagotonia, but was without clinical significance in 35% of these patients. The development of second-degree AV block was always pathological and associated with AV conduction disturbances, which occurred spontaneously during exercise. Isoprenaline infusion appeared to be a simple means to detect organic AV conduction disturbance in patients complaining of exercise or stress-related dizziness/syncope and unable to perform exercise test.


Classical and nonclassical germanium environments in high-pressure BaGe5.
A new crystalline form of BaGe(5) was obtained at a pressure of 15(2) GPa in the temperature range from 1000(100) to 1200(120) K. Single-crystal electron and powder X-ray diffraction patterns indicate a body-centered orthorhombic structure (space group Imma, Pearson notation oI24) with unit cell parameters a = 8.3421(8) Å, b = 4.8728(5) Å, and c = 13.7202(9) Å. The crystal structure of hp-BaGe(5) consists of four-bonded Ge atoms forming complex layers with Ge-Ge contacts between 2.560(6) and 2.684(3) Å; the Ba atoms are coordinated by 15 Ge neighbors in the range from 3.341(6) to 3.739(4) Å. Analysis of the chemical bonding using quantum chemical techniques in real space reveal charge transfer from the Ba cations to the anionic Ge species. Ge atoms having nearly tetrahedral environments show an electron-localizability-based oxidation number close to 0; the four-bonded Ge atoms with a Ψ-pyramidal environment adopt a value close to 1-. In agreement with the calculated electronic density of states, the compound is a metallic conductor (electrical resistivity of ca. 240 μΩ cm at 300 K), and magnetic susceptibility measurements evidence diamagnetic behavior with χ(0) = -95 × 10(-6) emu mol(-1).


Tumor-suppressor role of Notch3 in medullary thyroid carcinoma revealed by genetic and pharmacological induction.
Notch1-3 are transmembrane receptors that appear to be absent in medullary thyroid cancer (MTC). Previous research has shown that induction of Notch1 has a tumor-suppressor effect in MTC cell lines, but little is known about the biologic consequences of Notch3 activation for the progression of the disease. We elucidate the role of Notch3 in MTC by genetic (doxycycline-inducible Notch3 intracellular domain) and pharmacologic [AB3, novel histone deacetylase (HDAC) inhibitor] approaches. We find that overexpression of Notch3 leads to the dose-dependent reduction of neuroendocrine tumor markers. In addition, Notch3 activity is required to suppress MTC cell proliferation, and the extent of growth repression depends on the amount of Notch3 protein expressed. Moreover, activation of Notch3 induces apoptosis. The translational significance of this finding is highlighted by our observation that MTC tumors lack active Notch3 protein and reinstitution of this isoform could be a therapeutic strategy to treat patients with MTC. We demonstrate, for the first time, that overexpression of Notch3 in MTC cells can alter malignant neuroendocrine phenotype in both in vitro and in vivo models. In addition, our study provides a strong rationale for using Notch3 as a therapeutic target to provide novel pharmacologic treatment options for MTC.


Refractory Hypothyroidism Due to Improper Storage of Levothyroxine Tablets.
A not negligible part of hypothyroid patients on levothyroxine therapy do not normalize serum thyrotropin (TSH) concentrations. "Refractory hypothyroidism," i.e., a condition characterized by persistently abnormal serum TSH levels despite adequate titration of l-T4 substitution therapy, requires biochemical and instrumental investigation, but no definite etiology is found in up to 15% of cases. To report patients presenting with refractory hypothyroidism with proven improper storage of levothyroxine tablets. Patients on l-T4 substitution therapy referred to three Italian outpatient Clinics of Endocrinology between January 2013 and December 2015 for refractory hypothyroidism were investigated for levothyroxine tablet exposure to humidity, light, and high temperature. We report eight patients, accounting for approximately 1% of all hypothyroid patients and 5% of those with refractory hypothyroidism in our series. Careful anamnesis disclosed that these patients stored levothyroxine tablets inappropriately. Normalization of serum TSH concentrations was obtained in all cases by simply recommending to store the new levothyroxine tablets away from heat, light, and humidity. Refractory hypothyroidism linked to improper storage of l-T4 tablets does exist and might be an underrecognized entity. In addition to proper modalities of ingestion of l-T4 tablets, patients need to be instructed on proper modalities of storage, as well.


Long-latency auditory event-related potentials in epilepsy.
Long latency auditory event-related potentials have been shown to change in patients with cerebral dysfunction. Some seizure patients with no evidence of brain damage or mental retardation show altered interictal cognitive and memory function. Long-latency auditory event-related potentials to tone stimulation were recorded in nineteen control subjects and seventeen patients with complex partial or partial and secondarily generalized seizures who had no evidence of brain damage, retardation, or drug intoxication, and whose seizures were controlled when studied. The latencies of N2 and P3 components were significantly longer in seizure patients than control subjects, and the P3 waveform was significantly greater in amplitude in epileptics. These findings suggest that cognitive event-related potentials are affected by partial epilepsy. The changes may be related to the recently reported involvement of the hippocampus in ERP generation, or to loss or alteration of modulatory functions, possibly cholinergic in nature, in the temporal lobe consequent upon epileptogenesis.


Urinary biomarker profiling in transitional cell carcinoma.
Urinary biomarkers or profiles that allow noninvasive detection of recurrent transitional cell carcinoma (TCC) of the bladder are urgently needed. We obtained duplicate proteomic (SELDI) profiles from 227 subjects (118 TCC, 77 healthy controls and 32 controls with benign urological conditions) and used linear mixed effects models to identify peaks that are differentially expressed between TCC and controls and within TCC subgroups. A Random Forest classifier was trained on 130 profiles to develop an algorithm to predict the presence of TCC in a randomly selected initial test set (n = 54) and an independent validation set (n = 43) several months later. Twenty two peaks were differentially expressed between all TCC and controls (p < 10(-7)). However potential confounding effects of age, sex and analytical run were identified. In an age-matched sub-set, 23 peaks were differentially expressed between TCC and combined benign and healthy controls at the 0.005 significance level. Using the Random Forest classifier, TCC was predicted with 71.7% sensitivity and 62.5% specificity in the initial set and with 78.3% sensitivity and 65.0% specificity in the validation set after 6 months, compared with controls. Several peaks of importance were also identified in the linear mixed effects model. We conclude that SELDI profiling of urine samples can identify patients with TCC with comparable sensitivities and specificities to current tumor marker tests. This is the first time that reproducibility has been demonstrated on an independent test set analyzed several months later. Identification of the relevant peaks may facilitate multiplex marker assay development for detection of recurrent disease.


Patient adherence to guidelines for diabetes eye care: results from the diabetic eye disease follow-up study.
Early detection and treatment of diabetic eye disease can prevent blindness, yet many persons with diabetes lack regular eye care. This study followed 569 people with diabetes participating in blindness prevention programs during 1985 through 1987; it was found that 35% of subjects received dilated eye examinations before entering the programs, in comparison with 60% afterward. About 85% of participants referred for proliferative retinopathy treatment began such treatment, and, of these, 85% completed treatment. A lack of knowledge about the disease and limited finances were primary reasons for nonadherence. To improve the effectiveness of prevention programs, eye care providers and program staff must strive to eliminate these educational and financial barriers.


A wavefront adaptive sensing beamformer for ocean acoustic waveguides.
This paper addresses robust adaptive beamforming for passive sonar in uncertain, shallow-water environments. Conventional beamforming is still common in passive sonar because adaptive beamformers suffer from signal mismatch in complex multipath environments. Existing approaches to robust adaptive beamforming try to model and account for the uncertainty in the beamformer's hypothesized signal subspace by using additional linear or quadratic constraints. Doing so, however, reduces the adaptivity of the beamformer and is prone to insufficiently suppressing interference. Instead, this paper uses blind source separation methods to adaptively estimate the complex spatial wavefronts of both targets and interference without requiring detailed physical modeling of the channel. By exploiting the different temporal spectra and/or frequency-selective multipath fading of targets and interference, this approach constructs a "signal-free" covariance matrix without imposing directional gain constraints. In doing so, the wavefront adaptive sensing (WAS) beamformer is able to separate targets from strong interference that is within the conventional beam width of the target. Simulation results in a realistic shallow-water channel are presented as well as results using the SWellEx96 S59 data with an injected target to show that the proposed WAS beamformer outperforms conventional and minimum variance adaptive beamformers in a shallow-water scenario.


The reduction of formaldehyde by bacterial cells.
Formaldehyde is reduced to methyl alcohol by living cells of a creatinine-decomposing strain of Pseudomonas aeruginosa. The amount of HCHO taken up in 30 minutes by 3 x 10(10) cells of this organism is termed its reducing capacity. It was found to be 400 to 480 microg. The reaction takes place over wide pH and temperature ranges, is independent of the concentration of formaldehyde as long as the latter is not high enough to exert a toxic effect on the cell, but depends on the number of bacteria present. In cultures, 3 to 7 days old, there is a decline in reducing capacity without a proportionate decrease in the number of viable cells. On the other hand in cultures, 2 to 4 weeks old, the number of viable cells determines the amount of HCHO taken up. N/100 NaOH depresses the reducing capacity of the organism without affecting bacterial viability. Exposure of bacterial suspensions to temperatures of 46-52 degrees C. for 10 minutes causes a far more rapid decrease in the number of viable cells than in reducing capacity. Incubation of cellular suspensions with nutrient substances, which are able to support adequately the growth of the organism, for 30 minutes prior to the addition of HCHO, induces increases in reducing capacity. The uptake of HCHO by different microorganisms seems to be related to their gaseous and nutritional requirements. Strains of P. aeruginosa and P. fluorescens are predominantly aerobic, least fastidious in their nutritional requirements, most active against HCHO, and least susceptible to the action of aureomycin and chloromycetin. The potential significance of cellular reducing capacity is discussed.


Therapeutic targets for cholestatic liver injury.
Cholestasis is a reduction in bile flow that occurs during numerous pathologies. Blockage of the biliary tracts results in hepatic accumulation of bile acids or their conjugate bile salts. The molecular mechanisms behind liver injury associated with cholestasis are extensively studied, but not well understood. Multiple models of obstructive cholestasis result in a significant inflammatory infiltrate at the sites of necrosis that characterize the injury. This review will focus on direct bile acid toxicity during cholestasis, bile acid signaling processes and on the development and continuation of inflammation during cholestasis, with a focus on novel proposed molecular mediators of neutrophil recruitment. While significant progress has been made on these molecular mechanisms, a continued focus on how cholestasis and the innate immune system interact is necessary to discover targetable therapeutics that might protect the liver while leaving global immunity intact. While bile acid toxicity likely occurs in humans and other mammals when toxic bile acids accumulate, persistent inflammation is likely responsible for continued liver injury during obstructive cholestasis. Targeting molecular mediators of inflammation may help prevent liver injury during acute cholestasis both in murine models and human patients.


[Effect study of Sonic hedgehog overexpressed hair follicle stem cells in hair follicle regeneration].
To determine the expression level of Sonic hedgehog (Shh) in the passage of hair follicle stem cells (HFSCs), analyze the effect of Shh overexpression on the proliferation activity of HFSCs, and explore the survival of HFSCs after Shh overexpression and its effect on hair follicle regeneration. Hair follicles from the normal area (H1 group) and alopecia area (H2 group) of the scalp donated by 20 female alopecia patients aged 40-50 years old were taken, and the middle part of the hair follicle was cut under the microscope to culture, and the primary HFSCs were obtained and passaged; the positive markers (CD29, CD71) and negative marker (CD34) on the surface of the fourth generation HFSCs were identified by flow cytometry. The two groups of HFSCs were transfected with Shh-overexpressed lentivirus. Flow cytometry and cell counting kit 8 assay were used to detect the cell cycle changes and cell proliferation of HFSCs before and after transfection, respectively. Then the HFSCs transfected with Shh lentivirus were transplanted subcutaneously into the back of nude mice as the experimental group, and the same amount of saline was injected as the control group. At 5 weeks after cell transplantation, the expression of Shh protein in the back skin tissue of nude mice was detected by Western blot. HE staining and immunofluorescence staining were used to compare the number of hair follicles and the survival of HFSCs between groups. The isolated and cultured cells were fusiform and firmly attached to the wall; flow cytometry showed that CD29 and CD71 were highly expressed on the surface of the cells, while CD34 was lowly expressed, suggesting that the cultured cells were HFSCs. The results of real-time fluorescence quantitative PCR and Western blot showed that the expression levels of Shh protein and gene in the 4th, 7th, and 10th passages of cells in H1 and H2 groups decreased gradually with the prolongation of culture time in vitro. After overexpression of Shh, the proliferation activity of HFSCs in the two groups was significantly higher than that in the blank group (not transfected with lentivirus) and the negative control group (transfected with negative control lentivirus), and the proliferation activity of HFSCs in H1 group was significantly higher than that in H2 group before and after transfection, showing significant differences ( P<0.05). At 5 weeks after cell transplantation, Shh protein was stably expressed in the dorsal skin of each experimental group; the number of hair follicles and the expression levels of HFSCs markers (CD71, cytokeratin 15) in each experimental group were significantly higher than those in the control group, and the number of hair follicles and the expression levels of HFSCs markers in H1 group were significantly higher than those in H2 group, and the differences were significant ( P<0.05). Lentivirus-mediated Shh can be successfully transfected into HFSCs, the proliferation activity of HFSCs significantly increase after overexpression of Shh, which can secrete and express Shh continuously and stably, and promote hair follicle regeneration by combining the advantages of stem cells and Shh.


Get+Connected: Development and Pilot Testing of an Intervention to Improve Computer and Internet Attitudes and Internet Use Among Women Living With HIV.
For persons living with chronic medical conditions, the Internet can be a powerful tool for health promotion, and allow for immediate access to medical information and social support. However, women living with human immunodeficiency virus (HIV) in the United States face numerous barriers to computer and Internet use. Health behavior change models suggest that the first step towards adopting a new health behavior is to improve attitudes towards that behavior. To develop and pilot test Get+Connected, an intervention to improve computer and Internet attitudes and Internet use among women living with HIV. To develop Get+Connected, we reviewed the extant literature, adapted an existing curriculum, and conducted a focus group with HIV-positive women (n=20) at a community-based organization in the Bronx, New York. Get+Connected was comprised of five weekly sessions covering the following topics: basic computer knowledge and skills, identifying reliable health-related websites, setting up and using email and Facebook accounts, and a final review session. We recruited 12 women to participate in pilot testing. At baseline, we collected data about participants' sociodemographic information, clinical characteristics, and technology device ownership and use. At baseline, intervention completion, and three months postintervention, we collected data regarding attitudes towards computers and the Internet (Attitudes Towards Computers and the Internet Questionnaire [ATCIQ]; possible scores range from 5-50) as well as frequency of Internet use (composite measure). To examine changes in ATCIQ scores and Internet use over time, we used generalized estimating equations. We also collected qualitative data during intervention delivery. Among women in our sample, the median age was 56 years (interquartile range=52-63). All participants were black/African American and/or Latina. Seven participants (7/12, 58%) had a high school diploma (or equivalent) or higher degree. Ten participants (10/12, 83%) reported owning a mobile phone, while only one (1/12, 8%) reported owning a computer or tablet. Only one participant (1/12, 8%) reported having ever used the Internet or email. Internet nonusers cited lack of computer/Internet knowledge (6/11, 54%) and lack of access to a computer or similar device (4/11, 36%) as the main barriers to use. Over time, we observed an improvement in attitudes towards computers and the Internet (ATCIQ scores: 33.5 at baseline, 35 at intervention completion, and 36 at three months postintervention; P=.008). No significant increase in Internet use was observed (P=.61). Qualitative findings indicated excitement and enthusiasm for the intervention. In our sample of urban, technology-inexperienced HIV-positive women, participation in Get+Connected was associated with an improvement in attitudes towards computers and the Internet, but not Internet use. Changing attitudes is the first step in many health behavior change models, indicating that with improved access to computer and Internet resources, frequency of Internet use may also have increased. Future studies should consider addressing issues of access to technology in conjunction with Get+Connected.


[Persistent central diabetes insipidus in a very low birth weight infant].
Central diabetes insipidus (DI) is extremely rare during the neonatal period. Most cases of central DI are secondary to a known aetiology. Substitutive treatment with desmopressin is effective with nasal or oral preparation, but doses are variable and must be tailored individually. We report on a case in a very low birth weight infant with an idiopathic central DI during the first month of life. He was successfully treated with oral desmopressin. The treatment was maintained after discharge with low doses desmospressin.


Function of trans-acting genes of theachaete-scute complex in sensory organ patterning in the mesonotum ofDrosophila.
Cell-cell interactions play a fundamental role in the differentiation of nervous elements in constant patterns, both during embryogenesis and imaginal development. In this paper we analyse the role of genes of theachaete-scute andEnhancer of split complexes, plus the genesextramacrochaetae, Notch, Delta, andHairless in the patterning of sensory elements in the mesonotum ofDrosophila. The phenotypes of different alleles of these genes, including lethals in genetic mosaics, reveal their participation in two processes, the singling out from epidermal cells of sensory organ mother cells and their subsequent differentiation. Studies of allelic combinations of different genes lead to a model of the genetic interactions involved in the processes of pattern formation. In this model, theachaete-scute complex plays a central role, determining sensory organ mother cells and preventing neighbouring cells from following the same developmental pathway.


Synthesis and biological activity of D-glucopyranosyl peptide T derivatives.
The solid phase procedure, based on the Fmoc (9-fluorenylmethyloxycarbonyl) chemistry, was used to prepare some peptide T analogues in which D-glucopyranosyl units are beta-O-glycosidically linked to Thr4 and/or Thr5 side chains. All glycopeptides showed significant human monocyte chemotaxis and high resistance to degradation by plasma or brain enzymes.