bluuebunny/crossref_metadata_2025 huggingface dataset:
Ki67 immunohistochemistry: a valuable marker in prognostication but with a risk of misclassification: proliferation subgroups formed based on Ki67 immunoreactivity and standardized mitotic index
Authors: Jalava P , Kuopio T , Juntti‐Patinen L , Kotkansalo T , Kronqvist P , Collan Y
Published: April 2006

Aims : Counting mitotic figures is considered to be a reliable prognosticator, but evaluation of Ki67 immunohistochemistry has become more popular in evaluating proliferation. Our previous studies suggested an occasional discrepancy between mitotic figures and Ki67 fraction. The aim of this study was to investigate this more closely and also to study the associations between bcl‐2 and p53 expression and proliferation.

Methods and results : Two hundred and sixty‐five infiltrating breast carcinomas were immunostained for Ki67, p53 and bcl‐2. The standardized mitotic index (SMI) was determined. Four proliferation groups were based on Ki67 positivity fraction and SMI at optimal cut‐off points. Cox's multivariate model was used to test the power of the prognosticators. SMI and nodal status were the most powerful individual prognosticators. Ki67 was an independent prognosticator if nodal status, tumour size, age and histological grade were included in the analysis but not if analysed with SMI. The group with low SMI and low Ki67 fraction had the best prognosis. Groups with high SMI had the poorest prognosis. The group with low SMI and high Ki67 fraction had a favourable prognosis. Bcl‐2 negativity and p53 positivity correlated with proliferation.

Conclusions : We have found a ‘wrong positive’ Ki67 group with favourable prognosis. SMI cannot be replaced by Ki67 because of the danger of misclassification of some patients.
Immunohistochemistry increases the accuracy of diagnosis of benign papillary lesions in breast core needle biopsy specimens
Authors: Shah V I , Flowers C I , Douglas‐Jones A G , Dallimore N S , Rashid M
Published: April 2006

Aims : Recent studies have suggested that benign papillary lesions without atypia [benign papilloma (BP)] diagnosed on breast core needle biopsy (CNB) may not require excision. However, most have studied only small numbers of cases and scant data are available on the utility of immunohistochemistry in the categorization of papillary lesions on CNB. In the largest published series of BP identified on CNB, we studied the impact of immunohistochemistry on the accuracy of a CNB diagnosis of BP.

Methods and results : Breast CNBs (n = 129) with a diagnosis of papillary lesion were immunostained for calponin, p63 and cytokeratin 5/6. Haematoxylin and eosin and immunostained slides were independently reviewed by four breast pathologists. BP was the final excision diagnosis in 35 cases. With the use of immunohistochemistry, the postive predictive value (PPV) of BP diagnosis by the four individual pathologists increased from 72.7–83.3% (mean 79.2%) to 77.8–87.5% (82.1%), the negative predictive value (NPV) increased from 77.8–98.5% (88.6%) to 100% for all four participants and overall accuracy increased from 78.7–92.6% (84.7%) to 90.7–95.4% (92.8%). No case of invasive carcinoma was diagnosed as BP on CNB by any participant. The frequency of ductal carcinoma in situ following a BP diagnosis on CNB ranged from 2.5% to 4.8% (4%) but was only 0–3% (2.3%) after excluding cases that were radiologically suspicious for malignancy.

Conclusions : Immunohistochemistry increases accuracy of BP diagnosis in CNB specimens. Benign papillary lesions diagnosed on CNB do not require excision in the absence of suspicious clinical/radiological findings.
Detailed analysis of the T‐cell lymphocytic infiltrate in penile lichen sclerosus: an immunohistochemical and molecular investigation
Authors: Regauer S , Beham‐Schmid C
Published: April 2006

Aim : To determine the extent of clonal outgrowth in the lymphocytic tissue infiltrate of lichen sclerosus (LS). The presence of T cells with a monoclonally rearranged T‐cell receptor γ‐gene (TCRγ) has been described in up to 50% of biopsies of vulvar and penile LS.

Material and results : We analysed 33 foreskin specimens with LS for the presence of clonal T cells by conventional polymerase chain reaction (PCR) analysis and with TCRγ‐PCR‐based fluorescent fragment analysis. Eighteen of 33 patients revealed a band indicating a monoclonally rearranged TCRγ on conventional PCR analysis. Subsequent TCRγ‐PCR‐based fluorescent fragment analysis identified 8/18 patients with monoclonal T‐cell DNA ranging from 1.4% to 23.1% of total T‐cell DNA analysed and a size range from 56 to 72 base pairs. Four of 18 patients had an oligoclonal and 6/18 patients revealed a polyclonal banding pattern. The lymphocytic infiltrate contained low numbers of γδ T cells and cytotoxic T cells in comparable numbers to the low percentage of clonal TCRγ DNA.

Conclusions : The low percentage of clonal TCRγ DNA argues against a systemic neoplastic disease, but rather for a local immune disorder. The target antigen of the clonal outgrowth is unknown, but an exaggerated antigen‐dependent proliferation of T cells due to chronic local antigen exposure, probably an infectious antigen, is the most likely explanation.
Does life‐history variability in salmonids affect habitat use by juveniles? A comparison among streams open and closed to anadromy
Authors: MORINVILLE GENEVIÈVE R. , RASMUSSEN JOSEPH B.
Published: April 2006

Migratory and resident forms of salmonids coexist in many river systems. Although such coexistence is widespread, little is known about its ecological basis and no studies have compared the habitat use of premigratory juveniles and residents.

We employed a comparative approach to explore the differential habitat use of juvenile anadromous and resident brook trout. This required the investigation of habitat use in streams closed to anadromy, containing only resident brook trout Salvelinus fontinalis (‘resident‐only’ streams) and streams open to anadromy, containing coexisting Atlantic salmon Salmo salar and anadromous and resident brook trout (‘migrant‐resident’ streams).

We demonstrate that fast habitats (riffles) are occupied more frequently in streams with migratory brook trout relative to riffle habitats of streams with only resident brook trout. In contrast, occupation of slow current velocities (pools) was observed in both migrant‐resident and resident‐only streams as both stream types contain resident brook trout. The net effect is a wider distribution of occupied habitats (pool and riffles) in migrant‐resident streams relative to resident‐only streams, resulting in few, if any, unused habitats.

These results are consistent with previously reported bioenergetic, morphological and stable isotope differences observed between anadromous and resident brook trout.

Our findings suggest that a link exists between juvenile habitat use, metabolic costs and life‐history strategies.
Associations between apolipoprotein B, apolipoprotein AI, the apolipoprotein B/AI ratio and coronary heart disease: a literature‐based meta‐analysis of prospective studies
Authors: THOMPSON A. , DANESH J.
Published: April 2006

Objectives.  To assess associations of circulating levels of apolipoprotein (apo) AI, apoB and the apoB/AI ratio (apoB/A) with risk of incident coronary heart disease (CHD).

Design.  Literature‐based meta‐analysis of prospective studies.

Data sources.  Prospective studies in essentially general populations that reported on associations between apoAI, apoB or apoB/A and first incident CHD outcomes. Studies were identified by computer‐based searches and by manual searches of the relevant literature.

Results.  Data from 23 relevant studies were identified. For apoAI, with 6333 CHD cases in 21 studies, comparison of individuals in the bottom third with those in the top third of baseline values yielded a combined relative risk of 1.62 (95% confidence interval: 1.43–1.83), i.e. an inverse association. For apoB, a combined analysis of 6320 CHD cases from 19 studies gave a relative risk of 1.99 (1.65–2.39) for a comparison of individuals in the top third versus those in the bottom third of baseline values. For apoB/A, with 3730 CHD cases from seven studies, a comparison of individuals in the top third versus the bottom third of baseline values gave a combined relative risk of 1.86 (1.55–2.22). These associations were somewhat stronger following correction for within‐person variations in apolipoprotein levels. There was evidence of heterogeneity amongst the published studies, but it was only partly explained by available study‐level characteristics.

Conclusions.  The present quantitative review suggests the existence of moderately strong associations between baseline levels of each of apoAI, apoB, and apoB/A and risk of CHD. More detailed analysis, perhaps based on individual participant data from prospective studies, could help to overcome several limitations in the present review and to clarify any relevance of these apolipoproteins to disease prediction and aetiology.
Measurement and meaning of apolipoprotein AI and apolipoprotein B plasma levels
Authors: MARCOVINA S. , PACKARD C. J.
Published: April 2006

Apolipoproteins AI and B are structural components of lipoprotein particles, and also determinants of the metabolic fate of the encapsulated lipid, cholesterol and triglyceride. Development of accurate assays for these apolipoproteins has opened the way for their use as predictors of coronary heart disease risk. Interpretation of AI and apo B levels is best undertaken with background knowledge of the metabolic status of an individual, especially the lipolytic capacity as reflected in the triglyceride concentration. Those with raised triglyceride, in general, not only have an elevated apo B/apo AI ratio, but also apo B‐containing lipoproteins with a prolonged residence time and hence ample opportunity for modification and damage. Assessment of apolipoprotein levels is an aid to risk prediction and can be useful in tailoring treatment.
Crystal storing histiocytosis of the skin associated with multiple myeloma
Authors: Pock Lumír , Stuchlík David , Hercogová Jana
Published: April 2006

Background  Crystal storing histiocytosis (CSH) imitating rhabdomyom is a very rare disease entity involving different tissues. The skin is involved in extremely rare cases.

Objectives  To describe the clinical and histopathological characteristics in a patient with unusually extensive skin involvement.

Observations  A 62‐year‐old woman presented with a large red infiltrated verrucosus lesion on the anterior aspect of the chest and on the neck. The skin biopsy revealed histiocytes throughout the whole dermis containing thin crystaloid structures in the cytoplasm. Upon histopathological examination, crystal‐storing histiocytosis was diagnosed and consequently a hematological examination revealed multiple myeloma IgG Kappa. Skin involvement by CSH proceeded the diagnosis of multiple myeloma by 4 years.

Conclusions  Phagocytosis of crystals of immunoglobulins by histiocytes (crystals storing histiocytosis) is a rare symptom associated most often with lymphoproliferative disease. The clinical picture is not characteristic, in the histopathologic picture it is striking similarity to rhabdomyom. The skin involvement by crystal storing histiocytosis can be the first symptom of malignant lymphoma that can proceed the hematological malignancy by years.
Is xenotransplantation of vascularized organs just too hard?1
Authors: D'Apice Anthony J. F.
Published: April 2006

d’Apice AJF. Is xenotransplantation of vascularized organs just too hard?. Xenotransplantation 2006; 13: 182–185. © Blackwell Munksgaard, 2006
Increased capacity for axonal outgrowth using xenogenic tissue in vitro and in a rodent model of Parkinson's disease
Authors: Kuan Wei‐Li , Hurelbrink Carrie B , Barker Roger A.
Published: April 2006

Kuan W‐L, Hurelbrink CB, Barker RA. Increased capacity for axonal outgrowth using xenogenic tissue in vitro and in a rodent model of Parkinson's disease. Xenotransplantation 2006; 13: 233–247. © Blackwell Munksgaard, 2006

Abstract:  Background:  It has previously been proposed that grafted neurons may have the potential for more extensive axonal outgrowth in a xenogenic environment, and may thus possess a primary advantage over allografts in central nervous system repair and circuit reconstruction. In order to directly address this issue, fibre outgrowth from primary dopaminergic neurons was examined both in vitro and in vivo in an allogenic or xenogenic environment. A combination of species was used to circumvent problems relating to different gestational/developmental periods for such cells.

Methods:  In the in vitro experiments, axon length was measured over 2 to 14 days in cultures derived from either rat or mouse ventral mesencephalon (VM) tissue co‐cultured onto either a monolayer of the rat Neu7 inhibitory cell line or fetal rodent cortical tissue. In the in vivo experiments, fetal rat or mouse VM tissue was transplanted into the striatum or substantia nigra of 6‐hydroxydopamine‐lesioned athymic rats. Amphetamine‐induced rotations were observed for 3 months post‐transplantation and the degree of graft‐mediated neurite outgrowth was analyzed.

Results:  Embryonic VM manifested a greater capacity for neurite formation and outgrowth on xenogenic tissue, which was shown to be significant using co‐cultures of cortical cells. The transplantation study showed that xenograft‐derived fibres had a greater capacity for extensive fibre projection compared with those originating from allografts.

Conclusion:  Results from the present study provide evidence for the hypothesis that xenografts are less responsive to inhibitory molecules present in the adult host environment and as such can project over great distances. Thus neural xenotransplantation may have the potential for more complete circuit reconstruction within the damaged host brain than equivalent allografted tissue.
‘On being both professional and human’: a response
Authors: Little M.
Published: April 2006

A recent publication in theInternal Medicine Journaltouches on some sensitive points. It emphasizes deficiencies in communication between doctors and patients and between doctors and families of the patients, particularly in extreme medical circumstances that are likely to end in death. It stresses as well the trauma of seeing a loved one reduced from a human being with a distinctive biography to an impersonal clinical problem. Such articles have a long history but seldom produce any change in the attitudes or practices of the medical profession. There seem to be a number of reasons for this, including clinicians’ ambivalence towards the real importance of ethics in medicine and the lack of a forum in which consumers and doctors might air and discuss their experiences of suffering and disappointment. A forum for mutual discussion is suggested as the most constructive step to take. Medical education has not proven to be an answer to the problems of sensitive communication.
Insulin therapy in type 2 diabetes patients failing oral agents: cost‐effectiveness of biphasic insulin aspart 70/30 vs. insulin glargine in the US*
Authors: Ray J. A. , Valentine W. J. , Roze S. , Nicklasson L. , Cobden D. , Raskin P. , Garber A. , Palmer A. J.
Published: April 2006

Objectives: To project the long‐term clinical and economic outcomes of treatment with biphasic insulin aspart 30 (BIAsp 70/30, 30% soluble and 70% protaminated insulin aspart) vs. insulin glargine in insulin‐naïve type 2 diabetes patients failing to achieve glycemic control with oral antidiabetic agents alone (OADs).

Methods: Baseline patient characteristics and treatment effect data from the recent ‘INITIATE’ clinical trial served as input to a peer‐reviewed, validated Markov/Monte‐Carlo simulation model. INITIATE demonstrated improvements in HbA1c favouring BIAsp 70/30 vs. glargine (−0.43%; p < 0.005) and greater efficacy in reaching glycaemic targets among patients poorly controlled on OAD therapy. Effects on life expectancy (LE), quality‐adjusted life expectancy (QALE), cumulative incidence of diabetes‐related complications and direct medical costs (2004 USD) were projected over 35 years. Clinical outcomes and costs were discounted at a rate of 3.0%per annum. Sensitivity analyses were performed.

Results: Improvements in glycaemic control were projected to lead to gains in LE (0.19 ± 0.24 years) and QALE (0.19 ± 0.17 years) favouring BIAsp 70/30 vs. glargine. Treatment with BIAsp 70/30 was also associated with reductions in the cumulative incidences of diabetes‐related complications, notably in renal and retinal conditions. The incremental cost‐effectiveness ratio was $46 533 per quality‐adjusted life year gained with BIAsp 70/30 vs. glargine (for patients with baseline HbA1c ≥ 8.5%, it was $34 916). Total lifetime costs were compared to efficacy rates in both arms as a ratio, which revealed that the lifetime cost per patient treated successfully to target HbA1c levels of <7.0% and ≤ 6.5% were $80 523 and $93 242 lower with BIAsp 70/30 than with glargine, respectively.

Conclusions: Long‐term treatment with BIAsp 70/30 was projected to be cost‐effective for patients with type 2 diabetes insufficiently controlled on OADs alone compared to glargine. Treatment with BIAsp 70/30 was estimated to represent an appropriate investment of healthcare dollars in the management of type 2 diabetes.
Comparison of Separable Components in Different Samples
Authors: NEUMEYER NATALIE , SPERLICH STEFAN
Published: April 2006

Abstract. Imagine we have two different samples and are interested in doing semi‐ or non‐parametric regression analysis in each of them, possibly on the same model. In this paper, we consider the problem of testing whether a specific covariate has different impacts on the regression curve in these two samples. We compare the regression curves of different samples but are interested in specific differences instead of testing for equality of the whole regression function. Our procedure does allow for random designs, different sample sizes, different variance functions, different sets of regressors with different impact functions, etc. As we use the marginal integration approach, this method can be applied to any strong, weak or latent separable model as well as to additive interaction models to compare the lower dimensional separable components between the different samples. Thus, in the case of having separable models, our procedure includes the possibility of comparing the whole regression curves, thereby avoiding the curse of dimensionality. It is shown that bootstrap fails in theory and practice. Therefore, we propose a subsampling procedure with automatic choice of subsample size. We present a complete asymptotic theory and an extensive simulation study.
Causal connections in the acquisition of an orthographic rule: a test of Uta Frith's developmental hypothesis
Authors: Davis Claire , Bryant Peter
Published: April 2006

Background:  In a longitudinal study we tested Frith's causal hypothesis that children first gain orthographic knowledge through reading and then later, as a consequence, through spelling.

Method:  Children from Years 2 and 3 were tested three times over two years on their reading and spelling of pseudo‐words which conformed to the conditional orthographic rule, the ‘final –e’ or ‘split‐digraph’ rule.

Results:  Cross‐lagged panel correlation analyses suggested that the children's success in reading split‐digraph words was a causal determinant of their learning to use split‐digraphs in spelling, in the 7‐ to 8‐year period and, with one year‐group but not with the other, in the 8‐ to 9‐year period. In the 9‐ to 10‐year period children's success in reading no longer seemed to affect their spelling.

Conclusions:  These results strongly support Frith's causal hypothesis about the development of orthographic knowledge.
Isolation and characterization of polymorphic microsatellite markers for peacock wrasse (Symphodus tinca)
Authors: GALARZA J. A. , CARRERAS‐CARBONELL J. , MACPHERSON E. , TURNER G. F. , RICO C.
Published: April 2006

Eight polymorphic microsatellite loci were isolated and characterized for the peacock wrasse (Symphodus tinca), a labrid fish inhabiting the Mediterranean and Black seas. Characterization of 35 individuals from the western Mediterranean indicated a relatively high allelic diversity (mean = 12.4, range 9–17), and observed heterozygosity ranging from 0.65 to 0.91. We found no evidence of linkage disequilibrium between pairs of loci. Two loci showed significant departure from Hardy–Weinberg equilibrium. These polymorphic markers can be useful in most basic population genetic applications.
Differential regulation of IL‐2 and IL‐4 in patients with tobacco‐related oral squamous cell carcinoma
Authors: Manchanda P , Sharma SC , Das SN
Published: April 2006

Aim: The aim of the study was to investigate the systemic immunity in terms of major lymphocyte subsets and the expression of IL‐2 and IL‐4 in T‐cell subsets from peripheral blood of patients with tobacco‐related intraoral squamous cell carcinoma.

Methods: CD3+, CD4+and CD8+T‐cell subsets and CD16+ CD56+natural killer cells, and intracellular cytokines in T‐cell subsets were determined by two‐colour flow cytometry and confocal microscopy.

Results: Oral cancer patients showed a significantly reduced (P < 0.001) CD3+and CD4+T‐cell subsets with a lower CD4/CD8 ratio when compared with the normal controls. The frequency of CD3+ IL‐4+and CD8+ IL‐4+T cells were significantly higher (P < 0.001) while CD4+ IL‐2+were significantly lower (P < 0.02) in patients when compared with the normal controls. Late stage of the tumour was associated with reduced expression of IL‐2 in both CD4+(P < 0.05) and CD8+(P < 0.03) subsets.

Conclusions: The tobacco‐related intraoral squamous cell carcinoma seems to be associated with multiple systemic immune defects particularly, an impaired CD3+and CD4+T cells in the peripheral blood as well as a differential regulation of IL‐2 and IL‐4 in CD4+and CD8+T‐cell subsets. The cytokine response in these patients seems to be skewed from protective Th1 to immunosuppressive Th2 type. Thus these patients could be ideal candidate for immunomodulation therapy.
Prevalence of oral lesions in 13‐ to 16‐year‐old students in Duzce, Turkey
Authors: Parlak AH , Koybasi S , Yavuz T , Yesildal N , Anul H , Aydogan I , Cetinkaya R , Kavak A
Published: April 2006

Objective:  The aim of this study was to determine the prevalence of oral lesions in 13‐ to 16‐year‐old students.

Methods:  A cross‐sectional survey was carried out on students in Duzce, a province in the western Black Sea region of Turkey. A total of 993 children aged between 13 and 16 from eight secondary schools were examined. Oral lesions with recurrent behavior, if observed, were recorded at the time of examination. Venous blood samples were obtained for detecting hemoglobin levels.

Results:  Two hundred sixty adolescents (26.2%) were diagnosed with at least one oral mucosal lesion at the time of the examination. Thirteen different mucosal alterations were diagnosed, and the most common lesions were angular cheilitis (9%), linea alba (5.3%), and aphthous ulceration (3.6%). The correlation between occurrence of mucosal lesions and sex was not statistically significant (P > 0.05). Statistical evaluation of the data revealed a significant relationship only between the presence of angular cheilitis and anemia (P < 0.05).

Conclusion:  This study is the first epidemiologic study of oral mucosal lesions in adolescents in Turkey. Angular cheilitis was the only oral mucosal lesion that had a significant correlation with anemia.
The Photoelectric Effect Using LEDs as Light Sources
Authors: Garver Wayne P.
Published: April 2006

The photoelectric effect is demonstrated in many introductory physics courses. We have developed an apparatus for this experiment using a phototube and inexpensive LEDs as light sources instead of the usual mercury lamp. Planck's constant can be measured to better than 10% by using several LEDs in the spectrum from 470 nm to 631 nm. Changing the intensity of the LED allows us to measure the electron energy and photocurrent as a function of light intensity. The photocurrent time response also can be measured using a function generator and oscilloscope.
Top 10 Reasons You Should Attend a National Meeting
Authors: Riendeau Diane
Published: April 2006

This school year is drawing to a close and I hope you have found some things in the column that have been helpful to you. As you think about summer plans, consider attending the summer meeting for AAPT. Diane Riendeau, a member of the High School Committee and frequent contributor to TPT, shares her thoughts about attending national meetings.
Kinetics of the Imidazolium Ring-Opening of mRNA 5'-cap Analogs in Aqueous Alkali
Authors: Stachelska Alicja , Wieczorek Zbigniew J. , Stępiński Janusz , Jankowska-Anyszka Marzena , Lönnberg Harri , Darżynkiewicz Edward
Published: April 2006

Second-order rate constants for the hydroxide-ion-catalyzed imidazolium ring-opening of several mono- and dinucleosidic analogs of mRNA 5'-caphave been determined. Intramolecular stacking of the two nucleobases in the dinucleosidic analogs, m7GpppN (m7G = 7-methylguanosine, N = 5'-linked nucleoside), and electrostatic interaction between theN-alkylated imidazolium ring and phosphate moiety have been shown to shield the m7G moiety against the nucleophilic attack of hydroxide ion. In addition, the effect of methylation of the nucleobase amino groups and replacement of the 7-methyl group with other alkyl groups have been studied. The influence of all the structural modifications studied turned out to be modest, the cleavage rates of the most and least reactive analogs (with the exception of non-phosphorylated nucleosides) differing only by a factor of 5.
K+ channel KV3.1 associates with OSP/claudin-11 and regulates oligodendrocyte development
Authors: Tiwari-Woodruff Seema , Beltran-Parrazal Luis , Charles Andrew , Keck Thomas , Vu Trung , Bronstein Jeff
Published: April 2006

K+ channels are differentially expressed throughout oligodendrocyte (Olg) development. KV1 family voltage-sensitive K+ channels have been implicated in proliferation and migration of Olg progenitor cell (OPC) stage, and inward rectifier K+ channels (KIR)4.1 are required for OPC differentiation to myelin-forming Olg. In this report we have identified a Shaw family K+ channel, KV3.1, that is involved in proliferation and migration of OPC and axon myelination. Application of anti-KV3.1 antibody or knockout of Kv3.1 gene decreased the sustained K+ current component of OPC by 50% and 75%, respectively. In functional assays block of KV3.1-specific currents or knockout of Kv3.1 gene inhibited proliferation and migration of OPC. Adult Kv3.1 gene-knockout mice had decreased diameter of axons and decreased thickness of myelin in optic nerves compared with age-matched wild-type littermates. Additionally, KV3.1 was identified as an associated protein of Olg-specific protein (OSP)/claudin-11 via yeast two-hybrid analysis, which was confirmed by coimmunoprecipitation and coimmunohistochemistry. In summary, the KV3.1 K+ current accounts for a significant component of the total K+ current in cells of the Olg lineage and, in association with OSP/claudin-11, plays a significant role in OPC proliferation and migration and myelination of axons.
Two Opposing Roles of 4-AP–Sensitive K+ Current in Initiation and Invasion of Spikes in Rat Mesencephalic Trigeminal Neurons
Authors: Saito Mitsuru , Murai Yoshinaka , Sato Hajime , Bae Yong-Chul , Akaike Tadashi , Takada Masahiko , Kang Youngnam
Published: April 2006

The axon initial segment plays important roles in spike initiation and invasion of axonal spikes into the soma. Among primary sensory neurons, those in the mesencephalic trigeminal nucleus (MTN) are exceptional in their ability to initiate soma spikes (S-spikes) in response to synaptic inputs, consequently displaying two kinds of S-spikes, one caused by invasion of an axonal spike arising from the sensory receptor and the other initiated by somatic inputs. We investigated where spikes are initiated in such MTN neurons and whether there are any differences between the two kinds of S-spikes. Simultaneous patch-clamp recordings from the soma and axon hillock revealed a spike-backpropagation from the spike-initiation site in the stem axon to the soma in response to 1-ms somatic current pulse, which disclosed the delayed emergence of S-spikes after the current-pulse offset. These initiated S-spikes were smaller in amplitude than S-spikes generated by stimulation of the stem axon; however, 4-AP (≤0.5 mM) eliminated the amplitude difference. Furthermore, 4-AP dramatically shortened the delay in spike initiation without affecting the spike-backpropagation time in the stem axon, whereas it substantially prolonged the refractory period of S-spikes arising from axonal-spike invasion without significantly affecting that of presumed axonal spikes. These observations suggest that 4-AP–sensitive K+ currents exert two opposing effects on S-spikes depending on their origins: suppression of spike initiation and facilitation of axonal-spike invasion at higher frequencies. Consistent with these findings, strong immunoreactivities for Kv1.1 and Kv1.6, among 4-AP–sensitive and low-voltage–activated Kv1 family examined, were detected in the soma but not in the stem axon of MTN neurons.
Generalized preinvex functions and their properties
Authors: Noor Muhammad Aslam , Noor Khalida Inayat
Published: April 2006

We introduce some new classes of preinvex and invex functions, which are called ϕ‐preinvex and ϕ‐invex functions. We study some properties of these classes of ϕ‐preinvex (ϕ‐invex) functions. In particular, we establish the equivalence among the ϕ‐preinvex functions,
ϕ‐invex functions, and ϕη‐monotonicity of
their differential under some suitable conditions.
Discrete‐time systems with time‐varying time delay: Stability and stabilizability
Authors: Boukas El-Kébir
Published: April 2006

This paper deals with the class of linear discrete‐time systems with varying time delay. The problems of stability and stabilizability for this class of systems are considered. Given an upper bound and a lower bound on the time‐varying delay, sufficient conditions for checking the stability of this class of systems are developed. A control design algorithm is also provided. All the results developed in this paper are in the LMI formalism which makes their solvability easier using existing tools. A numerical example is provided to show the effectiveness of the established results.
Conventional MRI Is Inadequate to Delineate the Relationship between the Red Nucleus and Subthalamic Nucleus in Parkinson’s Disease
Authors: Danish Shabbar F. , Jaggi Jurg L. , Moyer Jason T. , Finkel Leif , Baltuch Gordon H.
Published: April 2006

Background: An understanding of the relationships between the anterior commissure-posterior commissure line (AC-PC), the subthalamic nucleus (STN), and red nucleus (RN) is imperative if these structures are to be used for targeting in deep brain stimulation. Currently, these relationships are incompletely understood and difficult to assess using conventional MRI. We examined the location and relationships of the STN and the RN to the AC-PC line and to each other in order to provide a greater understanding of their utility when targeting the STN, and the consistency of these anatomic relationships when examined using conventional MRI. Methods: A total of 52 STN and RN in 26 patients with Parkinson’s disease were evaluated on T2-weighted MR images. The anterior and posterior commissures and the border coordinates of the STN and RN were derived using frame coordinates. The distances from the midcommissural point (mcp) to the centers of the STN and RN, the diameters for each nucleus, and the distances between the nuclei were calculated in the x-, y-, and z-axes. Results: The mean AC-PC length was 26.1 ± 1.3 mm. The distance from the mcp to the center of the STN was 10 ± 0.7 mm in the x-axis, 0.2 ± 0.7 mm in the y-axis, and 3.3 ± 0.9 mm in the z-axis. The distance from the mcp to the center of the RN was 4.7 ± 0.6 mm in the x-axis, –5.9 ± 1.0 mm in the y-axis, and 6.1 ± 1.3 mm in the z-axis. The distance between the STN and RN was 2.3 ± 0.7 mm in the x-axis, 2.1 ± 1.0 mm in the y-axis, and –0.2 ± 1.3 mm in the z-axis. Conclusions: Although recent studies imply that the RN can be used as a relatively consistent marker for the position of the STN, the present data suggest otherwise. These data indicate that a single targeting method may be inadequate given the resolution of conventional MRI, and that it is imperative to use multiple anatomical measurements when targeting the STN for deep brain stimulation in Parkinson’s disease.
Gender and child neglect: theory, research and policy
Authors: Daniel Brigid M. , Taylor Julie
Published: April 2006

Neglect can lead to significantly poor outcomes for children in the short and long term. Definitions of neglect and research reflect underlying theoretical assumptions about gender roles. Research into professional practice with child abuse and neglect suggests that practice too is also highly gendered with a focus on mothers. Policies with regard to child protection in general, and child neglect in particular, do not address gender issues in an explicit fashion. In this paper it is suggested that social policy must be explicitly informed by an analysis of the gender issues that underlie understandings of neglect and response to neglect.
An unhealthy neglect? Examining the relationship between child health and gender in research and policy
Authors: Green Lorraine
Published: April 2006

This article examines health and social science research and literature in order to analyse the relationship between child health and gender. It contends that in general this is a neglected area, particularly in relation to the potential influence that gendered behavioural, cultural and psychological factors have on children’s health. The lack of attention to gender in the development and implementation of child health policy is illustrated and analysed using the Department of Health’s National Service Framework for Children, Young People and Maternity Services (2004) as an exemplar of contemporary child health policy. The article concludes with suggestions for future research, which could impact positively on policy and related practice, in terms of leading to a wider awareness of the impact gender can have on child health.
Imaginaries of Europe
Authors: Lewis Gail
Published: April 2006

This article explores some of the ways in which ideas about and attempts to construct a European identity and sense of belonging inscribe an imaginary of Europe that is exclusionary and elitist. It suggests that the symbolic figure of ‘the immigrant woman’ is a container category that simultaneously signifies the non-European and tests and destabilizes claims to Europe's essential characteristics. It also argues that traces of this imaginary of Europe can be found in feminist scholarship on global care chains and that the spatial category of ‘the domestic’ is the invisible seam that ties this scholarship to the hegemonic imaginary of Europe.
Gender Mainstreaming in the EU
Authors: Lombardo Emanuela , Meier Petra
Published: April 2006

This article explores the extent to which a feminist reading of gender mainstreaming is incorporated in the EU political discourse by analysing how family policy and gender inequality in politics are framed in EU policy documents. Gender mainstreaming is treated as an open signifier that can be filled with both feminist and non-feminist content. The article provides a set of criteria to assess whether a feminist reading of gender mainstreaming has been adopted. The frame analysis of EU documents on family policy and gender inequality in politics reveals but a partial adoption of a feminist understanding of gender mainstreaming and only in the area of gender inequality in politics.
Writing Differently
Authors: Grey Christopher , Sinclair Amanda
Published: April 2006

Here are some stories about writing critically. We have written them to beguile you and make you laugh. But we also want to provoke you to think about how and why you write. Interspersed are short, unashamedly idiosyncratic statements about what we think is wrong with much of the writing that goes on in the field, and why we think writing matters. We want to discourage pompous, impenetrable writing; writing that seems driven by desires to demonstrate one's cleverness, or to accrue publications as ends in themselves.
Blood neutrophil activation markers in severe asthma: lack of inhibition by prednisolone therapy
Authors: Mann Bhupinder S , Chung Kian Fan
Published: April 2006

Background

Neutrophils are increased in the airways and in induced sputum of severe asthma patients. We determined the expression of activation markers from circulating neutrophils in severe asthma, and their supressibility by corticosteroids.

Methods

We compared blood neutrophils from mild, moderate-to-severe and severe steroid-dependent asthma, and non-asthmatics (n = 10 each). We examined the effect of adding or increasing oral prednisolone (30 mg/day;1 week).

Results

Flow cytometric expression of CD35 and CD11b, but not of CD62L or CD18, was increased in severe asthma. F-met-leu-phe increased CD11b, CD35 and CD18 and decreased CD62L expression in all groups, with a greater CD35 increase in severe asthma. In severe steroid-dependent asthma, an increase in prednisolone dose had no effect on neutrophil markers particularly CD62L, but reduced CD11b and CD62L on eosinophils. Phorbol myristate acetate-stimulated oxidative burst and IL-8 release by IL-1β, lipopolysaccharide and GM-CSF in whole blood from mild but not severe asthmatics were inhibited after prednisolone. There were no differences in myeloperoxidase or neutrophil elastase release from purified neutrophils.

Conclusion

Because blood neutrophils in severe asthma are activated and are not inhibited by oral corticosteroids, they may be important in the pathogenesis of severe asthma.
Effect of data normalization on fuzzy clustering of DNA microarray data
Authors: Kim Seo Young , Lee Jae Won , Bae Jong Sung
Published: April 2006

Background

Microarray technology has made it possible to simultaneously measure the expression levels of large numbers of genes in a short time. Gene expression data is information rich; however, extensive data mining is required to identify the patterns that characterize the underlying mechanisms of action. Clustering is an important tool for finding groups of genes with similar expression patterns in microarray data analysis. However, hard clustering methods, which assign each gene exactly to one cluster, are poorly suited to the analysis of microarray datasets because in such datasets the clusters of genes frequently overlap.

Results

In this study we applied the fuzzy partitional clustering method known as Fuzzy C-Means (FCM) to overcome the limitations of hard clustering. To identify the effect of data normalization, we used three normalization methods, the two common scale and location transformations and Lowess normalization methods, to normalize three microarray datasets and three simulated datasets. First we determined the optimal parameters for FCM clustering. We found that the optimal fuzzification parameter in the FCM analysis of a microarray dataset depended on the normalization method applied to the dataset during preprocessing. We additionally evaluated the effect of normalization of noisy datasets on the results obtained when hard clustering or FCM clustering was applied to those datasets. The effects of normalization were evaluated using both simulated datasets and microarray datasets. A comparative analysis showed that the clustering results depended on the normalization method used and the noisiness of the data. In particular, the selection of the fuzzification parameter value for the FCM method was sensitive to the normalization method used for datasets with large variations across samples.

Conclusion

Lowess normalization is more robust for clustering of genes from general microarray data than the two common scale and location adjustment methods when samples have varying expression patterns or are noisy. In particular, the FCM method slightly outperformed the hard clustering methods when the expression patterns of genes overlapped and was advantageous in finding co-regulated genes. Thus, the FCM approach offers a convenient method for finding subsets of genes that are strongly associated to a given cluster.
How to decide? Different methods of calculating gene expression from short oligonucleotide array data will give different results
Authors: Millenaar Frank F , Okyere John , May Sean T , van Zanten Martijn , Voesenek Laurentius ACJ , Peeters Anton JM
Published: April 2006

Background

Short oligonucleotide arrays for transcript profiling have been available for several years. Generally, raw data from these arrays are analysed with the aid of the Microarray Analysis Suite or GeneChip Operating Software (MAS or GCOS) from Affymetrix. Recently, more methods to analyse the raw data have become available. Ideally all these methods should come up with more or less the same results. We set out to evaluate the different methods and include work on our own data set, in order to test which method gives the most reliable results.

Results

Calculating gene expression with 6 different algorithms (MAS5, dChip PMMM, dChip PM, RMA, GC-RMA and PDNN) using the same (Arabidopsis) data, results in different calculated gene expression levels. Consequently, depending on the method used, different genes will be identified as differentially regulated. Surprisingly, there was only 27 to 36% overlap between the different methods. Furthermore, 47.5% of the genes/probe sets showed good correlation between the mismatch and perfect match intensities.

Conclusion

After comparing six algorithms, RMA gave the most reproducible results and showed the highest correlation coefficients with Real Time RT-PCR data on genes identified as differentially expressed by all methods. However, we were not able to verify, by Real Time RT-PCR, the microarray results for most genes that were solely calculated by RMA. Furthermore, we conclude that subtraction of the mismatch intensity from the perfect match intensity results most likely in a significant underestimation for at least 47.5% of the expression values. Not one algorithm produced significant expression values for genes present in quantities below 1 pmol. If the only purpose of the microarray experiment is to find new candidate genes, and too many genes are found, then mutual exclusion of the genes predicted by contrasting methods can be used to narrow down the list of new candidate genes by 64 to 73%.
Bio++: a set of C++ libraries for sequence analysis, phylogenetics, molecular evolution and population genetics
Authors: Dutheil Julien , Gaillard Sylvain , Bazin Eric , Glémin Sylvain , Ranwez Vincent , Galtier Nicolas , Belkhir Khalid
Published: April 2006

Background

A large number of bioinformatics applications in the fields of bio-sequence analysis, molecular evolution and population genetics typically share input/ouput methods, data storage requirements and data analysis algorithms. Such common features may be conveniently bundled into re-usable libraries, which enable the rapid development of new methods and robust applications.

Results

We present Bio++, a set of Object Oriented libraries written in C++. Available components include classes for data storage and handling (nucleotide/amino-acid/codon sequences, trees, distance matrices, population genetics datasets), various input/output formats, basic sequence manipulation (concatenation, transcription, translation, etc.), phylogenetic analysis (maximum parsimony, markov models, distance methods, likelihood computation and maximization), population genetics/genomics (diversity statistics, neutrality tests, various multi-locus analyses) and various algorithms for numerical calculus.

Conclusion

Implementation of methods aims at being both efficient and user-friendly. A special concern was given to the library design to enable easy extension and new methods development. We defined a general hierarchy of classes that allow the developer to implement its own algorithms while remaining compatible with the rest of the libraries. Bio++ source code is distributed free of charge under the CeCILL general public licence from its website http://kimura.univ-montp2.fr/BioPP.
Algorithms for incorporating prior topological information in HMMs: application to transmembrane proteins
Authors: Bagos Pantelis G , Liakopoulos Theodore D , Hamodrakas Stavros J
Published: April 2006

Background

Hidden Markov Models (HMMs) have been extensively used in computational molecular biology, for modelling protein and nucleic acid sequences. In many applications, such as transmembrane protein topology prediction, the incorporation of limited amount of information regarding the topology, arising from biochemical experiments, has been proved a very useful strategy that increased remarkably the performance of even the top-scoring methods. However, no clear and formal explanation of the algorithms that retains the probabilistic interpretation of the models has been presented so far in the literature.

Results

We present here, a simple method that allows incorporation of prior topological information concerning the sequences at hand, while at the same time the HMMs retain their full probabilistic interpretation in terms of conditional probabilities. We present modifications to the standard Forward and Backward algorithms of HMMs and we also show explicitly, how reliable predictions may arise by these modifications, using all the algorithms currently available for decoding HMMs. A similar procedure may be used in the training procedure, aiming at optimizing the labels of the HMM's classes, especially in cases such as transmembrane proteins where the labels of the membrane-spanning segments are inherently misplaced. We present an application of this approach developing a method to predict the transmembrane regions of alpha-helical membrane proteins, trained on crystallographically solved data. We show that this method compares well against already established algorithms presented in the literature, and it is extremely useful in practical applications.

Conclusion

The algorithms presented here, are easily implemented in any kind of a Hidden Markov Model, whereas the prediction method (HMM-TM) is freely available for academic users at http://bioinformatics.biol.uoa.gr/HMM-TM, offering the most advanced decoding options currently available.