Embryonic development of Galloisiana yuasai Asahina, with special reference to external morphology (insecta: Grylloblattodea).
The embryogenesis of Grylloblattodea, one of the most primitive of the polyneopteran orders, is described using Galloisiana yuasai with special reference to external morphology. The egg membranes are characterized by an endochorion crossed by numerous vertical aeropyles and a fairly thin vitelline membrane, features shared by Mantophasmatodea. The inner layer formation is of the fault type. Serosal elements in the amnioserosal fold differentiate into hydropylar cells, to function in water absorption together with specialized amniotic structures, i.e., an amniotic strand and a thickened amnion. The germ band is of the short germ type. The germ band immerses deep into the yolk after its full elongation along the egg surface, and in this respect blastokinesis closely resembles that of Mantophasmatodea. The embryological features, i.e., those on egg membranes and blastokinesis, may suggest a closer affinity of Grylloblattodea and Mantophasmatodea. Appendages, ectodermal invaginations, and sternal and pleural sclerites are discussed in the light of serial homology, to provide a new basis for elucidating the insect body plan. Appendages are divided into the proximal coxopodite and distal telopodite, the former being divided further into the subcoxa and coxa. Subcoxal and coxal elements are identified in the mandible as well as in the abdominal appendages. The subcoxa is divided into the epimeron and episternum by the pleural suture in thoracic segments. Likewise, in the abdominal segments the subcoxa is divided into two, although the homologs of the epimeron and episternum are not sclerotized, and in the labial segment the subcoxal derivative or the postmentum is divided into the submentum and mentum. Two coxal endites bulge out from the medial side of the gnathal appendages. The mandibular molar and incisor, maxillary lacinia and galea, and labial glossa and paraglossa are serially homologous with each other. In the thoracic segments the original embryonic sternum or "protosternum" is largely replaced by subcoxal elements, and merely remains as a small anterior presternum and a posterior spinasternum. A major part of the venter is represented by the derivatives of the episternum such as an extensive basisternum, katepisternum, and trochantin and the medial element of the epimeron. The pleuron is derived from the episternal elements or the anepisternum and preepisternum, which bears a spiracle in the mesothorax and metathorax, and the lateral element of the epimeron. The homolog of the preepisternum in the prothorax is the cervical sclerite, but with no spiracle developed. A median ventral invagination arises in the thoracic segments as a spina, and the homolog of the spina develops into the eversible sac in the first abdominal segment.


Prophylactic antiparkinson drug use: II. Withdrawal after long-term maintenance therapy.
Although the efficacy of long-term neuroleptic treatment of schizophrenic patients is generally accepted, the use of concurrent antiparkinson drugs is less well defined. The value of prolonged antiparkinson drug use in preventing extrapyramidal side effects is controversial. More than 30 studies of antiparkinson drug withdrawal have attempted to answer this question. The authors reviewed all double-blind, placebo-controlled studies, and found most to contain serious methodologic or statistical flaws. There is evidence to support the long-term use of these agents in preventing extrapyramidal side effects. The authors offer an analysis of the benefits and risks that are involved with prophylactic antiparkinson drug use, and conclude that most patients would benefit from maintenance therapy.


EphrinB2/ephB2-mediated myenteric synaptic plasticity: mechanisms underlying the persistent muscle hypercontractility and pain in postinfectious IBS.
Patients with irritable bowel syndrome (IBS) show pain hypersensitivity and smooth muscle hypercontractility in response to colorectal distension (CRD). Synaptic plasticity, a key process of memory formation, in the enteric nervous system may be a novel explanation. This study aimed to explore the regulatory role of ephrinB2/ephB2 in enteric synaptic plasticity and colonic hyperreactive motility in IBS. Postinfectious (PI)-IBS was induced by Trichinella spiralis infection in rats. Isometric contractions of colonic circular muscle strips, particularly neural-mediated contractions, were recorded ex vivo. Meanwhile, ephrinB2/ephB2-mediated enteric structural and functional synaptic plasticity were assessed in the colonic muscularis, indicating that ephrinB2 and ephB2 were located on enteric nerves and up-regulated in the colonic muscularis of PI-IBS rats. Colonic hypersensitivity to CRD and neural-mediated colonic hypercontractility were present in PI-IBS rats, which were correlated with increased levels of cellular homologous fos protein (c-fos) and activity-regulated cystoskeleton-associated protein (arc), the synaptic plasticity-related immediate early genes, and were ameliorated by ephB2Fc (an ephB2 receptor blocker) or MK801 (an NMDA receptor inhibitor) exposure. EphrinB2/ephB2 facilitated synaptic sprouting and NMDA receptor-mediated synaptic potentiation in the colonic muscularis of PI-IBS rats and in the longitudinal muscle-myenteric plexus cultures, involving the Erk-MAPK and PI3K-protein kinase B pathways. In conclusion, ephrinB2/ephB2 promoted the synaptic sprouting and potentiation of myenteric nerves involved in persistent muscle hypercontractility and pain in PI-IBS. Hence, ephrinB2/ephB2 may be an emerging target for the treatment of IBS.-Zhang, L., Wang, R., Bai, T., Xiang, X., Qian, W., Song, J., Hou, X. EphrinB2/ephB2-mediated myenteric synaptic plasticity: mechanisms underlying the persistent muscle hypercontractility and pain in postinfectious IBS.


The effect of hepatic steatosis on survival following resection of colorectal liver metastases in patients without preoperative chemotherapy.
Hepatic steatosis, a common condition associated with insulin resistance and excess body weight, is reported to be associated with an increased risk for perioperative mortality in patients undergoing resection of colorectal liver metastases (CLM), but its impact upon longterm survival is less well documented. The effects of background liver pathology, categorized as 'normal', 'with steatosis' and 'other', on perioperative mortality, overall survival (OS) and cancer-specific survival (CSS) were assessed in patients undergoing resection for CLM according to data maintained in the LiverMetSurvey database. As preoperative chemotherapy may confound the effects of steatosis, patients who had been given preoperative chemotherapy were excluded. Survival analyses included log-rank tests for comparisons, and multivariate Cox models, including well-established prognosticators. Of 5853 patients who underwent first-time liver resection without preoperative chemotherapy, 1793 (30.6%) had background steatosis. Rates of 90-day perioperative mortality in patients with normal, steatosis and other pathologies were 2.8%, 2.1% and 4.9%, respectively. Steatosis was associated with improved 5-year OS (47.4% versus 43.0%; log rank, P = 0.0017) and CSS (56.1% versus 50.3%; P = 0.002) compared with normal background liver. After adjustments, the survival advantage associated with steatosis remained (hazard ratio = 0.806, 95% confidence interval 0.717-0.905 for CSS). The paradoxical survival advantage observed in patients with steatosis undergoing liver resection for CLM generates a hypothesis that peri-diagnosis of excess body adiposity has a survival protective effect that warrants further research.


PAOT-Liquid® Technology: An Easy Electrochemical Method for Evaluating Antioxidant Capacity of Wines.
Polyphenol compounds present in high quantity in wines are well-known to have potent cardio-protective properties through several biological mechanisms including antioxidant activity [1]. A large number of methods have been developed for evaluating the antioxidant capacity of food matrices. Most of them have, however, the disadvantage of being time consuming and require specific analytical protocols and devices. In the present study, we present the electrochemical PAOT (Pouvoir Antioxydant Total)-Liquid® Technology which can be easily used by winemakers for evaluating antioxidant activity of wine during all steps of making process. The methodology is based on the measurement of electric potential variation resulting from chemical reactions between wine polyphenols and a free radical mediator M• as source of oxidants. Total antioxidant activity as estimated by the PAOT-Liquid® activity was 6.8 fold higher in red wines (n = 14) when compared to rosé (n = 3) and white (n = 3) wines bought in a commercial market. Moreover, PAOT-Liquid® activity was highly correlated with total polyphenols content (TPC) of all wines (r = 0.9540, p < 0.0001) and the classical DPPH (2,2-diphenyl-1-picryhydrazyl) assay which is often used for evaluating antioxidant capacity of food matrices (r = 0.9102, p < 0.0001).


Helping older patients to cope with cardiac and pulmonary disease.
Family challenges, depression, and age-related developmental and psychological issues must be considered when structuring interventions for elder cardiopulmonary patients. Elderly patients tend to have difficulty coping when they face novel, unpredictable circumstances and are left to flounder in suspenseful anticipation. Furthermore, if support is not forthcoming during such times--or if they are treated in ways that strip them of control rather than in ways that bolster their sense of control--elderly patients are at great risk of quickly developing a passive, learned helplessness that can significantly complicate their rehabilitation. The overall well-being of elderly cardiopulmonary patients is affected by more than the actions of health-care providers. Poverty, pension and health-care plans, institutionalization, concomitant diseases, family issues, and other factors have a profound and, frequently, an overriding effect on the functional status of the elderly population. However, it is also true that the provision of spirit-enhancing care can make a tremendous difference in quality of life for elderly patients, independent of factors such as residential circumstance or health status. The most valued and valuable sources of social support for elderly patients come from family, church, and health-care providers. Our interventions either enhance or diminish an elderly patient's sense of autonomy and control. Our task-driven health-care system, replete with its growing emphasis on brevity of treatments and cost-effectiveness, can create a style and pace of delivering care that demoralizes an elderly patient. The results can be devastating: "When the spirit is broken, one has no will to marshall coping skills". But health-care providers who are attuned to the psychosocial issues relevant to the later life stages can make a profound difference in enhancing both rehabilitation and quality of life for elderly cardiopulmonary patients and their loved ones.


DNA Commission of the International Society of Forensic Genetics (ISFG): an update of the recommendations on the use of Y-STRs in forensic analysis.
The DNA Commission of the International Society of Forensic Genetics (ISFG) regularly publishes guidelines and recommendations concerning the application of DNA polymorphisms to the problems of human identification. A previous recommendation published in 2001 has already addressed Y-chromosome polymorphisms, with particular emphasis on short tandem repeats (STRs). Since then, the use of Y-STRs has become very popular, and numerous new loci have been introduced. The current recommendations address important aspects to clarify problems regarding the nomenclature, the definition of loci and alleles, population genetics and reporting methods


Effects of treatment history and centralized intake on drug treatment outcomes.
This study assesses differences between first-time treatment clients (n=90) and repeat treatment clients (n=361), including whether entering treatment through a central intake unit affects outcomes differently for the two groups. Interview data were collected at baseline, one-month and 12-month follow-up. Study groups were similar in gender, race and age, but repeat treatment participants were more educated, more likely to primarily use heroin and more likely to have ever injected drugs. First-time treatment clients were more likely to have been required to enter treatment, but less likely to have applied to another program or to be in the program they desired. First-time treatment clients were also more likely to be in outpatient or day treatment, and less likely to be in residential treatment. Problem severity decreased for both groups over time, with no significant differences between groups. There was one significant interaction effect of study group and length of stay on social problem severity, such that longer stays in treatment led to a greater reduction in social problems for repeat treatment clients. Route of treatment entry (CIU/non-CIU) was not associated with problem severity nor change in problem severity over time for either study group.


Production and characterization of T-cell clones specific for trinitrophenyl (TNP)-modified syngeneic spleen cells (TNP-self).
Using serial antigenic challenge as the method of selection and stimulation, continuous lines of cytotoxic T-lymphocytes (CTL) directed against TNBS-modified syngeneic spleen cells (TNP-self) have been generated. Spleen cells from C3H/HeJ (H-2k) mice were primed in vitro with autologous spleen cells modified with TNBS, and subsequently cloned by limiting dilution and in soft agar in the presence of IL2. These CTL clones grew continuously in medium supplemented with IL2 and in the presence of antigen. They are antigen specific and H-2 restricted in their target cell recognition. They all express Thyl and Lyt2 surface markers. None of the clones exhibit natural killer (NK) cell activity. All CTL clones tested so far are restricted in their target cell recognition to H-2Kk-TNP and none were found to be restricted to H-2Dk-TNP. These findings demonstrate at the clonal level the H-2K/D restriction of TNP-self specific CTL. These clones provide tools that may facilitate an understanding of the development and regulation of antigen specific CTL. They may also serve as models useful towards an understanding of the mechanism of lysis by CTL.


Dextran Enhances the Lentiviral Transduction Efficiency of Murine and Human Primary NK Cells.
The efficient transduction of specific genes into natural killer (NK) cells has been a major challenge. Successful transductions are critical to defining the role of the gene of interest in the development, differentiation, and function of NK cells. Recent advances related to chimeric antigen receptors (CARs) in cancer immunotherapy accentuate the need for an efficient method to deliver exogenous genes to effector lymphocytes. The efficiencies of lentiviral-mediated gene transductions into primary human or mouse NK cells remain significantly low, which is a major limiting factor. Recent advances using cationic polymers, such as polybrene, show an improved gene transduction efficiency in T cells. However, these products failed to improve the transduction efficiencies of NK cells. This work shows that dextran, a branched glucan polysaccharide, significantly improves the transduction efficiency of human and mouse primary NK cells. This highly reproducible transduction methodology provides a competent tool for transducing human primary NK cells, which can vastly improve clinical gene delivery applications and thus NK cell-based cancer immunotherapy.


The effectiveness of four interventions for the prevention of low back pain.
Low back pain affects 60% to 80% of US adults at some time during their lives. This review evaluates the effectiveness of four strategies to prevent low back pain for asymptomatic individuals: back and aerobic exercises, education, mechanical supports (corsets), and risk factor modification. The MEDLINE database was searched for all relevant articles published in English between 1966 and 1993. Bibliographies of identified articles were searched to ensure that all pertinent articles had been gathered and back pain specialists reviewed our final bibliography for completeness. A total of 190 articles were identified, and the 64 that contained original data about preventing low back pain were reviewed. Studies were graded according to strength of study design. There is limited evidence based on randomized trials and epidemiological studies that exercises to strengthen back or abdominal muscles and to improve overall fitness can decrease the incidence and duration of low back pain episodes. There is minimal evidence to support the use of educational strategies to prevent low back pain and insufficient evidence to recommend about the use of mechanical supports. Although there is no evidence supporting risk factor modification for preventing low back pain (smoking cessation and weight loss), there are other reasons to recommend the interventions. There is limited evidence to recommend exercise to prevent low back pain in asymptomatic individuals, but there is insufficient evidence to recommend other prevention strategies. These conclusions should be viewed cautiously since they are primarily based on studies conducted in the workplace rather than in clinical settings.


INBREEDING DEPRESSION IN FOUR POPULATIONS OF COLLINSIA HETEROPHYLLA NUTT (SCROPHULARIACEAE).
The effects of one and two generations of inbreeding were studied in plants from four natural populations of the annual plant, Collinsia heterophylla, using inbred and outcrossed plants generated by hand pollinations to create expected inbreeding coefficients ranging from 0-0.75. The selfing rates of the populations were estimated using allozyme markers to range from 0.37-0.69. Inbreeding depression was mild, ranging from 5-40%, but significant effects were detected for characters measured at all stages of the life cycle. Fitness components declined significantly with the inbreeding coefficient, and regression of fitness characters on inbreeding coefficients gave no evidence of any strongly synergistic effects attributable to the different genetic factors that contribute to decline in fitness under inbreeding. The magnitude of inbreeding depression did not clearly decrease with the populations' levels of inbreeding. This is not surprising because the selfing rates are similar enough that it is unlikely that the populations have been characterized for long periods of time by these different inbreeding levels.


c-Jun induces apoptosis of starved BM2 monoblasts by activating cyclin A-CDK2.
c-Jun is one of the major components of the activating protein-1 (AP-1), the transcription factor that participates in regulation of proliferation, differentiation, and apoptosis. In this study, we explored functional interactions of the c-Jun protein with several regulators of the G1/S transition in serum-deprived v-myb-transformed chicken monoblasts BM2. We show that the c-Jun protein induces expression of cyclin A, thus up-regulating activity of cyclin A-associated cyclin-dependent kinase 2 (CDK2), and causing massive programmed cell death of starved BM2cJUN cells. Specific inhibition of CDK2 suppresses frequency of apoptosis of BM2cJUN cells. We conclude that up-regulation of cyclin A expression and CDK2 activity can represent important link between the c-Jun protein, cell cycle machinery, and programmed cell death pathway in leukemic cells.


[Geo-herbalism study of Magnoliae Officinalis Cortex].
Magnoliae Officinalis Cortex( MOC),the stem bark of Magnolia officinalis( MO) and M. officinalis var. biloba( MOB),is a main ingredient in more than 200 types of Chinese formulae commonly used in clinics. MO and MOB are widely distributed in China,from Sichuan of the west to Zhejiang province of the east and from Shannxi province in the north to Guangxi province in the south. This review summarizes new findings on geo-heralism of MOC concerning textual research,plants taxonomy,genetic study,chemical study,and pharmacological activity,resulting in the following views. ①The original plants of MOC are suggested to be divided into three geographic clans according to the form of leave and the result of genetic research; ②Concentrations of magnolol,honokiol,magnoloside A,magnoloside B,magnoflorine,and β-eudesmol in samples collected from different geographic areas are varied;③Samples of MOC produced in Hubei and Sichuan were traditionally regarded as Dao-di herbs,which were called Chuanpo,and the pure haplotype of MOC produced in Hubei may become a genetic index.


Body Lateropulsion and Cerebellar Tremor in a Patient with Pontine Infarction.
Body lateropulsion is known to be caused commonly by lateral medullary lesions but rarely by pontine lesions. It is also known to be associated with lesions of the dorsal spinothalamic tract or ascending graviceptive pathways. We herein report the case of a 75-year-old woman presenting with contralateral lateropulsion and cerebellar tremor caused by pons infarction. To our knowledge, this is the first case report of pontine infarction causing both lateropulsion and cerebellar tremor. Our case may be helpful in anatomical studies of ascending graviceptive pathways.


Brain Control of Sexually Dimorphic Liver Function and Disease: The Endocrine Connection.
A multistep signaling cascade originates in brain centers that regulate hypothalamic growth hormone-releasing hormone (Ghrh) and somatostatin expression levels and release to control the pattern of GH secretion. This process is sexually fine-tuned, and relays important information to the liver where GH receptors can be found. The temporal pattern of pituitary GH secretion, which is sex-specific in many species (episodic in males and more stable in females), represents a major component in establishing and maintaining the sexual dimorphism of hepatic gene transcription. The liver is sexually dimorphic exhibiting major differences in the profile of more than 1000 liver genes related to steroid, lipid, and foreign compound metabolism. Approximately, 90% of these sex-specific liver genes were shown to be primarily dependent on sexually dimorphic GH secretory patterns. This proposes an interesting scenario in which the central nervous system, indirectly setting GH profiles through GHRH and somatostatin control, regulates sexual dimorphism of liver activity in accordance with the need for sex-specific steroid metabolism and performance. We describe the influence of the loss of sexual dimorphism in liver gene expression due to altered brain function. Among other many factors, abnormal brain sexual differentiation, xenoestrogen exposure and D2R ablation from neurons dysregulate the GHRH-GH axis, and ultimately modify the liver capacity for adaptive mechanisms. We, therefore, propose that an inefficient brain control of the endocrine growth axis may underlie alterations in several metabolic processes through an indirect influence of sexual dimorphism of liver genes.


Biochemical and structural exploration of the catalytic capacity of Sulfolobus KDG aldolases.
Aldolases are enzymes with potential applications in biosynthesis, depending on their activity, specificity and stability. In the present study, the genomes of Sulfolobus species were screened for aldolases. Two new KDGA [2-keto-3-deoxygluconate (2-oxo-3-deoxygluconate) aldolases] from Sulfolobus acidocaldarius and Sulfolobus tokodaii were identified, overexpressed in Escherichia coli and characterized. Both enzymes were found to have biochemical properties similar to the previously characterized S. solfataricus KDGA, including the condensation of pyruvate and either D,L-glyceraldehyde or D,L-glyceraldehyde 3-phosphate. The crystal structure of S. acidocaldarius KDGA revealed the presence of a novel phosphate-binding motif that allows the formation of multiple hydrogen-bonding interactions with the acceptor substrate, and enables high activity with glyceraldehyde 3-phosphate. Activity analyses with unnatural substrates revealed that these three KDGAs readily accept aldehydes with two to four carbon atoms, and that even aldoses with five carbon atoms are accepted to some extent. Water-mediated interactions permit binding of substrates in multiple conformations in the spacious hydrophilic binding site, and correlate with the observed broad substrate specificity.


Laparoscopic ureterolithotomy.
We report about the successful laparoscopic removal of ureteral stones. Since July 1993, 21 patients with large ureteral calculi have undergone laparoscopic ureterolithotomy. In 19 of 21 patients, laparoscopic ureterolithotomy was successful. The mean operating time was 90 minutes. The postoperative inhospital stay was 1 to 4 days. Laparoscopic ureterolithotomy offers an alternative to open surgery in patients with large ureteral stones or when less invasive measures fail.


Maguari Virus Associated with Human Disease.
Despite the lack of evidence for symptomatic human infection with Maguari virus (MAGV), its close relation to Cache Valley virus (CVV), which does infect humans, remains a concern. We sequenced the complete genome of a MAGV-like isolate (OBS6657) obtained from a febrile patient in Pucallpa, Ucayali, Peru, in 1998. To facilitate its classification, we generated additional full-length sequences for the MAGV prototype strain, 3 additional MAGV-like isolates, and the closely related CVV (7 strains), Tlacotalpan (1 strain), Playas (3 strains), and Fort Sherman (1 strain) viruses. The OBS6657 isolate is similar to the MAGV prototype, whereas 2 of the other MAGV-like isolates are located on a distinct branch and most likely warrant classification as a separate virus species and 1 is, in fact, a misclassified CVV strain. Our findings provide clear evidence that MAGV can cause human disease.


Whitening effects of marine pseudomonas extract.
Bacteria associated with marine invertebrates are a rich source of bioactive metabolites. The effects of marine bacteria extracts on pigmentation were investigated to find novel whitening agents. The marine bacteria collected near Gangwha Island in Korea were isolated and extracted using organic solvent. The organic extracts were screened and selected using the cell free tyrosinase activity. The whitening effects of the selected extract were further investigated using cultured melanocytes, cultured skin and in vivo zebrafish. The whitening mechanism of the marine extract was also investigated. The marine bacterial methylene chloride extract reduced the pigmentation of Melan-a cells, human melanocytes, cultured skin and in vivo zebrafish. The decrease in pigmentation was due to the inhibition of tyrosinase activity and the expression of tyrosinase and microphthalmia-associated transcription factor protein. These bacteria were identified as a novel Pseudomonas species. The methylene chloride extract of marine pseudomonas species possesses a whitening effect. Further chemical isolation and characterization of the active compounds from this marine bacterial extract are needed.


IgG and IgE antibody responses to dust mite allergens among children with asthma in Brazil.
We compared exposure and levels of IgE and IgG antibodies to inhalant allergens in 20 children with asthma and positive skin tests to Dermatophagoides pteronyssinus, living in São Paulo, to 20 control children without history of asthma or allergy and negative skin tests to D. pteronyssinus, D. farinae, and Blomia tropicalis. In 16/20 and 17/20 houses of asthmatic and control children, respectively, at least one sample was obtained which contained > 10 micrograms Der p I/g of dust. Serum IgE antibodies to D. pteronyssinus and Blomia tropicalis were > 200 RAST U/mL in 19/20 and in 16/20 asthmatic children, respectively. In the control group, IgE antibodies to either mite species were < 40 RAST U/mL in most cases. IgG anti-Der p I and anti-Der f I antibodies were detected in 17/20 asthmatics, as opposed to 3/20 controls. Neither cat nor cockroach allergens caused significant sensitization among asthmatic or control children. Although exposure to high levels of mite allergens was common in São Paulo, significant IgE and IgG antibody responses were detected only in children with asthma.


Synergistic Combinations of Curcumin, Sulforaphane, and Dihydrocaffeic Acid against Human Colon Cancer Cells.
Nutraceutical combinations that act synergistically could be a powerful solution against colon cancer, which is the second deadliest malignancy worldwide. In this study, curcumin (C), sulforaphane (S), and dihydrocaffeic acid (D, a chlorogenic acid metabolite) were evaluated, individually and in different combinations, over the viability of HT-29 and Caco-2 colon cancer cells, and compared against healthy fetal human colon (FHC) cells. The cytotoxic concentrations to kill 50%, 75%, and 90% of the cells (CC50, CC75, and CC90) were obtained, using the MTS assay. Synergistic, additive, and antagonistic effects were determined by using the combination index (CI) method. The 1:1 combination of S and D exerted synergistic effects against HT-29 at 90% cytotoxicity level (doses 90:90 µM), whereas CD(1:4) was synergistic at all cytotoxicity levels (9:36-34:136 µM) and CD(9:2) at 90% (108:24 µM) against Caco-2 cells. SD(1:1) was significantly more cytotoxic for cancer cells than healthy cells, while CD(1:4) and CD(9:2) were similarly or more cytotoxic for healthy cells. Therefore, the SD(1:1) combination was chosen as the best. A model explaining SD(1:1) synergy is proposed. SD(1:1) can be used as a basis to develop advanced food products for the prevention/co-treatment of colon cancer.


Genome-wide characterization of cellulases from the hemi-biotrophic plant pathogen, Bipolaris sorokiniana, reveals the presence of a highly stable GH7 endoglucanase.
Bipolaris sorokiniana is a filamentous fungus that causes spot blotch disease in cereals like wheat and has severe economic consequences. However, information on the identities and role of the cell wall-degrading enzymes (CWDE) in B. sorokiniana is very limited. Several fungi produce CWDE like glycosyl hydrolases (GHs) that help in host cell invasion. To understand the role of these CWDE in B. sorokiniana, the first step is to identify and annotate all possible genes of the GH families like GH3, GH6, GH7, GH45 and AA9 and then characterize them biochemically. We confirmed and annotated the homologs of GH3, GH6, GH7, GH45 and AA9 enzymes in the B. sorokiniana genome using the sequence and domain features of these families. Quantitative real-time PCR analyses of these homologs revealed that the transcripts of the BsGH7-3 (3rd homolog of the GH 7 family in B. sorokiniana) were most abundant. BsGH7-3, the gene of BsGH7-3, was thus cloned into pPICZαC Pichia pastoris vector and expressed in X33 P. pastoris host to be characterized. BsGH7-3 enzyme showed a temperature optimum of 60 °C and a pHopt of 8.1. BsGH7-3 was identified to be an endoglucanase based on its broad substrate specificity and structural comparisons with other such endoglucanases. BsGH7-3 has a very long half-life and retains 100% activity even in the presence of 4 M NaCl, 4 M KCl and 20% (v/v) ionic liquids. The enzyme activity is stimulated up to fivefold in the presence of Mn+2 and Fe+2 without any deleterious effects on enzyme thermostability. Here we reanalysed the B. sorokiniana genome and selected one GH7 enzyme for further characterization. The present work demonstrates that BsGH7-3 is an endoglucanase with a long half-life and no loss in activity in the presence of denaturants like salt and ionic liquids, and lays the foundation towards exploring the Bipolaris genome for other cell wall-degrading enzymes.


Gerstmann-Sträussler-Scheinker disease: immunohistological and experimental studies.
The older brother of the patient from whom the Fukuoka-1 strain was isolated was found to have numerous kuru plaques, the main finding common to both siblings. Other clinicopathological features including spongiform change were absent in the older brother. Immunostaining using anti-kuru plaque core protein and anti-beta-protein peptide revealed many kuru plaques and a few senile plaques in the older brother. Experimental transmission of the disease to laboratory animals was successful, using tissues from both siblings, through inoculation of fresh brain homogenates, purified prion protein, and formalin-fixed brain homogenates. Prion protein fractions from the patient's brain shortened the incubation periods and formalin-fixed mouse brains did not lengthen the periods. The disease in the two brothers can be classified as Gerstmann-Sträussler-Scheinker disease, a familial variant of Creutzfeldt-Jakob disease. Gerstmann-Sträussler-Scheinker disease manifests a variety of clinicopathological features. Immunohistological verification of kuru plaques has major diagnostic value in assessing dementia.


Marginal adaptation of CAD-CAM onlays: Influence of preparation design and impression technique.
Factors that may affect the marginal adaptation of computer-aided design and computer-aided manufacturing (CAD-CAM) restorations include preparation design, impression technique, and CAD-CAM system. The influence of impression technique and preparation design on CAD-CAM partial coverage restorations has not been fully addressed. The purpose of this in vitro study was to investigate the influence of direct and indirect digital scanning techniques and 2 preparation designs on the marginal adaptation of CAD-CAM onlays. Two mesio-occlusal buccal onlay preparations with reduction of the mesiobuccal cusp were made: conventional preparation (CP) with a 1.2-mm modified shoulder margin and modified preparation (MP) flat cuspal reduction without shoulder. Virtual models were generated from each preparation by using a digital scanner (BlueCam; Dentsply Sirona) from the plastic teeth (direct digital scan) or from the stone dies (indirect digital scan). Onlays were designed using a CAD-CAM system (CEREC 4.0; Dentsply Sirona), and nanoceramic resin blocks (Lava Ultimate Restorative; 3M ESPE) were milled using the CEREC MCX milling machine. Marginal discrepancy was evaluated using an optical stereomicroscope at ×25 magnification in 18 locations distributed along the margins of the preparation. The data were analyzed by using 3-way ANOVA followed by the Tukey HSD test (α=.05). CP presented a statistically significant reduced average marginal adaptation (59 ±50 μm) than did MP (69 ±58 μm) (P<.001). The Tukey HSD test showed the presence of a significantly larger marginal discrepancy in the mesial and buccal locations of MP when compared with CP. Regarding impression techniques, the buccal location presented the smallest average marginal discrepancy in restorations fabricated with indirect impression when compared with direct impression (42 ±33 μm and 60 ±39 μm) (P<.001). The results showed that conventional preparation with a modified shoulder margin presented improved marginal adaptation compared with modified preparation with flat cuspal reduction. Direct and indirect digital scanning techniques produced restorations within a clinically acceptable range; however, the indirect scanning technique resulted in the fabrication of restorations with superior marginal adaptation on the buccal location.


Identification of relaxin-3/INSL7 as a ligand for GPCR142.
We have recently identified the insulin-like peptide relaxin-3 (aka INSL7) as the endogenous ligand for an orphan G-protein-coupled receptor, GPCR135 (aka somatostatin- and angiotensin-like peptide receptor). Analysis of possible receptors related to GPCR135 revealed a single orphan receptor, GPCR142. Thus, we tested whether GPCR142 could also respond to relaxin-3 or related insulin-like molecules. Surprisingly, GPCR142 was activated by nanomolar concentrations of relaxin-3 but was completely unresponsive to all other known insulin-like peptides. We evaluated by reverse transcriptase-PCR the expression of GPCR142 mRNA in a variety of human tissues and found expression in brain, kidney, testis, thymus, placenta, prostate, salivary gland, thyroid, and colon. In an analysis of other species, we were able to find a full-length mouse homolog of GPCR142, but were unable to detect any complete GPCR142 transcripts in rat. With respect to intracellular signaling, GPCR142 is similar to GPCR135 in that it potently inhibits adenylate cyclase and stimulates 35S-GTPgammaS incorporation in response to relaxin-3. However, whereas GPCR135 signaling could be converted to calcium mobilization using a Gqi5 or Galpha16 G-proteins, GPCR142 was only capable of functioning in the presence of Galpha16. In the accompanying article (Liu, C., Eriste, E., Sutton, S., Chen, J., Roland, B., Kuei, C., Farmer, N., Jörnvall, H., Sillard, R., and Lovenberg, T. W. (2003) J. Biol. Chem. 278, 50754-50764), we present the case that relaxin-3, which has previously been shown to bind to the relaxin receptor LGR7, is most likely the endogenous ligand for GPCR135. In this report, we show an additional receptor, GPCR142, which is also selectively activated by relaxin-3. However, the anatomical localization of GPCR142 suggests that GPCR142 may have different physiological functions.


Demographics and natural history of HIV-1-infected spontaneous controllers of viremia.
HIV-1-infected persons spontaneously controlling viremia without treatment (SCV) are rare. Sex and race effects on prevalence and outcome are poorly defined, and it is unclear whether SCV qualitatively or quantitatively differs from typical infection. These issues are examined in this article. Medical records of 46 524 persons receiving outpatient care for HIV-1 infection were reviewed. Of these, 29 811 had adequate viremia testing for SCV screening. SCV was defined as at least three consecutive plasma viremia measurements <50 RNA copies/ml spanning at least 1 year without treatment. SCV loss was defined as at least three consecutive viremia measurements ≥50 RNA copies/ml or one ≥1000 RNA copies/ml. Demographics of persons with SCV were compared with the total population. Viremia and blood CD4 T-cell levels during SCV were compared between demographic subgroups and persons who maintained or lost SCV during observation. In total, 53 persons (0.18%) met SCV criteria. Prevalence was higher for women versus men and blacks versus whites; these appeared independent. Loss of SCV was observed at 1.22% per year, and significantly associated with viremia 'blips'. Blip magnitudes fit log-normal distributions with means below 50 RNA copies/ml. Our novel observation of higher SCV prevalence in women and blacks is consistent with prior studies of typical chronic infection. Viremia blips correspond to greater risk of loss of SCV, likely reflecting higher set-point viremia under the limit of detection. Our findings suggest that SCV represents an extreme along a continuum of HIV-1 infection, and not qualitative difference.


The impact of prothrombotic mutations on factor consumption in adult patients with severe hemophilia.
About 10% of patients with severe hemophilia exhibit a milder clinical phenotype with less frequent bleeds. Among many other factors, coinheritance of prothrombotic mutations have been proposed to act as modulators of clinical severity in severe hemophilia. We conducted a study to evaluate the impact of 3 prothrombotic mutations (factor V Leiden, factor II, and methylenetetrahydrofolate reductase mutations) on clinical phenotype of patients with severe hemophilia in our institution. For this purpose we compared the average annual factor concentrate consumption between carriers and noncarriers of prothrombotic mutations. A total of 38 hemophilia A and B patients with factor levels less than 1 were recruited between October 2006 and October 2007. Prothrombotic mutations were detected in venous blood using polymerase chain reaction amplification technique. Eighteen patients (47%) carried no prothrombotic mutations. The remaining 20 patients (53%) were found to be carriers of either 1 or 2 mutations. Median age in both carrier and the non-carrier groups was 27 years. None of the patients in either group gave a history of thromboembolic event. Median annual factor concentrate consumptions in carriers and noncarriers were 610 +/- 530 units/kg and 770 +/- 670 units/kg, respectively (P = .203). Our results demonstrated no significant difference in annual factor concentrate consumption between carriers and noncarriers of prothrombotic mutations. Considering that average annual factor consumption is a surrogate indicator of clinical phenotype, we concluded that coinheritance of prothrombotic mutations was not associated with occurrence of different clinical phenotypes in severe hemophilia.


Micrometer-sized TPM emulsion droplets with surface-mobile binding groups.
Colloids coated with lipid membranes have been widely employed for fundamental studies of lipid membrane processes, biotechnological applications such as drug delivery and biosensing, and more recently, for self-assembly. The latter has been made possible by inserting DNA oligomers with covalently linked hydrophobic anchors into the membrane. The lateral mobility of the DNA linkers on micrometer-sized droplets and solid particles has opened the door to creating structures with unprecedented structural flexibility. Here, we investigate micro-emulsions of TPM (3-(trimethoxysilyl)propyl methacrylate) as a platform for lipid monolayers and further functionalization with proteins and DNA oligonucleotides. TPM droplets can be produced with a narrow size distribution and are polymerizable, thus providing supports for model lipid membranes with controlled size and curvature. With fluorescence recovery after photobleaching, we observed that droplet-attached lipids, NeutrAvidin proteins, as well as DNA oligonucleotides all show mobility on the surface. We explored the assembly of micron-sized particles on TPM-droplets by exploiting either avidin-biotin interactions or double-stranded DNA with complementary single-stranded end groups. While the single molecules are mobile, the particles that are attached to them are not. We propose that this is caused by the heterogeneous nature of emulsified TPM, which forms an oligomer network that limits the collective motion of linkers, but allows the surface mobility of individual molecules.


Effect of mutation and vaccination on spread, severity, and mortality of COVID-19 disease.
Coronavirus disease 2019 (COVID-19) has had different waves within the same country. The spread rate and severity showed different properties within the COVID-19 different waves. The present work aims to compare the spread and the severity of the different waves using the available data of confirmed COVID-19 cases and death cases. Real-data sets collected from the Johns Hopkins University Center for Systems Science were used to perform a comparative study between COVID-19 different waves in 12 countries with the highest total performed tests for severe acute respiratory syndrome coronavirus 2 detection in the world (Italy, Brazil, Japan, Germany, Spain, India, USA, UAE, Poland, Colombia, Turkey, and Switzerland). The total number of confirmed cases and death cases in different waves of COVID-19 were compared to that of the previous one for equivalent periods. The total number of death cases in each wave was presented as a percentage of the total number of confirmed cases for the same periods. In all the selected 12 countries, Wave 2 had a much higher number of confirmed cases than that in Wave 1. However, the death cases increase was not comparable with that of the confirmed cases to the extent that some countries had lower death cases than in Wave 1, UAE, and Spain. The death cases as a percentage of the total number of confirmed cases in Wave 1 were much higher than that in Wave 2. Some countries have had Waves 3 and 4. Waves 3 and 4 have had lower confirmed cases than Wave 2, however, the death cases were variable in different countries. The death cases in Waves 3 and 4 were similar to or higher than Wave 2 in most countries. Wave 2 of COVID-19 had a much higher spread rate but much lower severity resulting in a lower death rate in Wave 2 compared with that of the first wave. Waves 3 and 4 have had lower confirmed cases than Wave 2; that could be due to the presence of appropriate treatment and vaccination. However, that was not reflected in the death cases, which were similar to or higher than Wave 2 in most countries. Further studies are needed to explain these findings.


Effects of dietary amino acids on brain amino acids and transmitter amines in rats with a portacaval shunt.
The etiologic relationship between disturbances in metabolism of amino acids and amines and hepatic coma was investigated by examining the effects of diets containing various mixtures of amino acids on brain amine metabolism in rats with a portacaval shunt, using a method for simultaneous analysis of amino acids and amines. Rats with a portacaval shunt were fed on four different amino acid compositions with increased amounts of various amino acids suspected to be etiologically related to hepatic coma, such as methionine, phenylalanine, tyrosine, and tryptophan. The animals were killed 4 weeks after operation. During the experimental period, these animals did not become comatose, but exhibited various behavioral abnormalities. Marked increase in the plasma and brain levels of the augmented amino acids, especially methionine and tyrosine, were observed in rats with a portacaval shunt. Brain noradrenaline, dopamine, and serotonin levels were significantly decreased when the brain tyrosine level was increased. These results indicate that in rats with a portacaval shunt the dietary levels of amino acids greatly influence the brain levels of both amino acids and transmitter amines.


How insects survive the cold: molecular mechanisms-a review.
Insects vary considerably in their ability to survive low temperatures. The tractability of these organisms to experimentation has lead to considerable physiology-based work investigating both the variability between species and the actual mechanisms themselves. This has highlighted a range of strategies including freeze tolerance, freeze avoidance, protective dehydration and rapid cold hardening, which are often associated with the production of specific chemicals such as antifreezes and polyol cryoprotectants. But we are still far from identifying the critical elements behind over-wintering success and how some species can regularly survive temperatures below -20 degrees C. Molecular biology is the most recent tool to be added to the insect physiologist's armoury. With the public availability of the genome sequence of model insects such as Drosophila and the production of custom-made molecular resources, such as EST libraries and microarrays, we are now in a position to start dissecting the molecular mechanisms behind some of these well-characterised physiological responses. This review aims to provide a state-of-the-art snapshot of the molecular work currently being conducted into insect cold tolerance and the very interesting preliminary results from such studies, which provide great promise for the future.


Profiling gene expression in kidney development.
Insights into the normal development of the kidney have been derived from metanephric organ cultures, knockout mice and the later definition of the responsible single genetic abnormalities in some human congenital renal tract malformations. Deciphering of the human genome and the ability to examine multiple messenger RNA has opened new vistas and the capacity to begin to understand the complex kidney developmental process. In this review we focus on recent large-scale gene expression profiles performed during normal murine and human nephrogenesis and suggest how they might provide insights into normal kidney development as well as aberrations of this normal process that may result in renal dysplasia or pediatric renal malignancy (Wilms' tumor).


Preparation and properties of the nanocomposites based on poly(methyl methacrylate-co-butyl acrylate) and multiwalled carbon nanotube.
Nanocomposites, based on multiwalled carbon nanotube (MWCNT) and various acrylic copolymers of poly(methyl methacrylate-co-butyl acrylate)s, were prepared and the effects of the copolymer compositions on the electrical and the dynamic mechanical properties of the nanocomposites investigated. Latices of the acrylic copolymer were prepared by emulsion polymerization, and then mixed with MWCNT dispersed in N-methylpyrrolidone to prepare the nanocomposites. The electrical resistivities of the nanocomposites showed threshold decreases with increasing MWCNT content, due to percolation. The critical MWCNT content (Pc) in the nanocomposites for percolation showed minimum with increasing butyl acrylate content within the poly(methyl methacrylate-co-butyl acrylate). Specifically, the nanocomposites of the acrylic copolymer with a butyl acrylate content of 20-40 wt% showed the lowest Pc value of all the nanocomposites investigated. The nanocomposites showed large increases in the storage moduli in the rubbery plateau region. A decrease in the glass transition temperature (Tg) was observed with the nanocomposites and attributed to the characteristics of the nanocomposites, where the large surface area of MWCNT makes the matrix polymers similar to those of free stand thin film polymers.


Repression of the alpha-fetoprotein gene promoter by progesterone and chimeric receptors in the presence of hormones and antihormones.
Using transient transfection assays, we showed that repression of the alpha-fetoprotein promoter by intact and deletion mutants of the progesterone receptor and by chimeric progesterone/glucocorticoid-estrogen receptors in the presence of their cognate hormones was closely correlated with their ability to bind to a progesterone/glucocorticoid-responsive element. This negative regulation was also observed in the presence of antihormones, providing evidence that receptor-antihormone complexes can bind to their responsive elements in vivo.


The parkinsonian neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) mediates release of l-3,4-dihydroxyphenylalanine (l-DOPA) and inhibition of l-DOPA decarboxylase in the rat striatum: a microdialysis study.
Reactive oxygen species (ROS) and reactive nitrogen species (RNS), particularly peroxynitrite, have been implicated as key participants in the dopaminergic neurotoxicity of 1-methyl-4-phenylpyridinium (MPP(+)). However, on the basis of available information, it is not clear whether the MPP(+)-induced overproduction of ROS and RNS occurs in the intraneuronal and/or extracellular compartment. Early steps in the neurotoxic mechanism evoked by MPP(+) include a profound dopaminergic energy impairment, which mediates a massive release of dopamine (DA), glutathione (GSH), and cysteine (CySH). In the event that MPP(+) mediates extracellular generation of ROS (such as superoxide and/or hydroxyl radicals) and/or peroxynitrite, released DA, GSH, and CySH should be oxidized forming thioethers of DA and disulfides. Using microdialysis experiments in which MPP(+) was perfused into the striatum of awake rats, the present study was unable to detect the presence of such biomarkers of extracellular ROS and/or RNS generation. However, MPP(+) induced a transient, concentration-dependent rise of extracellular l-3,4-dihydroxyphenylalanine (l-DOPA), identified on the basis of dialysate analysis using several HPLC methods and its conversion to DA by purified l-DOPA decarboxylase (DDC). Methamphetamine (30 mg/kg, i.p.) similarly caused a significant but transient rise of l-DOPA in the rat striatum. Antioxidants such as salicylate and mannitol had no effect on the MPP(+)-mediated elevation of extracellular l-DOPA, suggesting that it is not formed by nonenzymatic hydroxylation of l-tyrosine by ROS or RNS. Rather, in vivo, but not in vitro, MPP(+) caused rapid inhibition of DDC, which appears to result in intraneuronal accumulation and subsequent release of l-DOPA. Because l-DOPA can mediate l-glutamate release, as well as be an excitotoxin, the possibility is raised that l-DOPA may play a role in the dopaminergic neurotoxicity of MPP(+).


Convergence insufficiency in patients taking medicines.
The incidence of convergence insufficiency in patients taking medicines is compared with its incidence in patients taking no therapeutic drugs, in a sample of 648 taken from a normal optometric practice. It is found that the incidence was significantly higher in those patients on medicines considering the group as a whole. It is also found to be higher in older patients, and that most of the older patients were taking medicines whilst the younger patients were not. However, the increase in the incidence of convergence insufficiency in the older patients taking medicines was disproportionately high. It is concluded that age is not the only factor in the increased incidence, and that the taking of medicines as a possible indicator of poor general health, is also an important factor in the cause of convergence difficulties.


A Model for Types and Levels of Automation in Visual Analytics: A Survey, a Taxonomy, and Examples.
The continuous growth in availability and access to data presents a major challenge to the human analyst. As the manual analysis of large and complex datasets is nowadays practically impossible, the need for assisting tools that can automate the analysis process while keeping the human analyst in the loop is imperative. A large and growing body of literature recognizes the crucial role of automation in Visual Analytics and suggests that automation is among the most important constituents for effective Visual Analytics systems. Today, however, there is no appropriate taxonomy nor terminology for assessing the extent of automation in a Visual Analytics system. In this article, we aim to address this gap by introducing a model of levels of automation tailored for the Visual Analytics domain. The consistent terminology of the proposed taxonomy could provide a ground for users/readers/reviewers to describe and compare automation in Visual Analytics systems. Our taxonomy is grounded on a combination of several existing and well-established taxonomies of levels of automation in the human-machine interaction domain and relevant models within the visual analytics field. To exemplify the proposed taxonomy, we selected a set of existing systems from the event-sequence analytics domain and mapped the automation of their visual analytics process stages against the automation levels in our taxonomy.


Evaluating the effectiveness of ecological momentary assessment and intervention targeting body checking behaviors.
This study investigated the efficacy of using ecological momentary assessment and intervention (EMA/EMI) to target body checking behaviors. Body checking has been shown to increase body dissatisfaction and play a role in eating disorders, but few treatments specifically targeting body checking have been empirically evaluated. Forty-four female undergraduates who reported engaging in frequent body checking behaviors participated in a five-day study wherein they were assessed five times a day via smart phone. On the final two days of the study, intervention messages were sent containing cognitive-behavioral strategies for decreasing body checking. Body checking behaviors increased within each day, but decreased across the five day intervention period. Pretest to posttest analyses found healthy improvements in a number of body image related constructs. These results highlight that 1) body checking appears to increase throughout the day, and 2) targeting body checking behaviors through brief EMA/EMI may be a useful clinical tool.


Current antibiogram and clonal relatedness among drug-resistant Salmonella enterica serovar Typhi in Northern India.
In view of the changing sensitivity pattern of Salmonella, this study was carried out to investigate the current antibiogram and clonal relatedness among the drug-resistant Salmonella enterica serovar Typhi in Northern India. Re-emergence in the sensitivity to chloramphenicol and cotrimoxazole with increase in the resistance to various quinolones has been observed. The efficacy of nalidixic acid resistance to be used as a marker for decrease in sensitivity to ciprofloxacin may vary. Clonal differences on the basis of amplification of repetitive elements (rep-PCR) were found in the two different areas within the same region. The present study creates a paramount baseline for rationalizing the judicious use of quinolones and re-examine the use of chloramphenicol and cotrimoxazole. Molecular analysis of clinical Salmonella isolates depicts the clonal expansion of the isolates that may serve as a reference to which newer outbreak strains can be compared. rep-PCR techniques may be useful in molecular discrimination of isolates for better understanding of the Salmonella epidemiology and as a basis for development of rational control strategies.


[The Base of the Skull. Rudolf Virchow between Pathology and Anthropology].
Throughout his scientific career, the pathologist and anthropologist Rudolf Virchow (1821-1902) examined countless skulls, gradually changing his perspective on this object of research. Initially, he was mainly concerned with pathologically deformed skulls. From the 1850s onwards, he gradually developed a more anthropological approach, and anthropology increasingly came to dominate his scientific interest. This article shows how different influences became central for the establishment of his specific and dynamic model of the human skull development and its successful application in anthropology. Crucial for this process were Virchow's collaboration with his teacher Robert Froriep (1804-1861) in the department of pathology of the Charité, his research on cretinism and rickets, as well as his description of the base of the skull as the center of skull development. His research work was attended by and showed a reciprocal interaction with the buildup of large skull collections. This article uses Virchow's original publications on skull pathology as well as his still preserved skull specimens from the collection of the Berlin Museum of Medical History at the Charité for an integrated text and object based analysis.


Clinical and Statistical Validation of a Probabilistic Prediction Tool of Total Knee Arthroplasty Outcome.
Predicting patients at risk of a poor outcome would be useful in patient selection for total knee arthroplasty (TKA). Existing models to predict outcome have seen limited functional implementation. This study aims to validate a model and shared decision-making tool for both clinical utility and predictive accuracy. A Bayesian belief network statistical model was developed using data from the Osteoarthritis Initiative. A consecutive series of consultations for osteoarthritis before and after introduction of the tool was used to evaluate the clinical impact of the tool. A data audit of postoperative outcomes of TKA patients exposed to the tool was used to evaluate the accuracy of predictions. The tool changed consultation outcomes and identified patients at risk of limited improvement. After introduction of the tool, patients booked for surgery reported worse Knee Osteoarthritis and Injury Outcome Score pain scores (difference, 15.2; P < .001) than those not booked, with no significant difference prior. There was a 27% chance of not improving if predicted at risk, and a 1.4% chance if predicted to improve. This gives a risk ratio of 19× (P < .001) for patients not improving if predicted at risk. For a prediction tool to be clinically useful, it needs to provide a better understanding of the likely clinical outcome of an intervention than existed without its use when the clinical decisions are made. The tool presented here has the potential to direct patients to surgical or nonsurgical pathways on a patient-specific basis, ensuring patients who will benefit most from TKA surgery are selected.


Evaluation of semi-quantitative methods for protein and sugar estimation in urine.
To compare the accuracy of semi quantitative methods for estimation of protein and sugar in urine as shown by their agreement with the quantitative estimation. Hundred randomly collected samples of urine were analysed for levels of protein and sugar. Protein estimation was dine by dipstick and sulphosalicylic acid method (SSA) and sugar by dipstick and Benedict's semi-quantitative methods. Kappa analysis was done on Epi Info 6.03 software to assess the agreement of these semi quantitative methods with the quantitative estimation. Neither of the two tests for urine protein, dipstick or SSA, showed good agreement with the quantitative estimation (Kappa coefficient: 0.26 and 0.07 respectively). However, the dipstick was significantly better than SSA (p < 0.05). For urine sugar, both dipstick and Benedict's tests showed good agreement with the quantitative estimation (Kappa coefficient: 0.78 and 0.84 respectively). The difference between them was insignificant. Results demonstrate that for urine protein, dipstick or SSA show poor agreement with quantitative values. For urine sugar estimation, Benedict's semi-quantitative test shows good agreement with the quantitative values and is as good as the dipstick method.


Response of Anastrepha suspensa (Diptera: Tephritidae) to terminal diamines in a food-based synthetic attractant.
A current trapping system for Anastrepha fruit flies uses a two-component food-based synthetic attractant consisting of ammonium acetate and putrescine (1,4-diaminobutane). Development of more effective monitoring programs may be realized through identification of additional attractant chemicals. This study examined response of the Caribbean fruit fly, Anastrepha suspensa (Loew), to putrescine and four homologous terminal diamines, differing only in carbon chain length. Using a fixed dose of each diamine substrate, electroantennogram (EAG) responses from mature females to putrescine and cadaverine (1,5-diaminopentane) were not significantly different from each other but were significantly greater than responses to longer chain diamines. Over a range of doses tested, mean female EAG response was greater than male response to both putrescine and cadaverine. In an initial field test, capture of female flies in traps baited with ammonium acetate and either putrescine or cadaverine was higher than in traps baited with ammonium acetate and any of the other diamines. In a subsequent field test, traps baited with putrescine, cadaverine, or 1,6-diaminohexane in combination with ammonium acetate captured more female flies than traps baited with ammonium acetate alone. A significantly greater synergistic effect on female captures was observed with either putrescine or cadaverine than with 1,6-diaminohexane. Thus, of the diamines evaluated, cadaverine elicited both antennal and behavioral responses comparable to that of putrescine and will be studied further as a potential attractant for pest Anastrepha species.


Disease-related cardiac troponins alter thin filament Ca2+ association and dissociation rates.
The contractile response of the heart can be altered by disease-related protein modifications to numerous contractile proteins. By utilizing an IAANS labeled fluorescent troponin C, [Formula: see text], we examined the effects of ten disease-related troponin modifications on the Ca(2+) binding properties of the troponin complex and the reconstituted thin filament. The selected modifications are associated with a broad range of cardiac diseases: three subtypes of familial cardiomyopathies (dilated, hypertrophic and restrictive) and ischemia-reperfusion injury. Consistent with previous studies, the majority of the protein modifications had no effect on the Ca(2+) binding properties of the isolated troponin complex. However, when incorporated into the thin filament, dilated cardiomyopathy mutations desensitized (up to 3.3-fold), while hypertrophic and restrictive cardiomyopathy mutations, and ischemia-induced truncation of troponin I, sensitized the thin filament to Ca(2+) (up to 6.3-fold). Kinetically, the dilated cardiomyopathy mutations increased the rate of Ca(2+) dissociation from the thin filament (up to 2.5-fold), while the hypertrophic and restrictive cardiomyopathy mutations, and the ischemia-induced truncation of troponin I decreased the rate (up to 2-fold). The protein modifications also increased (up to 5.4-fold) or decreased (up to 2.5-fold) the apparent rate of Ca(2+) association to the thin filament. Thus, the disease-related protein modifications alter Ca(2+) binding by influencing both the association and dissociation rates of thin filament Ca(2+) exchange. These alterations in Ca(2+) exchange kinetics influenced the response of the thin filament to artificial Ca(2+) transients generated in a stopped-flow apparatus. Troponin C may act as a hub, sensing physiological and pathological stimuli to modulate the Ca(2+)-binding properties of the thin filament and influence the contractile performance of the heart.


Mapping the disease-specific LupusQoL to the SF-6D.
To derive a mapping algorithm to predict SF-6D utility scores from the non-preference-based LupusQoL and test the performance of the developed algorithm on a separate independent validation data set. LupusQoL and SF-6D data were collected from 320 patients with systemic lupus erythematosus (SLE) attending routine rheumatology outpatient appointments at seven centres in the UK. Ordinary least squares (OLS) regression was used to estimate models of increasing complexity in order to predict individuals' SF-6D utility scores from their responses to the LupusQoL questionnaire. Model performance was judged on predictive ability through the size and pattern of prediction errors generated. The performance of the selected model was externally validated on an independent data set containing 113 female SLE patients who had again completed both the LupusQoL and SF-36 questionnaires. Four of the eight LupusQoL domains (physical health, pain, emotional health, and fatigue) were selected as dependent variables in the final model. Overall model fit was good, with R(2) 0.7219, MAE 0.0557, and RMSE 0.0706 when applied to the estimation data set, and R(2) 0.7431, MAE 0.0528, and RMSE 0.0663 when applied to the validation sample. This study provides a method by which health state utility values can be estimated from patient responses to the non-preference-based LupusQoL, generalisable beyond the data set upon which it was estimated. Despite concerns over the use of OLS to develop mapping algorithms, we find this method to be suitable in this case due to the normality of the SF-6D data.


A neural network model of sensitization of evoked cortical responses in migraine.
Migraine patients show abnormalities of cerebral electrophysiology that manifest themselves mainly during the attack interval. Cortical-evoked potentials of migraineurs fail to habituate to repetitive presentations of visual stimuli, and the amplitude of components of their auditory cortical-evoked potentials have a higher dependence on the stimulus intensities than in healthy subjects. A computer model of a neural hetwork has been developed that is able to reproduce both these neurophysiological dysfunctions. It predicts a positive correlation between the magnitudes of both these dysfunctions. The model also offers an explanation of why mutations in the same ion channel gene with opposite consequences on channel function, e.g. P/Q Ca2+ channels in migraine, may lead to similar electrophysiological abnormalities.


Indeno[2,1-c]fluorene: a new electron-accepting scaffold for organic electronics.
A new class of fully conjugated indenofluorenes has been synthesized and confirmed by solid-state structure analysis. These indeno[2,1-c]fluorene molecules, containing an antiaromatic as-indacene core (in red), possess high electron affinities and show a broad absorption that reaches into the near-IR region of the electromagnetic spectrum. All of the featured compounds reversibly accept up to two electrons. Their electronic properties make this class of compounds attractive for applications in organic electronic devices.


The role of nitric oxide.
When studying the impact of endothelins (ETs) on physiology and pathophysiology, this needs to be done in the context of nitric oxide (NO) synthesis and action, since these two are closely intertwined in their action. Here, we will review the work demonstrating the crosstalk between endothelin-1 (ET-1) and NO, and the recent developments regarding the role of these two mediators in inflammatory processes. Moreover, we will discuss the role of NO in pro-inflammatory diseases and the potential mechanisms of the anti-inflammatory activity of ET receptor antagonism.


Linaclotide, novel therapy for the treatment of chronic idiopathic constipation and constipation-predominant irritable bowel syndrome.
Chronic constipation (CC) and irritable bowel syndrome with constipation (IBS-C) are common gastrointestinal (GI) disorders. Current treatment options, either prescription or nonprescription medications, have limited efficacy in a subset of patients. There is significant demand for more efficacious medications for the treatment of CC and IBS-C. Linaclotide, a secretagogue, has a novel mechanism of action designed to treat patients with CC and IBS-C. It has a low oral bioavailability with negligible systemic side effects, and it acts locally in the intestinal lumen. In several clinical trials, in health and disease, linaclotide has demonstrated durable efficacy and safety in CC and IBS-C. Linaclotide received approval by the Federal Drug Administration in August 2012 to treat chronic idiopathic constipation and IBS-C.


Amplification of a SV40 T antigen transgene is associated with sarcomagenesis in mice.
Transgenic mice harboring simian virus 40 large T antigen (Tag) gene fused to an erythroid-specific enhancer developed soft tissue sarcomas which expressed very high levels of T antigen. The Tag expression was not detectable in the animals' non-transformed tissues. While mice bearing several copies of the transgene developed tumors at an early age of 4-6 months, those with a single copy had a delayed onset of 10-16 months, and DNA analysis of their tumors showed amplification of the Tag transgene. Amplification of a Tag transgene has also been described previously in brain tumors. Our studies demonstrate that Tag transgene amplification is not restricted to a particular construct or a single tumor type. Therefore, this may be a general mechanism for Tag-mediated carcinogenesis, and our transgenic mouse system can be useful for elucidating the mechanisms that govern the amplification process of Tag sequences in vivo.


Time From Emergency Department Evaluation to Operation and Appendiceal Perforation.
In patients with appendicitis, the risk of perforation increases with time from onset of symptoms. We sought to determine if time from emergency department (ED) physician evaluation until operative intervention is independently associated with appendiceal perforation (AP) in children. We conducted a planned secondary analysis of children aged 3 to 18 years with appendicitis enrolled in a prospective, multicenter, cross-sectional study of patients with abdominal pain (<96 hours). Time of initial physical examination and time of operation were recorded. The presence of AP was determined using operative reports. We analyzed whether duration of time from initial ED physician evaluation to operation impacted the odds of AP using multivariable logistic regression, adjusting for traditionally suggested risk factors that increase the risk of perforation. We also modeled the odds of perforation in a subpopulation of patients without perforation on computed tomography. Of 955 children with appendicitis, 25.9% (n = 247) had AP. The median time from ED physician evaluation to operation was 7.2 hours (interquartile range: 4.8-8.5). Adjusting for variables associated with perforation, duration of time (≤ 24 hours) between initial ED evaluation and operation did not significantly increase the odds of AP (odds ratio = 1.0, 95% confidence interval, 0.96-1.05), even among children without perforation on initial computed tomography (odds ratio = 0.95, 95% confidence interval, 0.89-1.02). Although duration of abdominal pain is associated with AP, short time delays from ED evaluation to operation did not independently increase the odds of perforation.


Vesicle-associated membrane protein-associated protein-A (VAP-A) interacts with the oxysterol-binding protein to modify export from the endoplasmic reticulum.
Oxysterol-binding protein (OSBP) is 1 of 12 related proteins implicated in the regulation of vesicle transport and sterol homeostasis. A yeast two-hybrid screen using full-length OSBP as bait was undertaken to identify partner proteins that would provide clues to the function of OSBP. This resulted in the cloning of vesicle-associated membrane protein-associated protein-A (VAP-A), a syntaxin-like protein implicated in endoplasmic reticulum (ER)/Golgi vesicle transport, and phospholipid regulation in mammalian cells and yeast, respectively. By using a combination of yeast two-hybrid, glutathione S-transferase pull-down and immunoprecipitation experiments, the VAP-A-binding region in OSBP was localized to amino acids 351-442. This region did not include the pleckstrin homology (PH) domain but overlapped with the N terminus of the oxysterol binding and OSBP homology domains. C- and N-terminal truncations or deletions of VAP prevented interaction with OSBP but did not affect VAP multimerization. Although the OSBP PH domain was not necessary for VAP-A binding in vitro, interaction with VAP-A was enhanced in cells by mutation of the conserved PH domain tryptophan (OSBP W174A) or deletion of the C-terminal half of the PH domain (OSBP Delta 132-182). OSBP W174A retained oxysterol binding activity, association with phospholipid vesicles via the PH domain, and localized with VAP in unusual ER-associated structures. At 40 degrees C, misfolded ts045-vesicular stomatitis virus G protein fused to green fluorescent protein was co-localized with VAP-A/OSBP W174A structures on the ER but was exported to the Golgi when folded normally at 32 degrees C. A fluorescent ceramide analogue also accumulated in these ER inclusions, and export to the Golgi was partially inhibited as indicated by decreased Golgi staining and a 30% reduction in sphingomyelin synthesis. These studies show that OSBP binding to the ER and Golgi apparatus is regulated by its PH domain and VAP interactions, and the complex is involved at a stage of protein and ceramide transport from the ER.


Relative infectivity of hepatitis A virus by the oral and intravenous routes in 2 species of nonhuman primates.
Hepatitis A virus (HAV) is naturally transmitted by the fecal-oral route but can also be transmitted intravenously. To determine the relative infectivity of these 2 routes, an infectivity titration of a standard challenge pool of virulent HAV was performed in tamarins and chimpanzees. In both species, 1 oral dose of HAV was equivalent to 10(4.5) intravenous doses. These findings have relevance for attempts to develop live, attenuated HAV vaccines that can be administered orally.


Ultrastructural alterations of pancreatic beta cells in human diabetes mellitus.
Both types of diabetes are characterized by beta-cell failure and death, leading to insulin insufficiency. Very limited information is currently available about the ultrastructural alterations of beta cells in human diabetes. Our aim was to provide a comprehensive ultrastructural analysis of human pancreatic islets in type 1 (T1D) and type 2 (T2D) diabetic patients. We performed a morphometric electron microscopy evaluation of beta cells obtained from the pancreas of 8 nondiabetic (ND), 5 T1D, and 8 T2D organ donors. A lower amount of beta cells was found in both T1D and T2D than in ND islets, whereas alpha cells were increased only in T2D. An increased number of bi-hormonal cells (showing both insulin and glucagon granules in their cytoplasm) were found in T1D. Insulin granules were less represented in T2D than in ND beta cells, whereas no significant changes were found in T1D. Volume density of the endoplasmic reticulum was increased in T2D and unchanged in T1D; mitochondria number and volume were significantly higher in T2D than in ND beta cells, whereas no significant differences were found in T1D. In both T1D and T2D, more beta cells showed signs of apoptosis than in ND. Our results show that in each type of diabetes, beta cells exhibit specific ultrastructural alterations, whose better understanding might improve therapeutic strategies.


Longitudinal study of Doppler flow resistance indices of the uterine arteries after normal vaginal delivery.
To measure Doppler flow resistance indices in the uterine arteries, and to observe when the early diastolic notches appear during the normal puerperium. Some 45 women took part in this prospective longitudinal study after normal, vaginal delivery. Ultrasound examinations were scheduled for days 1, 3, 7, 14, 28 and 56 postpartum. A transabdominal probe was used during the first two postpartum weeks, and a transvaginal probe for the later examinations. The pulsatility (PI) and resistance (RI) indices in the uterine arteries were measured, and the presence or absence of early diastolic notches was recorded. Compared to day one, the resistance indices did not change markedly until day 28 postpartum. The mean PI was 1.23 at day 1, 1.22 at day 3, 1.22 at day 7, 1.33 at day 14, 1.81 at day 28, and 2.25 at day 56. The mean RI was 0.65 at day 1, 0.65 at day 3, 0.66 at day 7, 0.65 at day 14, 0.77 at day 28, and 0.84 at day 56. The presence of at least 1 uterine artery notch was found in 13.3% of the women at day 1, and in 90.6% at day 56 postpartum. Bilateral notches were recorded in 6.7% of the women at day 1, and in 84.4% at day 56 postpartum. Reference values of the resistance indices from uncomplicated puerperium are needed when the diagnostic efficacy of Doppler ultrasound for pathological conditions is to be tested. This study confirms that the time needed for the vascular physiology to revert from a pregnant to a non-pregnant state appears to be longer than previously assumed.


MCA/MR syndrome in a female infant with tetraploidy mosaicism: review of the human polyploid phenotype.
We report on a 3-month-old girl with unusual facial appearance, short neck with low posterior hairline, wide chest, valvular pulmonic stenosis, abnormal fingernails, and diploid-tetraploid mosaicism (46,XX/92,XXXX in 7.2% of peripheral leucocytes and in 29% of skin fibroblasts). Comparison with 11 previously reported cases with mosaic or complete tetraploidy does not establish an easily recognizable syndrome. However, a malformation pattern is apparent when tetraploidy patients are compared with 14 cases of triploid mosaicism and 44 previously reported cases of nonmosaic triploidy. A history of sex hormone exposure was present in 5 of 11 pregnancies resulting in tetraploidy; this exposure may correlate with the occurrence of tetraploidy in polycystic ovary syndrome and in tumors of the female reproductive tract. The mechanism of dysmorphogenesis involved in polyploidy is considered, including hypotheses of altered nuclear/cytoplasmic ratio, of trophoblastic alteration, of delayed cell division, or of altered autosome/active X chromosome ratio.


Setting of methods for analysis of mucosal antibodies in seminal and vaginal fluids of HIV seropositive subjects from Cambodian and Italian cohorts.
Genital mucosae play a key role in protection from STD and HIV infection, due to their involvement in both horizontal and vertical disease transmission. High variability of published observations concerning IgA isolation and quantification underlies the strong requirement of specific methods able to maximize investigation on HIV-specific IgA. Genital fluids from 109 subjects, including male and female cohorts from Italy and Cambodia, were collected, aliquoted and processed with different techniques, to assess optimal conditions maximizing mucosal antibody recovery. Three sampling techniques, up to sixteen preservation conditions, six ELISA methods and four purifications protocols were compared. The optimal method here described took advantage of Weck-Cel sampling of female mucosal fluids. Immediate processing of genital fluids, with the addition of antibiotics and EDTA, improved recovery of vaginal IgA, while the triple addition of EDTA, antibiotics and protease inhibitors provided the highest amount of seminal IgA. Due to low amount of IgA in mucosal fluids, a high sensitive sandwich ELISA assay was set; sensitivity was enhanced by milk-based overcoating buffer and by a two-step biotin-streptavidin signal amplification. Indeed, commercial antisera to detect human immunoglobulins showed weak cross-reactivity to different antibody types. Three-step affinity purification provided reproducible immunoglobulin recovery from genital specimens, while conventional immuno-affinity IgA purification was found poorly manageable. Affinity columns were suitable to isolate mucosal IgA, which are ten-fold less concentrated than IgG in genital specimens, and provided effective separation of IgA monomers, dimers, and J-chains. Jacalin-bound resin successfully separated IgA1 from IgA2 subfraction. Specific, effective and reliable methods to study local immunity are key items in understanding host mucosal response. The sequence of methods here described is effective and reliable in analysing humoral local responses, and may provide a solid advance to identify and measure the effective mucosal responses to HIV.


Various and Tunable Transport Properties of WSe2 Transistor Formed by Metal Contacts.
The abundant electronic and optical properties of 2D materials that are just one-atom thick pave the way for many novel electronic applications. One important application is to explore the band-to-band tunneling in the heterojunction built by different 2D materials. Here, a gate-controlled WSe2 transistor is constructed by using different work function metals to form the drain (Pt) and source (Cr) electrodes. The device can be gate-modulated to exhibit three modes of operation, i.e., the tunneling mode with remarkable negative differential resistance, the transition mode with a second electron tunneling phenomenon for backward bias, and finally the conventional diode mode with rectifying characteristics. In contrast to the heterojunctions built by different 2D materials, these devices show significantly enhanced tunneling current by two orders of magnitude, which may largely benefit from the clean interfaces. These results pave the way toward design of novel electronic devices using the modulation of metal work functions.


Cloning and expression of a Xenopus liver cDNA encoding a fructose-phosphate-insensitive regulatory protein of glucokinase.
Xenopus liver contains a protein inhibitor of glucokinase that, in contrast to the mammalian regulatory protein of glucokinase, is insensitive to fructose 6-phosphate and fructose 1-phosphate [Vandercammen A. & Van Schaftingen, E. (1993) Biochem. J. 294, 551-556]. The purpose of this work was to compare the primary structure and other properties of this Xenopus protein with those of its rat liver counterpart. A Xenopus laevis liver cDNA library was screened using the cDNA encoding the rat liver regulatory protein as a probe. The cloned cDNA was 2534 bp long and encoded a 619-amino-acid protein with a molecular mass of 68695 Da and 57% identity with the rat liver regulatory protein. This identity was only about 30% in an internal region (amino acids 349-381) and in the 70 carboxy terminal-residues. The Xenopus cDNA was expressed in Escherichia coli and the recombinant regulatory protein was purified to near homogeneity and found to have the same size, reactivity to antibodies and effects on the kinetics of glucokinase as the protein purified from Xenopus liver. In contrast to the rat liver regulatory protein, both recombinant and native Xenopus regulatory proteins were insensitive to fructose 6-phosphate, fructose 1-phosphate and to physiological concentrations of Pi, and they inhibited Xenopus glucokinase with greater affinity than rat glucokinase. These results allow one to conclude that the fructose-phosphate-insensitive protein of lower vertebrates is homologous to the fructose-6-phosphate-sensitive and fructose-1-phosphate-sensitive protein found in mammals.


Survey of academic pediatric emergency departments regarding use of evaluation and management codes.
The aims of the study were to determine the frequency at which each emergency medicine evaluation and management (E/M) code is used, to identify factors associated with their use by academic pediatric emergency departments (PEDs), and to compare PED E/M code utilization rates with rates reported by Centers for Medicare and Medicaid Services for general emergency departments (EDs). A 24-question survey was sent to 42 academic PED medical directors. Questions pertained to PED demographics, physician staff, records/documentation, billing education, and E/M coding data for 1 year. The general ED E/M code utilization rates were obtained from the published Centers for Medicare and Medicaid Services database. Descriptive statistics and odds ratios were used to report and compare the data. Twenty (48%) of the surveys were returned, and 9 (21%) completed the E/M coding data questions. From these 9 departments, the mean PED annual census was 46,065 (range, 23,531-92,910). The methods of PED medical record documentation were template (6), handwritten (2), and dictation/transcription (1). Charge documents were completed by the PED physician (3), professional service coders (4), and hospital coders (2). Coding/documentation in-services were provided to the physicians of 7 PEDs, and billing audits were performed in 5 PEDs. The total number of charges for the 9 PEDs was 325,129, 78.4% of the census. Multiple reasons were given for the discrepancy between census and charges. The percentage of each of the 5 levels of service billed was calculated for each of the 9 PEDs. The 2 lowest levels of service were used 38.3% of the time, whereas the 2 highest were used 19.2% of the time. The range for the highest level of service varied widely from 5.3% to 53.3%. Approximately 65% of E/M codes used by general EDs were for the 2 highest levels of service. The PED with the highest percentage of upper level charges (53.4%) was the only PED that used dictation/transcription for documentation. Although the response rate was low, and thus the validity of the results was limited, the findings may serve as a benchmark for E/M code utilization in PEDs. The large variation in use of the E/M codes among the PED in our study and the lower rate of using the highest E/M codes by the PEDs compared with the general EDs suggest potential opportunities for academic PEDs to improve billing practices.


[Reliability and Validity Indicators of Berkeley Expressivity Questionnaire in the Context of Culture and Gender].
The Berkeley Expressivity Questionaire (BEQ) was a scale, developed by Gross and John (1995) to measure emotion expression. The purpose of the present study was to investigate reliability and validity indicators of the BEQ in our culture. The sample composed of 213 (115 women) people whose average of age 35. The people were voluntered for the study and lived within the borders of Izmir. The validity indicators of the questionaire were investigated through explanatory and confirmatory factor analyses, gender differences between the scores and correlational analyses on Difficulties in Emotion Regulation Scale (DERS). Anyway, the realibility indicators of the questionaire were explored by internal consistency coefficient and test re-test reliability. Confirmatory and explanatory factor analyses revealed a three factor model explaining % 48 of the total variance. These factors were named as emotional expressivity, impulse strength and masking. The results showed a positive correlation between the DERS and the total BEQ scores, which were congruent with theoretical expectations. It was found that the women had higher scores in the BEQ, emotional expressivity and impulse strength subscales while the men had higher scores than women in the masking subscale, meaning the women might be more emotionally expressive and the intensity of their emotional experience were higher than men. In addition, the Cronbach's alpha value was .81 and test re-test values were .78 for the total BEQ. Based on these results it was concluded that The Turkish version of the BEQ has sufficiently high reliability and validity to justify its use as a tool in emotion expression studies.


Measuring the dielectric and optical response of millimeter-scale amorphous and hexagonal boron nitride films grown on epitaxial graphene.
Monolayer epitaxial graphene (EG), grown on the Si face of SiC, is an advantageous material for a variety of electronic and optical applications. EG forms as a single crystal over millimeter-scale areas and consequently, the large scale single crystal can be utilized as a template for growth of other materials. In this work, we present the use of EG as a template to form millimeter-scale amorphous and hexagonal boron nitride (a-BN and h-BN) films. The a-BN is formed with pulsed laser deposition and the h-BN is grown with triethylboron (TEB) and NH3 precursors, making it the first metal organic chemical vapor deposition (MOCVD) process of this growth type performed on epitaxial graphene. A variety of optical and non-optical characterization methods are used to determine the optical absorption and dielectric functions of the EG, a-BN, and h-BN within the energy range of 1 eV to 8.5 eV. Furthermore, we report the first ellipsometric observation of high-energy resonant excitons in EG from the 4H polytype of SiC and an analysis on the interactions within the EG and h-BN heterostructure.


Management of penetrating injuries of the suprarenal aorta.
Penetrating injuries of the thoracic and abdominal aorta are controlled and repaired successfully with increasing frequency. Penetration of the suprarenal abdominal aorta has been associated with a high mortality rate because of difficult exposure and associated injuries. Between January 1969 and July 1973, 28 patients have undergone operative treatment for traumatic injury to the suprarenal aorta and other associated thoraco-abdominal injuries with 10 long-term survivors. Eight survivors sustained their injuries during the last 3 years, when a medial mobilization of the viscera was the preferred approach. Dacron prosthetic material was employed in seven patients, and in two there was ligation of the celiac axis. With satisfactory exposure, control of exsanguinating hemorrhage, and utilization of available vascular reconstructive techniques, successful management of this relatively inaccessible intra-abdominal lesion can be accomplished in an increasing number of patients.


An interval-possibilistic basic-flexible programming method for air quality management of municipal energy system through introducing electric vehicles.
Contradictions of sustainable transportation development and environmental issues have been aggravated significantly and been one of the major concerns for energy systems planning and management. A heavy emphasis is placed on stimulation of electric vehicles (EVs) to handle these problems associated with various complexities and uncertainties in municipal energy system (MES). In this study, an interval-possibilistic basic-flexible programming (IPBFP) method is proposed for planning MES of Qingdao, where uncertainties expressed as interval-flexible variables and interval-possibilistic parameters can be effectively reflected. Support vector regression (SVR) is used for predicting electricity demand of the city under various scenarios. Solutions of EVs stimulation levels and satisfaction levels in association with flexible constraints and predetermined necessity degrees are analyzed, which can help identify the optimized energy-supply patterns that could plunk for improvement of air quality and hedge against violation of soft constraints. Results disclose that largely developing EVs can help facilitate the city's energy system with an environment-effective way. However, compared to the rapid growth of transportation, the EVs' contribution of improving the city's air quality is limited. It is desired that, to achieve an environmentally sustainable MES, more concerns should be focused on the integration of increasing renewable energy resources, stimulating EVs as well as improving energy transmission, transport and storage.


Functional analysis of Histoplasma capsulatum-reactive T-cell hybridomas.
Activation of CD4+ T cells is a crucial step in the elimination of Histoplasma capsulatum yeast cells from tissues. However, only a limited amount of information exists concerning the immunobiology of H. capsulatum-reactive T cells that are CD4+. To facilitate the analysis of the functional activities of this T-cell subpopulation, we developed a panel of 10 murine T-cell hybridomas from splenocytes of immune C57BL/6 mice. All hybridomas reacted with monoclonal anti-CD4+ antibody and released interleukin-2 after stimulation with histoplasmin. Within 3 weeks, the reactivity of hybridomas to histoplasmin declined dramatically, yet the cells responded vigorously to yeast-phase preparations that were enriched for cytosol, cell wall, or cell membrane. Of 10 hybridomas studied, only one recognized heterologous fungal antigens. Responsiveness to yeast-phase antigens was restricted by I-Ab. We mapped determinants in cytosol and cell wall or cell membrane by the technique of one-dimensional T-cell immunoblotting. The patterns of responses of hybridomas to cytosol were nearly uniform. All hybridomas responded to two immunodominant regions in cytosol with masses ranging from less than or equal to 18 to 26 kilodaltons (kDa) and 35 to 39 kDa. All hybridomas tested responded to determinants in the cell wall or cell membrane preparation with masses of 35 to 39 kDa. These hybridomas provide a useful tool for defining yeast-phase antigens that trigger T-cell activation.


The interleukin-6-572G/C gene polymorphism and the risk of intracranial aneurysms in a Chinese population.
Interleukin-6 (IL-6) is an important proinflammatory cytokine that plays an important role in the pathogenesis of intracranial aneurysms (IAs). The aim of this study was to investigate the association between the IL-6-572G/C polymorphism and the risk of IAs in a Chinese population. The IL-6-572G/C gene polymorphisms in 220 IA cases and 220 controls were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method. The IL-6-572GG (odds ratio [OR]=3.35, 95% confidence intervals [CIs]=1.65, 6.82; p=0.001) and G allele frequencies (OR=1.48, 95% CIs=1.09, 2.00; p=0.01) in the IA group were higher than those in the control group. The C allele frequencies (OR=0.68, 95% CIs=0.50, 0.92; p=0.01) were significantly lower in patients than in controls. When stratified by the site, shape, size, and the Fisher Grade of IAs, no statistically significant result was observed. This study suggested that the IL-6-572GG genotype was associated with a higher risk of IA in a Chinese population.


Synthesis and Characterization of a "Turn-On" photoCORM for Trackable CO Delivery to Biological Targets.
A designed photoactive CO releasing molecule (photoCORM), namely, fac-[MnBr(CO)3(pbt)] (1, pbt = 2-(2-pyridyl)benzothiazole), promotes CO-induced death of MDA-MB-231 human breast cancer cells upon illumination with broadband visible light. The CO release from this photoCORM can be tracked by rise in fluorescence within the cellular matrix due to deligation of the pbt ligand. The results of this study suggest the potential of 1 in eradication of cancer cells through CO delivery.


Chronic hemodynamic effects of tiapamil and felodipine in essential hypertension at rest and during exercise.
Sixteen men with previously untreated diastolic blood pressure of 100-120 mm Hg were studied hemodynamically at rest supine and sitting and during a 100 W bicycle exercise. Blood pressure (BP) was recorded intra-arterially, and cardiac output (CO) by the dye-dilution method. After initial study, patients were treated with tiapamil in increasing doses (300-600 mg b.i.d., with a mean daily dose of 980 mg). The patients were restudied and then changed to felodipine (5-10 mg b.i.d., with a mean daily dose of 15 mg). Casual (cuff) BP at rest sitting was as follows: end placebo, 166/105 mm Hg; 1 year of tiapamil, 148/92 mm Hg; 1 year of felodipine, 139/86 mm Hg. Pretreatment hemodynamic results at rest sitting were as follows: BP, 169/105 mm Hg; MAP, 129 mm Hg; cardiac index (CI), 2.43 L/min/m2; total peripheral resistance index (TPRI), 4,305 dyn s/cm-5/m2. Both drugs reduced systolic (SAP), diastolic (DAP), and mean (MAP) arterial pressure significantly in all situations. BP reduction seemed to be more pronounced on felodipine than on tiapamil. Felodipine reduced MAP by 15% at rest supine, 14% at rest sitting, and 11% during exercise. The BP reduction was entirely due to reduction in TPRI (15, 16, and 13%, respectively). CI as well as stroke index (SI) and heart rate (HR) were unchanged. Tiapamil did not reduce TPRI significantly and the fall in BP was due to a combination fall in TPRI and CI.


Enantioselective Morita-Baylis-Hillman reaction of isatins with acrylates: facile creation of 3-hydroxy-2-oxindoles.
The first tertiary amine catalyzed enantioselective Morita-Baylis-Hillman (MBH) reaction of isatins with acrylates has been demonstrated, allowing asymmetric synthesis of biologically significant 3-substituted-3-hydroxy-2-oxindoles in good yields and with excellent enantioselectivities. The C6'-OH group of β-isocupreidine (β-ICD) is believed to facilitate the key proton transfer step in the MBH reaction, via an intramolecular proton relay process.