bluuebunny/crossref_metadata_2025 huggingface dataset:
Recombinant human interleukin 6 (B cell stimulatory factor 2) enhances immunoglobulin secretion by single murine hapten-specific B cells in the absence of cell division
Authors: Alderson Mark R. , Pike Beverley L.
Published: January 2007

We have assessed the role of recombinant human IL-6 (r-hu-IL-6) In promotion of early actlvation, proliferation, and immunoglobulin(lg) secretion amongst single hapten-specific murine splenic B cells in vitro it was found that r-hu-IL-6 acting alone was able to induce early B cell activation in a proportion of B cells, as measured by a significant increase in cell diameter within 24 h. An enhanced effect was seen in the concomitant presence of a ‘T-Independent’ antigen. None of the B cells activated by r-hu-IL-6 appeared to divide, as the frequencies of proliferating clones Induced by either medium alone or antigen alone were virtually identical whether r-hu-IL-6 was present or absent. However, assay of the culture supernatants for the presence of Ig by ELlSA revealed that r-hu-IL-6 effected a significant 2-fold increase in the frequency of B cells secreting Ig. Thus, the prlme effect of r-hu-IL-6 appears to be to recruit more precursor B cells into Ig secretion, rather than to promote proliferation or to enhance the amount of Ig secreted by pre-committed but non-cycling B cells. Delayed addition experiments showed that r-hu-IL-6 enhanced Ig secretion late in the activation pathway. Kinetics studies demonstrated detectable Ig secretion as early as day 2, and when taken with its apparent ability to Induce early activation, these flndings suggest that IL-6 is not exclusively a late-acting Interleukin. Studies with size fractionated hapten-spectflc B cells showed the larger B cells to be preferentially responsive to r-hu-IL-6. The data presented strongly suggest that IL-6 may play a role In B cell maturation as a polyclonal stimulator of low rate Ig secretion. The bioactivity of IL-6 In this slngle cell system thus differed from that of IL-4 and/or IL-5. These findings are discussed with relevance to B cell activation in vivo.
Submandibular Gland Transfer for Severe Xerophthalmia
Authors: Paniello Randal C.
Published: January 2007

Objective: To report early clinical experience with a new microvascular reconstructive procedure for patients with severe xerophthalmia.

Study Design: Retrospective clinical series.

Methods: Patients with severe xerophthalmia were referred for treatment after having exhausted all conventional means of treatment. The ipsilateral submandibular gland was transferred to the temporal fossa, as described by Macleod et al., and revascularized using the superficial temporal artery and appropriate vein(s). The submandibular duct was directed to the superolateral fornix so that the saliva produced moistened the eye. Results and complications were reviewed.

Results: Seven microvascular submandibular gland transfer procedures were performed in five patients, ages 6 to 54. The etiology of severe xerophthalmia was Stevens‐Johnson syndrome in four and chemical burn in one. Follow‐up time was 4 to 20 months. Successful transfer with revascularization was achieved in six of seven (86%) cases. Schirmer's test scores improved from 1.3 pretransfer to 8.1 posttransfer (P = .005). Patients experienced symptomatic relief within 1 month, and the microenvironment of the eye surface improved enough to make them candidates for visual restorative eye surgery. There were no major complications.

Conclusions: Microvascular submandibular gland transfer is an effective approach for correcting severe xerophthalmia. The procedure should be within the skills of any reconstructive microsurgeon. This procedure offers a unique opportunity for otolaryngologist–head and neck reconstructive surgeons to help restore vision to this unfortunate group of patients.
Supracricoid Laryngectomy Outcomes: The Johns Hopkins Experience
Authors: Farrag Tarik Y. , Koch Wayne M. , Cummings Charles W. , Goldenberg David , Abou‐Jaoude Peter M. , Califano Joseph A. , Flint Paul W. , Webster Kimberly , Tufano Ralph P.
Published: January 2007

Objective: To report the oncologic and functional results from our experience in performing supracricoid laryngectomy (SCL) for selected patients with laryngeal cancer.

Study Design: Retrospective chart review.

Methods: Twenty‐four consecutive patients who underwent SCL for laryngeal cancer in our institution from December 2000 to March 2006 have been reviewed. Reports of the site and extent of tumor, type of reconstruction, preoperative or postoperative radiotherapy, and the final histopathologic examination were reviewed. In addition, the reports of the preoperative examination, inpatient course, and postoperative follow‐up were reviewed.

Results: A total of 24 patients were involved in the study; 19 had tumors involving the glottic region, and 5 patients had tumors involving both the glottic and supraglottic regions (transglottic). Ten patients had their SCL for postradiotherapy recurrence/persistence of disease. Eighteen patients underwent reconstruction through cricohyoidoepiglottopexy (CHEP), whereas six patients had cricohyoidopexy (CHP). Eleven patients had an arytenoid cartilage resected; 8 of 11 had CHEP, and 3 of 11 had CHP. All patients had a tracheostomy and percutaneous endoscopic gastrostomy (PEG) tube placement performed at the same time as the SCL. The median hospital stay period was 6 days. Twenty‐three of 24 had successful tracheostomy tube decannulation, with a median time to decannulation of 37 days. The median time to removal of the PEG tube was 70 days. The complications with SCL were postoperative wound infection in two patients (SCL/CHP) and the need for completion total laryngectomy secondary to intractable aspiration in one patient with SCL/CHP. One patient with SCL/CHEP had a ruptured pexy and subsequently underwent a second reconstruction with successful tracheostomy and PEG tube removal. One of 24 patients is still PEG tube dependant, and he had postoperative radiotherapy. Fifteen patients underwent concurrent neck dissection. None of the patients had any local or regional recurrence, with a median follow‐up period of 3 years. All final surgical margins were negative for tumor invasion. Three patients had postoperative radiotherapy, two patients because of nodal metastases in the excised lymph nodes and one because of perineural invasion on final histopathologic examination of the SCL specimen. There were no perioperative deaths.

Conclusion: SCL with CHEP or CHP represents an effective technique that can be taught and effectively used to avoid a total laryngectomy while maintaining physiologic speech and swallowing in selected patients with advanced stage primary laryngeal cancer or recurrent/persistent laryngeal cancer after radiotherapy. There is a good functional recovery with acceptable morbidity and an excellent oncologic outcome when strict selection criteria are applied and a formal swallowing rehabilitation program is followed.
Anxiety and Pain Symptoms in Children With Inflammatory Bowel Disease and Functional Gastrointestinal Disorders Undergoing Colonoscopy
Authors: Crandall Wallace V , Halterman Timothy E , Mackner Laura M
Published: January 2007

Objective:

To compare pain and anxiety scores between children with inflammatory bowel disease (IBD) and those with functional gastrointestinal disorders (FGID) undergoing colonoscopy and to examine the role of anxiety and procedure length in predicting reports of pain.

Materials and Methods:

Children ages 10 to 18 years undergoing colonoscopy (general anesthesia) for the first time completed pain and anxiety questionnaires immediately before the procedure and a pain questionnaire 48 hours after colonoscopy. The diagnosis was determined by chart review and physician interview.

Results:

Children with FGID had a longer duration of pain than those with IBD. Children with FGID endorsed a greater total number of the pain descriptors. The FGID group reported higher usual pain severity and greater postprocedural pain. No differences in anxiety were reported. However, higher levels of anxiety were associated with higher pain scores at the time of colonoscopy in children with IBD. It required significantly more time to perform colonoscopy in the IBD group than in the FGID group. Longer procedure duration was positively correlated with pain in children with FGID but not in children with IBD.

Conclusions:

Children with FGID report more usual pain symptoms and may describe more pain after a colonoscopy when compared with children with IBD. Anxiety appears to play a role in pain severity after colonoscopy in children presenting with IBD, but not in children with FGID.
Long‐term Therapeutic Efficacy of Lamivudine Compared With Interferon‐α in Children with Chronic Hepatitis B: The Younger the Better
Authors: Choe Byung‐Ho , Lee Ji Hye , Jang You Cheol , Jang Chang Hwan , Oh Ki Won , Kwon Soonhak , Hyun Myung Chul , Ko Cheol Woo , Lee Kun Soo , Lee Won Kee
Published: January 2007

Objectives:

To assess and compare the long‐term therapeutic response to lamivudine compared with interferon‐α (IFN‐α) in children with chronic hepatitis B.

Methods:

A total of 40 children (27 male; age, 1.3–18 y, mean, 7.7 y) with chronic hepatitis B who received lamivudine for at least 12 months were followed for a mean period of 39 (24–76) months. Their treatment efficacy was historically compared with that of 19 children (14 male; age, 2.1–17 y; mean, 10 y) who had been treated with IFN‐α and were followed for a mean period of 39 (24–104) months. Therapeutic responses were compared at 2 y after the initiation of either of the treatment methods.

Results:

Two years after the initiation of treatment, the results for children treated with lamivudine versus IFN‐α were as follows: hepatitis B e antigen (HBeAg) seroconversion occurred in 26 (65%) of the 40 children versus 7 (37%) of the 19 children, P < 0.05. In the lamivudine‐treated group, the results for children treated before the age of 7 versus age >7 were as follows: HBeAg seroconversion occurred in 17 (89%) of the 19 children versus 9 (43%) of the 21 children, P < 0.01, and loss of hepatitis B surface antigen (HBsAg) occurred in 8 (42%) versus 0%, P < 0.001.

Conclusions:

Long‐term treatment of lamivudine led to significant improvement in the seroconversion rate of HBeAg in children with chronic hepatitis B compared with IFN‐α therapy. Furthermore, in preschool‐age children, it led to significant improvement in the seroconversion rate of HBeAg and HBsAg compared with school‐age children.
Association of endogenous sex hormone with C‐reactive protein levels in middle‐aged and elderly men
Authors: Pour Hamid Reza Nakhai , Grobbee Diederick E. , Muller Majon , Van Der Schouw Yvonne T.
Published: January 2007

Background  In women, postmenopausal oestrogen supplementation increases levels of systemic markers of inflammation, which are important predictors of coronary heart disease (CHD) risk. Whether endogenous sex hormone levels in men are also related to systemic subclinical inflammation is still unknown.

Objective  We tested the hypothesis that higher endogenous sex hormones levels within the physiological range may be associated with systemic subclinical inflammation.

Methods  Circulating sex hormone and high‐sensitivity C‐reactive protein (hs‐CRP) levels were determined in 400 apparently healthy men aged between 40 and 80 years. We used multivariate linear regression analysis with the various sex hormones as determinant, and natural log hs‐CRP as outcome.

Results  Higher levels of total as well as bioavailable oestradiol (E2) were associated with increased natural log hs‐CRP levels, which remained statistically significant after adjustment for age and cardiovascular risk factors. Natural log hs‐CRP was 0·26 mg/l higher [95% confidence interval (CI) −0·02 to 0·54] in the fourth than in the first quartile of total E2; the P‐value for linear trend was 0·05. For bioavailable E2, the difference in natural log hs‐CRP between the fourth and the first quartile was 0·30 mg/l (95% CI 0·03–0·56; P‐value for linear trend 0·04). After adjustment for age and cardiovascular risk factors, physiological levels of total (TT) or bioavailable testosterone or dehydroepiandrosterone sulfate (DHEAS) were not associated with hs‐CRP.

Conclusion  Endogenous total and bioavailable E2 levels are significantly associated with CRP among middle‐aged and elder men.
Extraintestinal focal infections in adults with nontyphoid Salmonella bacteraemia: predisposing factors and clinical outcome
Authors: Chen P.‐L. , Chang C.‐M. , Wu C.‐J. , Ko N.‐Y. , Lee N.‐Y. , Lee H.‐C. , Shih H.‐I. , Lee C.‐C. , Wang R.‐R. , Ko W.‐C.
Published: January 2007

Background.  Nontyphoid Salmonella (NTS) isolates lead to not only self‐limited, acute gastrointestinal infections, but also bacteraemia with or without extraintestinal focal infections (EFIs). The risk factors associated with EFIs in adults with NTS bacteraemia were not clearly elucidated.

Methods.  In a medical center in southern Taiwan, patients aged ≥18 years with NTS bacteraemia between January 1999 and June 2005 were included for analysis.

Results.  Of 129 patients, 51 (39.5%) were complicated with EFIs. The most common EFI was mycotic aneurysm, followed by pleuropulmonary infections and spinal osteomyelitis. Compared to patients with primary bacteraemia, those with EFIs had higher leucocyte counts (P = 0.004) and higher serum levels of C‐reactive protein (P < 0.0001). The development of EFIs was associated with a higher mortality, more severe septic manifestations, longer hospital stays and duration of antimicrobial therapy. Univariate analysis revealed that diabetes mellitus (P = 0.02), hypertension (P = 0.02) and chronic lung disease (P = 0.006) were significantly associated with EFIs. However, patients with malignancy (P = 0.01) and immunosuppressive therapy (P = 0.03) were less likely to develop EFIs. On the basis of multivariate analysis, an independent factor for the occurrence of EFIs was age [adjusted odds ratio (aOR) 1.05; 95% confidence interval (CI) 1.02–1.07; P < 0.0001], whilst malignancy was negatively associated with EFIs (aOR 0.16; 95% CI 0.14–0.78; P = 0.01).

Conclusion.  Amongst patients with NTS bacteraemia, EFIs often occurred in the aged, and were associated with a higher mortality and morbidity. Recognition of specific host factors is essential for identification of EFIs which often demand early surgical interventions and prolonged antimicrobial therapy.
Mycosis fungoides – a review of the management of 28 patients and of the recent literature
Authors: Lenane Patsy , Powell F. C. , O’Keane C. , Dervan P. , O'Sullivan D. , Bourke E. , O’Loughlin S.
Published: January 2007

Background  Mycosis fungoides is an uncommon cutaneous T‐cell lymphoma characterized by malignant monoclonal proliferation of T‐helper lymphocytes. Its course is variable with a potential for lymphatic and hematogenous involvement. We report the investigations, staging, treatment, follow‐up, and outcome of 28 patients. This is the first such study reported from Ireland.

Methods  Twenty‐eight patients with mycosis fungoides (14 women, 14 men; average age, 52.5 years) were reviewed over 12 years in the dermatology clinic which assesses an average of 4500 patients per year. All mycosis fungoides patients were referred from their family physicians. The diagnosis was made in all cases from a combination of clinical findings, histology, and immunohistochemistry. TNM staging revealed 11 patients at diagnosis stage IA (T1), 12 at stage IB (T2), four at stage IIB (T3), and one at stage III (T4).

Results  The usual male preponderance was not found. Eight patients needed multiple biopsies to establish the diagnosis. Detailed investigations were not useful in the early stages. Patients were followed up over a 12‐year period. Thirteen patients died as a result of cutaneous lymphoma. Two patients with stage IA disease progressed rapidly and died, a feature reported in only 10% of patients at this stage. Five patients showed unusual features, including a long history prior to presentation, the development of the rarely reported bullous mycosis fungoides, and aggressive disease beginning at a young age.

Conclusions  Mycosis fungoides is rare; we reviewed 28 patients over 12 years. The prognosis is poor at the later stages; 13 patients died. Two patients who died were unusual in that they rapidly progressed from stage IA disease; however, in the majority of patients with this stage, the prognosis is excellent. Detailed investigations were unhelpful in early stage disease. Close clinical follow‐up is essential to identify disease progression.
Early recurrence of primary disease after pediatric renal transplantation: Two case reports and a review of the literature
Authors: Jain Supriya , John Eunice , Setty Suman , Benedetti Enrico
Published: January 2007

Abstract:  Recurrence of primary diseases such as FSGS or HUS is known to cause early graft dysfunction after pediatric renal transplantation. We report the unusual occurrence of early graft dysfunction following kidney transplant in two pediatric cases. Both subjects had biopsy proven recurrence of CGN in less than a week after transplantation. We were able to sustain the renal function in one of them following aggressive treatment. Hence, early recurrence of CGN should be considered in the differential diagnosis of early graft dysfunction.
Experimental evaluation of creep and fatigue behaviour for microscale solder interconnect
Authors: LU H. , SHI H. G. , ZHOU M.
Published: January 2007

This paper presents a novel experimental study for creep and fatigue of solder‐interconnects in microstructures. The strains are directly measured in the fillet area of solder‐joints with a typical linear dimension of 50 μm. An analytical approach is developed for calculating shear stress based on the shear strain measurement and the established solder constitutive relations. Also obtained is the strain‐rate as well as the separated elastic, plastic and creep components from the measured total strain. The data enables the determination of the strain energy density per temperature cycle for the characterization of the solder joint creep fatigue behaviour. Case studies provide evidence for the shear dominance and the creep fatigue mechanism in thermally induced solder joint deformation in surface‐mounted electronic assemblies. Though a similar trend of variation in stress–strain is found in the joints of different solders, the substantial differences in the hysteresis loop area and shape as well as in the creep rate suggest that the solder constitutive parameters should have a profound impact on the creep fatigue endurance of the joints.
SUBSTANTIAL IDENTITY AND THE RIGHT TO LIFE: A REJOINDER TO DEAN STRETTON
Authors: LEE PATRICK
Published: January 2007

In this article, I reply to criticisms of Dean Stretton of the pro‐life argument from substantial identity. When the criterion for the right to life proposed by most proponents of the pro‐life position is rightly understood – being a person, a distinct substance of a rational nature – this position does not lead to the difficulties Stretton claims it does.
The Concept of Solidarity: Emerging from the Theoretical Shadows?
Authors: Wilde Lawrence
Published: January 2007

The concept of solidarity has been relatively neglected by social scientists since Durkheim's pioneering work in the late 19th century. The discipline of politics has been guilty of overlooking this ‘subjective’ element of community life, but recent works by Stjernø and Brunkhorst reflect a growing awareness of the theoretical significance of the concept. Whereas early liberal attempts to theorise solidarity took the nation state to be the appropriate community for its realisation, the emergence of globalisation raises the possibility of human solidarity developing in the global community. Traditional forms of solidarity have been dissipated by the social changes accompanying globalisation, but they were often locked into the defence of particular interests. New forms may be emerging to rekindle the broader vision of human solidarity. Recent work by writers such as Habermas, Honneth, Rorty and Touraine focuses on widening and deepening democratic participation and/or the articulation of our ethical obligations in various ways. It is argued here that these perspectives need to be supplemented by a radical humanist approach grounded in a normative theory of human self-realisation.
Median‐voter Equilibria in the Neoclassical Growth Model under Aggregation*
Authors: Azzimonti Marina , De Francisco Eva , Krusell Per
Published: January 2007

We study a dynamic version of Meltzer and Richard's median‐voter model where agents differ in wealth. Taxes are proportional to income and are redistributed as equal lump‐sum transfers. Voting occurs every period and each consumer votes for the tax that maximizes his welfare. We characterize time‐consistent Markov‐perfect equilibria twofold. First, restricting utility classes, we show that the economy's aggregate state is mean and median wealth. Second, we derive the median‐voter's first‐order condition interpreting it as a tradeoff between distortions and net wealth transfers. Our method for solving the steady state relies on a polynomial expansion around the steady state.
DO STRUCTURAL ASYMMETRIES INCREASE THE GAINS FROM INTERNATIONAL FISCAL POLICY COORDINATION?*
Authors: SPANGE MORTEN
Published: January 2007

The paper studies international coordination of fiscal stabilization policies in a two‐country stochastic general equilibrium model. The countries are assumed to differ in the sense that wages in one country are flexible whereas wages in the other country are rigid in real terms. It is found that for the country with rigid wages it will always be optimal with procyclical tax revenues whereas for the flex wage country the result is ambiguous. Comparing the uncoordinated and coordinated policies, it is found that the coordinated policies may be either more or less procyclical than in the decentralized equilibrium. Quantitatively the additional gains from a utilitarian fiscal policy relative to the decentralized equilibrium are small.
“PURE” VERSUS “PRACTICAL” EPISTEMIC JUSTIFICATION
Authors: MONTMARQUET JAMES A.
Published: January 2007

Abstract: In this article I distinguish a type of justification that is “epistemic” in pertaining to the grounds of one's belief, and “practical” in its connection to what act(s) one may undertake, based on that belief. Such justification, on the proposed account, depends mainly on the proportioning of “inner epistemic virtue” to the “outer risks” implied by one's act. The resulting conception strikes a balance between the unduly moralistic conception of William Clifford and contemporary naturalist virtue theories.
Rationalisation, Race, and the Weimar Response to Jazz
Authors: Rippey Theodore F.
Published: January 2007

Surveying articles on jazz in the Weimar‐era popular press, one finds that commentators and critics commonly read the music as an expression of primitive blackness, a product of a rationally organised, industrial mode of composition, or a strange combination of both. The rationalised/industrialised and black elements perceived in jazz were generally understood as antithetical; the concept of blackness itself was rarely scrutinised. In exceptional cases, writers began to view blackness as a media‐generated construct and thereby re‐situate race itself as a product of modern popular culture. Siegfried Kracauer stands out in this regard. He recognised that the response to jazz was rarely about the music itself, and his critiques of jazz culture and the encompassing fascination with blackness contain an unusual degree of critical reflection on the public imagination of race in the Weimar Republic.
Social exclusion in Europe: some conceptual issues
Authors: O’Brien Martin , Penna Sue
Published: January 2007

In the late 20th and early 21st century, social exclusion has become something of a trope around which is pegged justifications for various reforms. The notion of social exclusion has found its way into the lexicon of all major global governance institutions. How has this happened, and what are its implications for scholars of contemporary welfare reforms? In this article, we consider the ‘rise and rise’ of the discourse of social exclusion, with particular reference to its development as a policy paradigm within the European Union. We note that its initial iteration was anchored in a functionalist discourse of social organisation but that this was quickly challenged both by post‐structuralist and post‐colonial perspectives and by research findings that undermined the view of mainstream institutions as fundamentally integrative and inclusive in nature. The debate about social exclusion, we suggest, is simultaneously a debate about the historical and social dynamics of European modernity.
GISP: a novel brain‐specific protein that promotes surface expression and function of GABABreceptors
Authors: Kantamneni Sriharsha , Corrêa Sônia A. L. , Hodgkinson Gina K. , Meyer Guido , Vinh Ngoc Nga , Henley Jeremy M. , Nishimune Atsushi
Published: January 2007

Synaptic transmission depends on the regulated surface expression of neurotransmitter receptors, but many of the cellular processes required to achieve this remain poorly understood. To better define specific mechanisms for the GABABreceptor (GABABR) trafficking, we screened for proteins that bind to the carboxy‐terminus of the GABAB1subunit. We report the identification and characterization of a novel 130‐kDa protein, GPCR interacting scaffolding protein (GISP), that interacts directly with the GABAB1subunit via a coiled‐coil domain. GISP co‐fractionates with GABABR and with the postsynaptic density and co‐immunoprecipitates with GABAB1and GABAB2from rat brain. In cultured hippocampal neurons, GISP displays a punctate dendritic distribution and has an overlapping localization with GABABRs. When co‐expressed with GABABRs in human embryonic kidney cells, GISP promotes GABABR surface expression and enhances both baclofen‐evoked extracellular signal‐regulated kinase (ERK) phosphorylation and G‐protein inwardly rectifying potassium channel (GIRK) currents. These results suggest that GISP is involved in the forward trafficking and stabilization of functional GABABRs.
Why Citizens Do and Do Not Attend Public Meetings about Local Cancer Cluster Investigations
Authors: McComas Katherine A. , Besley John C. , Trumbo Craig W.
Published: January 2007

Why do citizens choose to attend or not to attend community public meetings about possible cancer clusters? To answer this question, we examine self‐report data collected during a series of mail surveys conducted in six communities experiencing current health investigations into suspect levels of cancer or cancer clusters. We analyze the data using quantitative content analysis while also providing qualitative summaries and categorizations of survey participants' reasons for attending or not attending a specific public meeting in their community. In addition, we use survey data related to respondents' past participation and sociodemographic characteristics. The results found that rational reasons (e.g., to get information) dominated citizens' justifications for attending the public meetings, whereas socioeconomic and mobilization factors (e.g., did not hear about meeting, too busy) were most commonly cited as reasons for not attending. Less common but still present were relational considerations, such as believing the people in charge were fair. Taken together, the findings suggest that the majority of citizens who attended the public meetings could be categorized as the curious, the fearful, and the available. In comparison, the majority of citizens who did not attend could be described as the uninformed, the indifferent, the occupied, and the disaffected.
Nonparametric Estimation of the Joint Distribution of a Survival Time Subject to Interval Censoring and a Continuous Mark Variable
Authors: Hudgens Michael G. , Maathuis Marloes H. , Gilbert Peter B.
Published: January 2007

Summary This article considers three nonparametric estimators of the joint distribution function for a survival time and a continuous mark variable when the survival time is interval censored and the mark variable may be missing for interval‐censored observations. Finite and large sample properties are described for the nonparametric maximum likelihood estimator (NPMLE) as well as estimators based on midpoint imputation (MIDMLE) and coarsening the mark variable (CMLE). The estimators are compared using data from a simulation study and a recent phase III HIV vaccine efficacy trial where the survival time is the time from enrollment to infection and the mark variable is the genetic distance from the infecting HIV sequence to the HIV sequence in the vaccine. Theoretical and empirical evidence are presented indicating the NPMLE and MIDMLE are inconsistent. Conversely, the CMLE is shown to be consistent in general and thus is preferred.
Green fluorescent protein‐tagging reduces the nucleocytoplasmic shuttling specifically of unphosphorylated STAT1
Authors: Meyer Thomas , Begitt Andreas , Vinkemeier Uwe
Published: January 2007

Fluorescence recovery after photobleaching (FRAP) and related techniques using green fluorescent protein (GFP)‐tagged proteins are widely used to study the subcellular trafficking of proteins. It was concluded from these experiments that the cytokine‐induced nuclear import of tyrosine‐phosphorylated (activated) signal transducer and activator of transcription 1 (STAT1) was rapid, while the constitutive shuttling of unphosphorylated STAT1 was determined to be inefficient. However, unrelated experiments came to different conclusions concerning the constitutive translocation of STAT1. Because these discrepancies have not been resolved, it remained unclear whether or not unphosphorylated STAT1 is a relevant regulator of cytokine‐dependent gene expression. This study was initiated to examine the influence of GFP‐tagging on the nucleocytoplasmic shuttling of phosphorylated and unphosphorylated STAT1. In accordance with previous findings our results confirm the undisturbed rapid nuclear import of GFP‐tagged activated STAT1. However, we reveal an inhibitory influence of GFP specifically on the constitutive nucleocytoplasmic cycling of the unphosphorylated protein. The decreased shuttling of unphosphorylated STAT1‐GFP significantly reduced the activation level while nuclear accumulation was prolonged. Importantly, despite unimpaired nuclear import of activated STAT1 the transcription of a STAT1‐dependent reporter gene was more than halved after GFP‐tagging, which could be linked directly to reduced nucleocytoplasmic shuttling. In conclusion, it is demonstrated that GFP‐based techniques considerably underestimate the actual shuttling rate of unphosphorylated native STAT1. The results confirm that the activation of STAT1 and hence its transcriptional activity is proportional to the nucleocytoplasmic shuttling rate of the unphosphorylated protein. Moreover, our data indicate that GFP‐tagging may differently affect the mechanistically distinct translocation pathways of a shuttling protein.
RAPID RECOVERY OF DNA FROM AGAROSE GEL SLICE USING A MICROWAVE*
Authors: OUYANG XUEZHI , YU WENWEN , WANG QIANG , HE JIANGUO , LIU QIUYUN
Published: January 2007

A method for the rapid recovery of DNA from agarose gel slices for polymerase chain reaction (PCR) applications was described. DNA bands were excised from agarose gel and diluted with distilled water. One‐minute microwave treatment at full power was performed, immediately followed by 1‐min centrifugation. The supernatant thus recovered can be directly used in PCR amplifications with minimal delay. This protocol represents an ultrafast and inexpensive alternative to commercial kits.
COMPARISON OF ENRICHMENT BROTHS FOR DETECTION AND ISOLATION OF ENTEROBACTER SAKAZAKII FROM INFANT FORMULA MILK
Authors: OH SE‐WOOK , CHUNG HYUN‐JUNG , KANG DONG‐HYUN
Published: January 2007

Enterobacter sakazakii is a member of the Enterobacteriaceae and has physiological characteristics similar to those of Escherichia coli O157:H7 (negative D‐sorbitol fermentation, positive glucose and lactose fermentation, and negative H2S production). The purpose of this study was to evaluate the efficiency of enrichment broths recommended for E. sakazakii enrichment. Growth and recovery ratio of E. sakazakii were compared in media including modified tryptone soya broth supplemented with novobiocin (mTSB + N), modified Escherichia coli broth with novobiocin (mEC + N), Enterobacteriaceae enrichment (EE) broth, buffered peptone water supplemented with vancomycin, cefixime and cefsulodin (BPW + VCC), and rehydrated infant milk formula (IMF) with or without antibiotics. The EE broth that was recommended by the FDA showed the most effective enrichment for growth of E. sakazakii, followed by rehydrated IMF. Other media such as mTSB + N, mEC + N and BPW + VCC did not support growth of E. sakazakii compared to EE and rehydrated IMF. They were not considered suitable for the enrichment of E. sakazakii. When evaluated for recovery of E. sakazakii among other Enterobacteriaceae, strains of E. sakazakii were all recovered in EE broth after 6 and 18 h; thus, the EE broth was considered the most effective enrichment broth in this study. Rehydrated IMF also showed higher recovery ratios (3/4, 4/4) after 6 and 18 h than the other recommended enrichment broths.
Experimental and Numerical Investigation of a Gas Compressor Windback Seal
Authors: Al-Ghasem Adnan , Morrison G. L. , Platt John P.
Published: January 2007

The effectiveness of a computational fluid dynamics (CFD) commercial code to accurately predict the leakage rate for a windback seal was evaluated. The windback seal under consideration has a rectangular cavity and is similar in design to a gas tooth on stator annular labyrinth seal. The main difference is the windback seal has only one tooth, which continuously winds around the shaft like a screw thread. These seals are used in gas compressors to isolate the gas face seal from bearing oil. A purge gas is passed through the seal into the bearing housing. The helical design allows the seal to clear itself of any oil contamination. The objective is to determine if CFD simulations can be used along with a few experimental tests to study windback seals of this design. Comparison of measurement and predictions for a simple rectangular cavity windback seal shows predictions and measurements comparing very well with maximum differences of 5% for leakage rate. The variation of leakage with shaft speed and pressure ratio across the seal is accurately predicted by the CFD simulations.
Load-Responsive Hydrodynamic Bearing for Downhole Drilling Tools
Authors: Kalsi M. S. , Alvarez P. D. , Somogyi D. , Richie Aaron
Published: January 2007

A load-responsive hydrodynamic thrust bearing has been developed that has capabilities to operate under higher load and speed combinations than the current bearing designs used in roller cone drill bits, downhole drilling motors, and other downhole drilling tools. The bearing dynamic surface, which is initially flat, deflects elastically under load to provide an efficient hydrodynamic geometry that generates a lubricant film, with a minimum film thickness that varies from 0.25 to 2.0μm. The bearing operates with friction coefficients typically in the range of 0.003 to 0.005, which are significantly lower than the conventional roller cone bit thrust bearing designs that operate in a boundary/mixed lubrication regime. Lower friction will allow bit seals to run cooler, and higher load/speed capabilities will increase drilling efficiency and extend component life in hard rock formations. Additionally, the new bearing is suitable for applications where tilting pad thrust bearings are used, offering the advantage of being simple, compact, and more economical.
Frequent In Vitro Recombination in Internal Transcribed Spacers 1 and 2 during Genotyping of
Pneumocystis jirovecii
Authors: Beser Jessica , Hagblom Per , Fernandez Victor
Published: January 2007

Pneumocystis jirovecii
is the causative agent of
Pneumocystis
pneumonia (PCP) in immunocompromised persons. Knowledge of the transmission and epidemiology of PCP is still incipient, and investigations on these subjects are based exclusively on applications of molecular typing techniques. The polymorphic internal transcribed spacers ITS1 and ITS2 in the ribosomal DNA operon, which in the
P. jirovecii
genome exist as single-copy DNA, are commonly used as target loci for isolate typing. In the course of genotyping
P. jirovecii
in respiratory specimens from PCP patients by amplification and cloning of a large number of ITS sequences, we found mixed infections (two or more types) in 50% of the samples. In a majority of the specimens with mixed infections, we detected many ITS haplotypes (combinations of ITS1 and ITS2 types) that appeared to be products of recombination between globally common ITS haplotypes present in the same sample. Here we present results of a series of experiments showing that essentially all ITS recombinants are chimeras formed during the genotyping process. Under standard conditions, as many as 37% of the amplified sequences could be hybrid DNA artifacts. We show that by modifying PCR amplification conditions, ITS chimera formation could be largely abolished and the erroneous establishment of artifactual haplotypes avoided. The accurate assessment of genetic diversity is fundamental for a better understanding of the epidemiology and biology of
P. jirovecii
infections.
ATP-Dependent Minor Groove Recognition of TA Base Pairs Is Required for Template Melting by the E1 Initiator Protein
Authors: Schuck Stephen , Stenlund Arne
Published: January 2007

Template melting is an essential step in the initiation of DNA replication, but
the mechanism of template melting is unknown for any replicon. Here we
demonstrate that melting of the bovine papillomavirus type 1 ori is a
sequence-dependent process which relies on specific recognition of TA
base pairs in the minor groove by the E1 initiator. We show that
correct template melting is a prerequisite for the formation of a
stable double hexamer with helicase activity and that ori mutants that
fail to melt correctly are defective for ori unwinding and DNA
replication in vivo. Our results also indicate that melting of the DNA
is achieved by destabilization of the double helix along its length
through multiple interactions with E1, each of which is responsible for
melting of a few base pairs, resulting in the extensive melting that is
required for initiation of DNA
replication.
UNIQUENESS PROBLEM WITH TRUNCATED MULTIPLICITIES OF MEROMORPHIC MAPPINGS IN SEVERAL COMPLEX VARIABLES
Authors: THAI DO DUC , QUANG SI DUC
Published: January 2007

In this article, the uniqueness problem with truncated multiplicities of meromorphic mappings in several complex variables is studied. The recent results of Smiley, Ji, Fujimoto and Fujimoto's questions are deduced as consequences.
8-Oxoguanosine and uracil repair of nuclear and mitochondrial DNA in red and white skeletal muscle of exercise-trained old rats
Authors: Radak Zsolt , Kumagai Shuzo , Nakamoto Hideko , Goto Sataro
Published: January 2007

Oxoguanine DNA glycosylase (OGG1) and uracil DNA glycosylase (UDG) are two of the most important repair enzymes that are involved in the base excision repair processes to eliminate oxidative damage from mammalian DNA, which accumulates with aging. Red and white skeletal muscle fibers have very different antioxidant enzyme activities and resistance to oxidative stress. In this paper, we demonstrate that the activity of OGG1 is significantly higher in the red type of skeletal muscle compared with white fibers from old rats. Exercise training resulted in increased OGG1 activity in the nuclei of red fibers and decreased activity in nuclei of white fibers and in the mitochondria of both red and white fibers. The activities of UDG were similar in both red and white muscle fibers. Exercise training appears to increase the activity of UDG in the nuclei and mitochondria. However, exercise training affects the activity of OGG1 in nuclei and mitochondria differently, suggesting different regulation of the enzymes. In contrast, UDG showed similar activities in nuclei and mitochondrial extracts of exercise-trained animals. These data provide evidence for differential regulation of UDG and OGG1 in maintaining fidelity of DNA in oxidatively stressed cells.
Calibration of Visually Guided Reaching Is Driven by Error-Corrective Learning and Internal Dynamics
Authors: Cheng Sen , Sabes Philip N.
Published: January 2007

The sensorimotor calibration of visually guided reaching changes on a trial-to-trial basis in response to random shifts in the visual feedback of the hand. We show that a simple linear dynamical system is sufficient to model the dynamics of this adaptive process. In this model, an internal variable represents the current state of sensorimotor calibration. Changes in this state are driven by error feedback signals, which consist of the visually perceived reach error, the artificial shift in visual feedback, or both. Subjects correct for ≥20% of the error observed on each movement, despite being unaware of the visual shift. The state of adaptation is also driven by internal dynamics, consisting of a decay back to a baseline state and a “state noise” process. State noise includes any source of variability that directly affects the state of adaptation, such as variability in sensory feedback processing, the computations that drive learning, or the maintenance of the state. This noise is accumulated in the state across trials, creating temporal correlations in the sequence of reach errors. These correlations allow us to distinguish state noise from sensorimotor performance noise, which arises independently on each trial from random fluctuations in the sensorimotor pathway. We show that these two noise sources contribute comparably to the overall magnitude of movement variability. Finally, the dynamics of adaptation measured with random feedback shifts generalizes to the case of constant feedback shifts, allowing for a direct comparison of our results with more traditional blocked-exposure experiments.
Evaluating Information Transfer Between Auditory Cortical Neurons
Authors: Gourévitch Boris , Eggermont Jos J.
Published: January 2007

Transfer entropy, presented as a new tool for investigating neural assemblies, quantifies the fraction of information in a neuron found in the past history of another neuron. The asymmetry of the measure allows feedback evaluations. In particular, this tool has potential applications in investigating windows of temporal integration and stimulus-induced modulation of firing rate. Transfer entropy is also able to eliminate some effects of common history in spike trains and obtains results that are different from cross-correlation. The basic transfer entropy properties are illustrated with simulations. The information transfer through a network of 16 simultaneous multiunit recordings in cat's auditory cortex was examined for a large number of acoustic stimulus types. Application of the transfer entropy to a large database of multiple single-unit activity in cat's primary auditory cortex revealed that most windows of temporal integration found during spontaneous activity range between 2 and 15 ms. The normalized transfer entropy shows similarities and differences with the strength of cross-correlation; these form the basis for revisiting the neural assembly concept.
Clinicopathologic Analysis of Breast Cancers with PIK3CA Mutations in Japanese Women
Authors: Maruyama Naomi , Miyoshi Yasuo , Taguchi Tetsuya , Tamaki Yasuhiro , Monden Morito , Noguchi Shinzaburo
Published: January 2007

Purpose: Somatic mutations of PIK3CA, which encodes the p110α catalytic subunit of phosphatidylinositol 3-kinase, have recently been shown to play an important role in the pathogenesis and progression of human breast cancers. In this study, the frequency of PIK3CA mutations and their relationship with clinicopathologic and biological variables were investigated in Japanese breast cancers.

Experimental Design: Mutational analysis of PIK3CA was done in 188 primary breast cancers of Japanese women. Relationship of these mutations with various clinicopathologic variables [histologic type, tumor size, histologic grade, lymph node status, estrogen receptor (ER)-α and progesterone receptor status, and prognosis], biological variables [phospho-AKT (pAKT) and HER2 expression determined by immunohistochemistry], and p53 mutation status was studied.

Results: Missense mutations of PIK3CA were found in 44 of 158 invasive ductal carcinomas, 4 of 10 invasive lobular carcinomas, 1 of 4 mucinous carcinomas, 2 of 2 squamous carcinomas, and 2 of 2 apocrine carcinomas, but no mutation was found in 12 noninvasive ductal carcinomas. PIK3CA-mutated tumors were found to be more likely to be ER-α positive (P < 0.05) and pAKT positive (P < 0.05). There was no significant association between PIK3CA mutations and p53 mutation status. PIK3CA mutations were significantly (P < 0.05) associated with a favorable prognosis, and multivariate analysis showed that PIK3CA mutation status was a significant (P < 0.05) prognostic factor independent of the other conventional prognostic factors.

Conclusions: The frequency of PIK3CA mutations in Japanese breast cancers is similar to that of Caucasian breast cancers. Association of PIK3CA mutations with positive pAKT and positive ER-α suggests that PIK3CA mutations might exert their effects through activation of the phosphatidylinositol 3-kinase/AKT/ER-α pathway. PIK3CA mutations seem to have a potential to be used as an indicator of favorable prognosis.
Pancreatic islet cell therapy for type I diabetes: understanding the effects of glucose stimulation on islets in order to produce better islets for transplantation
Authors: Ren Jiaqiang , Jin Ping , Wang Ena , Liu Eric , Harlan David M , Li Xin , Stroncek David F
Published: January 2007

While insulin replacement remains the cornerstone treatment for type I diabetes mellitus (T1DM), the transplantation of pancreatic islets of Langerhans has the potential to become an important alternative. And yet, islet transplant therapy is limited by several factors, including far too few donor pancreases. Attempts to expand mature islets or to produce islets from stem cells are far from clinical application. The production and expansion of the insulin-producing cells within the islet (so called β cells), or even creating cells that secrete insulin under appropriate physiological control, has proven difficult. The difficulty is explained, in part, because insulin synthesis and release is complex, unique, and not entirely characterized. Understanding β-cell function at the molecular level will likely facilitate the development of techniques to manufacture β-cells from stem cells. We will review islet transplantation, as well as the mechanisms underlying insulin transcription, translation and glucose stimulated insulin release.