bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies on Escherichia coliHflKC suggest the presence of an unidentified λ factor that influences the lysis-lysogeny switch
Authors: Bandyopadhyay Kaustav , Parua Pabitra K , Datta Ajit B , Parrack Pradeep
Published: February 2011

Background

The lysis-lysogeny decision in the temperate coliphage λ is influenced by a number of phage proteins (CII and CIII) as well as host factors, viz. Escherichia coli HflB, HflKC and HflD. Prominent among these are the transcription factor CII and HflB, an ATP-dependent protease that degrades CII. Stabilization of CII promotes lysogeny, while its destabilization induces the lytic mode of development. All other factors that influence the lytic/lysogenic decision are known to act by their effects on the stability of CII. Deletion of hflKC has no effect on the stability of CII. However, when λ infects ΔhflKC cells, turbid plaques are produced, indicating stabilization of CII under these conditions.

Results

We find that CII is stabilized in ΔhflKC cells even without infection by λ, if CIII is present. Nevertheless, we also obtained turbid plaques when a ΔhflKC host was infected by a cIII-defective phage (λcIII

67
). This observation raises a fundamental question: does lysogeny necessarily correlate with the stabilization of CII? Our experiments indicate that CII is indeed stabilized under these conditions, implying that stabilization of CII is possible in ΔhflKC cells even in the absence of CIII, leading to lysogeny.

Conclusion

We propose that a yet unidentified CII-stabilizing factor in λ may influence the lysis-lysogeny decision in ΔhflKC cells.
Differential expression of THOC1 and ALY mRNP biogenesis/export factors in human cancers
Authors: Domínguez-Sánchez María S , Sáez Carmen , Japón Miguel A , Aguilera Andrés , Luna Rosa
Published: February 2011

Background

One key step in gene expression is the biogenesis of mRNA ribonucleoparticle complexes (mRNPs). Formation of the mRNP requires the participation of a number of conserved factors such as the THO complex. THO interacts physically and functionally with the Sub2/UAP56 RNA-dependent ATPase, and the Yra1/REF1/ALY RNA-binding protein linking transcription, mRNA export and genome integrity. Given the link between genome instability and cancer, we have performed a comparative analysis of the expression patterns of THOC1, a THO complex subunit, and ALY in tumor samples.

Methods

The mRNA levels were measured by quantitative real-time PCR and hybridization of a tumor tissue cDNA array; and the protein levels and distribution by immunostaining of a custom tissue array containing a set of paraffin-embedded samples of different tumor and normal tissues followed by statistical analysis.

Results

We show that the expression of two mRNP factors, THOC1 and ALY are altered in several tumor tissues. THOC1 mRNA and protein levels are up-regulated in ovarian and lung tumors and down-regulated in those of testis and skin, whereas ALY is altered in a wide variety of tumors. In contrast to THOC1, ALY protein is highly detected in normal proliferative cells, but poorly in high-grade cancers.

Conclusions

These results suggest a differential connection between tumorogenesis and the expression levels of human THO and ALY. This study opens the possibility of defining mRNP biogenesis factors as putative players in cell proliferation that could contribute to tumor development.
Targeting canine bladder transitional cell carcinoma with a human bladder cancer-specific ligand
Authors: Lin Tzu-yin , Zhang Hongyong , Wang Sisi , Xie Li , Li Bin , Rodriguez Carlos O , de Vere White Ralph , Pan Chong-xian
Published: February 2011

Objective

To determine if a human bladder cancer-specific peptide named PLZ4 can target canine bladder cancer cells.

Experimental Design

The binding of PLZ4 to five established canine invasive transitional cell carcinoma (TCC) cell lines and to normal canine bladder urothelial cells was determined using the whole cell binding assay and an affinitofluorescence assay. The WST-8 assay was performed to determine whether PLZ4 affected cell viability. In vivo tumor-specific homing/targeting property and biodistribution of PLZ4 was performed in a mouse xenograft model via tail vein injection and was confirmed with ex vivo imaging.

Results

PLZ4 exhibited high affinity and specific dose-dependent binding to canine bladder TCC cell lines, but not to normal canine urothelial cells. No significant changes in cell viability or proliferation were observed upon incubation with PLZ4. The in vivo and ex vivo optical imaging study showed that, when linked with the near-infrared fluorescent dye Cy5.5, PLZ4 substantially accumulated at the canine bladder cancer foci in the mouse xenograft model as compared to the control.

Conclusions and Clinical Relevance

PLZ4 can specifically bind to canine bladder cancer cells. This suggests that the preclinical studies of PLZ4 as a potential diagnostic and therapeutic agent can be performed in dogs with naturally occurring bladder cancer, and that PLZ4 can possibly be developed in the management of canine bladder cancer.
Partial abdominal evisceration and intestinal autotransplantation to resect a mesenteric carcinoid tumor
Authors: Kitchens William H , Elias Nahel , Blaszkowsky Lawrence S , Cosimi A Benedict , Hertl Martin
Published: February 2011

Background

Midgut carcinoids are neuroendocrine tumors that commonly metastasize to the intestinal mesentery, where they predispose to intestinal obstruction, ischemia and/or congestion. Because of their location, many mesenteric carcinoid tumors are deemed unresectable due to the risk of uncontrollable bleeding and prolonged intestinal ischemia.

Case Presentation

We report the case of a 60-year-old male with a mesenteric carcinoid tumor obstructing his superior mesenteric vein, resulting in intestinal varices and severe recurrent GI bleeds. While his tumor was thought to be unresectable by conventional techniques, it was successfully resected using intestinal autotransplantation to safely gain access to the tumor. This case is the first described application of this technique to carcinoid tumors.

Conclusions

Intestinal autotransplantation can be utilized to safely resect mesenteric carcinoid tumors from patients who were not previously thought to be surgical candidates. We review the literature concerning both carcinoid metastases to the intestinal mesentery and the use of intestinal autotransplantation to treat lesions involving the mesenteric root.
A national survey of 'inactive' physicians in the United States of America: enticements to reentry
Authors: Jewett Ethan A , Brotherton Sarah E , Ruch-Ross Holly
Published: February 2011

Background

Physicians leaving and reentering clinical practice can have significant medical workforce implications. We surveyed inactive physicians younger than typical retirement age to determine their reasons for clinical inactivity and what barriers, real or perceived, there were to reentry into the medical workforce.

Methods

A random sample of 4975 inactive physicians aged under 65 years was drawn from the Physician Masterfile of the American Medical Association in 2008. Physicians were mailed a survey about activity in medicine and perceived barriers to reentry. Chi-square statistics were used for significance tests of the association between categorical variables and t-tests were used to test differences between means.

Results

Our adjusted response rate was 36.1%. Respondents were fully retired (37.5%), not currently active in medicine (43.0%) or now active (reentered, 19.4%). Nearly half (49.5%) were in or had practiced primary care. Personal health was the top reason for leaving for fully retired physicians (37.8%) or those not currently active in medicine (37.8%) and the second highest reason for physicians who had reentered (28.8%). For reentered (47.8%) and inactive (51.5%) physicians, the primary reason for returning or considering returning to practice was the availability of part-time work or flexible scheduling. Retired and currently inactive physicians used similar strategies to explore reentry, and 83% of both groups thought it would be difficult; among those who had reentered practice, 35.9% reported it was difficult to reenter. Retraining was uncommon for this group (37.5%).

Conclusion

Availability of part-time work and flexible scheduling have a strong influence on decisions to leave or reenter clinical practice. Lack of retraining before reentry raises questions about patient safety and the clinical competence of reentered physicians.
Negative pressure characteristics of an evaporating meniscus at nanoscale
Authors: Maroo Shalabh C , Chung JN
Published: February 2011

This study aims at understanding the characteristics of negative liquid pressures at the nanoscale using molecular dynamics simulation. A nano-meniscus is formed by placing liquid argon on a platinum wall between two nano-channels filled with the same liquid. Evaporation is simulated in the meniscus by increasing the temperature of the platinum wall for two different cases. Non-evaporating films are obtained at the center of the meniscus. The liquid film in the non-evaporating and adjacent regions is found to be under high absolute negative pressures. Cavitation cannot occur in these regions as the capillary height is smaller than the critical cavitation radius. Factors which determine the critical film thickness for rupture are discussed. Thus, high negative liquid pressures can be stable at the nanoscale, and utilized to create passive pumping devices as well as significantly enhance heat transfer rates.
The transfer from survey (map-like) to route representations into Virtual Reality Mazes: effect of age and cerebral lesion
Authors: Carelli Laura , Rusconi Maria Luisa , Scarabelli Chiara , Stampatori Chiara , Mattioli Flavia , Riva Giuseppe
Published: February 2011

Background

To go from one place to another, we routinely generate internal representations of surrounding spaces, which can include egocentric (body-centred) and allocentric (world-centred) coordinates, combined into route and survey representations.

Recent studies have shown how both egocentric and allocentric representations exist in parallel and are joined to support behaviour according to the task.

Our study investigated the transfer from survey (map-like) to route representations in healthy and brain-damaged subjects. The aim was two-fold: first, to understand how this ability could change with age in a sample of healthy participants, aged from 40 to 71 years old; second, to investigate how it is affected after a brain lesion in a 8 patients' sample, with reference to specific neuropsychological frames.

Methods

Participants were first required to perform the paper and pencil version of eight mazes, then to translate the map-like paths into egocentric routes, in order to find the right way into equivalent Virtual Reality (VR) mazes.

Patients also underwent a comprehensive neuropsychological evaluation, including a specific investigation of some topographical orientation components.

Results

As regards the healthy sample, we found age-related deterioration in VR task performance. While education level and gender were not found to be related to performance, global cognitive level (Mini Mental State Examination), previous experience with computer and fluidity of navigation into the VR appeared to influence VR task results.

Considering the clinical sample, there was a difficulty in performing the VR Maze task; executive functions and visuo-spatial abilities deficits appeared to be more relevant for predicting patients' results.

Conclusions

Our study suggests the importance of developing tools aimed at investigating the survey to route transfer ability in both healthy elderly and clinical samples, since this skill seems high cognitive demanding and sensitive to cognitive decline.

Human-computer interaction issues should be considered in employing new technologies, such as VR environments, with elderly subjects and neurological patients.
Inflammatory and cytotoxic responses of an alveolar-capillary coculture model to silica nanoparticles: Comparison with conventional monocultures
Authors: Kasper Jennifer , Hermanns Maria I , Bantz Christoph , Maskos Michael , Stauber Roland , Pohl Christine , Unger Ronald E , Kirkpatrick James C
Published: February 2011

Background

To date silica nanoparticles (SNPs) play an important role in modern technology and nanomedicine. SNPs are present in various materials (tyres, electrical and thermal insulation material, photovoltaic facilities). They are also used in products that are directly exposed to humans such as cosmetics or toothpaste. For that reason it is of great concern to evaluate the possible hazards of these engineered particles for human health. Attention should primarily be focussed on SNP effects on biological barriers. Accidentally released SNP could, for example, encounter the alveolar-capillary barrier by inhalation. In this study we examined the inflammatory and cytotoxic responses of monodisperse amorphous silica nanoparticles (aSNPs) of 30 nm in size on an in vitro coculture model mimicking the alveolar-capillary barrier and compared these to conventional monocultures.

Methods

Thus, the epithelial cell line, H441, and the endothelial cell line, ISO-HAS-1, were used in monoculture and in coculture on opposite sides of a filter membrane. Cytotoxicity was evaluated by the MTS assay, detection of membrane integrity (LDH release), and TER (Transepithelial Electrical Resistance) measurement. Additionally, parameters of inflammation (sICAM-1, IL-6 and IL-8 release) and apoptosis markers were investigated.

Results

Regarding toxic effects (viability, membrane integrity, TER) the coculture model was less sensitive to apical aSNP exposure than the conventional monocultures of the appropriate cells. On the other hand, the in vitro coculture model responded with the release of inflammatory markers in a much more sensitive fashion than the conventional monoculture. At concentrations that were 10-100fold less than the toxic concentrations the apically exposed coculture showed a release of IL-6 and IL-8 to the basolateral side. This may mimic the early inflammatory events that take place in the pulmonary alveoli after aSNP inhalation. Furthermore, a number of apoptosis markers belonging to the intrinsic pathway were upregulated in the coculture following aSNP treatment. Analysis of the individual markers indicated that the cells suffered from DNA damage, hypoxia and ER-stress.

Conclusion

We present evidence that our in vitro coculture model of the alveolar-capillary barrier is clearly advantageous compared to conventional monocultures in evaluating the extent of damage caused by hazardous material encountering the principle biological barrier in the lower respiratory tract.
Modeling RNA interference in mammalian cells
Authors: Cuccato Giulia , Polynikis Athanasios , Siciliano Velia , Graziano Mafalda , di Bernardo Mario , di Bernardo Diego
Published: February 2011

Background

RNA interference (RNAi) is a regulatory cellular process that controls post-transcriptional gene silencing. During RNAi double-stranded RNA (dsRNA) induces sequence-specific degradation of homologous mRNA via the generation of smaller dsRNA oligomers of length between 21-23nt (siRNAs). siRNAs are then loaded onto the RNA-Induced Silencing multiprotein Complex (RISC), which uses the siRNA antisense strand to specifically recognize mRNA species which exhibit a complementary sequence. Once the siRNA loaded-RISC binds the target mRNA, the mRNA is cleaved and degraded, and the siRNA loaded-RISC can degrade additional mRNA molecules. Despite the widespread use of siRNAs for gene silencing, and the importance of dosage for its efficiency and to avoid off target effects, none of the numerous mathematical models proposed in literature was validated to quantitatively capture the effects of RNAi on the target mRNA degradation for different concentrations of siRNAs. Here, we address this pressing open problem performing in vitro experiments of RNAi in mammalian cells and testing and comparing different mathematical models fitting experimental data to in-silico generated data. We performed in vitro experiments in human and hamster cell lines constitutively expressing respectively EGFP protein or tTA protein, measuring both mRNA levels, by quantitative Real-Time PCR, and protein levels, by FACS analysis, for a large range of concentrations of siRNA oligomers.

Results

We tested and validated four different mathematical models of RNA interference by quantitatively fitting models' parameters to best capture the in vitro experimental data. We show that a simple Hill kinetic model is the most efficient way to model RNA interference. Our experimental and modeling findings clearly show that the RNAi-mediated degradation of mRNA is subject to saturation effects.

Conclusions

Our model has a simple mathematical form, amenable to analytical investigations and a small set of parameters with an intuitive physical meaning, that makes it a unique and reliable mathematical tool. The findings here presented will be a useful instrument for better understanding RNAi biology and as modelling tool in Systems and Synthetic Biology.
A phage-targeting strategy for the design of spatiotemporal drug delivery from grafted matrices
Authors: Sawada Ritsuko , Peterson Carrie Y , Gonzalez Ana Maria , Potenza Bruce M , Mueller Barbara , Coimbra Raul , Eliceiri Brian P , Baird Andrew
Published: February 2011

Background

The natural response to injury is dynamic and normally consists of complex temporal and spatial cellular changes in gene expression, which, when acting in synchrony, result in patent tissue repair and, in some instances, regeneration. However, current therapeutic regiments are static and most rely on matrices, gels and engineered skin tissue. Accordingly, there is a need to design next-generation grafting materials to enable biotherapeutic spatiotemporal targeting from clinically approved matrices. To this end, rather then focus on developing completely new grafting materials, we investigated whether phage display could be deployed onto clinically approved synthetic grafts to identify peptide motifs capable of linking pharmaceutical drugs with differential affinities and eventually, control drug delivery from matrices over both space and time.

Methods

To test this hypothesis, we biopanned combinatorial peptide libraries onto different formulations of a wound-healing matrix (Integra®) and eluted the bound peptides with 1) high salt, 2) collagen and glycosaminoglycan or 3) low pH. After three to six rounds of biopanning, phage recovery and phage amplification of the bound particles, any phage that had acquired a capacity to bind the matrix was sequenced.

Results

In this first report, we identify distinct classes of matrix-binding peptides which elute differently from the screened matrix and demonstrate that they can be applied in a spatially relevant manner.

Conclusions

We suggest that further applications of these combinatorial techniques to wound-healing matrices may offer a new way to improve the performance of clinically approved matrices so as to introduce temporal and spatial control over drug delivery.
Cerebrospinal fluid and blood flow in mild cognitive impairment and Alzheimer's disease: a differential diagnosis from idiopathic normal pressure hydrocephalus
Authors: El Sankari Soraya , Gondry-Jouet Catherine , Fichten Anthony , Godefroy Olivier , Serot Jean Marie , Deramond Hervé , Meyer Marc Etienne , Balédent Olivier
Published: February 2011

Background

Phase-contrast magnetic resonance imaging (PC-MRI) enables quantification of cerebrospinal fluid (CSF) flow and total cerebral blood (tCBF) flow and may be of value for the etiological diagnosis of neurodegenerative diseases. This investigation aimed to study CSF flow and intracerebral vascular flow in patients with Alzheimer's disease (AD) and patients with amnesic mild cognitive impairment (a-MCI) and to compare the results with patients with idiopathic normal pressure hydrocephalus (NPH) and with healthy elderly volunteers (HEV).

Methods

Ten a-MCI and 9 mild AD patients were identified in a comprehensive neurological and neuropsychological assessment. They underwent brain MRI; PC-MRI pulse sequence was performed with the following parameters: two views per segment; flip angle: 25° for vascular flow and 20° for CSF flow; field-of-view (FOV): 14 × 14 mm²; matrix: 256 × 128; slice thickness: 5 mm; with one excitation for exams on the 3 T machine, and 2 excitations for the 1.5 T machine exams. Velocity (encoding) sensitization was set to 80 cm/s for the vessels at the cervical level, 10 or 20 cm/s for the aqueduct and 5 cm/s for the cervical subarachnoid space (SAS). Dynamic flow images were analyzed with in-house processing software. The patients' results were compared with those obtained for HEVs (n = 12), and for NPH patients (n = 13), using multivariate analysis.

Results

Arterial tCBF and the calculated pulsatility index were significantly greater in a-MCI patients than in HEVs. In contrast, vascular parameters were lower in NPH patients. Cervical CSF flow analysis yielded similar values for all four populations. Aqueductal CSF stroke volumes (in μl per cardiac cycle) were similar in HEVs (34 ± 17) and AD patients (39 ± 18). In contrast, the aqueductal CSF was hyperdynamic in a-MCI patients (73 ± 33) and even more so in NPH patients (167 ± 89).

Conclusion

Our preliminary data show that a-MCI patients present with high systolic arterial peak flows, which are associated with higher mean total cerebral arterial flows. Aqueductal CSF oscillations are within normal range in AD and higher than normal in NPH. This study provides an original dynamic vision of cerebral neurodegenerative diseases, consistent with the vascular theory for AD, and supporting primary flow disturbances different from those observed in NPH.
Association between synovial fluid levels of aggrecan ARGS fragments and radiographic progression in knee osteoarthritis
Authors: Larsson Staffan , Englund Martin , Struglics André , Lohmander L Stefan
Published: February 2011

Introduction

Aggrecanase cleavage at the 392Glu-393Ala bond in the interglobular domain (IGD) of aggrecan, releasing N-terminal 393ARGS fragments, is an early key event in arthritis and joint injuries. We determined whether synovial fluid (SF) levels of ARGS-aggrecan distinguish subjects with progressive radiographic knee osteoarthritis (ROA) from those with stable or no ROA.

Methods

We studied 141 subjects who, at examination A, had been given meniscectomies an average of 18 years earlier (range, 15 to 22 years). Seventeen individuals without surgery, and without known injury to the menisci or cruciate ligaments, were used as references. At examinations A and B, with a mean follow-up time of 7.5 years, we obtained SF and standing tibiofemoral and skyline patellofemoral radiographs. SF ARGS-aggrecan was measured with an electrochemiluminescence immunoassay, and we graded radiographs according to the OARSI atlas. The association between SF ARGS levels at examination A and progression of radiographic features of knee OA between examinations A and B was assessed by using logistic regression adjusted for age, gender, body mass index, and time between examinations, and stratified by ROA status at examination A.

Results

We found a weak negative association between SF ARGS concentrations and loss of joint space: the likelihood of progression of radiographic joint space narrowing decreased 0.9 times per picomole per milliliter increase in ARGS (odds ratio (OR) 0.89; 95% confidence interval (CI), 0.79 to 0.996). In subjects with and without preexisting ROA at examination A, the association was OR, 0.96; 0.81 to 1.13; and 0.77; 0.62 to 0.95, respectively. Average levels of SF ARGS 18 years after meniscectomy were no different from those of reference subjects and were not correlated to radiographic status at examination A.

Conclusions

In subjects with previous knee meniscectomy but without ROA, levels of SF ARGS-aggrecan were weakly and inversely associated with increased loss of joint space over a period of 7.5 years.
Circulating soluble urokinase plasminogen activator receptor is stably elevated during the first week of treatment in the intensive care unit and predicts mortality in critically ill patients
Authors: Koch Alexander , Voigt Sebastian , Kruschinski Carsten , Sanson Edouard , Dückers Hanna , Horn Andreas , Yagmur Eray , Zimmermann Henning , Trautwein Christian , Tacke Frank
Published: February 2011

Introduction

suPAR is the soluble form of the urokinase plasminogen activator receptor (uPAR), which is expressed in various immunologically active cells. High suPAR serum concentrations are suggested to reflect the activation of the immune system in circumstances of inflammation and infection, and have been associated with increased mortality in different populations of non-intensive care patients. In this study we sequentially analyzed suPAR serum concentrations within the first week of intensive care in a large cohort of well characterized intensive care unit (ICU) patients, in order to investigate potential regulatory mechanisms and evaluate the prognostic significance in critically ill patients.

Methods

A total of 273 patients (197 with sepsis, 76 without sepsis) were studied prospectively upon admission to the medical intensive care unit (ICU), on Day 3 and Day 7, and compared to 43 healthy controls. Clinical data, various laboratory parameters as well as investigational inflammatory cytokine profiles were assessed. Patients were followed for approximately one year.

Results

Upon admission to the ICU suPAR serum concentrations were elevated in critically ill patients as compared with healthy controls. In sepsis patients suPAR levels were higher than in non-sepsis patients (with or without systemic inflammatory response syndrome (SIRS)). During the first week after admission to the ICU serum suPAR concentrations remained stably elevated. suPAR serum concentrations measured upon admission were closely and independently correlated to various laboratory parameters, specifically biomarkers of inflammation (tumor necrosis factor (TNF), C-reactive protein (CRP)), hepatic and renal dysfunction. High suPAR levels at admission and at Day 3 were a strong independent predictor for both ICU and long-term mortality in critically ill patients.

Conclusions

In sepsis and non-sepsis patients suPAR serum concentrations are increased upon admission to the ICU, likely reflecting the activation state of the immune system, and remain stably elevated in the initial course of treatment. Low suPAR levels are a positive predictor of ICU- and overall survival in critically ill patients, including sepsis and non-sepsis patients. Aside from its value as a promising new prognostic biomarker, both experimental and clinical studies are required in order to understand the specific effects and regulatory mechanisms of suPAR in SIRS and sepsis, and may reveal new therapeutic options.
Cerebrospinal fluid lactate concentration to distinguish bacterial from aseptic meningitis: a systemic review and meta-analysis
Authors: Huy Nguyen T , Thao Nguyen TH , Diep Doan TN , Kikuchi Mihoko , Zamora Javier , Hirayama Kenji
Published: February 2011

Introduction

Making a differential diagnosis between bacterial meningitis and aseptic meningitis is a critical clinical problem. The utility of a cerebrospinal fluid (CSF) lactate assay for this purpose has been debated and is not yet routinely clinically performed. To adequately evaluate this assay, a systematic review and meta-analysis of studies of the CSF lactate concentration as a marker for both bacterial meningitis and aseptic meningitis was performed.

Methods

Electronic searches in PubMed, Scopus, the MEDION database and the Cochrane Library were conducted to identify relevant articles published before March 2009. A manual search of reference lists from selected articles was also conducted. Two reviewers independently selected relevant articles and extracted data on study characteristics, quality and accuracy.

Results

Twenty-five articles were identified that met the eligibility criteria. Diagnostic odds ratios were considerably homogenous (Chi-square P = 0.1009, I
2
= 27.6%), and the homogeneity was further confirmed by a Galbraith plot and meta-regression analysis using several covariates. The symmetrical summary receiver-operator characteristic curve (SROC), fitted using the Moses-Shapiro-Littenberg method, was positioned near the upper left corner of the SROC curve. The Q value and area under the curve were 0.9451 and 0.9840, respectively, indicating excellent accuracy. The diagnostic accuracy of the CSF lactate concentration was higher than those of other four conventional markers (CSF glucose, CSF/plasma glucose quotient, CSF protein, and CSF total number of leukocytes) using a head to head meta-analysis of the 25 included studies.

Conclusions

To distinguish bacterial meningitis from aseptic meningitis, CSF lactate is a good single indicator and a better marker compared to other conventional markers.
Variants in the Toll-interacting protein gene are associated with susceptibility to sepsis in the Chinese Han population
Authors: Song Zhenju , Yin Jun , Yao Chenling , Sun Zhan , Shao Mian , Zhang Yaping , Tao Zhengang , Huang Peizhi , Tong Chaoyang
Published: February 2011

Introduction

Deregulated or excessive host immune responses contribute to the pathogenesis of sepsis. Toll-like receptor (TLR) signaling pathways and their negative regulators play a pivotal role in the modulation of host immune responses and the development of sepsis. The objective of this study was to investigate the association of variants in the TLR signaling pathway genes and their negative regulator genes with susceptibility to sepsis in the Chinese Han population.

Methods

Patients with severe sepsis (n = 378) and healthy control subjects (n = 390) were enrolled. Five genes, namely TLR2, TLR4, TLR9, MyD88 and TOLLIP, were investigated for their association with sepsis susceptibility by a tag single nucleotide polymorphism (SNP) strategy. Twelve tag SNPs were selected based on the data of Chinese Han in Beijing from the HapMap project and genotyped by direct sequencing. The mRNA expression levels of TOLLIP were determined using real-time quantitative Polymerase Chain Reaction (PCR) assays, and concentrations of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA).

Results

Our results showed that the minor C-allele of rs5743867 in TOLLIP was significantly associated with the decreased risk of sepsis (P
adj
= 0.00062, odds ratio (OR)
adj
= 0.71, 95% confidence interval (CI) 0.59 to 0.86) after adjustment for covariates in multiple logistic regression analysis. A 3-SNP haplotype block harboring the associated SNP rs5743867 also displayed strong association with omnibus test P value of 0.00049. Haplotype GTC showed a protective role against sepsis (P
adj
= 0.0012), while haplotype GCT showed an increased risk for sepsis (P
adj
= 0.00092). After exposure to lipopolysaccharide (LPS), TOLLIP mRNA expression levels in peripheral blood mononuclear cells (PBMCs) from homozygotes for the rs5743867C allele were significantly higher than in heterozygotes and homozygotes for the rs5743867T allele (P = 0.013 and P = 0.01, respectively). Moreover, the concentrations of TNF-α and IL-6 in culture supernatants were significantly lower in the subjects of rs5743867CC genotype than in CT and TT genotype subjects (P = 0.016 and P = 0.003 for TNF-α; P = 0.01 and P = 0.002 for IL-6, respectively).

Conclusions

Our findings indicated that the variants in TOLLIP were significantly associated with sepsis susceptibility in the Chinese Han population.
A statistical framework for modeling gene expression using chromatin features and application to modENCODE datasets
Authors: Cheng Chao , Yan Koon-Kiu , Yip Kevin Y , Rozowsky Joel , Alexander Roger , Shou Chong , Gerstein Mark
Published: February 2011

We develop a statistical framework to study the relationship between chromatin features and gene expression. This can be used to predict gene expression of protein coding genes, as well as microRNAs. We demonstrate the prediction in a variety of contexts, focusing particularly on the modENCODE worm datasets. Moreover, our framework reveals the positional contribution around genes (upstream or downstream) of distinct chromatin features to the overall prediction of expression levels.
Vitamin D Deficiency Is Associated with Depletion of Circulating Endothelial Progenitor Cells and Endothelial Dysfunction in Patients with Type 2 Diabetes
Authors: Yiu Yuen-Fung , Chan Yap-Hang , Yiu Kai-Hang , Siu Chung-Wah , Li Sheung-Wai , Wong Lai-Yung , Lee Stephen W. L. , Tam Sidney , Wong Eric W. K. , Cheung Bernard M. Y. , Tse Hung-Fat
Published: February 2011

Context:

Vitamin D (Vit-D) deficiency is associated with type 2 diabetes mellitus (DM) and endothelial dysfunction. The relationship of Vit-D deficiency with circulating endothelial progenitor cells and endothelial dysfunction in type 2 DM patients nonetheless remains unclear.

Objective:

We aimed to investigate the cross-sectional association of Vit-D status with brachial flow-mediated dilation (FMD) and circulating endothelial progenitor cell (EPC) numbers in type 2 DM patients.

Design, Setting, and Participants:

We conducted a cross-sectional study of 280 patients (59% male, aged 68 ± 10 yr) with type 2 DM recruited in outpatient clinics during the winter period.

Main Outcome Measure:

We measured serum 25-hydroxyvitamin D [25(OH)D] by an ELISA kit, circulating CD34+/kinase insert domain-containing receptor (KDR)+ and CD133+/KDR+ EPCs by flow cytometry and brachial artery FMD by vascular ultrasound, respectively.

Results:

The mean serum 25(OH)D concentration was 25.00 ± 9.17 ng/ml, and 34.3% of patients had Vit-D deficiency [25(OH)D < 20 ng/ml]. Serum 25(OH)D concentration had a significant correlation with hemoglobin A1c level [B = −0.018, 95% confidence interval (CI) −0.035 to −0.002, P = 0.032]. Patients with Vit-D deficiency status had significantly lower brachial FMD (mean difference −1.43%, 95% CI −2.31 to −0.55, P = 0.001) and CD133+/KDR+EPC counts (mean difference −0.12%, 95% CI −0.21 to −0.019, P = 0.022) than those with sufficient Vit-D status after adjustment for age, sex, and cardiovascular risk factors, including hemoglobin A1c levels.

Conclusions:

Our results demonstrate that serum 25(OH)D status was significantly associated with brachial artery FMD and circulating CD133+/KDR+EPCs. This suggests that Vit-D deficiency might contribute to depletion of EPCs and endothelial dysfunction in patients with type 2 DM.
Indium Chloride‐induced Micronuclei in In Vivo and In Vitro Experimental Systems
Authors: Takagi Ryo , Suzuki Yuji , Seki Yoshiko , Ikehata Masateru , Kajihara Chieko , Shimizu Hidesuke , Yanagisawa Hiroyuki
Published: February 2011

Indium Chloride‐induced Micronuclei in In Vivo and In Vitro Experimental Systems: Ryo Takagi, et al. Department of Public Health and Environmental Medicine, Jikei University School of Medicine—

Objectives

The aim of this study was to investigate the genotoxic effects of indium trichloride (InCl3·4H 2O; InCl3) using the in vivo bone marrow micronucleus test and the in vitro CHL/IU cell micronucleus test.

Method

BALB/c mice were administered a single intraperitoneal (i.p.) injection of InCl 3 at a dose 0.625, 1.25, 2.5, 5, or 10 mg/kg b.w. The frequency of micronuclei, the ratio of polychromatic erythrocytes to normochromatic erythrocytes (P/N ratio) and body weight gain were determined 24 h after administration of the InCl In the in vitro micronucleus test, CHL/IU cells were treated continuously for 24, 48, or 72 h in the absence of S9mix (the continuous treatment method) and/or for 6 h with or without S9 mix followed by an 18, 42 or 66 h recovery time (the short time treatment method). The frequency of micronuclei was determined at the end of each culture period.

Results

The frequency of micronuclei induced by InCl3 increased in the in vivo erythroblast‐erythrocyte micronucleus test using BALB/c mice at doses of 2.5 and 5 mg/kg b.w. The P/N ratio, a marker of bone marrow toxicity, decreased significantly following the injection of InCl3. Body weight gain was also inhibited by InCl3. InCl 3 induced micronuclei in the CHL/IU cell micronucleus test in both the continuous treatment method and the short time treatment method, both with and without S9mix.

Conclusions

These results suggest that InCl3 has a genotoxic effect on mammalian cells both in vivo and in vitro.
Fracture Orientation and Proppant Selection for Optimizing Production in Horizontal Wells
Authors: Shah Subhash N. , Vincent M. C. , Rodriquez Robert , Palisch Terry
Published: February 2011

In recent years, oil and gas well operators have frequently specified highly-deviated or horizontal wells to improve reservoir contact. Although some reservoirs can be efficiently developed with unstimulated horizontal laterals, in most formations hydraulic fracturing will further improve production rates, ultimate hydrocarbon recovery, and overall field economics.

The Bombay offshore basin is the largest oil reservoir in India, and has been successfully developed with both vertical and horizontal wellbores. Despite the success of current horizontal drilling techniques, significant improvements are possible in the stimulation of these horizontal wells. Although many considerations for stimulating horizontal wells are similar to stimulation of vertical wells, there are some special challenges for horizontal well stimulation that must be addressed.

In this paper, two of these issues, fracture orientation and proppant selection, are discussed in detail. Related topics including wellbore orientation, reservoir contact, flow convergence, perforation strategies, and realistic proppant conductivity are addressed. Field examples demonstrate that hydrocarbon production can be improved with careful treatment design. It is found that the fracture orientation, proppant type, and proppant size have significant effect on ultimate production results. Experience gained from hydraulically fractured horizontal wells in North America, Siberia, and the North Sea is described.

With this rich experience through horizontal well technology, it is possible to improve hydrocarbon recovery in the Bombay offshore basin with more effectively stimulated horizontal wells.
Non-Uniform Slotted Liner Completion, a New Approach to Obtain Uniform Production Profile along Horizontal Wells
Authors: Mohammadsalehi M. , Goodarzian S. , Assef M. R.
Published: February 2011

Slotted liner is commonly used for well completion to maintain borehole integrity and control production of sand, both in land and offshore. Due to length of horizontal wells, there is a pressure drop within producing wellbore, as a result of friction and turbulent flow. Additionally, radius of damaged zone caused by drilling fluid invasion is not constant along the horizontal well. Significant amount wellbore pressure drop and/or near well formation damage leads to non-uniform production profile along horizontal well. Consequently, unbalanced depletion of reservoir and problem of gas or water coning will occur.

This paper represents an approach to eliminate occurrence of water or gas coning into producing horizontal wells which is based on precise manipulations and design of slotted liner parameters in such a way that the effect of wellbore pressure drop is compensated. Therefore, instead of running slotted liner with constant design parameters, they will vary deliberately along the well. Calculations performed by simulation software, developed based on theoretical concepts, which have been elaborately explained in this paper, comparisons between calculated data and measured field data have been made.

When the modified parameters applied, total pressure drop along horizontal well approaches to an identical value. Additionally, this procedure of design can be used directly offset the effect of invaded zone around well. As the significant outcomes, with the help of this design method, production along the wellbore will be balanced and uniform. Additionally, if coning occurs, it will occur at tip of the well rather than happening at heel of horizontal well.
Rapid Estimation of Carbon Dioxide Compressibility Factor Using Simple Predictive Tool
Authors: Bahadori A. , Vuthaluru H. B.
Published: February 2011

In this work, a simple predictive tool which is easier than existing approaches involving a fewer number of parameters, requiring less complicated and shorter computations, is presented to accurately predict carbon dioxide compressibility factor as a function of reduced temperature and reduced pressure. The proposed predictive tool shows consistently accurate results across the proposed pressure and temperature ranges. Predictions show an average absolute deviation of 0.55 % compared to existing Peng-Robinson (PR) and Soave-Redlich–Kwong (SRK) SRK equations of state which show an average absolute deviations of 0.58% and 2.30% respectively. This simple-to-use predictive tool can be of significant practical value for the engineers and scientists to have a quick check on carbon dioxide compressibility factor for temperatures up to 1000°C and pressures up to 50,000 kPa without the necessity of any experimental measurements. This is expected to benefit and making design decisions leading to informed decisions for rapid and accurate prediction carob dioxide compressibility factor in any process industry.
Efficient Hydraulic Fracturing Treatments Using Produced Formation Water in Western Siberia
Authors: Fedorov Andrey Vladimirovich , Fedorov A. , Fu D-K. , Mullen K. , Kochmar L. , Lungwitz B. , Dessinges M.
Published: February 2011

An appropriate fracturing fluid is one of the key elements for success of hydraulic fracturing treatments. In western Siberia, borate crosslinked polymer fluid has been widely used because of the high viscosity required for placement of large-size proppants. The first step to obtain the viscosity is to hydrate or dissolve a dry form of polymer and prepare a linear gel. This operation requires a minimum temperature of 25°C. Because the average temperature is below 20°C all year and as low as – 40°C in the winter (Fig. 1), this temperature requirement, coupled with the lack of freshwater sources in some locations, presents both logistical and operational challenges.Figure 1Average temperature in Tyumen Region, W. Siberia

Water produced from the Cenoman formation is readily available in many locations in western Siberia (Blackbourn Report 2010). With temperatures ranging from 35 to 50°C, Cenoman water could be an ideal source for preparing fracturing fluids. However, the water contains boron and a high level of magnesium and calcium that cause undesirable instant crosslinking of linear gel and shear and thermal instability. To eliminate the impacts of those elements, we introduced a chelating additive to the water to sequester the cations species and optimized the initial fluid pH to improve thermal stability. The concentration of chelating agent is further adjustable to ensure consistency in crosslinking delay time and to provide shear insensitivity.

Using Cenoman water and equipment for continuous mixing of fracturing fluid has greatly improved the operational efficiency and service quality of fracturing treatments in western Siberia. The time to complete a single fracturing treatment was reduced from 2 days to less than 1 day. In some cases, two treatments were performed in 1 day. As of December 2008, more than 500 fracturing treatments had been performed using Cenoman water with an average of over 94% proppant-placement rate.
Successful Re-entry in a Challenging Drilling Environment: A Case Study
Authors: Ghulam Nabi Agha , Ahmad Qureshi Saeed , Usman Arif Muhammad , Salmoon Ilyas Muhammad
Published: February 2011

Yaqut -1 well (Afiband) is located in Safedkoh Block of Dewan Petroleum Pvt Ltd at about 20km WSW of Taunsa City, district D.G. Khan- Pakistan. Well was originally drilled in 1986. Well was drilled to 2020m, tested and was declared as Dry.

Dewan Petroleum, on the basis of seismic data, Re-entered the existing borehole and deepen the same to explore the targets as Lower Cretaceous (Sand Bodies), Lower Cretaceous Sand and Jurassic Limestone. There were big challenges to face before making well usable for evaluation and testing purposes. These challenges included Installation of Wellhead, drilling of cement plugs and cement squeezing of 307m (Selective) perforations in total 792m zone against four different horizons, Drilling of 1356m of 6” hole, conducting wireline logs, running in 5” Liner and successfully cementing it against loss zones. Another challenge was of severe losses because of under-hydrostatic pore-pressure regime/ profile.

Detailed evaluation of cement slurry designs of offset wells, where there was poor cementation history; a long debate was opened between well services companies. Discussion included nine possible options, and on the basis of SWOT Analysis one with “Ultra- Light” cement slurry was selected.

This paper discusses in detail the strategy of Installing wellhead, Drilling cement plugs & squeezing-off long interval of perforations and their pressure test, along with strategy of overcoming drilling challenges, Centralization of Liner and landing the same successfully and discussion of different 5” Liner Cement Slurry design options. Furthermore it will show lab results, subsequent study results and will outline different steps used in carrying out the design, the execution and evaluation of the results of successful operations, which resulted in a restoration of high productivity.
Sophisticated ROP Prediction Technologies Based on Neural Network Delivers Accurate Drill Time Results
Authors: Moran David , Ibrahim Hani , Purwanto Arifin , Osmond Jerry
Published: February 2011

Accurately predicting the rate of penetration (ROP) is a prominent factor affecting economic and engineering decisions during well planning. However, ROP prediction based on simple algorithms applied to offset wells has historically yielded mixed results. To improve ROP predicting capabilities, the provider is applying an artificial neural network (ANN) to analyze offset drilling data. The system has significantly improved the ability to accurately predict drilling performance, despite expected changes in lithology, hole size, bit type and mud properties. The flexibility of the software package allows engineers to analyze a wide range of information and deliver high-quality ROP predictions based on previous experience and data from offset wells. The process includes detail scrutiny of the offset and training of the ANN system until the neural network is validated. The simulation is then run to solve expected ROP, using any changed drilling conditions as input.

In a recent case, an operator required a well that would have to be drilled deeper than offsets and with different borehole sizes. By applying the neural network capabilities, engineers were able to deliver analytical ROP predictions for the planned well, including quality result for different lithologies with a wide range of rock strength values. This paper will focus on the new ANN technologies being utilized for predicting drilling performance. It will also include a case study that documents its successful application.