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Major Limitation (major + limitation)

Distribution by Scientific Domains
Medical Sciences43%
Life Sciences29%
Chemistry6%
Engineering5%
Earth and Environmental Science5%
Business, Economics, Finance and Accounting3%
3 Other Domains9%
Distribution within Medical Sciences
Cardiovascular Disease11%
Gastroenterology & Hepatology6%
16 Other Subdomains60%

Selected Abstracts

Effects of Interactions of Moisture Regime and Nutrient Addition on Nodulation and Carbon Partitioning in Two Cultivars of Bean (Phaseolus vulgaris L.)

JOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 4 2001
T. Boutraa
Major limitations of bean (Phaseolus vulgaris L.) production in arid and semiarid regions are lack of moisture and low soil fertility. An experiment was conducted to determine the effects of soil moisture and N : P : K (20 : 10 : 10) fertilizer on root and shoot growth of two cultivars of bean: cv. Carioca, an indeterminate Brazilian landrace, and cv. Prince, a determinate cultivar grown in Europe. Carioca appears generally stress-tolerant while Prince is intolerant. Seedlings were grown in pots of non-sterile soil at 30, 60 or 90 % field capacity (FC), and given 0, 0.1 or 1 g (kg soil),1 of compound fertilizer. The soil contained a population of effective Rhizobium. Growth of both cultivars was greatest in the high moisture and high nutrient treatments. Root fractions were highest at low nutrient supply; the effect of water was not significant. Leaf fraction decreased as root fraction increased. Numbers of nodules were highest at high and intermediate moisture when no fertilizer was applied. Numbers were lowest at 30 % FC and at the highest fertilizer rate. Masses of nodules and fractions followed the same pattern. Decreasing water regime reduced the relative growth rate (RGR) of Prince, while Carioca maintained high RGR at unfavourable conditions of water and nutrients. Net assimilation rates (NAR) were unaffected by nutrient addition, and reduced by low moisture regime. Water use efficiencies (WUEs) were reduced by water stress but increased by nutrient deficiency. The water utilization for dry matter production was optimal at 60 % FC. Einflüsse der Interaktionen von Bodendenfeuchte und Düngung auf die Knöllchenbildung und Kohlenstoff verteilung bei zwei Bohnenkultivaren (Phaseolus vulgaris L.) Der begrenzende Hauptfaktor der Bohnenproduktion in ariden und semiariden Regionen sind der Feuchtigkeitsmangel und die Bodenfruchbarkeit. Es wurde ein Experiment durchgeführt, um die Wirkungen des Bodenwassers und von N : P : K (20 : 10 : 10) Dünger auf das Wurzel- und Sproßwachstum an zwei Kultivaren von Bohnen (Phaseolus vulgaris L. cv. Carioca, eine brasilianischen, indeterminierte Landsorte und cv. Prince, eine determinierter in Europa angebauter Kultivar) zu untersuchen. Carioca erscheint grundsätzlich streßtoleranter im Vergleich zu Prince. Die Sämlinge wurden in Gefäßen mit nichtsterilisiertem Boden unter Feldkapazitäten von 30,60 oder 90 % mit 0, 0,1 oder 1 g eines Volldüngers angezogen. Der Boden enthielt eine Population von wirksamem Rhizobium. Das stärkste Wachstum wurde bei beiden Kultivaren unter dem Einfluß des höchsten Feuchtigkeitsgehaltes und der höchsten Düngermenge gefunden. Der Wurzelanteil war bei der geringen Düngermenge am niedrigsten. Der Einfluß der Bodenfeuchtigkeit war nicht signifikant. Der Blattanteil nahm mit zunehmendem Wurzelanteil ab. Die Anzahl der Knötchen war bei hoher und mittlerer Bodenfeuchte und ohne Düngeranwendung am höchsten. Die Anzahl war am geringsten bei 30 % FC und der höchsten Düngermenge. Die Knötchenmasse und ihr Anteil reagierte entsprechend. Abnehmende Bodenfeuchte reduzierte die relative Wachtumsrate (RGR) von Prince, während Carioca einen hohen RGR auch bei ungünstigen Bedingungen bezüglich Wasser und Düngung behielt. Die Nettoassimilationsraten wurden durch die Düngung nicht beeinflußt; sie gingen bei geringer Bodenfeuchte zurück. Die Wassernutzungseffiziens (WUE) wurde bei Wasserstreß reduziert, nahm aber bei Düngermangel zu. Die Wassernutzung für die Trockenmasseproduktion war bei 60 % Feldkapazität am höchsten. [source]

Function of a long-term, GLP-1-treated, insulin-secreting cell line is improved by preventing DPP IV-mediated degradation of GLP-1

DIABETES OBESITY & METABOLISM, Issue 5 2005
B. D. Green
Glucagon-like peptide-1 (GLP-1) is an important insulinotropic hormone with potential in the treatment of type 2 diabetes. However, the short biological half-life of the peptide after cleavage by dipeptidylpeptidase IV (DPP IV) is a major limitation. Inhibition of DPP IV activity and the development of resistant GLP-1 analogues is the subject of ongoing research. In this study, we determined cell growth, insulin content, insulin accumulation and insulin secretory function of a insulin-secreting cell line cultured for 3 days with either GLP-1, GLP-1 plus the DPP IV inhibitor diprotin A (DPA) or stable N -acetyl-GLP-1. Native GLP-1 was rapidly degraded by DPP IV during culture with accumulation of the inactive metabolite GLP-1(9,36)amide. Inclusion of DPA or use of the DPP IV-resistant analogue, N -acetyl-GLP-1, improved cellular function compared to exposure to GLP-1 alone. Most notably, basal and accumulated insulin secretion was enhanced, and glucose responsiveness was improved. However, prolonged GLP-1 treatment resulted in GLP-1 receptor desensitization regardless of DPP IV status. The results indicate that prevention of DPP IV action is necessary for beneficial effects of GLP-1 on pancreatic , cells and that prolonged exposure to GLP-1(9,36)amide may be detrimental to insulin secretory function. These observations also support the ongoing development of DPP-IV-resistant forms of GLP-1, such as N -acetyl-GLP-1. [source]

Surgery for Ruptured Sinus of Valsalva Aneurysm into Right Ventricular Outflow Tract: Role of Intraoperative 2D and Real Time 3D Transesophageal Echocardiography

ECHOCARDIOGRAPHY, Issue 7 2010
Shrinivas Gadhinglajkar M.D.
A major limitation of the 2D echocardiography during surgery for a complex cardiac lesion is its inability to provide an accurate spatial orientation of the structure. The real time 3D transesophageal echocardiography (RT-3D-TEE) technology available in Philips IE 33 ultrasound machine is relatively new to an operation suite. We evaluated its intraoperative utility in a patient, who was operated for repair of a ruptured sinus of Valsalva aneurysm (RSOVA) and closure of a supracristal ventricular septal defect. The VSD and RSOVA were visualized through different virtual windows in a more promising way on intraoperative RT-3D-TEE than on the 2D echocardiography. The acquired images could be virtually cropped and displayed in anatomical views to the operating surgeon for a clear orientation to the anatomy of the lesion. RT-3D-TEE is a potential intraoperative monitoring tool in surgeries for complex cardiac lesions. (Echocardiography 2010;27:E65-E69) [source]

Electroanalysis of Norepinephrine at Bare Gold Electrode Pure and Modified with Gold Nanoparticles and S-Functionalized Self-Assembled Layers in Aqueous Solution

ELECTROANALYSIS, Issue 13 2009
Teresa, uczak
Abstract Gold nanoparticles (Au-NPs), cystamine (CA) and 3,3,-dithiodipropionic acid (DTDPA) modified gold bare electrodes were applied in voltammetric sensors for simultaneous detection of norepinephrine (NEP), ascorbic (AA) and uric (UA) acids. A linear relationship between norepinephrine concentration and current response was obtained in the range of 0.1,,M to 600,,M M with the detection limit ,0.091,,M for the electrodes modified at 2D template and in the range of 0.1,,M to 700,,M M with the detection limit ,0.087,,M for the electrodes modified at 3D template The results have shown that using modified electrodes it is possible to perform electrochemical analysis of norepinephrine without interference of ascorbic and uric acids, whose presence is the major limitation in norepinephrine determination at a bare gold electrode. The modified SAMs electrodes show good selectivity, sensitivity, reproducibility and high stability. [source]

A reversibly immortalized human hepatocyte cell line as a source of hepatocyte-based biological support

ADDICTION BIOLOGY, Issue 4 2001
Naoya Kobayashi
The application of hepatocyte transplantation (HTX) is increasingly envisioned for temporary metabolic support during acute liver failure and provision of specific liver functions in inherited liver-based metabolic diseases. Compared with whole liver transplantation, HTX is a technically simple procedure and hepatocytes can be cryopreserved for future use. A major limitation of this form of therapy in humans is the worldwide shortage of human livers for isolating an adequate number of transplantable human hepatocyes when needed. Furthermore, the numbers of donor livers available for hepatocyte isolation is limited by competition for their use in whole organ transplantation. Considering the cost of hepatocyte isolation and the need for immediate preparation of consistent and functional cells, it is unlikely that human hepatocytes can be obtained on such a scale to treat a large number of patients with falling liver functions. The utilization of xenogenic hepatocytes will result in additional concerns regarding transmission of infectious pathogens and immunological and physiological incompatibilities between animals and humans. An attractive alternative to primary human hepatocytes is the use of tightly regulated human hepatocyte cell lines. Such cell lines can provide the advantages of unlimited availability, sterility and uniformity. We describe here methods for creating transplantable human hepatocyte cell lines using currently available cell cultures and gene transfer technology. [source]

Microbial biofilms associated with biliary stent clogging

FEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2010
Emilio Guaglianone
Abstract Endoscopic stenting is a palliative approach for the treatment of diseases involving biliary obstruction. Its major limitation is represented by stent occlusion, followed by life-threatening cholangitis, often requiring stent removal and replacement. Although it has been suggested that microbial colonization of biliary stents could play a role in the clogging process, the so far available data, particularly on the role of anaerobic bacteria, are not enough for a comprehensive description of this phenomenon. Our study was focused on the analysis of 28 explanted biliary stents by culturing, denaturing gradient gel electrophoresis and scanning electron microscopy to identify all the aerobic/anaerobic bacteria and fungi involved in the colonization of devices and to verify the ability of isolated anaerobic bacterial strains to form a biofilm in order to better understand the mechanisms of stent clogging. [source]

The Performance of State,Owned Enterprises Revisited

FINANCIAL ACCOUNTABILITY & MANAGEMENT, Issue 4 2002
Richard Bozec
Many theoretical and empirical studies look at the ownership,performance relationship. So far, the literature in finance and in accounting mainly refers to the property rights, agency and public choice theories. Despite the fact that the results of these studies are more or less conclusive, it is usually considered that the private enterprise performs better than the state,owned enterprise. In this article, we argue that these studies suffer from one major limitation. They do not recognize that the goals of the state,owned enterprise are different from the ones espoused by the private firm. Using a sample of state,owned entreprises and private firms for the period 1976,1996, we present empirical evidence that the state,owned enterprises, when their main goal is to maximize profit, perform as well as the privately owned enterprises. Therefore, the alleged under,performance of the state,owned enterprises may only be the result of pursuing other goals while the poor quality of public managers may be another urban myth. [source]

Bivariate association analyses for the mixture of continuous and binary traits with the use of extended generalized estimating equations

GENETIC EPIDEMIOLOGY, Issue 3 2009
Jianfeng Liu
Abstract Genome-wide association (GWA) study is becoming a powerful tool in deciphering genetic basis of complex human diseases/traits. Currently, the univariate analysis is the most commonly used method to identify genes associated with a certain disease/phenotype under study. A major limitation with the univariate analysis is that it may not make use of the information of multiple correlated phenotypes, which are usually measured and collected in practical studies. The multivariate analysis has proven to be a powerful approach in linkage studies of complex diseases/traits, but it has received little attention in GWA. In this study, we aim to develop a bivariate analytical method for GWA study, which can be used for a complex situation in which continuous trait and a binary trait are measured under study. Based on the modified extended generalized estimating equation (EGEE) method we proposed herein, we assessed the performance of our bivariate analyses through extensive simulations as well as real data analyses. In the study, to develop an EGEE approach for bivariate genetic analyses, we combined two different generalized linear models corresponding to phenotypic variables using a seemingly unrelated regression model. The simulation results demonstrated that our EGEE-based bivariate analytical method outperforms univariate analyses in increasing statistical power under a variety of simulation scenarios. Notably, EGEE-based bivariate analyses have consistent advantages over univariate analyses whether or not there exists a phenotypic correlation between the two traits. Our study has practical importance, as one can always use multivariate analyses as a screening tool when multiple phenotypes are available, without extra costs of statistical power and false-positive rate. Analyses on empirical GWA data further affirm the advantages of our bivariate analytical method. Genet. Epidemiol. 2009. © 2008 Wiley-Liss, Inc. [source]

Hyperphosphorylation of replication protein A in cisplatin-resistant and -sensitive head and neck squamous cell carcinoma cell lines

HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 5 2010
Karoline C. Manthey MS
Abstract Background Resistance to chemotherapy is a major limitation in the treatment of head and neck squamous cell carcinomas (HNSCCs), accounting for high mortality rates in patients. Here, we investigated the role of replication protein A (RPA) in cisplatin and etoposide resistance. Methods We used 6 parental HNSCC cell lines. We also generated 1 cisplatin-resistant progeny subline from a parental cisplatin-sensitive cell line, to examine cisplatin resistance and sensitivity with respect to RPA2 hyperphosphorylation and cell-cycle response. Results Cisplatin-resistant HNSCC cell levels of hyperphosphorylated RPA2 in response to cisplatin were 80% to 90% greater compared with cisplatin-sensitive cell lines. RPA2 hyperphosphorylation could be induced in the cisplatin-resistant HNSCC subline. The absence of RPA2 hyperphosphorylation correlated with a defect in cell-cycle progression and cell survival. Conclusion Loss of RPA2 hyperphosphorylation occurs in HNSCC cells and may be a marker of cellular sensitivities to cisplatin and etoposide in HNSCC. © 2009 Wiley Periodicals, Inc. Head Neck, 2010 [source]

Training as a vehicle to empower carers in the community: more than a question of information sharing

HEALTH & SOCIAL CARE IN THE COMMUNITY, Issue 2 2001
MSc (Econ), Nicholas Clarke BSc MSc
Abstract Much confusion still surrounds the concept of empowerment and how it is to be translated into practice within the context of community care for service users and carers. A major limitation has been the tendency to treat empowerment as synonymous with participation in decision-making with little attention given to the ,ecological' model of empowerment where linkages have been found between community participation and measures of psychological empowerment. Training has been suggested as a means through which carers might become empowered, yet to date little empirical evidence has appeared within the literature to support this proposition. This study investigated whether attendance on a training programme to empower carers resulted in improvements in carers' levels of perceived control, self-efficacy and self-esteem as partial measures of psychological empowerment. The findings demonstrated that whereas carers' knowledge of services and participation increased as a result of the programme, no changes were found in measures of carer empowerment. The failure to consider how training needs to be designed in order to achieve changes in individual competence and self-agency are suggested as the most likely explanation for the lack of change observed in carers' psychological empowerment. It is suggested that community care agencies should focus greater energies in determining how the policy objectives of empowerment are to be achieved through training, and in so doing make far more explicit the supposed linkages between training content, design, and its posited impact on individual behaviour or self-agency. [source]

Sampling variability of liver fibrosis in chronic hepatitis C

HEPATOLOGY, Issue 6 2003
Pierre Bedossa M.D.
Fibrosis is a common endpoint of clinical trials in chronic hepatitis C, and liver biopsy remains the gold standard for fibrosis evaluation. However, variability in the distribution of fibrosis within the liver is a potential limitation. Our aim was to assess the heterogeneity of liver fibrosis and its influence on the accuracy of assessment of fibrosis with liver biopsy. Surgical samples of livers from patients with chronic hepatitis C were studied. Measurement of fibrosis was performed on the whole section by using both image analysis and METAVIR score (reference value). From the digitized image of the whole section, virtual biopsy specimens of increasing length were produced. Fibrosis was assessed independently on each individual virtual biopsy specimen. Results were compared with the reference value according to the length of the biopsy specimen. By using image analysis, the coefficient of variation of fibrosis measurement with 15-mm long biopsy specimens was 55%; and for biopsy specimens of 25-mm length it was 45%. By using the METAVIR scoring system, 65% of biopsies 15 mm in length were categorized correctly according to the reference value. This increased to 75% for a 25-mm liver biopsy specimen without any substantial benefit for longer biopsy specimens. Sampling variability of fibrosis is a significant limitation in the assessment of fibrosis with liver biopsy. In conclusion, this study suggests that a length of at least 25 mm is necessary to evaluate fibrosis accurately with a semiquantitative score. Sampling variability becomes a major limitation when using more accurate methods such as automated image analysis. [source]

Further testing of the Integrated Hydrology Model (InHM): event-based simulations for a small rangeland catchment located near Chickasha, Oklahoma

HYDROLOGICAL PROCESSES, Issue 7 2005
Keith Loague
In the paper that is the foundation for this study, VanderKwaak and Loague (2001. Water Resources Research37: 999,1013) reported a demonstration of a fully coupled comprehensive physics-based hydrologic-response model, InHM (Integrated Hydrology Model), for two rainfall-runoff events from the small rangeland catchment known as R-5. The InHM simulations reported herein address (in three phases) limitations in the VanderKwaak and Loague (2001. Water Resources Research37: 999,1013) simulations. In Phase I, a new finite-element mesh was selected to represent R-5. In Phase II, with the new mesh in place, evaporation was considered for the R-5 events. In Phase III, with the new mesh in place and evaporation considered, the geology of R-5 was approximated. Each phase, compared with the results reported by VanderKwaak and Loague (2001. Water Resources Research37: 999,1013), shows a change in the simulated near-surface response. The performance of InHM for 15 R-5 events is also reported herein. The results from two stages of model calibration are presented. The uncertainty in initial soil-water content estimates for event-based simulation is shown to be a major limitation for physics-based models. The performance of InHM, relative to past event-based simulation efforts with a quasi-physically based rainfall-runoff model, is better for both peak stormflow and the time to peak stormflow, but worse for stormflow depth. The InHM simulations reported here set the stage for continuous simulation of near-surface response for the R-5 catchment with InHM. Copyright © 2004 John Wiley & Sons, Ltd. [source]

Knowledge-Based Approach towards Hydrolytic Degradation of Polymer-Based Biomaterials

ADVANCED MATERIALS, Issue 32-33 2009
Dieter Hofmann
Abstract The concept of hydrolytically degradable biomaterials was developed to enable the design of temporary implants that substitute or fulfill a certain function as long as required to support (wound) healing processes or to control the release of drugs. Examples are surgical implants, e.g., sutures, or implantable drug depots for treatment of cancer. In both cases degradability can help to avoid a second surgical procedure for explanation. Although degradable surgical sutures are established in the clinical practice for more than 30 years, still more than 40% of surgical sutures applied in clinics today are nondegradable.1 A major limitation of the established degradable suture materials is the fact that their degradation behavior cannot reliably be predicted by applying existing experimental methodologies. Similar concerns also apply to other degradable implants. Therefore, a knowledge-based approach is clearly needed to overcome the described problems and to enable the tailored design of biodegradable polymer materials. In this Progress Report we describe two methods (as examples for tools for this fundamental approach): molecular modeling combining atomistic bulk interface models with quantum chemical studies and experimental investigations of macromolecule degradation in monolayers on Langmuir,Blodgett (LB) troughs. Finally, an outlook on related future research strategies is provided. [source]

Toxicity Evaluation for Safe Use of Nanomaterials: Recent Achievements and Technical Challenges

ADVANCED MATERIALS, Issue 16 2009
Saber M. Hussain
Abstract Recent developments in the field of nanotechnology involving the synthesis of novel nanomaterials (NM) have attracted the attention of numerous scientists owing to the possibility of degradative perturbations in human health. This Review evaluates previous investigations related to NM toxicity studies using biological models and describes the limitations that often prevent toxicologists from identifying whether NM pose a real hazard to human health. One major limitation to assess toxicity is the characterization of the NM prior to and after exposure to living cells or animals. The most relevant physicochemical characteristics of NM are: size, surface chemistry, crystallinity, morphology, solubility, aggregation tendency, homogeneity of dispersions, and turbidity. All of these properties need to be assessed in order to determine their contribution to toxicity. Due to the lack of appropriate methods to determine the physicochemical nature of nanoparticles in biological systems, the exact nature of NM toxicity is not fully described or understood at this time. This Review emphasizes the need for state-of-the-art physicochemical characterization, the determination of appropriate exposure protocols and reliable methods for assessing NM internalization and their kinetics in living organisms. Once these issues are addressed, optimal experimental conditions could be established in order to identify if NM pose a threat to human health. Multidisciplinary research between materials scientists and life scientists should overcome these limitations in identifying the true hazards of NM. [source]

Genetic characterization of Erwinia amylovora strains by amplified fragment length polymorphism

JOURNAL OF APPLIED MICROBIOLOGY, Issue 2 2004
A. Rico
Abstract Aims:,Erwinia amylovora is one of the most important pathogens of pear and apple and is subject to strict quarantine regulations worldwide, although its patterns of dispersal are largely unknown. Previous attempts to fingerprint E. amylovora strains by molecular techniques have detected very little polymorphism because of the high genetic homogeneity of this bacterium. Our aim was to establish and test a typing method to quantify genetic diversity among strains of this plant pathogen. Methods and Results:, Twenty-two strains from different hosts and geographical locations were examined by PCR fingerprinting with four primers and by amplified fragment length polymorphism (AFLP) with four selected combinations of primers with a single base extension. PCR fingerprinting revealed little polymorphism producing the same amplification patterns for 17 strains, while the combined AFLP patterns yielded 78 polymorphic bands (34% of total bands) and allowed the differentiation of all but two strains. Clustering of strains in the resulting dendrogram was not correlated with host, year or country of isolation, and questions previous genealogies based on PFGE patterns. Conclusions:, The AFLP technique allowed the detection of an unprecedented number of genetic markers in E. amylovora and proved to be the most useful tool so far for discriminating among strains of this pathogen. The results obtained in this study strongly suggest the occurrence of multiple introductions of the pathogen in Spain and other European countries. Significance and Impact of the Study:, A major limitation in understanding the ecology of fire blight is the lack of typing techniques with a high power of discrimination. This study demonstrates the high resolution and the usefulness of the AFLP technique to differentiate among E. amylovora strains. [source]

Device-Related Infection Among Patients With Pacemakers and Implantable Defibrillators: Incidence, Risk Factors, and Consequences

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 7 2010
PABLO B. NERY M.D.
Risk Factors and Complications of Pacemaker and ICD Infection.,Background: Device-related infection is a major limitation of device therapy for cardiac arrhythmia. Methods: The authors analyzed the incidence and risk factors for cardiac device infection (CDI) among consecutive patients implanted with pacemaker (PM) or implantable cardioverter defibrillator (ICD) (including cardiac resynchronization therapy devices) at a tertiary health center in Hamilton, Ontario, Canada. Most patients with device-related infections were identified by an internal infection control system that reports any positive wound and blood cultures following surgery, between 2005 and the present. A retrospective review of patient records was also performed for all patients who received an ICD or PM between July 1, 2003 and March 20, 2007. Results: A total of 24 infections were identified among 2,417 patients having device surgery (1%). Fifteen of these infections (60%) were diagnosed within 90 days of the last surgical procedure. Univariate analysis showed that patients presenting with CDI were more likely to have had a device replacement, rather than a new implant, had more complex devices (dual/triple chamber vs single), and were more likely to have had a prior lead dislodgement. Multivariate analysis found device replacement (P = 0.02) and cardiac resynchronization therapy (CRT)/dual-chamber devices (P = 0.048) to be independent predictors of infection. One patient developed septic pulmonary emboli after having laser-assisted lead extraction. No patient died and 22 patients received a new device. Conclusion: CDI occurs in about 1% of cases in high volume facilities. Pulse generator replacement surgery and dual- or triple-chamber device implantation were associated with a significantly increased risk of infection. (J Cardiovasc Electrophysiol, Vol. pp. 786-790, July 2010) [source]

Proliferative drive and liver carcinogenesis: Too much of a good thing?

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 12 2009
Narci C Teoh
Abstract There have been innumerable studies published in the attempt to identify gene expression signatures in hepatocellular carcinoma (HCC). When all the regulators and targets of the differentially expressed genes are analyzed from larger studies, the most striking theme is upregulation of mitosis-promoting and cell proliferation genes in HCC compared with ,liver-specific gene clusters' in non-tumorous tissue. A major limitation of expression profiling is that it only provides a ,snapshot' of what is an evolving process and thus cannot distinguish the differences in gene expression that are primary effectors of dysregulated growth from those that represent downstream consequences. The development of HCC in a chronically diseased liver, often referred to as hepatocarcinogenesis, is a multistep process characterized by the progressive accumulation and interplay of genetic alterations causing aberrant growth, malignant transformation of liver parenchymal cells, followed by vascular invasion and metastasis. This review will discuss HCC precursor lesions, draw on the ,proliferation cluster' genes highlighted from HCC expression profiling studies, relate them to a selection of regulatory networks important in liver regeneration, cell cycle control and their potential significance in the pathogenesis of HCC or primary liver cancer. [source]

What Leads to Romantic Attraction: Similarity, Reciprocity, Security, or Beauty?

JOURNAL OF PERSONALITY, Issue 4 2009
Evidence From a Speed-Dating Study
ABSTRACT Years of attraction research have established several "principles" of attraction with robust evidence. However, a major limitation of previous attraction studies is that they have almost exclusively relied on well-controlled experiments, which are often criticized for lacking ecological validity. The current research was designed to examine initial attraction in a real-life setting,speed-dating. Social Relations Model analyses demonstrated that initial attraction was a function of the actor, the partner, and the unique dyadic relationship between these two. Meta-analyses showed intriguing sex differences and similarities. Self characteristics better predicted women's attraction than they did for men, whereas partner characteristics predicted men's attraction far better than they did for women. The strongest predictor of attraction for both sexes was partners' physical attractiveness. Finally, there was some support for the reciprocity principle but no evidence for the similarity principle. [source]

Impact on adherence and sustained virological response of psychiatric side effects during peginterferon and ribavirin therapy for chronic hepatitis C

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2006
L. CASTERA
Summary Background The psychiatric side effects of interferon, often responsible for dose reduction or treatment discontinuation, represent a major limitation in the treatment of chronic hepatitis C (CHC). Aim To prospectively assess the impact on adherence and sustained virological response (SVR) of the occurrence of psychiatric side effects during peginterferon and ribavirin therapy for CHC. Methods Ninety-eight consecutive treatment-naïve CHC patients receiving a standard course of peginterferon plus ribavirin were systematically screened for psychiatric side effects, using DSM-IV, at baseline and both during and after treatment. Results Psychiatric side effects occurred in 38 patients (39%), mostly within the first 12 weeks (87%), and always consisted of mood disorders. Overall, 68% of patients achieved an SVR (71% of patients with mood disorders and 68% of those without; P = N.S.). Peginterferon and ribavirin dose reductions did not differ between patients with mood disorders and those without (46% vs. 37%, respectively; P = N.S. and 13% vs. 22%, respectively; P = N.S.). Anti-viral therapy had to be discontinued in four patients (nonresponse: two, hyperthyroidism: one, psychiatric event: one). Conclusion Early detection and appropriate management of psychiatric side effects during peginterferon and ribavirin therapy for CHC allow optimizing adherence and virological efficacy. [source]

The natural history of parallel transjugular intrahepatic portosystemic stent shunts using uncovered stent: the role of host-related factors

LIVER INTERNATIONAL, Issue 5 2006
Ahmed Helmy
Abstract: Objectives: Parallel shunts (PS) are used in the management of transjugular intrahepatic portosystemic stent-shunt (TIPS) insufficiency, a major limitation of the technique. This study describes the natural history of PS, and uses them as a model to assess the role of host factors in the development of primary shunt insufficiency. Methods: Out of 338 patients with TIPS, 40 (11.8%) patients required insertion of a PS. Baseline and follow-up data of these patients were collected. Regular shunt surveillance involved biannual clinic visits and transjugular portography. Results: The non-PS group (group 1; n=298) and the PS group (group 2; n=40) had similar baseline demographic and disease characteristics. Index shunts of both groups and the PS produced a significant portal pressure gradient drop (P<0.001), which was less in the index shunts of Group 2 (P<0.02 for both). PS had similar cumulative shunt patency rates to those of the index shunts of Group 1, and both were greater than those of index shunts in Group 2 (P<0.001 for both). The intervention rate (number of interventions/number of check portograms × 100) was similar for PS and the index shunts of Group 1 (38.7% and 43% respectively), but was significantly higher in the index shunts of Group 2 (85.6%; P<0.01 for both). In Group 1 and Group 2, 144 patients (48.3%) and 21 patients (52.5%) died during follow-up after a median period of 23.4 and 8.9 months respectively. Conclusions: These findings do not support the hypothesis that shunt insufficiency is related to host factors. [source]

PERMANENT GENETIC RESOURCES: Isolation and characterization of microsatellite DNA loci from the southern flounder, Paralichthys lethostigma

MOLECULAR ECOLOGY RESOURCES, Issue 2 2008
C. W. SHAO
Abstract Paucity of polymorphic molecular markers in southern flounder (Paralichthys lethostigma) has been a major limitation in genetic improvement of this important economic fish. Hence, we constructed a repeat-enriched genomic library from P. lethostigma. A total of 39 new microsatellites were identified, for which 33 primer pairs were designed. After validating and scoring, 10 of these loci were polymorphic in a test population with the range of alleles from two to nine per locus. The observed and expected heterozygosities ranged from 0.2500 to 0.9000 and from 0.4469 to 0.8514, respectively. These polymorphic microsatellites will be useful for genetic diversity analysis and linkage map construction for P. lethostigma. [source]

Factors affecting the in vitro action of cumulus cells on the maturing mouse oocytes

MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 1 2008
Li Ge
Abstract The removal of cumulus cells (CCs) from oocytes at the germinal vesicle (GV) stage still represents a major limitation in such embryo techniques as GV transfer, somatic cell haploidization, and oocyte cryopreservation. However, no efficient in vitro maturation (IVM) system for CC-denuded oocytes (DOs) has been established in mammalian species. Although follicular cells are considered to play an important role in oocyte maturation, the specific role and mechanisms of action of different cell types are poorly understood. Reports on whether junctional association between CCs and the oocyte is essential for the beneficial effect of CC co-culture on oocyte maturation are in conflict. Our objective was to try to address these issues using the mouse oocyte model. The results indicated that while co-culture with the CC monolayer could only partially restore the developmental potential of DOs without corona cells, it restored the competence of corona-enclosed DOs completely. Culture in medium conditioned with CC monolayer also promoted maturation of DOs. However, co-culture with the monolayer of mural granulosa cells had no effect. The efficiency of CC co-culture was affected by various factors such as density and age of the CCs, the presence of gonadotropin in the maturation medium and the duration for in vivo (IVO) gonadotropin priming. It is concluded that mouse CCs produce a diffusible factor(s) that support DO maturation in a CC-oocyte junctional communication dependent manner. The data will contribute to our understanding the mechanisms by which CCs promote oocyte maturation and to the establishment of an efficient DO IVM system. Mol. Reprod. Dev. 75: 136,142, 2008. © 2007 Wiley-Liss, Inc. [source]

Neuroprotective therapy in Parkinson's disease and motor complications: A search for a pathogenesis-targeted, disease-modifying strategy

MOVEMENT DISORDERS, Issue S11 2005
C. Warren Olanow MD, FRCPC
Abstract The introduction of levodopa in the late 1960s represented a landmark in the therapy of Parkinson's disease (PD). However, motor complications of chronic levodopa therapy have emerged as a major limitation of this otherwise effective therapy. Advancing medical and surgical treatment of these complications has been the main objective of clinical trials during the past few decades. In addition, basic research has focused on better understanding of the mechanisms of motor complications and how to prevent them. Slowing or delaying the progression of the disease delays the need for levodopa therapy; therefore, neuroprotective strategies may play an important role in preventing the onset and reducing the severity of levodopa-related adverse effects. In this introductory review, we present the rationale for current and experimental therapies designed to favorably modify the progression of PD. If implemented early in the course of the disease, such treatments, if found effective, may not only alter the natural progression of the disease but may also delay or minimize motor and nonmotor complications associated with levodopa. © 2005 Movement Disorder Society [source]

Low donor-to-recipient weight ratio does not negatively impact survival of pediatric heart transplant patients

PEDIATRIC TRANSPLANTATION, Issue 6 2010
Liwen Tang
Tang L, Du W, Delius RE, L'Ecuyer TJ, Zilberman MV. Low donor-to-recipient weight ratio does not negatively impact survival of pediatric heart transplant patients. Pediatr Transplantation 2010: 14:741,745. © 2010 John Wiley & Sons A/S. Abstract:, A major limitation to success in pediatric heart transplantation is donor organ shortage. While the use of allografts from donors larger than the recipient is accepted, the use of undersized donor grafts is generally discouraged. Using the UNOS database, we wanted to evaluate whether using smaller donor hearts affects the short- and long-term survival of pediatric heart transplant patients. A retrospective analysis of data entered into the UNOS database from April 1994 to May 2008 was performed. Pediatric heart transplant recipients (ages 0,18 yr) with DRWR <2.0 were identified and divided into two groups: Low-DRWR (<0.8) and Ideal-DRWR (0.8,2.0). Patients' demographics, pretransplant diagnoses, age at transplantation, severity of pretransplant condition, and rate of complications prior to hospital discharge after transplantation were noted. Fisher's exact, chi-square, and Wilcoxon rank sum tests were used to compare patients' baseline characteristics. Kaplan,Meier curves and Cox proportional hazard regression were used to compare patients' survival and to identify independent risk factors for outcomes. There were 3048 patients (204 with Low- and 2844 with Ideal-DRWR). The Low-ratio group patients were older (8.3 vs. 6.9 yr; p = 0.001), there was a slight male predominance in the Low-DRWR group (p = 0.055). The Low-DRWR group had longer transplant wait time than the Ideal-DRWR group (97 vs. 85 days; p = 0.04). The groups did not differ in race, primary diagnoses, severity of pretransplant condition (medical urgency status, need for ventilation, inotropic support, ECMO, nitric oxide, or dialysis, the PVR for those with bi-ventricular anatomy), or post-transplant complications (length of stay, need for inotropic support, dialysis, and rate of infections). The Low-DRWR patients had less episodes of acute rejection during the first-post-transplant month. Infants with DRWR 0.5,0.59 had lower 30-day survival rate (p = 0.045). There was no difference in short- and long-term survival between the patients with DRWR 0.6,0.79 and DRWR 0.8,2.0. Use of smaller allografts (DRWR 0.6,0.8) has no negative impact on the short- and long-term survival of pediatric heart transplant patients. [source]

Replication of the Scandinavian Simvastatin Survival Study using a primary care medical record database prompted exploration of a new method to address unmeasured confounding

PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 7 2008
Mark G. Weiner M.D.
Abstract Purpose To examine whether identifiable study characteristics and/or analytic methods used determine observational study validity, as assessed by replicating randomized controlled trials using observational data. Methods A cohort from the United Kingdom General Practice Research Database (GPRD) was used to replicate the Scandinavian Simvastatin Survival Study RCT, which investigated statin treatment of hypercholesterolemic subjects with coronary heart disease. All aspects of the RCT except randomization were replicated to the extent possible in the GPRD study, which included 2,871 Unexposed and 1,280 statin-treated Exposed subjects. Results Overall mortality [adjusted hazard ratio 0.71 (0.53,0.96)] and myocardial infarction [adjusted HR 0.79 (0.61,1.02)] decreased in the GPRD study similar to the RCT. Coronary revascularization increased two-fold in the GPRD study, whereas it decreased significantly in the RCT [0.63 (0.54,0.74)]. This latter disparity prompted use of a new methodology to adjust for unmeasured confounding, which yielded an adjusted HR [1.0 (0.75,1.33)] more comparable to the RCT. Conclusions This study provides additional evidence that a replicated GPRD observational study can yield results reasonably similar to a RCT. More important, it provides preliminary evidence suggesting that a new analytic methodology may adjust for unmeasured confounding, the major limitation to research using observational data. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Isolation and characterization of microsatellite markers from guineagrass (Panicum maximum) for genetic diversity estimate and cross-species amplification

PLANT BREEDING, Issue 1 2010
A. Chandra
With 1 figure and 1 table Abstract Guineagrass (Panicum maximum Jacq.) is one of the major forage grasses in tropical and semitropical regions, largely apomictic and predominantly exist as tetraploid. Non-availability of polymorphic molecular markers has been a major limitation in its characterization and improvement. We report isolation and characterization of microsatellites in P. maximum and cross-species results with other five Panicum species. Based on microsatellite-motifs, 15 functional and polymorphic simple sequence repeat (SSR) primer-pairs were designed, validated and employed in estimating genetic relationship among 34 guineagrass accessions. Thirteen primer-pairs amplified single locus and remaining two generated more than two loci with an average of 3.57 bands per locus amounts to 63 bands with 34 guineagrass accessions. Average expected heterozygosity (HE) of 0.35 (maximum 0.97) and observed heterozygosity (HO) of 0.37 (maximum 0.91) established the efficiency of developed markers for discriminating guineagrass accessions. Dice's similarity coefficients-based unweighted pair group with arithmetic average method-clustering supported with high bootstrap values (,40) indicated its significance and distinguished all accessions except IG97-93 and IG97-6. Utility of these new SSR loci in genetic diversity study of P. maximum and other cross,amplified species is discussed. [source]

Intraspecific variation in the Populus balsamifera drought transcriptome

PLANT CELL & ENVIRONMENT, Issue 10 2010
ERIN T. HAMANISHI
ABSTRACT Drought is a major limitation to the growth and productivity of trees in the ecologically and economically important genus Populus. The ability of Populus trees to contend with drought is a function of genome responsiveness to this environmental insult, involving reconfiguration of the transcriptome to appropriately remodel growth, development and metabolism. Here we test hypotheses aimed at examining the extent of intraspecific variation in the drought transcriptome using six different Populus balsamifera L. genotypes and Affymetrix GeneChip technology. Within a given genotype there was a positive correlation between the magnitude of water-deficit induced changes in transcript abundance across the transcriptome, and the capacity of that genotype to maintain growth following water deficit. Genotypes that had more similar drought-responsive transcriptomes also had fewer genotypic differences, as determined by microarray-derived single feature polymorphism (SFP) analysis, suggesting that responses may be conserved across individuals that share a greater degree of genotypic similarity. This work highlights the fact that a core species-level response can be defined; however, the underpinning genotype-derived complexities of the drought response in Populus must be taken into consideration when defining both species- and genus-level responses. [source]

Equalizer technology , Equal rights for disparate beads

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 11 2010
Eva-Maria Keidel
Abstract One major limitation in proteomics is the detection and analysis of low-abundant proteins, i.e. in plasma. Several years ago, a technique to selectively enrich the relative concentration of low-abundant proteins was introduced by Boschetti and co-workers. It is based on a specific and saturable interaction of proteins to a high diversity of binding sites, realized by a hexapeptide library coupled to beads. This technology was commercialized as Equalizer beads or ProteoMiner. However, during application of ProteoMiner beads to plasma samples unexpected results questioned the proposed mode of action. Therefore, ProteoMiner beads were compared with chromatographic beads exhibiting completely different surface chemistry. Sepabeads FP-OD400 octadecyl, FP-DA400 diethylamine, FP-BU400 butyl, FP-HG400 hydroxyl and EXE056 epoxy were used. The results show that ProteoMiner or the different Sepabeads behave surprisingly similarly in the separation of complex protein mixtures. ProteoMiner beads interact with protein mixtures according to a general hydrophobic binding mechanism, where diversity in surface ligands plays only a negligible role. [source]

Genetic or chemical protease inhibition causes significant changes in the Bacillus subtilis exoproteome

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 13 2008
Lidia Westers
Abstract Bacillus subtilis is a prolific producer of enzymes and biopharmaceuticals. However, the susceptibility of heterologous proteins to degradation by (extracellular) proteases is a major limitation for use of B. subtilis as a protein cell factory. An increase in protein production levels has previously been achieved by using either protease-deficient strains or addition of protease inhibitors to B. subtilis cultures. Notably, the effects of genetic and chemical inhibition of proteases have thus far not been compared in a systematic way. In the present studies, we therefore compared the exoproteomes of cells in which extracellular proteases were genetically or chemically inactivated. The results show substantial differences in the relative abundance of various extracellular proteins. Furthermore, a comparison of the effects of genetic and/or chemical protease inhibition on the stress response triggered by (over) production of secreted proteins showed that chemical protease inhibition provoked a genuine secretion stress response. From a physiological point of view, this suggests that the deletion of protease genes is a better way to prevent product degradation than the use of protease inhibitors. Importantly however, studies with human interleukin-3 show that chemical protease inhibition can result in improved production of protease-sensitive secreted proteins even in mutant strains lacking eight extracellular proteases. [source]

Body fluid proteomics: Prospects for biomarker discovery

PROTEOMICS - CLINICAL APPLICATIONS, Issue 9 2007
Sung-Min Ahn
Abstract Many diseases are caused by perturbations of cellular signaling pathways and related pathway networks as a result of genetic aberrations. These perturbations are manifested by altered cellular protein profiles in the fluids bathing tissue/organs (i.e., the tissue interstitial fluid, TIF). A major challenge of clinical chemistry is to quantitatively map these perturbed protein profiles , the so-called "signatures of disease" , using modern proteomic technologies. This information can be utilized to design protein biomarkers for the early detection of disease, monitoring disease progression and efficacy of drug action. Here, we discuss the use of body fluids in the context of prospective biomarker discovery, and the marked 1000,1500-fold dilution of body fluid proteins, during their passage from TIF to the circulatory system. Further, we discuss proteomics strategies aimed at depleting major serum proteins, especially albumin, in order to focus on low-abundance protein/peptides in plasma. A major limitation of depletion strategies is the removal of low-molecular weight protein/peptides which specifically bind major plasma proteins. We present a prototype model, using albumin, for understanding the multifaceted nature of biomarker research, highlighting the involvement of albumin in Alzheimer's disease. This model underscores the need for a system-level understanding for biomarker research and personalized medicine. [source]