bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of zero eigenvalue for solving the potential, heat, and wave equations using a sequence of special functions
Authors: Masjed-Jamei Mohammad , Dehghan Mehdi
Published: April 2006

In the solution of boundary value problems, usually zero
eigenvalue is ignored. This case also happens in calculating the
eigenvalues of matrices, so that we would often like to find the
nonzero solutions of the linear system AX = λX when λ ≠ 0. But λ = 0 implies that detA = 0 for X ≠ 0 and then the rank of matrix A is reduced at least one degree.
This comment can similarly be stated for boundary value problems.
In other words, if at least one of the eigens of equations related
to the main problem is considered zero, then one of the solutions
will be specified in advance. By using this note, first we study a
class of special functions and then apply it for the potential,
heat, and wave equations in spherical coordinate. In this way,
some practical examples are also given.
Sequential laminates in multiple‐state optimal design problems
Authors: Antonic Nenad , Vrdoljak Marko
Published: April 2006

In the study of optimal design related to
stationary diffusion problems with multiple‐state equations, the
description of the set for given vectors a1, …,am ∈ ℝd (m < d) is crucial. denotes all composite materials (in the sense of homogenisation theory) with given
local proportion θ of the first material. We prove that the
boundary of is attained by sequential laminates of rank at
most m with matrix phase αI and core βI (α < β). Examples showing that the information on the
rank of optimal laminate cannot be improved, as well as the fact
that sequential laminates with matrix phase αI are preferred to those with matrix phase βI, are presented.
This result can significantly reduce the complexity of optimality
conditions, with obvious impact on numerical treatment, as
demonstrated in a simple numerical example.
Analytic solution of Stokes second problem for second‐grade fluid
Authors: Asghar S. , Nadeem S. , Hanif K. , Hayat T.
Published: April 2006

Using Laplace transformation and perturbation techniques,
analytical solution is obtained for unsteady Stokes′ second
problem. Expressions for steady and transient solutions are
explicitly determined. These solutions depend strongly upon the
material parameter of second‐grade fluid. It is shown that phase
velocity decreases by increasing material parameter of
second‐grade fluid.
The effect of service constraint on EPQ model with random defective rate
Authors: Huang Yung-Fu
Published: April 2006

Chiu studied the effect of service‐level constraint on
the economic production quantity (EPQ) model with random defective
rate. In this note, we will offer a simple algebraic approach to
replace his differential calculus skill to find the optimal
solution under the expected annual cost minimization.
Bernoulli serial production lines with quality control devices: Theory and application
Authors: Chiang Shu-Yin
Published: April 2006

This paper develops the procedure for the analysis of
the production systems with quality control devices. The
evaluation of the production system requires an expression for the
system performance measures as functions of the machine and buffer
parameters. This paper presents a method for evaluating these
functions and illustrates their practical utility using a case
study at a production plant.
Regular and chaotic motion of a bush‐shaft system with tribological processes
Authors: Awrejcewicz Jan , Pyryev Yuriy
Published: April 2006

The methods of both analysis and modeling of contact bush‐shaft
systems exhibiting heat generation and wear due to friction are
presented [3–5]. From the mathematical point of view, the
considered problem is reduced to the analysis of ordinary
differential equations governing the change of velocities of the
contacting bodies, and to the integral Volterra‐type equation
governing contact pressure behavior. In the case where
tribological processes are neglected, thresholds of chaos are
detected using bifurcation diagrams and Lyapunov exponents
identification tools. In addition, analytical Mel′nikov′s method
is applied to predict chaos. It is shown, among the others, that
tribological processes play a stabilizing role. The following
theoretical background has been used in the analysis: perturbation
methods, Mel′nikov′s techniques [7,8], Laplace
transformations, the theory of integral equations, and various
variants of numerical analysis.
Lentiviral-Mediated Fetal Gene Therapy for Monogenic Disorders: Development of an in vitro Rabbit Model
Authors: Huang Louis , Reebye Stacy C. , Yeung Adam Y. , Jia William W. , Skarsgard Erik D.
Published: April 2006

Objective: Fetal gene replacement is a novel, potential therapy for monogenic disorders which are diagnosed prenatally. The purpose of this study was to develop in vitro, respiratory-epithelium targeted, lentiviral (LV)-mediated gene transfer in fetal rabbit tracheas. Methods: Via triple plasmid transfection, vesicular stomatitis virus-G (VSV-G)-pseudotyped LV vector containing green fluorescent protein (GFP) marker gene, under the control of a cytomegalovirus promoter was constructed. LV bioavailability in rabbit amniotic fluid (AF) was evaluated by infectivity assays of 293T cell monolayers in variable concentrations of AF. Fetal tracheas from time-mated rabbits (term gestation, G = 31 days) were collected on G 23–25 days, and placed in tissue culture (substrate-enriched DMEM, 37°C, 5% CO2/room air). The tracheal cultures were transfected with 1 × 105 LV particles, and analyzed daily for: reporter gene by polymerase chain reaction, and reporter gene product (GFP) by whole-mount fluoroscopy and immunohistochemistry. Results: 293T cell infectivity assays confirmed bioavailability of LV in rabbit AF. Following in vitro transfection, GFP DNA and GFP were detectable in fetal rabbit tracheas by 4 and 5 days, respectively. Immunocytochemistry localized GFP to the luminal aspect of tracheal epithelium. Conclusions: In vitro, LV-mediated GFP gene transfer to fetal rabbit tracheas occurs within 4 days, and gene expression is evident by 5 days post-transfection. This observation, and the bioavailability of LV through AF, suggests the appropriateness of this model for the future evaluation of in vivo, transamniotic gene delivery strategies.
Minimal Alteration in the Ratio of Circulatory Fetal DNA to Fetal Corticotropin-Releasing Hormone mRNA Level in Preeclampsia
Authors: Zhong Xiao Yan , Holzgreve Wolfgang , Gebhardt Stefan , Hillermann Renate , Carelse Tofa Kashefa , Gupta Anurag Kumar , Huppertz Berthold , Hahn Sinuhe
Published: April 2006

Objectives: We have recently observed that fetal DNA and fetal corticotropin-releasing hormone (CRH) mRNA are associated with in vitro generated syncytiotrophoblast-derived microparticles, and that the ratio of fetal DNA to mRNA (CRH) varied according to whether the particles were derived by predominantly apoptotic, apo-necrotic or necrotic pathways. Hence, we examined whether these ratios varied in maternal plasma samples taken from normotensive and preeclamptic pregnancies in vivo. Methods: Maternal plasma samples were collected from 18 cases with preeclampsia and 29 normotensive term controls. Circulatory fetal CRH mRNA and DNA levels were quantified by real-time PCR and RT-PCR. Results: Circulatory fetal mRNA and fetal DNA levels were significantly elevated in the preeclampsia study group when compared to normotensive controls. Alterations in the fetal mRNA to DNA ratio between the study and control groups were minimal, even when stratified into early (<34 weeks of gestation) and late (>34 weeks of gestation) onset preeclampsia. Conclusions: Our data suggest that although circulatory fetal DNA and mRNA levels are significantly elevated in preeclampsia, the ratios in maternal plasma are not dramatically altered.
Recurrent Fetal Hydrops due to Mucopolysaccharidoses Type VII
Authors: Venkat-Raman Narayanaswamy , Sebire Neil J. , Murphy Karl W.
Published: April 2006

Hydrops fetalis is associated with a wide range of abnormalities. In about 20% of cases of non-immune fetal hydrops, no cause is found despite investigations including routine post-mortem examination and enzyme studies may be indicated to detect an underlying metabolic storage disease. Fetal hydrops due to mucopolysaccharidosis type VII is very rare and a prenatal diagnosis is not usually made. We report a case of mucopolysaccharidosis type VII presenting as recurrent fetal hydrops and review the clinico-pathological features of this disorder.
Screening for Trisomy 21 with Maternal Age, Fetal Nuchal Translucency and Maternal Serum Biochemistry at 11–14 Weeks: A Regional Experience from Germany
Authors: Soergel P. , Pruggmayer M. , Schwerdtfeger R. , Mühlhaus K. , Scharf A.
Published: April 2006

Objective: To examine the efficacy of first trimester screening for trisomy 21 using a combination of maternal age, fetal nuchal translucency (NT), maternal serum free β-human chorionic gonadotropin (free β-hCG) and pregnancy-associated plasma protein A (PAPP-A) in a regional setting [maternity unit of the Women’s University Hospital, Hannover Medical School (study center); two regional private centers for prenatal diagnosis and human genetics; laboratory for prenatal diagnosis and human genetics]. Methods: Fetal NT, crown-rump length, maternal serum free β-hCG and PAPP-A were measured at 11–14 weeks of gestation. Risk calculation was carried out using the FMF computer algorithm. The patients were informed and counseled about possible invasive test options if the risk was 1 in 300 or greater. Fetal outcome was obtained by questionnaires given to the patients or sent to their gynecologists. The detection and false-positive rates for the different screening strategies were calculated. Results: Pregnancy outcome was obtained in 2,497 cases, of which 2,196 cases had completed first trimester screening with NT and maternal serum biochemistry and 301 additional cases had NT measurement only. The median age was 32.5 years. In our population 11 affected fetuses were found. The estimated risk for trisomy 21 was 1 in 300 or greater in 64, 82, 88 and 88% of affected fetuses using maternal age alone, in combination with nuchal translucency, with maternal serum biochemical markers or with both NT and biochemical markers for a false-positive rate of 28.2, 5.1, 15.3 and 4.0%. Conclusions: First trimester screening using maternal age, NT, free β-hCG and PAPP-A is highly effective for the detection of trisomy 21 and is associated with a sensitivity of about 90% for 5% false-positive patients.
West Nile Virus during Pregnancy: A Case Study of Early Second Trimester Maternal Infection
Authors: Skupski Daniel W. , Eglinton Gary S. , Fine Anne D. , Hayes Edward B. , O’Leary Daniel R.
Published: April 2006

A woman who contracted West Nile virus (WNV) neuroinvasive illness during her second trimester subsequently elected to terminate her pregnancy due to concerns of possible adverse effects of WNV on her developing fetus. Consent was obtained to test maternal and post-mortem fetal tissues for WNV infection. Fetal blood, liver, kidneys, spleen, umbilicus and amniotic fluid were negative for WNV RNA by polymerase chain reaction and negative for WNV IgM antibodies by ELISA, indicating that in this case there was no evidence of WNV transmission to the fetus. Until further information regarding outcomes of WNV infection during pregnancy is available, pregnant women in areas where WNV is transmitted should take precautions to avoid mosquito bites. Women with WNV illness during pregnancy should undergo regular prenatal checkups including ultrasound examinations to assess fetal development, and healthcare providers should promptly report cases of WNV in pregnant women to their state or local health department or to CDC.
Prenatal Ultrasound Diagnosis, Follow-Up, and Outcome of Congenital Varicella Syndrome
Authors: Meyberg-Solomayer G.C. , Fehm T. , Müller-Hansen I. , Enders G. , Poets C. , Wallwiener D. , Solomayer E.-F.
Published: April 2006

Objectives: To report on a case of fetal varicella infection following the diagnosis of maternal infection at 16 weeks of gestation. Methods: Diagnosis was based on serology testing and prenatal ultrasound, confirmed by DNA detection in amniotic fluid (Lightcycler-PCR). Serial ultrasound examinations were performed. Results: Sonographic anomalies included borderline ventriculomegaly, intracerebral, intrahepatic and myocardial calcifications, limb deformities, articular effusions, and intrauterine growth retardation (confirmed postpartally). The newborn showed a severe encephalopathy and could not be stabilized sufficiently. The child died 23 days after birth. Conclusion: The outcome of an affected fetus may be very serious and prenatal ultrasound is a helpful tool to recognize the severity of the infection.
Conduction System Disease in Fetuses Evaluated for Irregular Cardiac Rhythm
Authors: Cuneo Bettina F. , Strasburger Janette F. , Wakai Ronald T. , Ovadia Marc
Published: April 2006

Objectives: To determine the prevalence of 1st and 2nd degree AV block in fetuses with an irregular cardiac rhythm, and to summarize outcome of these pregnancies. Background: The diagnosis of irregular cardiac rhythm or ‘skipped beats’ includes isolated ectopy that resolves spontaneously. Recently, Doppler measurements of the ‘mechanical’ PR interval have been shown to identify AV conduction disease prenatally. Prenatal therapy of these conduction abnormalities may limit the progression to more advanced disease either in utero or after birth. Methods: A retrospective review was performed of fetuses evaluated between 1996 and 2004 with the findings of irregular cardiac rhythm. 1st or 2nd degree AV block was diagnosed on Doppler and M-mode recordings, and confirmed using either fetal magnetocardiography (fMCG) or postnatal 12-lead ECG. Dexamethasone was administered to 4 mothers with abnormal fetal AV conduction in the setting of anti-Ro/anti-La antibodies. Results: Of 702 fetuses initially referred for arrhythmia, 306 had an irregular rhythm. Eight (2.6%) had intermittent 1st or 2nd degree AV block confirmed by fMCG and/or postnatal 12-lead ECG. AV block was presumed idiopathic in 2, associated with congenital long QT syndrome in 2 or with clinically unsuspected maternal anti-Ro or anti-La antibodies in 4. During the intrauterine period there was no progression to complete AV block and all were born alive at 34–40 weeks of gestation. Conclusion: A small but clinically significant population of fetuses with irregular rhythm will have 1st or 2nd degree AV block. Transplacental therapy may limit the intrauterine progression to more advanced disease.
Rehabilitation Therapy and Urinary Incontinence after Radical Retropubic Prostatectomy
Authors: Viola Domenico , Comerci Francesco , Martorana Giuseppe
Published: April 2006

Introduction: To assess the efficacy and evidence-based data in the literature about rehabilitation therapy in patients with post-prostatectomy urinary incontinence. Materials and Methods: An analysis of published full-length papers identified by a Medline search from 1990 through 2004 was carried out. Abstracts published in peer-reviewed journals in the same period of time were also considered. Results: Efficacy, tolerability and safety of rehabilitation therapy were evaluated, according to the available data in the literature, with special regard to randomized controlled trials in order to define a clear-cut, evidence-based efficacy of this form of therapy. Conclusions: Rehabilitation therapy is a simple and safe way of managing post-prostatectomy urinary incontinence. Nonetheless, few randomized controlled studies have been carried out so far to establish its evidence-based efficacy and it is thus not possible to be scientifically sure of its value. It is therefore necessary to undertake well-designed randomized controlled studies, with a large number of patients, a well-matched control group and an adequate follow-up.
Impact of Comorbidities on Post-Prostatectomy Incontinence
Authors: Wille S. , Heidenreich A. , von Knobloch R. , Hofmann R. , Engelmann U.
Published: April 2006

Introduction: The aim of this retrospective study was to evaluate various factors that may influence post-prostatectomy incontinence (PPI). Patients and Methods: 1,088 men with prostate cancer underwent radical retropubic prostatectomy. 742 patients were evaluable for analysis. Continence was defined as usage of no or one pad daily. Mean follow-up was 45 months (12–143). Results: Based on protective pad requirement 100% and 76% of men were continent at baseline and at the time of questionnaire evaluation (at least 12 months), respectively. Univariate analysis was performed to identify factors that may influence the return of continence. Age, body mass index (BMI), previous TUR-P, smoking, hypertension, diabetes and attempted nerve sparing did not predict postoperative continence status. Conclusions: In contrast to several reports, our analysis revealed that age, BMI, previous TUR-P, smoking, hypertension and diabetes do not have a statistically significant impact on continence after radical retropubic prostatectomy and are therefore not useful as predictors for PPI.
Usefulness of the Nadir Value of Serum Prostate-Specific Antigen Measured by an Ultrasensitive Assay as a Predictor of Biochemical Recurrence after Radical Prostatectomy for Clinically Localized Prostate Cancer
Authors: Sakai Iori , Harada Ken-ichi , Kurahashi Toshifumi , Muramaki Mototsugu , Yamanaka Kazuki , Hara Isao , Inoue Taka-aki , Miyake Hideaki
Published: April 2006

Introduction: The objective of this study was to determine whether the nadir value of serum prostate-specific antigen (PSA) measured by an ultrasensitive assay could be a useful predictor of biochemical recurrence after radical prostatectomy for clinically localized prostate cancer. Materials and Methods: This study included 127 patients who underwent radical prostatectomy for clinically localized prostate cancer without neoadjuvant hormonal therapy and were pathologically diagnosed as negative for lymph node metastasis. The serum PSA value was measured using an ultrasensitive PSA assay system (Roche Diagnostics, Mannheim, Germany), and the findings were analyzed with respect to several clinicopathological factors. In this series, biochemical recurrence was defined as PSA persistently >0.2 ng/ml. Results: Based on the nadir PSA value, we divided 127 patients into three groups as follows: group A (n = 99): ≤0.01 ng/ml; group B (n = 16): 0.01–0.05 ng/ml, and group C (n = 12): ≧0.05 ng/ml. The nadir PSA value was significantly associated with preoperative PSA value, but not other conventional clinicopathological prognostic parameters. During the observation period (median 31 months, range 6–75 months), biochemical recurrence occurred in 16 patients, that is, 1 in group A (6.3%), 4 in group B (25.0%), and 11 in group C (91.7%). Multivariate analysis using the Cox proportional hazards regression model indicated that the nadir PSA value was an independent predictor for biochemical recurrence after radical prostatectomy. Conclusion: These findings suggest that the nadir serum PSA value measured by an ultrasensitive assay could be a useful predictor of biochemical recurrence after radical prostatectomy for clinically localized prostate cancer, and that careful follow-up should be considered in cases demonstrating a nadir PSA value >0.01 ng/ml because of the significantly higher probability of biochemical recurrence in such cases.
Metastatectomy prior to Immunochemotherapy for Metastatic Renal Cell Carcinoma
Authors: Lee Sang Eun , Kwak Cheol , Byun Seok-Soo , Gill Myung Chul , Chang In Ho , Kim Yong June , Hong Sung Kyu
Published: April 2006

Introduction: We reviewed our experiences in performing cytoreductive metastatectomy before initiating systemic immunochemotherapy and tried to investigate potential prognostic factors for such an approach. Patients and Methods: A retrospective analysis of 57 patients who received interleukin-2, interferon-α, and 5-fluorouracil immunochemotherapy for metastatic renal cell carcinoma was conducted. Before undergoing immunochemotherapy, 20 of the 57 patients had received metastatectomy along with nephrectomy (metastatectomy group) and the other 37 nephrectomy alone (non-metastatectomy group). Results: The metastatectomy group demonstrated median disease-specific and progression-free survival of 23 and 13 months, respectively. The patients in the metastatectomy group were identified as having a better performance status and primarily demonstrating pulmonary metastasis compared with those in the non-metastatectomy group. As assessed in the metastatectomy group, factors such as the number of metastatic lesions, completeness of metastatectomy, and location of metastatic lesions (lung only vs. others) were observed to be significantly associated with overall survivals on univariate analysis. Conclusions: Metastatectomy may still play a significant therapeutic role for metastatic renal cell carcinoma even in the era of immunochemotherapy as part of a multidisciplinary treatment approach in a selected group of patients in adequate general condition who have pulmonary-limited metastasis that can be completely resected.
Human Chorionic Gonadotropin Deteriorates the Histology of Rat Testes
Authors: Kaya Cevdet , Karaman M. Ihsan , Pirincci Necip , Ozturk Metin , Yilmazgumrukcu Gulistan
Published: April 2006

Objectives: It is not yet certain whether early hormonal treatment in cryptorchidism is safe for germ cells. We investigated the histologic effects of human chorionic gonadotropin (hCG) therapy on descended testes of rats. Design and Setting: Thirty male Wistar albino rats were randomized into two groups. The rats of the hCG group (n = 15) were administered 50 IU/kg/day hCG once daily via the subcutaneous route for 15 days. Fifteen rats received subcutaneous isotonic saline and acted as controls. At the first month, testicular tissue was obtained after scarification in both groups. The histological examination was performed to evaluate the seminiferous tubular diameter, germinal membrane thickness, and the percentage of the open seminiferous tubule lumen in each testis to compare the two groups. Results: The percentage of the open seminiferous tubular lumen in testicular tissues of hCG-treated rats was higher than that of controls (p < 0.05). The mean germinal membrane thickness in testicular tissues of the hCG group was statistically lower than that of the control group (p < 0.05). There was no statistical difference between mean seminiferous tubular diameter in testicular tissues of hCG-treated rats and controls, as expected (p > 0.05). Additionally, there were two interesting cases of Sertoli cell only appearance in the hCG group. Conclusions: We may assume that hCG impairs the seminiferous tubule histology in normal testes of rats. Thus, further experimental studies on dose dependency and the reversibility of these effects are warranted.
Evolution of Cognitive Deficits and Conversion to Dementia in Patients with Mild Cognitive Impairment: A Very-Long-Term Follow-Up Study
Authors: Hodges John R. , Erzinçlioğlu Sharon , Patterson Karalyn
Published: April 2006

Ten patients with mild cognitive impairment (MCI) underwent extensive neuropsychological evaluation at 12-monthly intervals for a minimum of 6 years. All 10 patients declined and 5 have now died. The onset of dementia, as defined by a fall in global cognitive function (MMSE <24) or activities of daily living (Clinical Dementia Rating Scale; CDR) ranged from 1 to 8 years with generally good concordance between these measures. The rate of decline on the MMSE was highly variable ranging from 0.86 to 2.83 points per year. Other than a consistent impairment on tests of episodic memory and category fluency (8 out of 10), other early cognitive deficits were difficult to define and tended to be unstable in the early stages. Impairment of semantic memory, visuo-spatial and attentional abilities eventually developed but the sequence of deficit acquisition was heterogeneous. These findings are discussed in the light of current views of MCI. Amnestic MCI may not be an accurate concept unless semantic memory impairment is also considered as an integral core deficit. Full-blown dementia may take many years to develop in patients with MCI but was a universal feature in this study.
Influence of Sex on the Pharmacokinetics of Ciprofloxacin and Ofloxacin
Authors: Konieczna Lucyna , Chmielewska Aleksandra , Lamparczyk Henryk
Published: April 2006

The pharmacokinetics of orally administered ciprofloxacin and ofloxacin were studied in healthy volunteers to assess the influence of sex on drug bioavailability. The first group of subjects (9 males and 9 females) received a single oral dose of 200 mg ofloxacin, and the second group of volunteers included 24 subjects (12 males and 12 females) treated with a single oral dose of 100 mg ciprofloxacin. Blood samples (3 ml) were collected and investigated in this parallel design study in both groups, and ciprofloxacin and ofloxacin concentrations were determined. These experimental data, which had not been changed by any mathematical operation, were collected and used to determine the effect of sex on the pharmacokinetic profile using parametric and non-parametric tests as well as multivariate classification tools like cluster analysis (CA) and principal component analysis (PCA). The following variables demonstrated significant differences (p < 0.05) in c0.5, c1.5, c2.0, c4.0, c10, c12.0, c24 and c6.0, c8.0, c10.0 for ofloxacin and ciprofloxacin, respectively, using Student’s t test and ANOVA. Therefore the alternative hypothesis about sex differences between males and females was accepted. The CA and PCA plot separated females from males and allowed to select subjects accounting for differences between males and females. Data on the whole pharmacokinetic profile enabled to determine subtle sex differences between males and females.
Linezolid and Human Polymorphonuclear Leukocyte Function
Authors: Naess Are , Stenhaug Kilhus Kristin , Nystad Tone W. , Sørnes Steinar
Published: April 2006

Background: To examine whether linezolid, a new oxazolidinone antibiotic, has an effect on human polymorphonuclear leukocyte (PMN) function. Methods: Flow-cytometric techniques for the demonstration of PMN chemotaxis towards zymosan-activated serum, and phagocytosis and respiratory burst after incubation in linezolid. Results: Linezolid at concentrations of 10– 160 mg/l did not significantly influence PMN function as measured by chemotaxis, phagocytosis and respiratory burst. Conclusions: Linezolid at therapeutic or supratherapeutic concentrations does not influence human PMN function. This applies to the chemically pure substance as well as to the commercial preparation containing additives for intravenous infusion.
Molecular Markers of Multiple Drug Resistance in Breast Cancer
Authors: O’Driscoll L. , Clynes M.
Published: April 2006

Breast cancer is a significant health problem in terms of both morbidity and mortality, with approximately 12% of women directly affected by this disease. Chemotherapy, given to patients with earlier stage disease, has a good survival impact and may contribute to cure. The failure of chemotherapeutic drugs to eradicate cancer cells in more advanced disease states may be due to intrinsic or acquired drug resistance, including multiple drug resistance. The drug resistance observed in breast cancer patients is likely to be multifactorial, involving mechanisms such as altered expression and/or activity of drug efflux pumps, nuclear DNA-binding enzymes, metabolizing and conjugating enzymes, and mismatch repair deficiency. More extensive transcriptomic and proteomic analyses of breast tumour and normal biopsies, followed by functional genomic studies in relevant cell line models, should increase our understanding of this phenomenon and lead to therapies being individualized for identifiable subgroups of breast cancer patients.
Prolactin Serum Levels and Alcohol Craving – An Analysis Using Lesch’s Typology
Authors: Hillemacher Thomas , Bayerlein Kristina , Wilhelm Julia , Frieling Helge , Sperling Wolfgang , Kornhuber Johannes , Bleich Stefan
Published: April 2006

Background: Prolactin secretion is closely connected to dopaminergic transmission that is known to play a crucial role in mediating reinforcement and craving in alcoholism. Objectives: The study was performed to analyze the association between prolactin serum levels and alcohol craving during withdrawal differentiating alcohol-dependent patients using Lesch’s typology. Methods: We assessed 115 male patients with the Obsessive Compulsive Drinking Scale at early alcohol withdrawal. In addition, serum was obtained to measure prolactin concentration and the patients were classified according to Lesch’s typology into one of four subgroups. Results:Correlation analysis showed a significant association between prolactin serum levels and the extent of craving in Lesch’s type 2 patients (r = 0.32, p = 0.015; n = 57); however, no association was found for any other subgroup. The results were confirmed comparing patients with low and high craving (Mann-Whitney U test: Z = –2.805, p = 0.005). Conclusions: In patients of Lesch’s type 2, who are characterized to suffer from anxiety and to use alcohol because of its anxiolytic effects, prolactin is associated with craving during early alcohol withdrawal.
Development Indices
Authors: Kochak Anjani K.
Published: April 2006

Both India and China have grown impressively in recent years. This article seeks to unravel the various dimensions in which development has taken place in the two countries. The first section discusses the various indicators that are generally used to measure economic progress in any economy. The second section explains the methodology used by UNDP to construct four important indices, namely the Human Development Index (HDI), the Gender Related Development Index (GDI), the Gender Empowerment Index (GEM) and the Human Poverty Index (HPI), and their respective limitations. The third section compares the progress made by India and China in terms of these indices and looks at some other important indicators of development for the two countries. The final section seeks to draw some conclusions and spell out the policy implications.
Breakthrough. and Beyond
Authors: Mishra Sandip Kumar
Published: April 2006

Four rounds of the Six-Party talks to resolve the North Korean nuclear issue have taken place so far. In the first three rounds no substantial progress was achieved, and only in the fourth round was a ‘breakthrough’ claimed when North Korea declared its intention to abandon its nuclear programme. North Korea, at the same time, emphasised its right to peaceful use of nuclear energy and the Light Water Reactors that had been promised in the Nuclear Accord of 1994 between North Korea and the US. The process of negotiations has so far been predicated on mutual mistrust and lack of understanding of the threat perception of each other. A close scrutiny of the ‘breakthrough’ of the fourth round of talks reveals that there still is not any consensus on the main contentious issues. To move ahead, it must be recognised that the process of negotiations has been following a wave-like movement in which the fourth round constitutes a crest. Rather than resorting to coercive measures, more confidence building measures should be undertaken between North Korea and the other parties involved, especially the US.The growing consensus among the regional powers to engage North Korea might be effective in facilitating such measures. In particular, it is necessary for Washington to review its aggressive policy vis-É-vis North Korea. Any imposition of a ‘solution’ by the US on North Korea, devoid of mutual trust between the two countries, might again lead to breach of commitment by one side or the other, as happened with the Nuclear Accord of 1994.
Incentives for Attracting FDI in South Asia
Authors: Das Sandwip Kumar , Pant Manoj
Published: April 2006

Incentive offers along with performance requirements are a notable feature of the Foreign Direct Investment (FDI) policies of South Asian countries after they opened up to trade and investment in the 1990s. Since FDI operates in an imperfect market environment, a government policy that tries to counter this imperfection by insisting on performance requirements could well improve welfare. Incentives are then offered to soften the impact of performance requirements. There are no systematic studies to assess the cost and benefits of these incentives offered competitively in South Asian countries. Often, the purpose of these incentives may have been to generate funds for side payments to the bureaucracy of host countries. Incentives seem to affect mainly footloose FDI or, at best, lead to relocation of FDI within a region. This latter advantage disappears when countries of a region tend to compete in incentives. The limited number of studies on the South Asian region that are available seem to identify an increase in employment and/or wages, reduced prices or improved product quality, more revenues for the government and indirect benefits through professionalism, learning and technology diffusion as benefits. The impact of providing facilitation to foreign investors on national savings, deterioration in trade conditions and balance of payments are cited as the cost of incentives. Coordination in FDI policy making among South Asian countries is the main policy prescription that emerges out of this study.
The US Congress and the 1971 Crisis in East Pakistan
Authors: Rao P.V.
Published: April 2006

In the wake of Pakistan's military crackdown on East Pakistan and the consequent crisis situation in the subcontinent, the American Congress demanded an immediate policy response from the White House. But the Nixon Administration's .massive inaction. towards the East Pakistan situation failed to satisfy Congressional concern. Congress reacted by suspending American military and economic aid to Pakistan until the conflict was resolved by Pakistan's military regime and international relief work was allowed in the affected areas. The US government's continued shipping of arms to Pakistan, despite suspension, angered the Congress and India. Unconvinced by the Administration's explanation, the Congress undertook the unusual step of touring the subcontinent and visiting refugee relief camps both in East Pakistan and India. The East Pakistan crisis exemplified both the strength and limitations of the US Congress in playing a role, along with the executive, in foreign policy matters.
Exploring Consensus in Practice with Youth Who Are Sexually Abusive: Findings from a Delphi Study of Practitioner Views in the United Kingdom and the Republic of Ireland
Authors: Hackett Simon , Masson Helen , Phillips Sarah
Published: April 2006

This article presents the findings of a study exploring current levels of consensus among practitioners in the United Kingdom (UK) and the Republic of Ireland (ROI) about good practice in relation to youth who are sexually abusive. A three-stage Delphi procedure was used to survey the views of 78 practitioners, experienced in this field, on a range of matters relating to preferred responses to this population. The exercise indicated high levels of agreement that youth who are sexually abusive should be seen as a group clinically distinct from adult sex offenders and that all of their developmental needs, and their problematic behavior, should be targeted in intervention. A strong level of consensus was found among respondents about the goals and content of ideal practice with this user group, although there was less consensus about the theoretical models that should underpin practice.
Funding of Child Abuse Evaluations: Survey of Child Abuse Evaluation Programs
Authors: Kairys Steven , Ricci Laurence , Finkel Martin A.
Published: April 2006

This article delineates the current fiscal management and reimbursement for child abuse examinations. These financial issues are high priority for child abuse programs because most programs lack the revenues to meet the demands for service, education, advocacy and research. Programs may share medical protocols and standards but have yet to share management solutions. The authors present the administrative details of 75 child abuse evaluation programs and highlight innovative approaches to increase funding and stabilize the funding for the programs. They present information on billing, contracts, costs of care, and state-based initiatives that can be reproduced by other programs and states.
Apical sorting of ADAMTS13 in vascular endothelial cells and Madin-Darby canine kidney cells depends on the CUB domains and their association with lipid rafts
Authors: Shang Dezhi , Zheng X. Wu , Niiya Masami , Zheng X. Long
Published: April 2006

ADAMTS13 biosynthesis appeared to occur mainly in hepatic stellate cells, but detection of ADAMTS13 mRNA in many other tissues suggests that vascular endothelium may also produce ADAMTS13. We showed that ADAMTS13 mRNA and protein were detectable in human umbilical vein endothelial cells, aortic endothelial cells, and endothelium-derived cell line (ECV304). ADAMTS13 in cell lysate or serum-free conditioned medium cleaved von Willebrand factor (VWF) specifically. ADAMTS13 and VWF were localized to the distinct compartments of endothelial cells. Moreover, ADAMTS13 was preferentially sorted into apical domain of ECV304 and Madin-Darby canine kidney (MDCK) cells. Apical sorting of ADAMTS13 depended on the CUB domains and their association with lipid rafts. A mutation in the second CUB domain of ADAMTS13 (4143-4144insA), naturally occurring in patients with inherited thrombotic thrombocytopenic purpura, resulted in a significant reduction of ADAMTS13 secretion and a reversal of its polarity in MDCK cells. These data demonstrated that ADAMTS13 is synthesized and secreted from endothelial cells; the apically secreted ADAMTS13 from endothelial cells may contribute significantly to plasma ADAMTS13 proteases. The data also suggest a critical role of the CUB domains and a novel cargo-selective mechanism for apical sorting of a soluble ADAMTS protease in polarized cells.
Temporally and spatially coordinated roles for Rho, Rac, Cdc42 and their effectors in growth cone guidance by a physiological electric field
Authors: Rajnicek Ann M. , Foubister Louise E. , McCaig Colin D.
Published: April 2006

Although it is known that neuronal growth cones migrate towards the cathode of an applied direct current (DC) electric field (EF), resembling the EF present in the developing nervous system, the underlying mechanism remains unclear. Here, we demonstrate temporally and spatially coordinated roles for the GTPases Rac, Cdc42 and Rho and their effectors. Growth cones of cultured Xenopus embryonic spinal neurons turned towards the cathode but collective inhibition of Rho, Rac and Cdc42 attenuated turning. Selective inhibition of Rho, Cdc42 or Rac signalling revealed temporally distinct roles in steering by an electrical gradient. Rho, Rac and Cdc42 are each essential for turning within the initial 2 hours (early phase). Later, Rho and Cdc42 signals remain important but Rac signalling dominates. The EF increased Rho immunofluorescence anodally. This correlated spatially with collapsed growth cone morphology and reduced anodal migration rates, which were restored by Rho inhibition. These data suggest that anodally increased Rho activity induces local cytoskeletal collapse, biasing growth cone advance cathodally. Collapse might be mediated by the Rho effectors p160 Rho kinase and myosin light chain kinase since their inhibition attenuated early turning. Inhibitors of phosphoinositide 3-kinase, MEK1/2 or p38 mitogen-activated protein kinase (MAPK) did not affect turning behaviour, eliminating them mechanistically. We propose a mechanism whereby Rac and Cdc42 activities dominate cathodally and Rho activity dominates anodally to steer growth cones towards the cathode. The interaction between Rho GTPases, the cytoskeleton and growth cone dynamics is explored in the companion paper published in this issue. Our results complement studies of growth cone guidance by diffusible chemical gradients and suggest that growth cones might interpret these co-existing guidance cues selectively.
Novel Functional Group Transformation from Acetylene Cobalt Complex to Ketone via Ligand Exchange
Authors: Hamajima Akinari , Nakata Hiyoku , Goto Masako , Isobe Minoru
Published: April 2006

A new transformation of acetylene dicobalt tetracarbonyl dppm complexes was found to convert to ketones with high regioselectivity under ligand exchange condition.
Carbonic Anhydrases (α‐Class)
Authors: Duda David M , McKenna Robert
Published: April 2006

Carbonic anhydrases (CAs) are zinc metalloenzymes that catalyze the hydration of carbon dioxide and the dehydration of bicarbonate:, a process that has physiological importance in respiration, acid–base homeostasis, photosynthesis, and biosynthetic pathways. The α‐class of CA (and the CA domains in more complex isoforms) is monomeric with a molecular weight of approximately 30 kDa. At present, 14 isoforms of the α‐class are known with varying tissue distributions and catalytic activity. The catalytic turnover number of CAs varies from the maximal rate of 106s−1for isozyme II to 103s−1for isozyme III. The central structural motif of the α‐CAs can be described as a 10‐stranded twisted β‐sheet, which is flanked by seven α‐helices. The active‐site cavity consists of a single zinc ion tetrahedrally coordinated by three histidine residues (His94, 96, and 119) and a bound water molecule. In most of the α‐CAs, the resultant proton formed by the dehydration reaction of bicarbonate is transferred to bulk solution through the formation of a proton wire, mediated by residue His64, that lies at the mouth of the active site. Known inhibitors of CAs have been shown to bind to the metal ion and displace the zinc‐bound water, whereas activators have been shown to bind at the entrance of the active site and mimic the characteristics of the proton‐shuttling residue His64.
Streptomyces AlbusGD‐Ala‐D‐Ala Carboxypeptidase
Authors: Charlier Paulette , Wery Jean‐Pierre , Dideberg Otto , Frère Jean‐Marie
Published: April 2006

The zincD‐Ala‐D‐Ala carboxypeptidase hydrolyzes the C‐terminal peptide bond of peptides of general structure R‐D‐Ala‐D‐Xaa. The lytic activity of the enzyme and its extracellular location suggest that it might be used byStreptomycesfor fighting competitors in its ecological niche since the enzyme does not hydrolyze theStreptomycespeptidoglycan.

The sequence of the 213‐residue mature protein is related to the VanX, VanY, and VanXY proteins of vancomycin‐resistant enterococci. The molecule is an ellipsoid consisting of two globular domains in which the N‐terminal and the C‐terminal ends are pulled apart. The small N‐terminal domain, from residue Asp1 to Pro83, has an all‐α‐helices structure and exhibits a typical three‐helix bundle fold, characteristic of the peptidoglycan binding domain. The largest C‐terminal domain belongs to the α + β type secondary structure, and is related to the N‐terminal domain of the murine sonic hedgehog, a signaling protein involved in natal morphogenesis and formation of embryonic patterning centers, and to the VanXD‐Ala‐D‐Ala dipeptidase ofEnterococcus faecium, a protein involved in the vancomycin resistance systems in streptococci. The mixed five‐stranded β‐sheet forms the core of the C‐terminal domain and the lining of one side of the catalytic cavity. One zinc ion occupies a roughly central position in the active site and is coordinated by the His154 NE2, the Asp161 OD1, and the His197 ND1. Classical β‐lactam compounds, which readily inactivate active site serineDD‐peptidases, are very sluggish inactivators of the zincD‐Ala‐D‐Ala carboxypeptidase. The best competitive inhibitors are thiol derivatives such as 2‐ and 3‐mercaptopropionate (Ki = 50 and 5 nM) that might behave as bidentate ligands of the Zn2+ion.
Leucine Aminopeptidase
Authors: Sträter Norbert , Lipscomb William N
Published: April 2006

Leucine aminopeptidase belongs to the metallohydrolase family M17. In this family, two X‐ray diffraction structures are known for bovine lens LAP (blLAP) and for theEscherichia coliaminopeptidase A (PepA). These two peptidases are large homohexamers of 32 symmetry, and both have a large central solvent cavity near the active sites. Each active center contains two Zn2+separated by 3.0 Å. In PepA, maximal activity occurs in the presence of Mn2+. blLAP is activated by Mn2+, Mg2+or Co2+, but zinc is bound most strongly and is supposed to be the physiological cofactor. In the proposed catalytic mechanism, both metal ions stabilize substrate binding and formation of the transition state. In addition, a lysine side chain contributes by polarizing the substrate's carbonyl group, and an arginine side chain binds a bicarbonate anion (or carbonate ion) that is in a position to act, at least in PepA, as a general base to deprotonate the zinc‐bound water nucleophile.
Calpain
Authors: Davies Peter L , Campbell Robert L , Moldoveanu Tudor
Published: April 2006

Calpains are intracellular cysteine proteases that participate in Ca
2+
signaling. Some structural information is available for the ubiquitous mammalian isoforms m‐ and μ‐calpain. These 110‐kDa heterodimeric, multidomain enzymes differ in the level of Ca
2+
required for activation. A structural explanation for the Ca
2+
requirement is that the papain‐like active site is not assembled in the Ca
2+
‐free (apo) state. Moreover, the circular arrangement of domains appears to constrain the two protease core domains from assembling into an active conformation. Ca
2+
binding to the two penta–EF‐hand domains and to a C2‐like domain flanking the protease core may release these constraints. However, active site assembly requires the cooperative binding of Ca
2+
to two non–EF‐hand sites, one on each of the catalytic domains. These novel Ca
2+
binding sites appear to be an evolutionary addition to the papain‐like protease core. Thus, Ca
2+
acts at several different levels, at different sites, to tightly control the activity of this potent protease within the cell.