bluuebunny/crossref_metadata_2025 huggingface dataset:
Homogenization of Hamilton‐Jacobi‐Bellman equations with respect to time‐space shifts in a stationary ergodic medium
Authors: Kosygina Elena , Varadhan S. R. S.
Published: October 2007

We consider a family {uϵ(t, x, ω)}, ϵ < 0, of solutions to the equation ∂uϵ/∂t+ ϵΔuϵ/2 +H(t/ϵ,x/ϵ, ∇uϵ, ω) = 0 with the terminal datauϵ(T, x, ω) =U(x). Assuming that the dependence of the HamiltonianH(t, x, p, ω) on time and space is realized through shifts in a stationary ergodic random medium, and thatHis convex inpand satisfies certain growth and regularity conditions, we show the almost sure locally uniform convergence, in time and space, ofuϵ(t, x, ω) as ϵ → 0 to the solutionu(t, x) of a deterministic averaged equation ∂u/∂t+H̄(∇u) = 0,u(T, x) =U(x). The “effective” HamiltonianH̄is given by a variational formula. © 2007 Wiley Periodicals, Inc.
Investigating the performance of a middleware protocol architecture for tele‐measurement
Authors: Berruti Luca , Vignola Stefano , Zappatore Sandro
Published: October 2007

The rapid growth of network infrastructures and the large availability of instrumentation supporting remote control have encouraged the deployment of complex and sophisticated laboratories and the design of software platforms for accessing the resources present there. Although the market offers several solutions to remotely manage equipment, little attention has been paid to the hardware and software architectures devoted to control distance learning experimental environments and to manage laboratories consisting of heterogeneous devices. The paper illustrates the architectural approach adopted within the LABNET project and describes in detail the main software components of the devised platform, which allows to exploit the instrumentationviaa common Web user interface, thus making the system available independent of any specific (commercial) environment or application. Specifically, attention is focused on the LABNET server (LNS), which represents the supervising central unit and, therefore, a very critical element of the system. The paper mainly points out the architecture and protocols at the basis of the LNS and discusses a set of performance tests aimed at proving the effectiveness of the system and comparing it with a well‐known commercial solution. Copyright © 2007 John Wiley & Sons, Ltd.
A neural network system for authenticating remote users in multi‐server architecture
Authors: Lin Iuon‐Chang
Published: October 2007

Authenticating the legitimacy of a remote user is an important issue in modern computer systems. In this paper, a neural network system for authenticating remote users is presented. The benefits of the proposed scheme include that (1) it is suitable for multi‐server environment; (2) it does not maintain a verification table; (3) users can freely choose their password; and (4) it can withstand replay attack, off‐line password guessing attack, and privileged insider attacks. Furthermore, some drawbacks, such as the users who choose the same passwords will have the same identities and unavailability for evicting a user from the system, will also be eliminated. Copyright © 2007 John Wiley & Sons, Ltd.
Pancreatic scintigraphy with 99mTc‐interleukin‐2 at diagnosis of type 1 diabetes and after 1 year of nicotinamide therapy
Authors: Chianelli M. , Parisella M. G. , Visalli N. , Mather S. J. , D'Alessandria C. , Pozzilli P. , Signore A. ,   IMDIAB study group
Published: October 2007

Background

To evaluate the clinical utility of pancreatic scintigraphy with 99mTc‐interleukin‐2 to identify Type 1 diabetic patients with pancreatic inflammation at diagnosis.

Methods

99mTc‐interleukin‐2 scintigraphy was performed on 42 newly diagnosed Type 1 diabetic patients, before and after 1 year of treatment with nicotinamide (25 or 50 mg/kg/day) in addition to intensive insulin therapy. Metabolic status was monitored every 3 months for 1 year. Sixteen normal subjects were studied as control.

Results

Significant pancreatic accumulation of 99mTc‐interleukin‐2 was found in 31% of the patients at the time of diagnosis. Patients positive or negative for pancreatic accumulation of interleukin‐2 scintigraphy did not show any difference in metabolic or immunologic parameters at diagnosis. Positive patients, however, showed higher C‐peptide values at 3 months and lower insulin requirement at 1 year, compared to negative patients (insulin requirement (IR): 0.33 ± 0.11 vs 0.67 ± 0.24 IU/kg/day, positive vs negative patients; p = 0.0001); patients positive to IL2 scintigraphy treated with nicotinamide at 25 mg/kg were the only group showing a significant reduction in IR 1 year after diagnosis (IRt0: 0.53 ± 0.30 vs IRt12: 0.28 ± 0.07 IU/kg/day; p = 0.013). After 1 year, all the positive patients showed a significant decrease in pancreatic uptake of 99mTc‐interleukin‐2 (P/B: 7.87 ± 2.28 at diagnosis vs 5.00 ± 1.23 after 1 year; p < 0.0001 paired t‐test).

Conclusion

99mTc‐interleukin‐2 scintigraphy at diagnosis of Type 1 diabetes may identify patients with pancreatic inflammation. In such patients, treated with nicotinamide at 25 mg/kg, insulin requirement and pancreatic inflammation after 1 year were significantly reduced suggesting that IL2 scintigraphy may be of potential use for assessing the autoimmune phenomena in endocrine pancreas. Copyright © 2007 John Wiley & Sons, Ltd.
Impact of lowering the criterion for impaired fasting glucose on identification of individuals with insulin resistance. The GISIR database.
Authors: Sesti Giorgio , Andreozzi Francesco , Bonadonna Riccardo C. , De Mattia Giancarlo , Leonetti Frida , Luzi Livio , Marini Maria Adelaide , Natali Andrea , Vettor Roberto , Bonora Enzo ,   on behalf of the Group of Italian Scientists of Insulin Resistance (GISIR)
Published: October 2007

Objective

We assessed the accuracy of the American Diabetes Association (ADA)2003 definition of impaired fasting glucose (IFG) in identifying subjects with low insulin sensitivity, and determined cardiovascular risk factors in ADA2003 IFG subjects.

Research Design and Methods

This study included 930 non‐diabetic Italian Caucasians from the GISIR database in which subjects underwent a hyperinsulinaemic‐euglycaemic clamp performed with a standard technique. Low insulin sensitivity was defined as being in the lower quartile of glucose metabolized during the last hour of the clamp (M). Subjects were stratified in the following groups: normal fasting glucose (NFG) (<100 mg/dL), IFG100 (100–109 mg/dL), ADA1997 IFG110 (110–125 mg/dL), and ADA2003 IFG (100–125 mg/dL).

Results

The sensitivity of identifying subjects with low insulin sensitivity increased adopting the ADA2003 criterion. After Bonferroni correction for multiple comparisons, both IFG100 and ADA1997 IFG110 showed significantly higher body mass index (BMI), waist, systolic blood pressure (SBP) and diastolic blood pressure (DBP), triglyceride, fasting plasma insulin (FPI) and fasting plasma glucose (FPG), and lower insulin sensitivity as compared with NFG. As compared with IFG100, ADA1997 IFG110 showed significantly higher BMI, waist, SBP, FPI, FPG, and lower insulin sensitivity. ADA2003 IFG group showed significantly higher BMI, waist, SBP and DBP, triglyceride, cholesterol, FPI, and FPG, but lower HDL levels and insulin sensitivity compared with NFG subjects.

Conclusions

Although neither the ADA2003 nor the ADA1997 definition of IFG appears to be particularly efficacious for the identification of subjects' low insulin sensitivity, lowering the criterion to the ADA2003 glucose threshold increased the sensitivity without affecting the specificity. ADA2003 IFG showed a worse cardiovascular risk profile compared with NFG.Copyright © 2007 John Wiley & Sons, Ltd.
Insulin glargine and receptor‐mediated signalling: clinical implications in treating type 2 diabetes
Authors: Le Roith Derek
Published: October 2007

Most patients with type 2 diabetes mellitus will eventually require insulin therapy to achieve or maintain adequate glycaemic control. The introduction of insulin analogues, with pharmacokinetics that more closely mimic endogenous insulin secretion, has made physiologic insulin replacement easier to achieve for many patients. However, there are also concerns regarding alteration of binding affinities for the insulin receptor (IR) or insulin‐like growth factor‐1 receptor (IGF‐1R) may increase the mitogenic potential of some analogues. Therefore, this article will review the relevant preclinical and clinical data to assess the mitogenic potential of insulin glargine, a basal insulin analogue, compared with regular human insulin (RHI).

Searches of the PubMed database were performed using terms that included ‘IR,’ ‘insulin‐like growth factor‐1,’ ‘IGF‐1R,’ ‘type 2 diabetes mellitus,’ and ‘insulin glargine.’ Original articles and reviews of published literature were retrieved and reviewed.

Although one study reported increased binding affinity of insulin glargine for the IGF‐1R and increased mitogenic potential in cells with excess IGF‐1Rs (Saos/B10 osteosarcoma cells), most in vitro binding‐affinity and cell‐culture studies have demonstrated behaviour of insulin glargine comparable to that of RHI for both IR and IGF‐1R binding, insulin signalling, and metabolic and mitogenic potential.

Currently published in vivo carcinogenic studies and human clinical trial data have shown that insulin glargine is not associated with increased risk for either cancer or the development or progression of diabetic retinopathy. Copyright © 2007 John Wiley & Sons, Ltd.
Genetic Study of Saudi Diabetes (GSSD): significant association of the KCNJ11 E23K polymorphism with type 2 diabetes
Authors: Alsmadi Osama , Al‐Rubeaan Khalid , Wakil Salma M. , Imtiaz Faiqa , Mohamed Gamal , Al‐Saud Haya , Al‐Saud Nouran Abu , Aldaghri Nasser , Mohammad Shahinaz , Meyer Brian F
Published: October 2007

Background

The E23K variant of KCNJ11 has been associated with type 2 diabetes (T2D) in several but not all populations studied. Thus far, despite a high incidence of T2D, the role of this variant in Arabs has not been established.

Methods

We performed a case‐control association study using 550 T2D Saudi patients (WHO criteria), and 335 controls (age ≥ 60; fasting plasma glucose < 7 mmol/L). E23K genotyping was performed by using molecular beacon‐based real time PCR assays.

Results

The difference in K or risk allele frequency of cases and controls was significant with an OR of 1.7 (p = 0.0001). The K allele is more common among T2D patients (21%) than in the age and sex matched controls (13.6%). This was consistent with a likely eventual conversion to T2D of younger normoglycemic individuals as they grow older.

Conclusions

Our results report for the first time a positive association of the E23K variant with T2D in an Arab population. Confirmation by a larger study is indicated. Copyright © 2007 John Wiley & Sons, Ltd.
PAI‐1 activity, but not fibrinogen or von Willebrand factor, is inversely related to LDL particle size in type 2 diabetes
Authors: Mertens Ilse , Lemieux Isabelle , Verrijken An , Després Jean‐Pierre , Van Gaal Luc F.
Published: October 2007

Background

Levels of fibrinogen, von Willebrand factor (vWF) and plasminogen activator inhibitor‐1 (PAI‐1) have been associated with small low‐density lipoprotein (LDL) particles. However, it is not clear whether these associations are independent of visceral adiposity or other components of the metabolic syndrome such as triglycerides or insulin resistance.

Methods

Visceral adipose tissue (VAT; CT‐scan), fibrinogen, von Willebrand factor antigen (vWF : Ag), PAI‐1 activity and different metabolic parameters such as total cholesterol (chol), HDL‐chol, triglycerides, insulin resistance (homeostasis model assessment; HOMA‐IR) were determined in 41 women and 78 men with type 2 diabetes. LDL particle size was assessed by polyacrylamide gradient gel electrophoresis.

Results

PAI‐1 activity was inversely related to LDL particle size after adjustment for age and body mass index (BMI) (r = − 0.28; p = 0.006) or age and VAT (r = − 0.26; p = 0.01), but not after adjustment for age and HOMA‐IR (r = − 0.15; p = 0.148) or age and triglycerides (r = − 0.04; p = 0.679). In multiple regression analysis, LDL particle size did not independently determine PAI‐1 activity levels. Fibrinogen and vWF : Ag did not seem to be related to LDL size.

Conclusions

PAI‐1 activity levels, in contrast to fibrinogen and vWF : Ag, seem to be related to the small LDL phenotype in patients with type 2 diabetes. However, this relationship was not independent of insulin resistance or triglycerides. Copyright © 2007 John Wiley & Sons, Ltd.
PANDAS anorexia nervosa—Endangered, extinct or nonexistent?
Authors: Puxley Frances , Midtsund Marie , Iosif Alina , Lask Bryan
Published: October 2007

Objective:

Substantial evidence exists for the concept of pediatric autoimmune neuropsychiatric disorders associated with streptoccoccal infection (PANDAS) such as some cases of obsessive‐compulsive disorder and tics/Tourette's syndrome. More recently PANDAS‐AN has been described. The aim of this article is to provide a critical review of this concept.

Method:

The literature was searched using Medline, Psychinfo, and Google.

Results:

There is some evidence for the entity of PANDAS‐AN but this is considerably limited by a wide range of methodological problems, including the seemingly low prevalence, the lack of clarity in diagnostic criteria, and the lack of specificity in the diagnostic tests. Innovative treatment approaches hold promise but require further evaluation.

Conclusion:

Further research into PANDAS‐AN, using more clearly defined and consistent diagnostic criteria is needed, given the potential for enhancing the understanding of the pathogenesis of AN and for more effective treatments. © 2007 by Wiley Periodicals, Inc. Int J Eat Disord 2008
The diagnostic validity of the criteria for binge eating disorder
Authors: Latner Janet D. , Clyne Courtney
Published: October 2007

Objective:

This paper considers whether the criteria currently used to classify the diagnosis of binge eating disorder (BED) are valid and appropriate.

Method:

We review evidence that reflects on the validity of the current criteria for binge eating episodes and BED, using literature retrieved through major psychology and psychiatry search engines (e.g., PsycInfo, PubMed).

Results:

Evidence from experimental research points to the relative importance of episode frequency, the amount of food consumed at episodes, the subjective sense of loss of control over eating, and several additional criteria associated with binge episodes in BED. Evidence on the differences in psychopathology between BED and bulimia nervosa and between BED and obesity without binge eating, as related to diagnostic criteria, is reviewed.

Conclusion:

Although evidence concerning the diagnostic criteria of BED is mixed, broadening certain diagnostic criteria for binge eating episodes and BED might more accurately reflect the research literature and increase the number of individuals eligible for inclusion in treatment programs. © 2007 by Wiley Periodicals, Inc. Int J Eat Disord 2008
Suicidal behavior in adolescents: Relationship to weight status, weight control behaviors, and body dissatisfaction
Authors: Crow Scott , Eisenberg Marla E. , Story Mary , Neumark‐Sztainer Dianne
Published: October 2007

Objective:

Suicide is associated with full syndromal eating disorders, but it is unclear whether subsyndromal eating disorders carry the same risk. This study examined associations between suicidal behaviors and extreme and less extreme weight control behaviors (EWCB and LWCB, such as fasting, vomiting, meal skipping, etc.), body dissatisfaction, and weight status in adolescents.

Method:

Data on body dissatisfaction, depressive symptoms, suicidal ideation and attempts, and body mass index (BMI) were drawn from Project EAT, a survey of 4,746 7th–12th grade students. Multivariate logistic regression examined associations between eating‐ and weight‐related variables and suicidality.

Results:

Suicidal ideation and suicide attempts were more commonly observed in adolescents with EWCB (boys: ideation OR = 2.12, attempts OR = 4.10; girls: ideation OR = 1.66, attempts OR = 2.29), LWCB (boys: ideation OR = 1.33, attempts OR = 1.76; girls: ideation OR = 1.77, attempts OR = 1.80), as well as body dissatisfaction (boys: ideation OR = 1.75, attempts OR = 2.23; girls: ideation OR = 1.77, attempts OR = 1.81), even after controlling for depressive symptoms. No association was observed between BMI and suicidal attempts or ideation.

Conclusion:

Thus, it appears that suicidal behavior in adolescents is associated even with low‐level eating disorder symptoms. © 2007 by Wiley Periodicals, Inc. Int J Eat Disord 2008
Expressed emotion in eating disorders assessed via self‐report: An examination of factors associated with expressed emotion in carers of people with anorexia nervosa in comparison to control families
Authors: Kyriacou Olivia , Treasure Janet , Schmidt Ulrike
Published: October 2007

Objective:

High expressed emotion (EE) has been linked to outcome in anorexia nervosa (AN). Traditional interview measures of EE require considerable resources. The aim was to compare EE, measured with a self report tool, in parents of people with AN (carers; N = 151) with that of parents of healthy people (controls; N = 93), and to explore factors associated with EE.

Method:

A cross‐sectional design was used to assess EE (Family Questionnaire) and psychological distress (Hospital Anxiety and Depression Scale).

Results:

Over 60% (96/151) of carers showed high emotional over‐involvement (EOI) compared with 3% (3/93) of controls, whereas 47% (71/151) of carers showed high criticism (CC) compared with 15% (14/93) of controls. The most significant variable related to CC was “negative/difficult behaviors,” and anxiety, for EOI.

Conclusion:

The FQ was sensitive both to CC and EOI. Interventions aimed at reducing EE may need to focus on decreasing carers' anxiety and teaching skills to moderate difficult behaviors. © 2007 by Wiley Periodicals, Inc. Int J Eat Disord 2008
Effects of dieting‐related messages on psychological and weight control variables
Authors: Roehrig Megan , Thompson J. Kevin , Cafri Guy
Published: October 2007

Objective:

The current study sought to empirically examine the immediate and short‐term effects of dieting‐related psychoeducational messages on established risk factors for eating pathology and weight control variables.

Method:

One‐hundred thirty nine participants were randomly assigned to a prodieting, antidieting, or control message condition. Variables were assessed at baseline, post‐test, and 2‐week follow‐up.

Results:

The prodieting condition produced significantly greater dieting intentions, perceived pressure to lose weight, and internalization intentions, whereas the antidieting message yielded significantly lower bulimic intentions. Healthy eating significantly increased from baseline to follow‐up in the prodieting condition. No other behavioral changes were found. Perceived pressure to lose weight mediated the relationship between diet message and post‐test weight control intentions, state negative‐affect, and body dissatisfaction.

Conclusion:

The findings provide initial support for the short‐term efficacy of the prodieting message to increase healthy eating behaviors; however, immediate increases in established risk factors for eating pathology also emerged. Implications are discussed. © 2007 by Wiley Periodicals, Inc. Int J Eat Disord 2008
A DRD4/BDNF gene–gene interaction associated with maximum BMI in women with bulimia nervosa
Authors: Kaplan Allan S. , Levitan Robert D. , Yilmaz Zeynep , Davis Caroline , Tharmalingam Subi , Kennedy James L.
Published: October 2007

Objective:

The goals of the current study were threefold: 1) to examine whether the hypofunctional 7R allele of the DRD4 gene contributes to maximal lifetime body mass in women with BN; 2) to determine whether the BDNF gene contributes to maximal BMI on its own, and 3) to explore possible BDNF/DRD4 gene‐gene interactions in mediating maximum lifetime BMIs in BN.

Method:

We tested two General Linear Models predicting maximum lifetime BMI with the exon 3 VNTR polymorphism of the dopamine‐4 receptor gene (DRD4) and either the Val66Met or the ‐270C/T polymorphism of BDNF respectively in 163 female probands with BN, purging subtype.

Results:

In these bulimic subjects, the hypofunctional 7R allele of DRD4 predicted maximal BMI (p < .01). There was also a significant interaction between the DRD4 gene and the BDNF gene in predicting maximal BMI. The Val66Met rather than the 270C/T polymorphism of BDNF interacting with DRD4 predicted maximum BMI in this BN sample (p < .01). Probands carrying both the hypofunctional 7R allele of DRD4 and the Met66 allele of BDNF had significantly higher maximal BMI than did probands in the other gene‐gene interaction groups.

Conclusion:

These results provide further evidence that the hypofunctional 7R allele of DRD4 contributes to weight gain in women with BN and that the BDNF gene interacts with DRD4 to influence weight regulation in these subjects. © 2007 by Wiley Periodicals, Inc. Int J Eat Disord 2008
A critical evaluation of the efficacy of self‐help interventions for the treatment of bulimia nervosa and binge‐eating disorder
Authors: Sysko Robyn , Walsh B. Timothy
Published: October 2007

Objective:

Cognitive behavioral therapy (CBT) is efficacious for the treatment of bulimia nervosa (BN) and binge‐eating disorder (BED). As a number of factors limit the availability of CBT, self‐help manuals have been developed to make the treatment more widely available.

Method:

Published studies evaluating the efficacy of self‐help programs in the treatment of BN and BED were reviewed.

Results:

Controlled studies of self‐help programs for BN and BED have often employed a waiting list control group, and indicate that self‐help provides more benefit than remaining on a waiting list. However, fewer studies have utilized a more active control group, and these studies have not been as positive.

Conclusion:

In general, open and wait‐list trials indicate that self‐help is helpful in treating BN and BED, but there is little evidence for the specific efficacy of self‐help in comparison to other treatments. Additional studies of self‐help are needed to determine the specific utility of self‐help interventions for BN and BED. © 2007 by Wiley Periodicals, Inc. Int J Eat Disord 2008
Eating problems, body image disturbances, and academic achievement: Preliminary evaluation of the eating and body image disturbances academic interference scale
Authors: Yanover Tovah , Thompson J. Kevin
Published: October 2007

Objective:

To examine the relationships between a new scale, the Eating and Body Image Disturbances Academic Interference Scale (EBIDAIS), and measures of eating disturbance, body image, and academic achievement.

Method:

One thousand five hundred eighty‐four college undergraduates completed the measures in an online survey and were awarded class credit for their participation. Measures included the Eating Disorder Inventory Bulimia, Drive for Thinness, Body Dissatisfaction, and Perfectionism subscales. Grade point average (GPA) was also reported.

Results:

Academic interference and GPA were significantly correlated, indicating that higher interference scores were related to lower GPA. EBIDAIS was also significantly correlated with drive for thinness, bulimia, and body dissatisfaction, but was not significantly associated with perfectionism. The correlation between interference and GPA was substantially higher for a subsample of individuals who scored in the elevated range on eating and body dissatisfaction.

Conclusion:

Academic interference may be a relatively unexamined, but potentially important, outcome for individuals who experience eating problems and body image disturbance. © 2007 by Wiley Periodicals, Inc. Int J Eat Disord 2008
Synthesis of 3‐Fluorofuran‐2(5H)‐ones Based on Z/E Photoisomerisation and Cyclisation of 2‐Fluoro‐4‐hydroxybut‐2‐enoates
Authors: Pomeisl Karel , Čejka Jan , Kvíčala Jaroslav , Paleta Oldřich
Published: October 2007

Mixtures of some (E)‐ and (Z)‐2‐fluoroalk‐2‐enoates prepared from the corresponding 2‐hydroxycarbonyl compounds and ethyl 2‐(diethoxyphosphoryl)‐2‐fluoroacetate have been transformed in high conversions into the target 3‐fluorofuran‐2(5H)‐ones by an efficient Z/E photoisomerisation of noncyclisable Z isomers followed by acid‐catalysed cyclisation. In contrast, the acid‐catalysed deprotection of ethyl (E)‐ and (Z)‐4‐[tert‐butyl(dimethyl)silyloxy]‐2‐fluoro‐4‐phenylbut‐2‐enoates resulted in the displacement of vinylicfluorine, affording ethyl (E)‐2‐oxo‐4‐phenylbut‐3‐enoate. 3‐Fluoro‐4‐phenylfuran‐2(5H)‐one was transformed into 2‐[tert‐butyl(dimethyl)silyloxy]‐3‐fluoro‐5‐methylfuran as a novel fluorinated building block.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Rapid and Easy Access to (E)‐1,3‐Enynes, 1,3‐Diynes and Allenes Starting from Propargylic Acetals, Exploiting the Different Reactivity of Lithium and Mixed Lithium–Potassium Organometallic Reagents
Authors: Blangetti Marco , Deagostino Annamaria , Rosso Helèna , Prandi Cristina , Zavattaro Chiara , Venturello Paolo
Published: October 2007

The treatment of propargylic acetals with various lithium and mixed lithium–potassium Schlosser reagents, has allowed a one‐pot synthesis of (E)‐1,3‐enynes, 1,3‐diynes and allenes, depending on the reaction conditions and the selected base. Various reaction conditions were investigated in order to control the selectivity of the reactions and to obtain pure products. The metallation–elimination sequence in the presence of a suitable electrophile has provided a linear route to functionalized (E)‐conjugated enynes, diynes and allenes.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Isolation, Enantioselective Total Synthesis and Structure Determination of the Anthrapyran Metabolite SS 43405‐e
Authors: Tietze Lutz F. , Singidi Ramakrishna Reddy , Gericke Kersten M. , Böckemeier Henning , Laatsch Hartmut
Published: October 2007

The first enantioselective total synthesis of the anthrapyran metabolite SS 43405‐e, isolated from a marine‐derived streptomycete, is described, which also allows the determination of the so far unknown absolute (R) configuration of the natural product. For the synthesis the bromoanthracene derivative 3 is lithiated and coupled with the enantiopure aldehyde (S)‐4 to give 9, which is oxidatively transformed into the corresponding anthraquinone 10 and further into the ketone 2. The final step is the cyclization of 2 under acidic conditions to give the desired antibiotic (S)‐1. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Induction of Helical Handedness and DNA Binding Properties of Peptide Nucleic Acids (PNAs) with Two Stereogenic Centres
Authors: Sforza Stefano , Tedeschi Tullia , Corradini Roberto , Marchelli Rosangela
Published: October 2007

A systematic study on the combined effects of two lysine‐derived stereogenic centres at C2 and C5 of a PNA monomer inserted within an achiral PNA strand was performed by circular dichroism, UV spectroscopy and ESI mass spectrometry by taking into account all four diastereomers. The stereogenic centres induced different preferential helix handednesses in the PNA strands, which in turn affected their ability to bind to the complementary DNA. The helical induction, studied on the PNA–PNA duplexes, evidenced that in the case of “chiral conflict” (induction of opposite helices), the stereogenic centre at C5 was clearly prevalent in determining the preferential helix handedness. The PNA–DNA duplex stability was found to be related to the number and the position of the stereogenic centres inducing a preference for a right‐handed helix, as well as with the strength of the helical induction. Thermodynamic parameters evaluated by the Van't Hoff model clearly outlined the different enthalpic and entropic contributions of the substitutions at C2 and C5. These findings expand the knowledge of the role of punctual stereogenic centres in inducing supramolecular chirality in PNAs, demonstrate the ability of right‐handed DNA to act as a chiral selector and are essential for the future design of chiral PNAs with improved DNA affinity.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Synthesis of Optically Active (+)‐Canangone, Its 6‐Epimer, and Determination of Absolute Configuration
Authors: Koripelly Girish , Saak Wolfgang , Christoffers Jens
Published: October 2007

The first synthesis of canangone and its 6‐epimer is reported. The products are obtained in optically active form by an asymmetric Robinson annulation. The relative and absolute configuration of the natural product is established for the first time. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Molecular deformation and free‐solution electrophoresis of DNA‐uncharged polymer conjugates at high field strengths: Theoretical predictions Part 2: Stretching
Authors: McCormick Laurette C. , Slater Gary W.
Published: October 2007

DNA sequencing by electrophoresis can be dramatically sped up by overcoming the need for the sieving medium. Normally it is possible to separate DNA based on size in free solution; however, not end‐labeled free‐solution electrophoresis (ELFSE) uses a neutral drag‐tag molecule to make it possible. In experiments to date, the drag‐tag and DNA together form a random coil conformation; while with future generation drag‐tags and high fields, deformation of this conformation may occur. In the first paper in this series we investigated the conditions under which the DNA and label become hydrodynamically distinct (or segregated), based on a theoretical approach developed for the electrophoresis of polyampholytes. In this paper we study further deformation wherein either the DNA and/or a polymeric label stretch. We show that deformation may dramatically improve the capabilities of ELFSE, especially when both the DNA and a polymeric drag‐tag fully stretch; however, reaching these regimes will require extremely high field intensities, something that only microchip technologies may be able to achieve.
Development of a CE method for the determination of mycophenolic acid in human plasma: A comparison with HPLC
Authors: Carlucci Filippo , Anzini Maurizio , Rovini Michele , Cattaneo Dario , Merlini Simona , Tabucchi Antonella
Published: October 2007

Mycophenolate mofetil (MMF) is a widely used drug for the maintenance of immunosuppressive therapy in renal‐transplant recipients. MMF is rapidly metabolized in vivo to mycophenolic acid (MPA), a reversible, noncompetitive inhibitor of inosine monophosphate dehydrogenase, which represents a limiting enzyme in lymphocyte proliferation. MPA shows large interindividual pharmacokinetic variability: its monitoring is therefore of primary importance to achieve adequate immunosuppression with minimized risk of graft rejection or toxicity. We developed a CE method for the determination of total MPA (tMPA) in plasma, based on easy sample preparation; CE evaluation of tMPA was performed in 30 mmol/L sodium‐borate with 10 mmol/L SDS (pH 10.00) at 25°C using a 60 cm (54.5 to window) uncoated capillary with UV detection at 254 nm wavelength. MPA was readily detectable in plasma; the CE method was linear in the range of 0.7–120 μg/mL (r >0.992). Intra‐ and interassay imprecision was <7% except for the lowest spiked MPA concentration, which had an intra‐assay RSD% of 14.7 compared to 18.3 interassay. Data by CE were compared with results obtained by a validated HPLC method. CE assay of tMPA exhibited a very good correlation (r2 >0.988) with respect to HPLC; Bland–Altman difference versus average showed a mean of −0.18 μg/mL ± 1.14 SD. CE determination of tMPA is a robust, sensitive and reproducible method with the advantage over HPLC of being fast, simple and unexpensive, also enabling quick assessment of MPA for pharmacokinetic studies.
Analysis and purification of peptide nucleic acids by denaturing PAGE
Authors: Dodd David W. , Hudson Robert H. E.
Published: October 2007

A flexible and convenient protocol for the analysis and purification of peptide nucleic acid (PNA) oligomers and PNA‐peptide chimeras by denaturing PAGE is described. Vertical slab gel electrophoresis, 26% in polyacrylamide and 8 M urea at pH 3, was suitable for analysis of oligomers ranging in size from tetramers (4‐mers) to tetradodecamers (24‐mers). Single‐base resolution of oligomers was achieved and separations are generally superior to those given by standard RP‐HPLC techniques. The separation of a related series of PNA oligomers showed the distance migrated was linearly dependent on the logarithm of the molecular weight. The migration of oligomers through the gel is dependent on the number of basic functional groups present, such as amino groups, and the A and C content of the oligomer. PNAs are amenable to detection by UV‐shadowing technique illuminated at 260 nm or Coomassie blue staining, both with similar, sub‐microgram per band detection limits.
Carrier ampholytes for IEF, on their fortieth anniversary (1967–2007), brought to trial in court: The verdict
Authors: Righetti Pier Giorgio , Simó Carolina , Sebastiano Roberto , Citterio Attilio
Published: October 2007

The present review summarizes the data accumulated in 1‐year work, by exploring,viaa 3‐D methodology (Rotofor fractionation followed by CE‐MS), all the narrow (2 pH unit wide) carrier ampholyte (CA) compounds for IEF, produced by three companies (Pharmacia with Pharmalyte and Ampholine, BioRad with Bio‐Lyte and Serva with Servalyt). All species have been assessed by measuring the types of pH gradient produced, the total number of individual chemicals (withMrvalues) and isoforms and their focusing behavior (‘good’ or ‘poor’ ampholytes). Servalyt contains a grand total of 686 chemical entities and no less than 3899 isoforms; Pharmalyte 643 and 2211; Bio‐Lyte 255 and 1192; Ampholine 294 and 1182, respectively. In terms ofMrdistribution, although all 2‐pH‐unit ranges start with the same lowMrvalues (ca.200) their upper limits are quite different. Thus, Pharmalyte reaches an upperMrvalue of 1179 (in the pH 4–6 range),versus907 for Servalyt, 835 for Bio‐Lyte and 893 for Ampholine. In general, in going towards the more alkaline pH intervals (e.g.pH 8–10) the molecular mass of carrier ampholytes (CAs) is reduced to as low as 491 (Bio‐Lyte), indicating that the alkaline species are probably made with shorter oligoamines and are, in general, less substituted. All acidic pH intervals (up to pH 6–8) appear to be constituted by a very large proportion of well focusing species, indicating small values of ΔpKacross their pI. Above pH 8, all brands of CAs worsen, the vast majority being unable to focus properly and sustain adequately the pH gradient. General guidelines are given for the synthesis of new alkaline species for improving the basic pH ranges.
DNA is more negatively supercoiled in bacterial plasmids than in minichromosomes isolated from budding yeast
Authors: Mayán‐Santos María‐Luisa , Martínez‐Robles María‐Dolores , Hernández Pablo , Krimer Dora , Schvartzman Jorge B.
Published: October 2007

A series of circular shuttle vectors were constructed that could replicate and transcribe in the cells of both Escherichia coli and Saccharomyces cerevisiae. 2‐D agarose gel electrophoresis run without or in the presence of different concentrations of chloroquine (CHL) revealed that bacterial plasmids were more negatively (−) supercoiled than minichromosomes isolated from budding yeast. Attempts to increase (−) supercoiling in S. cerevisiae or to reduce it in E. coli have deleterious biological consequences. These observations indicate that DNA supercoiling can vary in different species but cells are exquisitely sensitive to sudden changes in supercoiling. In E. coli, the observation that cell growth as well as ColE1 plasmid copy number decrease when DNA relaxes suggests that supercoiling could affect cell viability by regulating the initiation of both transcription and replication.
Using DNA sequencing electrophoresis compression artifacts as reporters of stable mRNA structures affecting gene expression
Authors: Kapoor Divya , Chandrayan Sanjeev Kumar , Ahmed Shubbir , Guptasarma Purnananda
Published: October 2007

The formation of secondary structure in oligonucleotide DNA is known to lead to “compression” artifacts in electropherograms produced through DNA sequencing. Separately, the formation of secondary structure in mRNA is known to suppress translation; in particular, when such structures form in a region covered by the ribosome either during, or shortly after, initiation of translation. Here, we demonstrate how a DNA sequencing compression artifact provides important clues to the location(s) of translation‐suppressing secondary structural elements in mRNA. Our study involves an engineered version of a gene sourced from Rhodothermus marinus encoding an enzyme called Cel12A. We introduced this gene into Escherichia coli with the intention of overexpressing it, but found that it expressed extremely poorly. Intriguingly, the gene displayed a remarkable compression artifact during DNA sequencing electrophoresis. Selected “designer” silent mutations destroyed the artifact. They also simultaneously greatly enhanced the expression of the cel12A gene, presumably by destroying stable mRNA structures that otherwise suppress translation. We propose that this method of finding problem mRNA sequences is superior to software‐based analyses, especially if combined with low‐temperature CE.
Deriphat 2‐DE to visualize polyphenol oxidase in Moscato and Prosecco grapes
Authors: Zocca Federico , Lomolino Giovanna , Spettoli Paolo , Lante Anna
Published: October 2007

The Deriphat 2‐DE was used to visualize polyphenol oxidase (PPO) isoforms of Moscato and Prosecco grape extracts, partially purified and characterized. Catecholase has similar values in the two varieties, whereas Moscato cresolase data are almost 54% higher. In the first dimension, the PPO of both varieties may be detected by SDS‐PAGE, but native PAGE (N‐PAGE) gave negative results. For this reason, the samples were solubilized in the zwitteronic detergent Deriphat, which was also included in the gel and the cathodic buffer. Deriphat migrated together with the cathodic buffer, maintaining protein solubility and revealing the PPO profiles of Moscato and Prosecco extracts in native conditions. The combination of Deriphat‐PAGE (D‐PAGE) and SDS‐PAGE (2‐DE) also resulted in improved separation efficiency in resolving PPO and specialized stains in evaluating PPO activities. The control, represented by IEF for the first‐dimensional separation, had a lower number of spots, demonstrating the higher capacity of Deriphat 2‐DE to isolate PPO isoforms from grape extracts. The Deriphat 2‐DE method described here is simple but powerful, and the resulting information will be a useful tool for further proteomic research.
Portuguese version of the Delirium Rating Scale‐Revised‐98: reliability and validity
Authors: Negreiros Daniel Philippi de , Meleiro Alexandrina Maria Augusto da Silva , Furlanetto Letícia M. , Trzepacz Paula T.
Published: October 2007

Objective

To assess the validity and the reliability of the Portuguese version of the Delirium Rating Scale‐Revised‐98 (DRS‐R‐98).

Methods

The scale was translated into Portuguese and back‐translated into English. After assessing its face validity, five diagnostic groups (n = 64; delirium, depression, dementia, schizophrenia and others) were evaluated by two independent researchers blinded to the diagnosis. Diagnosis and severity of delirium as measured by the DRS‐R‐98 were compared to clinical diagnosis, Mini‐Mental State Exam, Confusion Assessment Method, and Clinical Global Impressions scale (CGI).

Results

Mean and median DRS‐R‐98 total scores significantly distinguished delirium from the other groups (p < 0.001). Inter‐rater reliability (ICC between 0.9 and 1) and internal consistency (α = 0.91) were very high. DRS‐R‐98 severity scores correlated highly with the CGI. Mean DRS‐R‐98 severity scores during delirium differed significantly (p < 0.01) from the post‐treatment values. The area under the curve established by ROC analysis was 0.99 and using the cut‐off value of 20 the scale showed sensitivity and specificity of 92.6% and 94.6%, respectively.

Conclusion

The Portuguese version of the DRS‐R‐98 is a valid and reliable measure of delirium that distinguishes delirium from other disorders and is sensitive to change in delirium severity, which may be of great value for longitudinal studies. Copyright © 2007 John Wiley & Sons, Ltd.
TC‐tuned biocompatible suspension of La0.73Sr0.27MnO3 for magnetic hyperthermia
Authors: Prasad N. K. , Rathinasamy K. , Panda D. , Bahadur D.
Published: October 2007

La1−xSrxMnO3, a ferromagnet with high magnetization and Curie temperature TC below 70°C, enables its use for magnetic hyperthermia treatment of cancer with a possibility of in vivo temperature control. We found that La0.73Sr0.27MnO3 particles of size range 20–100 nm showed saturation magnetization around 38 emu/g at 20 kOe and a TC value of 45°C. Aqueous suspension of these nanoparticles was prepared using a polymer, acrypol 934, and the biocompatibility of the suspension was examined using HeLa cells. A good heating ability of the magnetic suspension was obtained in the presence of AC magnetic field, and it was found to increase with the amplitude of field. The suspension having concentration of 0.66 mg/mL (e.g., 0.66 mg of nanoparticles with acropyl per milliliter of culture media) was observed to be biocompatible even after 96 h of treatment, as estimated by sulforhodamine B and trypan blue dye exclusion assays. Further, the treatment with the aforementioned concentration did not alter the microtubule cytoskeleton or the nucleus of the cells. However, the bare particles (concentration of 0.66 mg of nanoparticles per milliliter of culture media, but without acropyl) decreased the viability of cell significantly. Our in vitro studies suggest that the suspension (concentration of 0.66 mg/mL) may further be analyzed for in vivo studies. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008
FACTS: Fast analytical continuum treatment of solvation
Authors: Haberthür Urs , Caflisch Amedeo
Published: October 2007

An efficient method for calculating the free energy of solvation of a (macro)molecule embedded in a continuum solvent is presented. It is based on the fully analytical evaluation of the volume and spatial symmetry of the solvent that is displaced from around a solute atom by its neighboring atoms. The two measures of solvent displacement are combined in empirical equations to approximate the atomic (or self) electrostatic solvation energy and the solvent accessible surface area. The former directly yields the effective Born radius, which is used in the generalized Born (GB) formula to calculate the solvent‐screened electrostatic interaction energy. A comparison with finite‐difference Poisson data shows that atomic solvation energies, pair interaction energies, and their sums are evaluated with a precision comparable to the most accurate GB implementations. Furthermore, solvation energies of a large set of protein conformations have an error of only 1.5%. The solvent accessible surface area is used to approximate the nonpolar contribution to solvation. The empirical approach, called FACTS (Fast Analytical Continuum Treatment of Solvation), is only four times slower than using the vacuum energy in molecular dynamics simulations of proteins. Notably, the folded state of structured peptides and proteins is stable at room temperature in 100‐ns molecular dynamics simulations using FACTS and the CHARMM force field. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
Manager–worker‐based model for the parallelization of quantum Monte Carlo on heterogeneous and homogeneous networks
Authors: Feldmann Michael T. , Cummings Julian C. , Kent David R. , Muller Richard P. , Goddard William A.
Published: October 2007

A manager–worker‐based parallelization algorithm for Quantum Monte Carlo (QMC‐MW) is presented and compared with the pure iterative parallelization algorithm, which is in common use. The new manager–worker algorithm performs automatic load balancing, allowing it to perform near the theoretical maximal speed even on heterogeneous parallel computers. Furthermore, the new algorithm performs as well as the pure iterative algorithm on homogeneous parallel computers. When combined with the dynamic distributable decorrelation algorithm (DDDA) [Feldmann et al., J Comput Chem 28, 2309 (2007)], the new manager–worker algorithm allows QMC calculations to be terminated at a prespecified level of convergence rather than upon a prespecified number of steps (the common practice). This allows a guaranteed level of precision at the least cost. Additionally, we show (by both analytic derivation and experimental verification) that standard QMC implementations are not “perfectly parallel” as is often claimed. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2008
An eco‐efficient rationalized leather process
Authors: Saravanabhavan Subramani , Raghava Rao Jonnalagadda , Unni Nair Balachandran , Ramasami Thirumalachari
Published: October 2007

BACKGROUND: The leather industry is under pressure to develop environmentally efficient leather‐making processes to comply with modern pollution and discharge legislation. Conventional leather‐processing methods are known to contribute significant pollution loads in tannery wastewaters. The rationalized process described here involves a salt‐free curing, lime and sulfide‐free beamhouse process and post‐tanning followed by tanning employing a reverse leather‐processing technique.

RESULTS: Scanning electron microscopy (SEM) analysis substantiated that the grain surface, fibre separation and tight packing of fibres are similar for leathers from conventional and rationalized processes. The functional performance of the leathers is found to be on par with that of conventionally processed leathers. The rationalized leather process reduces the usage and discharge of chemicals by 68% and 82%, respectively. It also enjoys the reduction in biochemical oxygen demand (BOD), chemical oxygen demand, Cl−, SO42− and total solids loads by 58%, 62%, 95%, 66% and 85%, respectively. The rationalized process also results in reduction of water consumption and discharge and energy by 37%, 37% and 38%, respectively.

CONCLUSION: The rationalized process utilizes resources efficiently with reduced environmental impact without compromising leather qualities and can be seen as being eco‐efficient compared to the conventional leather process. Copyright © 2007 Society of Chemical Industry
Hybrid drift‐diffusion–TLM analysis of high‐speed and high‐output UTC traveling‐wave photodetectors
Authors: Pasalic Damir , Vahldieck Rüdiger
Published: October 2007

The scope of the hybrid drift‐diffusion (DD)–TLM method is extended to include the analysis of unitraveling‐carrier (UTC) photodetectors. The extended method takes into account the overshoot velocity at which electrons in the collector of an UTC photodiode drift. The method is used for large and small signal analysis of the UTC traveling‐wave photodetector (TWPD) and near‐ballistic (NB) UTC TWPD. It is shown that there is a trade‐off between the UTC TWPD's bandwidth and saturation current that has to be considered in the design. A higher bias voltage reduces the bandwidth, but also increases the saturation current of the photodetector. The presented UTC TWPD has bandwidths of 110 and 83 GHz and saturation currents of 15 and 30 mA under 1 and 5 V biases, respectively. To improve the performance under high bias voltage, the NB‐UTC TWPD is investigated. A maximum RF power of 6.5 dBm was obtained at 110 GHz under 5 V bias voltage. Copyright © 2007 John Wiley & Sons, Ltd.