bluuebunny/crossref_metadata_2025 huggingface dataset:
Ets-1: a new player in the pathogenesis of systemic lupus erythematosus?
Authors: Pan H-F , Leng R-X , Tao J-H , Li X-P , Ye D-Q
Published: March 2011

v-ets erythroblastosis virus E26 oncogene homolog 1 (avian) (Ets-1) is a member of the Ets family of transcription factors that share a unique Ets DNA binding domain. They control a wide variety of cellular processes including cell proliferation and differentiation. Recently, two genome-wide association studies in systemic lupus erythematosus (SLE) independently identified genetic variants in Ets-1 associated with SLE. Interestingly, previous studies have found that Ets-1-deficient mice develop lupus-like disease characterized by high titers of IgM and IgG autoantibodies, immune complex-mediated glomerulonephritis, and local activation of complement. In addition, Ets-1 is also involved in many cellular abnormalities that are known to participate in SLE pathogenesis, such as its role in negative regulation of Th17 cell and B cell differentiation. All these findings suggest that Ets-1 may play an important role in the pathogenesis of SLE. This article will focus on current understanding of the role of Ets-1 in the physiological and pathological functions associated with SLE. It is the intention of the article to provide insights which may assist in the development of Ets-1 based approaches for the treatment of SLE.
Topsy Turvy: Functions of Climbing and Mossy Fibers in the Vestibulo-Cerebellum
Authors: Barmack Neal H. , Yakhnitsa Vadim
Published: March 2011

The cerebellum’s role in sensory-motor control and adaptation is undisputed. However, a key hypothesis pertaining to the function of cerebellar circuitry lacks experimental support. It is universally assumed that the discharge of mossy fibers accounts for modulation of Purkinje cell “simple spikes” (SSs). This assumption acts as a prism through which all other functions of cerebellar circuitry are viewed. The vestibulo-cerebellum (nodulus and uvula) receives a large, unilateral, vestibular primary afferent mossy fiber projection. We can test its role in modulating Purkinje cell SSs by recording the modulated activity of both mossy fiber terminals and Purkinje cell SSs evoked by identical natural vestibular stimulation. Sinusoidal rotation about the longitudinal axis (roll) modulates the activity of vestibular primary afferent mossy and climbing fibers as well as Purkinje cell SSs and complex spikes (CSs). Remarkably, vestibular primary afferent mossy fibers discharge 180 degrees out of phase with SSs. This indicates that mossy fibers cannot account for SS modulation unless an inhibitory synapse is interposed between mossy fibers or vestibular climbing fibers and Purkinje cells. The authors review several experiments that address the relative contributions of mossy and climbing fiber afferents to the modulation of SSs. They conclude that climbing fibers, not mossy fibers, are primarily responsible for the modulation of SSs as well as CSs and they propose revised functions for these two afferent systems.
Propagation of Spinal Nociceptive Activity in the Spatial and Temporal Domains
Authors: Jongen Joost L.M. , Holstege Jan C.
Published: March 2011

Nociceptive stimuli are transmitted through thinly myelinated or unmyelinated primary afferent fibers called nociceptors, which terminate mainly in the superficial dorsal horn of the spinal cord. While most nociceptive fibers terminate in the spinal segment of the entrance, (collateral) fibers may ascend and descend several segments upon their entry into the spinal cord, which is reflected in the receptive fields of central nociceptive neurons. In chronic pain states like inflammatory or neuropathic pain, the area of nociceptive activity may expand even further in rostrocaudal and mediolateral directions. Also, within minutes (inflammatory pain) or days (neuropathic pain), an increased sensitivity of peripheral and central nociceptive neurons will develop, which is referred to as sensitization. While anatomical, physiological, and psychophysical techniques have focused on one particular aspect of central sensitization at a time, functional imaging techniques like functional MRI, intrinsic optical imaging, and autofluorescent flavoprotein imaging (AFI) are able to capture both spatial and temporal dimensions of central sensitization simultaneously. AFI and other neuroimaging techniques may clarify fundamental aspects relating to the spread of nociceptive activity within the spinal cord and may thus provide a practical tool to test the efficacy of new analgesic drugs or procedures in animals and ultimately in humans.
Clinical outcomes of a pharmacist-managed anticoagulation service for breast cancer patients
Authors: Jones Kellie L , Barnett Chad , Gauthier Michelle , Boster Bonnie , Espirito Janet L , Michaud Laura B
Published: March 2011

Purpose. Report descriptive outcome measures related to the quality of pharmacist-managed anticoagulation care with warfarin in patients with breast cancer since the formation of the anticoagulation management service (AMS).

Methods. Retrospective review of 145 patients with breast cancer (median age 54 years) receiving warfarin therapy for venous thromboembolism (VTE) managed by the pharmacist-run AMS between 1998 and 2005.

Results. The median time followed by the AMS was 151 days. Fifty three percent ( n = 1651) of total lab draws ( n = 3129) were within the target therapeutic INR range 2–3. Recurrent thrombosis occurred in 4.1% of patients. Minor bleeding occurred in 18.6% of patients and major bleeding occurred in three patients (2.1%, gastrointestinal, intra-abdominal, and subdural hematoma).

Conclusion. To date, this is the largest known published database of cancer patients receiving anticoagulation in a pharmacist-managed anticoagulation service. Recurrent VTE rates, major and minor bleeding rates, and percentage of time spent within the therapeutic range are slightly different in our patient population compared to an oncology population receiving warfarin and a non-oncology population with warfarin managed by AMS. Oral anticoagulation with warfarin is an effective, albeit complicated, treatment for venous thromboembolism in the oncology population. Although low-molecular weight heparin (LMWH) therapy is now the preferred treatment for thrombosis in malignancy, warfarin is still relevant in patients who are unable to receive treatment with LMWH. This report provides valuable information supporting coordinated anticoagulation therapy with a pharmacist-managed service in a breast cancer-specific population, and contributes to the growing data supporting the challenging nature of maintaining warfarin anticoagulation in patients with cancer.
Differentiation syndrome in patients with acute promyelocytic leukemia
Authors: Rogers Jane E , Yang Daisy
Published: March 2011

Objective. To review the pathophysiology, risk factors, and management of differentiation syndrome (DS) associated with acute promyelocytic leukemia (APL).

Data source. A MEDLINE search was conducted (1977–November 2010) using the terms APL, DS, all- trans retinoic acid (ATRA), retinoic acid syndrome, and arsenic trioxide (ATO).

Methods of study selection. English articles identified from the MEDLINE search were evaluated.

Data extraction and synthesis. With ATRA, ATO, and chemotherapy, a complete remission is achievable for most newly diagnosed APL patients. However, treatment with the differentiating agents, ATRA and ATO, can lead to the development of DS. Signs and symptoms of this syndrome include hyperleukocytosis and cardiorespiratory compromise. Severe complications can develop, if DS is not recognized early and treated promptly with corticosteroids. In addition, patients with a high white blood cell count at diagnosis may benefit from prophylactic steroids.

Conclusions. Early recognition and prompt initiation of corticosteroids are key factors in the management of DS. Healthcare professionals need to be familiar with this complication which can arise from differentiation agents.
Toward a Conceptual Integration of Cultural Responsiveness and Schoolwide Positive Behavior Support
Authors: Vincent Claudia G. , Randall Carla , Cartledge Gwendolyn , Tobin Tary J. , Swain-Bradway Jessica
Published: March 2011

Within the context of widely documented racially disproportionate discipline outcomes, we describe schoolwide positive behavior support (SWPBS) as one approach that might provide a useful framework for culturally responsive behavior support delivery. We conceptualize cultural and linguistic diversity as the result of a divergence between individual students’ and entire schools’ cultural identities and identify culturally responsive educational practices that might facilitate greater continuity between students from culturally and linguistically diverse backgrounds and school environments. Based on practical recommendations derived from the literature, we propose an expansion of the key features of SWPBS implementation (practices, data, systems, and outcomes) to facilitate culturally responsive behavior support delivery. We propose (a) systemically promoting staff members’ cultural knowledge and self-awareness, (b) commitment to culturally relevant and validating student support practices, and (c) culturally valid decision making to enhance culturally equitable student outcomes. We provide recommendations for future research and present the efforts of one school district to blend SWPBS implementation with training in cultural responsiveness.
Relationships Among Stress Measures, Risk Factors, and Inflammatory Biomarkers in Law Enforcement Officers
Authors: Ramey Sandra L. , Downing Nancy R. , Franke Warren D. , Perkhounkova Yelena , Alasagheirin Mohammad H.
Published: March 2011

Law enforcement officers suffer higher morbidity and mortality rates from all causes than the general population. Cardiovascular disease (CVD) accounts for a significant portion of the excess illness, with a reported prevalence as high as 1.7 times that of the general population. To determine which occupational hazards cause this increased risk and morbidity, it is imperative to study law enforcement officers before they retire. The long-range goal of our research is to reduce the incidence of CVD-related illness and death among aging law enforcement officers. The purpose of the present study was to measure pro- and anti-atherogenic inflammatory markers in blood samples from law enforcement officers ( n = 71) and determine what types of occupation-related stress correlate with differences in these markers. For each outcome variable of interest, we developed separate regression models. Two groups of potential predictors were examined for inclusion in the models. Selected measures of stress were examined for inclusion in the models, in addition to general covariates, such as gender, ethnicity, years in law enforcement, and body mass index. Our results revealed statistically significant relationships between several physiologic variables and measures of stress.
Relationship of Weight Status and Cardiometabolic Outcomes for Adolescents in the TEAMS Study
Authors: Bindler Ruth C. , Daratha Kenneth B.
Published: March 2011

The increase in the prevalence of obesity among youth is alarming. Relationships exist between excess weight and adverse cardiometabolic markers. The aims of this study among adolescents in the Teen Eating and Activity Mentoring in Schools (TEAMS) project were to describe selected demographic characteristics, anthropometric measurements, and laboratory values of middle school students; contrast differences in rates of cardiometabolic markers for participants with body mass index (BMI) ≥ 95th percentile and <95th percentile; examine rates of exceeding cardiometabolic cutoffs by weight status; and predict the odds ratio for one or more adverse cardiometabolic outcomes when BMI ≥95th percentile. Students ( N = 151) were significantly more likely to exceed cut-off points for high-density lipoprotein cholesterol (HDL-C) and blood pressure (BP) when BMI was ≥95th percentile. Students whose BMI was ≥the 95th percentile were nearly five times as likely to have the deleterious cardiometabolic outcomes of low HDL-C, high triglycerides, elevated homeostasis model assessment of insulin resistance (HOMA-IR), or elevated systolic BP than those whose BMI was <the 95th percentile. Nurses and other clinicians should view BMI ≥95th percentile as an indicator of other risk factors that merits additional assessments and interventions to improve health.
Lexical processing in individuals with high-functioning autism and Asperger’s disorder
Authors: Speirs Samantha , Yelland Greg , Rinehart Nicole , Tonge Bruce
Published: March 2011

The presence or absence of clinically delayed language development prior to 3 years of age is a key, but contentious, clinical feature distinguishing autism from Asperger’s disorder. The aim of this study was to examine language processing in children with high-functioning autism (HFA) and Asperger’s disorder (AD) using a task which taps lexical processing, a core language ability. Eleven individuals with HFA, 11 with AD and 11 typically developing (TD) individuals completed a masked priming task, a psycholinguistic paradigm that directly examines lexical processes. Within-group analyses revealed the AD and TD groups had intact lexical processing systems and orthographic processing of the written word. The outcomes for the HFA group were ambiguous, suggesting that their lexical processing system is either delayed or is structurally different. This suggests that fundamental differences in lexical processing exist between HFA and AD and remain evident later in development.
Language performance in siblings of nonverbal children with autism
Authors: Levy Yonata , Bar-Yuda Chanit
Published: March 2011

The study focuses on language and cognitive abilities of siblings of the linguistically most affected children with autism (i.e. siblings of nonverbal children — SIBS-ANV). Twenty-eight SIBS-ANV (17 boys), ages 4—9 years, took part in the study. All children attended regular schools, and none had received a diagnosis of autism. Controls were 27 typically developing children (SIBS-TD; 16 boys) matched to the SIBS-ANV on age, family background, socioeconomic status and type of school they attended. Significant IQ differences, as well as language differences as measured on the Clinical Evaluation of Language Fundamentals (CELF), emerged between SIBS-ANV and SIBS-TD. However, differences in the language scores mostly disappeared when PIQ and FSIQ were controlled for. Furthermore, grammatical analysis of spontaneous speech samples produced in the course of testing did not reveal any significant differences between the groups. These results add to recent work suggesting that language deficits may not be part of the Broad Autism Phenotype (BAP). It further suggests that the cognitive deficit characteristic of nonverbal people with autism may be familial.
Quantitative analysis of the shape of the corpus callosum in patients with autism and comparison individuals
Authors: Casanova Manuel F. , El-Baz Ayman , Elnakib Ahmed , Switala Andrew E. , Williams Emily L. , Williams Diane L. , Minshew Nancy J. , Conturo Thomas E.
Published: March 2011

Multiple studies suggest that the corpus callosum in patients with autism is reduced in size. This study attempts to elucidate the nature of this morphometric abnormality by analyzing the shape of this structure in 17 high-functioning patients with autism and an equal number of comparison participants matched for age, sex, IQ, and handedness. The corpus callosum was segmented from T1 weighted images acquired with a Siemens 1.5 T scanner. Transformed coordinates of the curvilinear axis were aggregated into a parametric map and compared across series to derive regions of statistical significance. Our results indicate that a reduction in size of the corpus callosum occurs over all of its subdivisions (genu, body, splenium) in patients with autism. Since the commissural fibers that traverse the different anatomical compartments of the corpus callosum originate in disparate brain regions our results suggest the presence of widely distributed cortical abnormalities in people with autism.
The Memory Club: Providing Support to Persons with Early-Stage Dementia and Their Care Partners
Authors: Gaugler Joseph E. , Gallagher-Winker Karen , Kehrberg Kathy , Lunde Angela M. , Marsolek Connie M. , Ringham Kathryn , Thompson Gerise , Barclay Michelle
Published: March 2011

There is a growing emphasis on delivering services for persons with early-stage dementia (ie, ‘‘persons with memory loss,’’ or PWMLs) and their family members (care partners). The goal of this evaluation was to determine whether participation in the Memory Club, a 10- to 13-session joint support group, would result in decreased distress, enhanced preparation for care, and improved feelings of confidence managing the challenges of early-stage dementia. The single group, pre-/post-test evaluation included 63 PWMLs and 61 care partners who participated in three Memory Club sites in Minnesota. Paired T-test results found that care partners reported significant (P < .05) increases in preparation activities, feelings of preparation, and confidence in managing memory loss. The results suggest that the Memory Club can fill an important gap in early-stage dementia care by offering care partners the opportunity to plan, prepare, and increase coping skills in the face of early dementia progression.
Impact of Acute Hepatitis A Virus (HAV) Infection on HIV Viral Load in HIV-Infected Patients and Influence of HIV Infection on Acute HAV Infection
Authors: Gallego M. , Robles M. , Palacios R. , Ruiz J. , Nuño E. , Márquez M. , Andrade R. , Santos J.
Published: March 2011

Purpose: To assess the effect of hepatitis A virus (HAV) infection on HIV viral load (VL) and the influence of HIV on the clinical expression of HAV infection. Methods: Single-center study of 23 HIV-positive patients and 41 HIV-negative patients diagnosed with acute HAV infection during 2008-2009. The impact of HAV on HIV VL was defined as an increase of >0.5 log10 during the event, or a detectable VL for those previously suppressed patients. Results: The impact of acute HAV on VL was observed in 37.5% patients. HIV-negative patients were younger (27 vs 34 years, P < .0001), and serum transaminases levels normalized earlier than in the HIV-positive patients (121 vs 178 days, P < .05). Conclusions: Acute HAV infection may have an impact on HIV VL. The interactions between the 2 viruses may not only prolong the HAV viremia, with a potential increase in the transmission of infection, but the impact on HIV may increase the risk of HIV transmission. Studies with higher sample size are needed to confirm our results.
Virologic and Immunologic Outcomes of the Second-Line Regimens of Antiretroviral Therapy Among HIV-Infected Patients in Thailand
Authors: May Myat Win  , Maek-a-nantawat Wirach , Phonrat Benjaluck , Kiertiburanakul Sasisopin , Sungkanuparph Somnuek
Published: March 2011

Goal of the second-line therapy among HIV-1-infected patients is to re-establish virological suppression, although treatment options in resource-limited settings are limited. An observational cohort of patients with first-line antiretroviral therapy (ART) failure was conducted in a university hospital in Thailand. Of 95 patients, mean age 39 years, 65% were male. Median CD4 and HIV-1 RNA at second-line ART initiation were 158 cells/mm3 and 4.1 copies/mL, respectively. Boosted protease inhibitor plus 2 nucleoside reverse transcriptase inhibitors (NRTIs), indicated by genotype results, was commonly used as second-line regimen. At 6, 12, 24, and 36 months of second-line ART, 67%, 62%, 84%, and 90% of patients achieved HIV-1 RNA <50 copies/mL; median CD4 were 258, 366, 444, and 522 cells/mm 3, respectively. Good adherence, high baseline CD4, and early Centers for Centers for Disease Control and Prevention (CDC) staging were associated with virologic success (P < .05). Second-line ART based on the results of genotype testing yields the good virologic and immunologic outcomes in a resource-limited setting, and scaling-up of second-line ART is indicated.
Creating an Age of Depression
Authors: Horwitz Allan V.
Published: March 2011

One type of study in the sociology of mental health examines how social and cultural factors influence the creation and consequences of psychiatric diagnoses. Most studies of this kind focus on how diagnoses emerge from struggles among advocacy organizations, economic and political interest groups, and professionals. In contrast, intraprofessional dynamics rather than external pressures generated perhaps the major transformation resulting from the Diagnostic and Statistical Manual of Mental Disorders, third edition, diagnostic revolution in 1980—the rise of Major Depressive Disorder as the central diagnosis of the psychiatric profession. Other interests, including the drug industry and advocacy groups, capitalized on the features of this diagnosis only after its promulgation. The social construction of depression illustrates how social and cultural processes can have fundamental influences over diagnostic processes even in the absence of struggles among forces external to the mental health professions. It also indicates how diagnoses themselves can have major professional, economic, political, and social consequences.
Medicalization, Direct-to-Consumer Advertising, and Mental Illness Stigma
Authors: Payton Andrew R. , Thoits Peggy A.
Published: March 2011

In late 1997, the U.S. Food and Drug Administration (FDA) issued new guidelines that allowed pharmaceutical companies to air prescription drug ads on television. These guidelines have expanded the pharmaceutical industry’s role as one of the major “engines” of medicalization. One arena in which there has been a dramatic increase in direct-to-consumer advertising (DTCA) of pharmaceuticals is the marketing of psychotherapeutic drugs, especially for depression. Because medicalization is thought to reduce blame and stigma attached to deviant conditions such as mental illness, the rise of DTCA for depression drugs may be altering public conceptions of mental illness in general and of depression specifically. The authors examine this possibility by comparing changes in attitudes toward persons with schizophrenia (for which no drugs have been advertised on television) and major depression (the focus of considerable advertising) from 1996 to 2006, 1 year before and nearly 10 years after the FDA’s new guidelines. The authors use the Mental Health Modules in the General Social Survey in these years. Contrary to expectations, despite the surge in DTCA they find no changes in stigmatized views of persons with schizophrenia or depression. However, the public’s beliefs about appropriate treatments for mental illness (regardless of disorder type) shifted further toward medical interventions.
Hawaii Data: Women's Marital Surname Change by Bride's Age and Jurisdiction of Residence
Authors: MacEacheron Melanie D
Published: March 2011

AbstractRetaining or hyphenating one's premarital surname among brides marrying in Hawaii in 2006 was significantly correlated with average income of women and the average income of men in the bride's state of residence. Only the average women's income in the bride's state of residence, however, was a marginally significant predictor, where both that of men and women were used as regression predictors of retention or hyphenation. Older brides were more likely to hyphenate or retain their premarital surnames upon marriage in Hawaii in 2006. Raw data concerning 28,680 marriages celebrated in 2006 in the state of Hawaii were provided by Brian Horiuchi, of the Hawaii State Department of Health.
The Sociocultural Significance of Niitsitapi Personal Names: An Ethnographic Analysis
Authors: Lombard Carol G
Published: March 2011

AbstractThis article presents a discussion of ethnographic research carried out by the author on the nature and functions of Niitsitapi "Blackfoot" personal names. The research indicates that these names are an integral and inseparable part of traditional Niitsitapi socioculture, and perform a number of important sociocultural functions. Most notably, Niitsitapi personal names seem to function as vehicles of oral knowledge transfer through which Niitsitapi cultural norms, beliefs, and values are conveyed. The traditional Niitsitapi approach to personal naming also appears to be strongly underpinned by certain Niitsitapi cultural concepts, which are reinforced within Niitsitapi communities through continued adherence to traditional personal naming practices. Niitsitapi personal names thus appear to play a crucial role in maintaining Niitsitapi culture and perceptions of cultural identity.
A Note on the Names of Mathematical Problems and Puzzles
Authors: Nuessel Frank
Published: March 2011

AbstractThis note examines selectively the names given to mathematical problems, puzzles, conjectures, and equations. It shows that many derive from the surnames of their inventors. Others, however, are associated with narratives that describe some salient aspect of the problem or puzzle.
High strain rate superplasticity of TiNP/2014Al composite
Authors: Hu H. E. , Zhen L. , Imai T.
Published: March 2011

Superplasticity of the TiNp/2014AI composite prepared by powder metallurgy method was investigated by tensile tests conducted at different temperatures (773, 798, 818 and 838 K) with different strain rates range from 1·7×10° to 1·7×10−3s−1. Results show that a maximum elongation of 351 is achieved at 818 K and 3·3·10−1s−1. At different deformation temperatures, the curves of m value can be divided into two stages with the variation of strain rate and the critical strain rate is 10−1 s−1. Superplastic deformation activation energy in the TiNp/2014AI composite is 417 kJ mol−1, which is related to liquid phase formation at triple points of grain boundaries and interfaces between the matrix and the reinforcement. Superplastic deformation mechanism of the TiNp/2014AI composite is grain boundary sliding accommodate mechanism when the strain rate is lower than 10−1 s−1, and transfers to grain boundary sliding accommodation mechanism plus liquid phase helper accommodation mechanism when the strain rate is higher than 10−1 s−1
Preparation of polyurethane/poly(vinylidene fluoride) blend hollow fibre membrane using melt spinning and stretching
Authors: Hu X. Y. , Chen Y. B. , Liang H. X. , Xiao C. F.
Published: March 2011

Melt spinning and stretching process was used to prepare polyurethane/poly(vinylidene difluoride) (PU/PVDF) blend hollow fibre membrane in this study. Rheological properties of melts of PU, PVDF and their blends were studied by observing their melting viscosity changing with shear rate and temperature. Morphologies of PU/PVDF blend hollow fibre membranes with different mass ratios were also observed by SEM and results showed that PU/PVDF mass ratio of 3:1 was relatively better condition for membrane preparation. The forming mechanism of the interfacial microvoids in PU/PVDF blends was also investigated and PU/PVDF blend hollow fibre membrane with water flux of ∼2174 L m−2 h−1 was finally obtained under the pressure of 0·1 MPa.
The Impact of the Global Financial Crisis on the City of London: Towards the End of Hegemony?
Authors: Talani Leila Simona
Published: March 2011

This paper seeks to understand whether the global financial crisis — and the subsequent, alleged, crisis of the City of London — is likely to modify the relationship between the industrial and the financial components of the British capitalist elite and put an end to British ‘exceptionalism’. I argue that the crisis mostly impacted on the labour force of the British and global financial sector and produced a restructuring that consolidated and enhanced the political economy relevance of the City of London. By no means did the crisis resut in a decrease of the hegemonic power of the City of London. Instead, it confirmed its capacity to influence the decisionmaking process of the British government in favour of its preferences.
Finance Unravelled: A Historical Materialist Analysis of EU Public Policy
Authors: MaCartney Huw
Published: March 2011

The 2007–09 financial crisis has prompted critical self-reflection, not least because of the socioeconomic costs to more susceptible social groups. This paper targets public policy accounts of EU integration for their agent-centred, pluralist analysis, which systematically failed to address latent asymmetries and inequalities. For this reason, these accounts are largely incapable of either explaining the crisis except in contingent terms or of suggesting fruitful political responses. Instead I outline a historical materialist apparatus to contextualize the financial crisis within the longer-term rise of financialized capitalism in Europe, its key agents and dominant world-views. In turn, I employ this apparatus to examine post-2000 EU financial integration before suggesting certain key lessons for a post-crisis agenda.
Neutron Strain measurement
Authors: Krawitz A. D.
Published: March 2011

The use of neutrons has extended the technique of diffraction strain measurement from an essentially two-dimensional, near-surface tool using X-rays to a true three-dimensional method. The depth scale has gone from micrometres to millimetres. This initially gave rise to subsurface measurements of type I residual macrostresses in weldments and type II residual microstresses in anisotropic and multiphase metals, and composites. Soon the possibilities of in situ applied stress measurements became apparent and today they represent a significant portion of the work being carried out. This perspective focuses on the current state of the art, the prospects and developments necessary for further progress. The transition from two- to three-dimensions raised the issues of stress free reference values, methodology for general tensor measurements, beam optics and experimental design. Workers invested great effort in resolving these issues. In addition, the development of pulsed source instruments has enabled in situ measurements of slip, fatigue, load partitioning, twinning, high T stress-strain response, thermal cycling and the shape memory effect. Most recently, the SNS instrument, VULCAN, has introduced torsion and continuous recording of data which can later be binned in the shortest statistically significant time intervals.
CX3CR1 expression defines 2 KLRG1+ mouse NK-cell subsets with distinct functional properties and positioning in the bone marrow
Authors: Sciumè Giuseppe , De Angelis Giulia , Benigni Giorgia , Ponzetta Andrea , Morrone Stefania , Santoni Angela , Bernardini Giovanni
Published: March 2011

During development in the bone marrow (BM), NK-cell positioning within specific niches can be influenced by expression of chemokine or adhesion receptors. We previously demonstrated that the maintenance in the BM of selected NK-cell subsets is regulated by the CXCR4/CXCL12 axis. In the present study, we showed that CX3CR1 is prevalently expressed on KLRG1+ NK cells, a subset considered terminally differentiated. Two KLRG1+ NK-cell populations endowed with distinct homing and functional features were defined according to CX3CR1 expression. In the BM, KLRG1+/CX3CR1− NK cells were mainly positioned into parenchyma, while KLRG1+/CX3CR1+ NK cells exhibited reduced CXCR4 expression and were preferentially localized in the sinusoids. We also showed that α4 integrin plays a pivotal role in the maintenance of NK cells in the BM sinusoids and that α4 neutralization leads to strong reduction of BM KLRG1+/CX3CR1+ NK cells. Moreover, we found that KLRG1+/CX3CR1+ cells originate from KLRG1+/CX3CR1− NK-cell population and display impaired capability to produce IFN-γ and to lyse YAC-1 target cells on cytokine stimulation. Altogether, our findings show that CX3CR1 represents a marker of a KLRG1+ NK-cell population with unique properties that can irreversibly differentiate from the KLRG1+/CX3CR1− NK cells during steady state conditions.
Evidence of canonical somatic hypermutation in hairy cell leukemia
Authors: Arons Evgeny , Roth Laura , Sapolsky Jeffrey , Suntum Tara , Stetler-Stevenson Maryalice , Kreitman Robert J.
Published: March 2011

To compare hairy cell leukemia (HCL) with chronic lymphocytic leukemia (CLL) and normal B cells with respect to their B-cell receptors, somatic hypermutation (SHM) features in HCL were examined in a series of 130 immunoglobulin gene heavy chain rearrangements, including 102 from 100 classic (HCLc) and 28 from 26 variant (HCLv) patients. The frequency of unmutated rearrangements in HCLc was much lower than that in HCLv (17% vs 54%, P < .001) or historically in CLL (17% vs 46%, P < .001), but HCLv and CLL were similar (P = .45). As previously reported for CLL, evidence of canonical SHM was observed in HCLc rearrangements, including: (1) a higher ratio of replacement to silent mutations in the complementarity determining regions than in the framework regions (2.83 vs 1.41, P < .001), (2) higher transition to transversion ratio than would be expected if mutations were random (1.49 vs 0.5, P < .001), and (3) higher than expected concentration of mutations within RGYW hot spots (13.92% vs 3.33%, P < .001). HCLv met these 3 criteria of canonical SHM to a lesser extent. These data suggest that, whereas HCLc cells may recognize antigen-like CLL and normal B cells before malignant transformation, HCLv cells from some patients may originate differently, possibly without undergoing antigen recognition.
Localization of Helicobacter spp. in the fundic mucosa of laboratory Beagle dogs: an ultrastructural study
Authors: Lanzoni Anna , Faustinelli Ivo , Cristofori Patrizia , Luini Mario , Simpson Kenneth W , Scanziani Eugenio , Recordati Camilla
Published: March 2011

In dogsHelicobacterspp. are found in all gastric regions usually localized in the surface mucus, gastric glands and parietal cells. The aim of this study was to detail the distribution ofHelicobacterspp. in the fundic mucosa of asymptomatic Beagle dogs and their intracellular localization within parietal cells, in order to evaluate species-specific pathogenetic effects on gastric cells. The presence ofHelicobacterspp. was investigated by immunohistochemistry, TEM, and PCR in the fundic mucosa of six Beagle dogs.Helicobacterspp. were found in all dogs examined, andH. bizzozeroniiandH. feliswere identified by PCR and confirmed by TEM. In the lumen of the fundic glands, co-localization was common.H. bizzozeroniiwas present in larger numbers thanH. felisin both intraluminal and intraparietal localization. The amounts ofH. bizzozeroniiwere similar in superficial and basal portions of the glands.H. feliswas predominantly localized in the superficial portions of gastric glands but almost absent from the base. Within parietal cells, mostHelicobacterorganisms were intracanalicular, but intact and degenerateHelicobacterorganisms were also visualized free in the cytoplasm or in secondary lysosomes. No specific degenerative lesions were found in infected parietal cells.Helicobacterorganisms were also observed within macrophages in the lamina propria. In conclusion, there is a differential distribution ofH. bizzozeroniiandH. felisin the fundic mucosa of Beagle dogs, and their intracellular localization in parietal cells and macrophages suggests novel pathogenic scenarios for the development of immune response and maintenance of chronic gastritis in dogs.
A Computational Framework for Proteome-Wide Pursuit and Prediction of Metalloproteins using ICP-MS and MS/MS Data
Authors: Lancaster W Andrew , Praissman Jeremy L , Poole Farris L , Cvetkovic Aleksandar , Menon Angeli Lal , Scott Joseph W , Jenney Francis E , Thorgersen Michael P , Kalisiak Ewa , Apon Junefredo V , Trauger Sunia A , Siuzdak Gary , Tainer John A , W Adams Michael W
Published: March 2011

Background

Metal-containing proteins comprise a diverse and sizable category within the proteomes of organisms, ranging from proteins that use metals to catalyze reactions to proteins in which metals play key structural roles. Unfortunately, reliably predicting that a protein will contain a specific metal from its amino acid sequence is not currently possible. We recently developed a generally-applicable experimental technique for finding metalloproteins on a genome-wide scale. Applying this metal-directed protein purification approach (ICP-MS and MS/MS based) to the prototypical microbe Pyrococcus furiosus conclusively demonstrated the extent and diversity of the uncharacterized portion of microbial metalloproteomes since a majority of the observed metal peaks could not be assigned to known or predicted metalloproteins. However, even using this technique, it is not technically feasible to purify to homogeneity all metalloproteins in an organism. In order to address these limitations and complement the metal-directed protein purification, we developed a computational infrastructure and statistical methodology to aid in the pursuit and identification of novel metalloproteins.

Results

We demonstrate that our methodology enables predictions of metal-protein interactions using an experimental data set derived from a chromatography fractionation experiment in which 870 proteins and 10 metals were measured over 2,589 fractions. For each of the 10 metals, cobalt, iron, manganese, molybdenum, nickel, lead, tungsten, uranium, vanadium, and zinc, clusters of proteins frequently occurring in metal peaks (of a specific metal) within the fractionation space were defined. This resulted in predictions that there are from 5 undiscovered vanadium- to 13 undiscovered cobalt-containing proteins in Pyrococcus furiosus. Molybdenum and nickel were chosen for additional assessment producing lists of genes predicted to encode metalloproteins or metalloprotein subunits, 22 for nickel including seven from known nickel-proteins, and 20 for molybdenum including two from known molybdo-proteins. The uncharacterized proteins are prime candidates for metal-based purification or recombinant approaches to validate these predictions.

Conclusions

We conclude that the largely uncharacterized extent of native metalloproteomes can be revealed through analysis of the co-occurrence of metals and proteins across a fractionation space. This can significantly impact our understanding of metallobiochemistry, disease mechanisms, and metal toxicity, with implications for bioremediation, medicine and other fields.
Identification of surface proteins in Enterococcus faecalis V583
Authors: Bøhle Liv Anette , Riaz Tahira , Egge-Jacobsen Wolfgang , Skaugen Morten , Busk Øyvind L , Eijsink Vincent GH , Mathiesen Geir
Published: March 2011

Background

Surface proteins are a key to a deeper understanding of the behaviour of Gram-positive bacteria interacting with the human gastro-intestinal tract. Such proteins contribute to cell wall synthesis and maintenance and are important for interactions between the bacterial cell and the human host. Since they are exposed and may play roles in pathogenicity, surface proteins are interesting targets for drug design.

Results

Using methods based on proteolytic "shaving" of bacterial cells and subsequent mass spectrometry-based protein identification, we have identified surface-located proteins in Enterococcus faecalis V583. In total 69 unique proteins were identified, few of which have been identified and characterized previously. 33 of these proteins are predicted to be cytoplasmic, whereas the other 36 are predicted to have surface locations (31) or to be secreted (5). Lipid-anchored proteins were the most dominant among the identified surface proteins. The seemingly most abundant surface proteins included a membrane protein with a potentially shedded extracellular sulfatase domain that could act on the sulfate groups in mucin and a lipid-anchored fumarate reductase that could contribute to generation of reactive oxygen species.

Conclusions

The present proteome analysis gives an experimental impression of the protein landscape on the cell surface of the pathogenic bacterium E. faecalis. The 36 identified secreted (5) and surface (31) proteins included several proteins involved in cell wall synthesis, pheromone-regulated processes, and transport of solutes, as well as proteins with unknown function. These proteins stand out as interesting targets for further investigation of the interaction between E. faecalis and its environment.
Subsequent chemotherapy reverses acquired tyrosine kinase inhibitor resistance and restores response to tyrosine kinase inhibitor in advanced non-small-cell lung cancer
Authors: Guo Renhua , Chen Xiaofen , Wang Tongshan , Zhang Zhiyuan , Sun Jin , Shu Yongqian
Published: March 2011

Background

Patients with advanced or metastatic non-small cell lung cancer (NSCLC) can develop acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib. Here, we report the successful treatment with alternating chemotherapy and TKIs of two cases of advanced NSCLC who developed resistance to TKI.

Case presentation

Two patients with advanced or metastatic NSCLC were treated with palliative chemotherapy followed by erlotinib/gefitinib. When TKI therapy failed, two cycles of chemotherapy were provided, which were followed by re-challenge with erlotinib or gefitinib.

Conclusion

NSCLC patients with acquired TKI resistance should be managed aggressively whenever possible. Subsequent chemotherapy and target treatment is one of the reasonable choices for those with an initial dramatic clinical response with erlotinib/gefitinib treatment. Further studies are warranted to substantiate the association of erlotinib /gefitinib treatment with the efficacy of NSCLC patients with acquired TKI failure.
Radiographs and low field MRI (0.2T) as predictors of efficacy in a weight loss trial in obese women with knee osteoarthritis
Authors: Gudbergsen Henrik , Boesen Mikael , Christensen Robin , Astrup Arne , Bliddal Henning
Published: March 2011

Background

To study the predictive value of baseline radiographs and low-field (0.2T) MRI scans for the symptomatic outcome of clinically significant weight loss in obese patients with knee osteoarthritis.

Methods

In this study we hypothesize that imaging variables assessed with radiographs and MRI scans pre-treatment can predict the symptomatic changes following a recommended clinically significant weight reduction Patients were recruited from the Department of Rheumatology, Frederiksberg Hospital, Denmark. Eligibility criteria were: age >18 years; primary osteoarthritis according to ACR; BMI > 28 kg/m2; motivation for weight loss. Subjects were randomly assigned to either intervention by low-energy diet (LED) for 8 weeks followed by another 24 weeks of dietary instruction or control-group. MRI scans and radiographs were scored for structural changes and these parameters were examined as independent predictors of changes in osteoarthritis symptoms after 32 weeks. The outcome assessor and statistician were blinded to group allocation.

Results

No significant correlations were found between imaging variables and changes in Western Ontario and McMaster Universities Index of Osteoarthritis (Spearman's test, r < 0.33 and P > 0.07).

Only the LED group achieved a weight loss, with a mean difference of 16.3 kg (95%CI: 13.4-19.2;P < 0.0001) compared to the control group. The total WOMAC index showed a significant difference favouring LED, with a group mean difference of - 321.3 mm (95%CI: -577.5 to -65.1 mm; P = 0.01). No significant adverse events were reported.

Conclusion

Stage of joint destruction, assessed on either radiographs or low-field MRI (0.2T), does not preclude a symptoms relief following a clinically relevant weight loss in elderly obese female patients with knee osteoarthritis.
Measurement of diffusion in articular cartilage using fluorescence correlation spectroscopy
Authors: Lee Jeong Ik , Sato Masato , Ushida Kiminori , Mochida Joji
Published: March 2011

Background

Fluorescence correlation spectroscopy (FCS) provides information about translational diffusion of fluorescent molecules in tiny detection volumes at the single-molecule level. In normal states, cartilage tissue lacks vascularity, so chondrocyte metabolism depends on diffusion for molecular exchanges. The abundant extracellular matrix (ECM) of cartilage is maintained by a limited number of chondrocytes. ECM plays an important role in the regulation of chondrocyte functions. In this study, FCS was used to measure diffusion behaviors of albumin, the major protein of the intra-articular space, using normal and degenerated cartilage. Preliminary investigation of fluorescence dyes including Alexa 488, Rhodamine 6G and Rhodamine 123 was conducted to evaluate their properties in cartilage.

Results

The results indicate that the diffusion behaviors of fluorescently lableded albumin can be observed using FCS in both normal and chemically degenerated cartilage.

Conclusions

This work demonstrates the capability of FCS for direct measurement of diffusion in cartilaginous ECM. When the diffusion characteristics of fluorescent probes in ECM are clarified using FCS evaluation, FCS will be applicable as a method for early diagnosis of osteoarthritis, which is accompanied by increased abnormalities of ECM and also as tool for evaluating bio-engineered artificial cartilage for autologous chondrocyte implantation.
Oxygen transfer rate during the production of alginate by Azotobacter vinelandii under oxygen-limited and non oxygen-limited conditions
Authors: Lozano Esteban , Galindo Enrique , Peña Carlos F
Published: March 2011

Background

The oxygen transfer rate (OTR) and dissolved oxygen tension (DOT) play an important role in determining alginate production and its composition; however, no systematic study has been reported about the independent influence of the OTR and DOT. In this paper, we report a study about alginate production and the evolution of the molecular mass of the polymer produced by a wild-type A. vinelandii strain ATCC 9046, in terms of the maximum oxygen transfer rate (OTRmax) in cultures where the dissolved oxygen tension (DOT) was kept constant.

Results

The results revealed that in the two dissolved oxygen conditions evaluated, strictly controlled by gas blending at 0.5 and 5% DOT, an increase in the agitation rate (from 300 to 700 rpm) caused a significant increase in the OTRmax (from 17 to 100 mmol L-1 h-1 for DOT of 5% and from 6 to 70 mmol L-1 h-1 for DOT of 0.5%). This increase in the OTRmax improved alginate production, as well as the specific alginate production rate (SAPR), reaching a maximal alginate concentration of 3.1 g L-1 and a SAPR of 0.031 g alg g biom
-1 h-1 in the cultures at OTRmax of 100 mmol L-1 h-1. In contrast, the mean molecular mass (MMM) of the alginate isolated from cultures developed under non-oxygen limited conditions increased by decreasing the OTRmax, reaching a maximal of 550 kDa at an OTRmax of 17 mmol L-1 h-1 . However, in the cultures developed under oxygen limitation (0.5% DOT), the MMM of the polymer was practically the same (around 200 kDa) at 300 and 700 rpm, and this remained constant throughout the cultivation.

Conclusions

Overall, our results showed that under oxygen-limited and non oxygen-limited conditions, alginate production and its molecular mass are linked to the OTRmax, independently of the DOT of the culture.