bluuebunny/crossref_metadata_2025 huggingface dataset:
ENU-induced phenovariance in mice: inferences from 587 mutations
Authors: Arnold Carrie N , Barnes Michael J , Berger Michael , Blasius Amanda L , Brandl Katharina , Croker Ben , Crozat Karine , Du Xin , Eidenschenk Celine , Georgel Philippe , Hoebe Kasper , Huang Hua , Jiang Zhengfan , Krebs Philippe , La Vine Diantha , Li Xiaohong , Lyon Stephen , Moresco Eva Marie Y , Murray Anne R , Popkin Daniel L , Rutschmann Sophie , Siggs Owen M , Smart Nora G , Sun Lei , Tabeta Koichi , Webster Victoria , Tomisato Wataru , Won Sungyong , Xia Yu , Xiao Nengming , Beutler Bruce
Published: October 2012

Background

We present a compendium of N-ethyl-N-nitrosourea (ENU)-induced mouse mutations, identified in our laboratory over a period of 10 years either on the basis of phenotype or whole genome and/or whole exome sequencing, and archived in the Mutagenetix database. Our purpose is threefold: 1) to formally describe many point mutations, including those that were not previously disclosed in peer-reviewed publications; 2) to assess the characteristics of these mutations; and 3) to estimate the likelihood that a missense mutation induced by ENU will create a detectable phenotype.

Findings

In the context of an ENU mutagenesis program for C57BL/6J mice, a total of 185 phenotypes were tracked to mutations in 129 genes. In addition, 402 incidental mutations were identified and predicted to affect 390 genes. As previously reported, ENU shows strand asymmetry in its induction of mutations, particularly favoring T to A rather than A to T in the sense strand of coding regions and splice junctions. Some amino acid substitutions are far more likely to be damaging than others, and some are far more likely to be observed. Indeed, from among a total of 494 non-synonymous coding mutations, ENU was observed to create only 114 of the 182 possible amino acid substitutions that single base changes can achieve. Based on differences in overt null allele frequencies observed in phenotypic vs. non-phenotypic mutation sets, we infer that ENU-induced missense mutations create detectable phenotype only about 1 in 4.7 times. While the remaining mutations may not be functionally neutral, they are, on average, beneath the limits of detection of the phenotypic assays we applied.

Conclusions

Collectively, these mutations add to our understanding of the chemical specificity of ENU, the types of amino acid substitutions it creates, and its efficiency in causing phenovariance. Our data support the validity of computational algorithms for the prediction of damage caused by amino acid substitutions, and may lead to refined predictions as to whether specific amino acid changes are responsible for observed phenotypes. These data form the basis for closer in silico estimations of the number of genes mutated to a state of phenovariance by ENU within a population of G3 mice.
Polymorphisms in the p63 and p73 genes are associated with ovarian cancer risk and clinicopathological variables
Authors: Guan Xiao , Zhang Ning , Yin Yongshuo , Kong Beihua , Yang Qifeng , Han Zhiyan , Yang Xingsheng
Published: October 2012

Objective

p73 and p63 are two structural and functional homologs of p53, and their biological functions in cancer progression have attracted attention due to the presence of variants generated by genetic polymorphisms. Recently, three single nucleotide polymorphisms (SNPs) in the p63 and p73 genes have been associated with female reproduction. In the present study, we aimed to evaluate the relationship between these SNPs and ovarian cancer susceptibility and clinical pathology.

Methods

We genotyped the p63 (rs873330 [Genbank, refSNP ID] T > C [T: original base, C: mutant base]) and p73 (rs4648551 G > A and rs6695978 G > A) SNPs in ovarian cancers and healthy controls and analyzed the distributions of genotype frequencies to evaluate the association of the genotypes with the risk of ovarian cancer and the clinicopathological characteristics. Logistic regression models were applied in statistical analyses.

Results

Our research revealed that p73 rs6695978 G > A was significantly associated with ovarian cancer patients. Women with the A allele were at increased risk of ovarian cancer compared to carriers of the G allele (OR = 1.55; 95% CI:1.07–2.19; P = 0.003). Meanwhile, the at-risk A allele was positively related with the occurrence of mucinous ovarian cancer (OR = 3.48; 95% CI:1.15-6.83; P = 0.001), low degree of differentiation (OR = 1.87; 95% CI:1.03-3.47; P = 0.003), lymph node metastasis (OR = 1.69; 95% CI: 1.14-2.75; P = 0.010) and estrogen receptor positive (OR = 2.72; 95% CI: 1.38-4.81; P = 0.002). However, we were unable to find any associations of the polymorphisms in another two SNPs (rs4648551 G > A, rs873330 T > C) with ovarian cancer risk and clinicopathological parameters.

Conclusions

The p73 rs6695978 G > A polymorphism will serve as a modifier of ovarian cancer susceptibility and prognosis. Further investigations with large sample sizes and of the mechanistic relevance of p73 polymorphism will be warranted
Development and promotion in translational medicine: perspectives from 2012 sino‐american symposium on clinical and translational medicine
Authors: Qian Mengjia , Wu Duojiao , Wang Ena , Marincola Francesco M , Wang Wei , Rhodes William , Liebman Michael , Bai Chunxue , Lam Ching‐Wan , Marko‐Varga Gyorgy , Fehniger Thomas E , Andersson Roland , Wang Xiangdong
Published: October 2012

Background

Clinical translational medicine (CTM) is an emerging area comprising multidisciplinary research from basic science to medical applications and entails a close collaboration among hospital, academia and industry.

Findings

This Session focused discussing on new models for project development and promotion in translational medicine. The conference stimulated the scientific and commercial communication of project development between academies and companies, shared the advanced knowledge and expertise of clinical applications, and created the environment for collaborations.

Conclusions

Although strategic collaborations between corporate and academic institutions have resulted in a state of resurgence in the market, new cooperation models still need time to tell whether they will improve the translational medicine process.
Influence of Cr3+ substitution on the electrical and magnetic properties of Ni0.4Cu0.4Zn0.2Fe2O4 nanoparticles
Authors: Kadam Ramkrishna H , Karim Asif , Kadam Ankush B , Gaikwad Anil S , Shirsath Sagar E
Published: October 2012

The Ni0.4Cu0.2Zn0.4ferrites with different concentrations of Cr3+were synthesized at a low temperature (450°C) using sol–gel auto-combustion method. The X-ray diffraction analysis of the samples confirms the formation of a single-phase cubic spinel structure. The lattice constant decreases from 8.331 to 8.253 Å with an increase in Cr3+substitution. Bulk density decreases from 4.95 to 4.71 gm/cm3whereas porosity increases from 9.34% to 14.76% with an increase in Cr3+substitution. Transmission electron microscopy was adopted to determine the particle size. Particle size decreases from 19 to 13 nm with the addition of Cr3+ions. Saturation magnetization, coercivity, and other hysteresis parameters were measured using a vibrating sample magnetometer at room temperature with a maximum magnetic field of 8 kOe. Magnetization decreases from 62 to 48 emu/g, whereas coercivity increases from 65 to 180 Oe. The direct current (DC) resistivity increases from 3.62 × 106to 4.21 × 106Ω cm with Cr3+contentx. The dielectric constant (ε′) decreases with increasing concentration of Cr3+ions.
Polymorphisms in hormone metabolism and growth factor genes and mammographic density in Norwegian postmenopausal hormone therapy users and non-users
Authors: Ellingjord-Dale Merete , Lee Eunjung , Couto Elisabeth , Ozhand Ali , Qureshi Samera Azeem , Hofvind Solveig , Van Den Berg David J , Akslen Lars A , Grotmol Tom , Ursin Giske
Published: October 2012

Introduction

Mammographic density (MD) is one of the strongest known breast cancer risk factors. Estrogen and progestin therapy (EPT) has been associated with increases in MD. Dense breast tissue is characterized by increased stromal tissue and (to a lesser degree) increased numbers of breast epithelial cells. It is possible that genetic factors modify the association between EPT and MD, and that certain genetic variants are particularly important in determining MD in hormone users. We evaluated the association between MD and 340 tagging single nucleotide polymorphisms (SNPs) from about 30 candidate genes in hormone metabolism/growth factor pathways among women who participated in the Norwegian Breast Cancer Screening Program (NBCSP) in 2004.

Methods

We assessed MD on 2,036 postmenopausal women aged 50 to 69 years using a computer-assisted method (Madena, University of Southern California) in a cross-sectional study. We used linear regression to determine the association between each SNP and MD, adjusting for potential confounders. The postmenopausal women were stratified into HT users (EPT and estrogen-only) and non-users (never HT).

Results

For current EPT users, there was an association between a variant in the prolactin gene (PRL; rs10946545) and MD (dominant model, Bonferroni-adjusted P (Pb) = 0.0144). This association remained statistically significant among current users of norethisterone acetate (NETA)-based EPT, a regimen common in Nordic countries. Among current estrogen-only users (ET), there was an association between rs4670813 in the cytochrome P450 gene (CYP1B1) and MD (dominant model, Pb = 0.0396). In never HT users, rs769177 in the tumor necrosis factor (TNF) gene and rs1968752 in the region of the sulfotransferase gene (SULT1A1/SULT1A2), were significantly associated with MD (Pb = 0.0202; Pb = 0.0349).

Conclusions

We found some evidence that variants in the PRL gene were associated with MD in current EPT and NETA users. In never HT users, variants in the TNF and SULT1A1/SULT1A2 genes were significantly associated with MD. These findings may suggest that several genes in the hormone metabolism and growth factor pathways are implicated in determining MD.
Optimal Mode of clearance in critically ill patients with Acute Kidney Injury (OMAKI) - a pilot randomized controlled trial of hemofiltration versus hemodialysis: a Canadian Critical Care Trials Group project
Authors: Wald Ron , Friedrich Jan O , Bagshaw Sean M , Burns Karen EA , Garg Amit X , Hladunewich Michelle A , House Andrew A , Lapinsky Stephen , Klein David , Pannu Neesh I , Pope Karen , Richardson Robert M , Thorpe Kevin , Adhikari Neill KJ
Published: October 2012

Introduction

Among critically ill patients with acute kidney injury (AKI) needing continuous renal replacement therapy (CRRT), the effect of convective (via continuous venovenous hemofiltration [CVVH]) versus diffusive (via continuous venovenous hemodialysis [CVVHD]) solute clearance on clinical outcomes is unclear. Our objective was to evaluate the feasibility of comparing these two modes in a randomized trial.

Methods

This was a multicenter open-label parallel-group pilot randomized trial of CVVH versus CVVHD. Using concealed allocation, we randomized critically ill adults with AKI and hemodynamic instability to CVVH or CVVHD, with a prescribed small solute clearance of 35 mL/kg/hour in both arms. The primary outcome was trial feasibility, defined by randomization of >25% of eligible patients, delivery of >75% of the prescribed CRRT dose, and follow-up of >95% of patients to 60 days. A secondary analysis using a mixed-effects model examined the impact of therapy on illness severity, defined by sequential organ failure assessment (SOFA) score, over the first week.

Results

We randomized 78 patients (mean age 61.5 years; 39% women; 23% with chronic kidney disease; 82% with sepsis). Baseline SOFA scores (mean 15.9, SD 3.2) were similar between groups. We recruited 55% of eligible patients, delivered >80% of the prescribed dose in each arm, and achieved 100% follow-up. SOFA tended to decline more over the first week in CVVH recipients (-0.8, 95% CI -2.1, +0.5) driven by a reduction in vasopressor requirements. Mortality (54% CVVH; 55% CVVHD) and dialysis dependence in survivors (24% CVVH; 19% CVVHD) at 60 days were similar.

Conclusions

Our results suggest that a large trial comparing CVVH to CVVHD would be feasible. There is a trend toward improved vasopressor requirements among CVVH-treated patients over the first week of treatment.

Trial Registration

ClinicalTrials.gov: NCT00675818
Establishment of transgene-free induced pluripotent stem cells reprogrammed from human stem cells of apical papilla for neural differentiation
Authors: Zou Xiao-Ying , Yang Hsiao-Ying , Yu Zongdong , Tan Xiao-Bing , Yan Xing , Huang George T-J
Published: October 2012

Introduction

Induced pluripotent stem cells (iPSCs) are a potent cell source for neurogenesis. Previously we have generated iPSCs from human dental stem cells carrying transgene vectors. These exogenous transgenes may affect iPSC behaviors and limit their clinical applications. The purpose of this study was to establish transgene-free iPSCs (TF-iPSCs) reprogrammed from human stem cells of apical papilla (SCAP) and determine their neurogenic potential.

Methods

A single lentiviral 'stem cell cassette' flanked by the loxP site (hSTEMCCA-loxP), encoding four human reprogramming factors, OCT4, SOX2, KLF4, and c-MYC, was used to reprogram human SCAP into iPSCs. Generated iPSCs were transfected with plasmid pHAGE2-EF1α-Cre-IRES-PuroR and selected with puromycin for the TF-iPSC subclones. PCR was performed to confirm the excision of hSTEMCCA. TF-iPSC clones did not resist to puromycin treatment indicating no pHAGE2-EF1α-Cre-IRES-PuroR integration into the genome. In vitro and in vivo analyses of their pluripotency were performed. Embryoid body-mediated neural differentiation was undertaken to verify their neurogenic potential.

Results

TF-SCAP iPSCs were generated via a hSTEMCCA-loxP/Cre system. PCR of genomic DNA confirmed transgene excision and puromycin treatment verified the lack of pHAGE2-EF1α-Cre-IRES-PuroR integration. Transplantation of the TF-iPSCs into immunodeficient mice gave rise to teratomas containing tissues representing the three germ layers -- ectoderm (neural rosettes), mesoderm (cartilage and bone tissues) and endoderm (glandular epithelial tissues). Embryonic stem cell-associated markers TRA-1-60, TRA-2-49 and OCT4 remained positive after transgene excision. After neurogenic differentiation, cells showed neural-like morphology expressing neural markers nestin, βIII-tubulin, NFM, NSE, NeuN, GRM1, NR1 and CNPase.

Conclusions

TF-SCAP iPSCs reprogrammed from SCAP can be generated and they may be a good cell source for neurogenesis.
The Mad1–Mad2 balancing act – a damaged spindle checkpoint in chromosome instability and cancer
Authors: Schuyler Scott C. , Wu Yueh-Fu , Kuan Vivian Jen-Wei
Published: October 2012

Cancer cells are commonly aneuploid. The spindle checkpoint ensures accurate chromosome segregation by controlling cell cycle progression in response to aberrant microtubule–kinetochore attachment. Damage to the checkpoint, which is a partial loss or gain of checkpoint function, leads to aneuploidy during tumorigenesis. One form of damage is a change in levels of the checkpoint proteins mitotic arrest deficient 1 and 2 (Mad1 and Mad2), or in the Mad1:Mad2 ratio. Changes in Mad1 and Mad2 levels occur in human cancers, where their expression is regulated by the tumor suppressors p53 and retinoblastoma 1 (RB1). By employing a standard assay, namely the addition of a mitotic poison at mitotic entry, it has been shown that checkpoint function is normal in many cancer cells. However, in several experimental systems, it has been observed that this standard assay does not always reveal checkpoint aberrations induced by changes in Mad1 or Mad2, where excess Mad1 relative to Mad2 can lead to premature anaphase entry, and excess Mad2 can lead to a delay in entering anaphase. This Commentary highlights how changes in the levels of Mad1 and Mad2 result in a damaged spindle checkpoint, and explores how these changes cause chromosome instability that can lead to aneuploidy during tumorigenesis.
Self-cleaning in tree frog toe pads; a mechanism for recovering from contamination without the need for grooming
Authors: Crawford Niall , Endlein Thomas , Barnes W. Jon P.
Published: October 2012

Tree frogs use adhesive toe pads for climbing on a variety of surfaces. They rely on wet adhesion, which is aided by the secretion of mucus. In nature, the pads will undoubtedly get contaminated regularly through usage, but appear to maintain their stickiness over time. Here, we show in two experiments that the toe pads of White's tree frogs (Litoria caerulea) quickly recover from contamination through a self-cleaning mechanism. We compared adhesive forces prior to and after contamination of (1) the whole animal on a rotatable platform and (2) individual toe pads in restrained frogs mimicking individual steps using a motorised stage. In both cases, the adhesive forces recovered after a few steps but this took significantly longer in single toe pad experiments from restrained frogs, showing that use of the pads increases recovery. We propose that both shear movements and a ‘flushing’ effect of the secreted mucus play an important role in shedding particles/contaminants.
The “bridging sign”: A MR finding for combined full-thickness tears of the subscapularis tendon and the supraspinatus tendon
Authors: Jung Jin Young , Yoon Young Cheol , Cha Dong Ik , Yoo Jae-Chul , Jung Jee Young
Published: October 2012

Background

In daily practice, we discovered one of the secondary magnetic resonance (MR) findings of the subscapularis (SSC) tendon tear, the “bridging sign”, which has not been previously described.

Purpose

To describe the “bridging sign” on shoulder MR imaging and its radiological and clinical significance in patients with SSC tendon tear.

Material and Methods

Twenty-nine patients who had undergone shoulder arthroscopy and had full-thickness tear of the subscapularis tendon were enrolled. The medical records of the 29 patients were retrospectively reviewed for the duration of shoulder pain, rotator cuff tears, and associated arthroscopic findings: biceps tendon abnormality and superior glenoid labral tear. Then, preoperative shoulder MR images were retrospectively reviewed for the presence or absence of the “bridging sign” and associated MR findings: periarticular fluid and fatty atrophy of the supraspinatus and subscapularis muscles. The type of rotator cuff tear associated with the “bridging sign” was assessed and the sensitivity, specificity, and accuracy of the “bridging sign” for the diagnosis of a certain type of rotator cuff tear were calculated. Associated arthroscopic and MR findings and mean duration of the shoulder pain between the patients with and without the “bridging sign” were compared.

Results

The “bridging sign” was seen in 17 of 29 patients and corresponded to a complex of the torn and superomedially retracted subscapularis tendon, coracohumeral ligament, and superior glenohumeral ligament, adhered to the anterior margin of the torn supraspinatus (SSP) tendon on arthroscopy. All patients with the “bridging sign” had combined full-thickness tear (FTT) of the cranial 1/2 portion of the subscapularis tendon and anterior 1/2 portion of the SSP tendon. The sensitivity, specificity, and accuracy of the “bridging sign” for the diagnosis of combined FTTs of the SSC tendon and anterior portion of the SSP tendon were 81.0%, 100%, and 86.2%, respectively. The patients with the “bridging sign” had longer duration of shoulder pain and more frequent associated arthroscopic and MR findings than the patients without the “bridging sign”.

Conclusion

The “bridging sign” is a highly specific finding for combined full-thickness tears of the subscapularis tendon and anterior portion of the supraspinatus tendon, associated with more chronic shoulder pain and more sever rotator cuff tear.
Intrablastocyst injection with human CD34+/CD133+ cells increase survival of immunocompetent fumarylacetoacetate hydrolase knockout mice
Authors: Marra Emanuele , Turrini Paolo , Tripodi Marco , Ciliberto Gennaro , Padron Julio , Aurisicchio Luigi
Published: October 2012

Mice harbouring a humanized liver represent a powerful tool for translating preclinical studies of drug metabolism and pharmacokinetics into humans, as well as the exploitation of basic studies on liver pathophysiology including hepatitis C virus (HCV) infection. Human adult stem cells injected into immunocompetent mice at preimmune stages of development, generate chimeric animals harbouring a liver with relatively discrete foci of human hepatocyte-like cells. In this study, we have evaluated whether similar protocol of xenotransplantation in the presence of selective pressure might lead to a higher human-into-mouse liver repopulation, leading to a relevant improvement of liver function. Human CD34+/CD133+ cells were microinjected into blastocysts from genetically-modified mice committed to develop a lethal hepatopathy, due to the absence of the enzyme fumarylacetoacetate hydrolase (FAH). Following xenotransplantation, mouse survival was followed over time and histochemical evidence of liver chimerism was assessed. The survival expectancy of seven out of 21 intrablastocyst xenotransplanted FAH knockout ( Fah−/−) mice was significantly higher as compared with non-xenotransplanted mice. Several nodules of human hepatocyte-like cells were revealed by immunohistochemistry in the liver of rescued mice. Our data positively support the hypothesis that preimmune xenotransplantation of human stem cells into immunocompetent mice harbouring a lethal hepatic disease might lead to a functionally relevant human-mouse liver chimerism and marks a significant advancement towards the establishment of a novel translational preclinical model for liver diseases.
In vitro fertility rate of 129 strain is improved by buserelin (gonadotropin-releasing hormone) administration prior to superovulation
Authors: Vasudevan K , Sztein J M
Published: October 2012

The 129 mice are well recognized for their low fertility and it is speculated that this lack of fertility may be due to the oocyte condition. In this study we investigated superovulation regimens for the 129S1/SvImJ mouse strain to improve the oocyte quality and fertility rate of in vitro fertilization (IVF). Female mice were divided into four groups based on hormone and timing of injection. Group 1 received pregnant mare serum gonadotropin (PMSG) and 48 h later human chorionic gonadotropin (hCG); using the same dose, group 2 received hCG 52 h post-PMSG and group 3, 55 h post-PMSG. Group 4 received buserelin (gonadotropin-releasing hormone agonist [GnRH]) followed 24 h later by PMSG and then hCG 55 h post-PMSG. IVF was performed using 129S1/SvImJ oocytes and sperm; C57BL/6J sperm with 129S1/SvImJ oocytes was used as fertility control. The IVF fertility rate was 1% (Groups 1 and 2), 17% (Group 3) and 55% (Group 4) for 129 oocytes fertilized with 129 sperm. For 129 oocytes fertilized with C57BL/6J sperm, the fertility rate was 5% (Group 1), 10% (Group 2), 40% (Group 3) and 59% (Group 4). These results suggest that extending the interval time between PMSG and hCG and giving GnRH in addition to the standard PMSG and hCG treatments can improve IVF fertility rate of 129S1/SvImJ mouse strains significantly.
Managing patient pathways to achieve lung cancer waiting time targets: mixed methods study
Authors: Ip Hugh , Amer Tarik , Dangoor Michael , Zamir Affan , Gibbings-Isaac Darryl , Kochhar Ranjeev , Heymann Timothy
Published: October 2012

Objectives

England's National Health Service (NHS) introduced a 62-day target, from referral to treatment, to make lung cancer patient pathways more efficient. This study aims to understand pathway delays that lead to breaches of the target when patients need care in both secondary and tertiary setting, so more than one institution is involved.

Design

Mixed methods cross case analysis.

Setting

Two tertiary referral hospitals in London.

Participants

Database records of 53 patients were analysed. Nineteen sets of patient notes were used for pathway mapping. Seventeen doctors, four nurses, eight managers and administrators were interviewed.

Main outcome measures

Qualitative methods include pathway mapping and semi-structured interviews. Quantitative analysis of patient pathway times from cancer services records.

Results

The majority of the patient pathway (68.4%) is spent in secondary centres. There is more variability in the processes of secondary centres but tertiary centres do not have perfect processes either. Three themes emerged from discussions: information flows, pathway performance and the role of the multidisciplinary approach.

Conclusions

The actions of secondary centres have a greater influence on whether a patient breaches the 62-day target, compared with tertiary centres. Nevertheless variability exists in both, with potential for improvement.
Experimental Study of Polymer Flooding in Fractured Systems Using Five-Spot Glass Micromodel: The Role of Fracture Geometrical Properties
Authors: Abedi Behbood , Ghazanfari Mohammad Hossein , Kharrat Riyaz
Published: October 2012

Water flooding is being widely used in the petroleum industry and has been considered as a simple inexpensive secondary recovery method. But in fractured formations, existence of fracture system in reservoir rock induces an adverse effect on oil recovery by water flooding. Polymer flooding has been successfully applied as an alternative enhanced oil recovery method in fractured formations. But, the role of fracture geometrical properties on macroscopic efficiency of polymer flooding is not yet well-understood, especially in fractured five-spot systems. In this work five-spot glass micromodel, because of micro-visibility, ease of multiple experimentations and also presence of the unexplored issues, was used to experimentally investigate the influence of fracture geometrical characteristics such as fracture orientation, fracture spacing, fracture overlap and etc on the macroscopic efficiency of polymer flooding. The tests were performed on the fractured models which are initially saturated with the crude oil at fixed flow rate conditions and in a horizontally mounting. The results revealed that the macroscopic efficiency of polymer flooding depends on fracture geometrical properties. Fracture orientation showed more imposing effect than other fracture geometrical properties, and fracture with 45 degree inclination to the mean flow direction, gives greatest oil recovery factor. Large spacing fractures give more recovery than small spacing ones and in case of overlapping, fractures with less overlapping help polymer to better propagate which could be related to their greater effective fracture length. This pre-called effect could be responsible to show how continuity and width to length ratio of fractures affect recovery factor, less fracture discontinuity as well as more length to width ratio of fracture give more swept zone. Also, increasing number of fractures decreases oil recovery factor. The results of this work can be helpful to better understanding the role of fracture geometrical properties on macroscopic efficiency of polymer flooding in five-spot fractured systems.
Geochemistry and Origins of Natural Gases in the Southwestern Junggar Basin, Northwest China
Authors: Sun Ping'an , Cao Jian , Wang Xulong , Zhang Yueqian , Tang Yong , Abulimiti  , Xiang Baoli , Wu Ming
Published: October 2012

The southwestern Junggar Basin in northwest China is a significant target of basin's hydrocarbon exploration and exploitation at present. It is petroliferous mainly in oil production. However, natural gas should have good prospects because multiple sets of gas-prone source rocks are developed. Thus, in order to expand the field of hydrocarbon exploration (natural gas in particular), origins of the gases were discussed in this paper based on relatively comprehensive analyses of gas geochemistry, which include components, carbon isotopes and light hydrocarbons of gas and biomarkers of associated condensates. The results indicate two typical genetic types of gases. The first type is the coal-type and oil-type gases sourced from Permian lacustrine mudstones in the Shawan sag. It is distributed mainly in the Chepaizi area, whose most distinctive geochemical feature is the θ13C2 value (ranging from −30.29‰ to −25.09‰ with an average of −27.03‰.) The gas exploration potential is good. By contrast, the second type of gas is the coal-type gas sourced from Jurassic coal-bearing rocks in the southern basin. It is distributed mainly in the western area of the southern basin, with a few in the southern part of the Chepaizi area. θ13C2 value of the gases ranges from −27.14‰ to −21.74‰ with an average of −24.81‰, sharply heavier than that of the first type of gas. Gas exploration potential is fairly good, mainly being controlled by source-rock maturity.
Fast Predicting of Water Injection Breakthrough Time by Percolation Theory
Authors: Shegeftfard M , Zamanzadeh S.M.
Published: October 2012

One particular practical problem in oil recovery is to predict the time to breakthrough of an injected fluid in one well and the subsequent decay in the production rate of oil in another. Because we only have a stochastic view of the distribution of rock properties, we need to predict the uncertainty in the breakthrough time and post-breakthrough behavior in order to calculate the economic risk. In this paper, we apply scaling laws from percolation theory to predict the distribution of breakthrough times that can be calculated algebraically rather than directly via very time-consuming numerical simulation of large number of realizations. The main contribution is to show that percolation theory, when applied to a realistic model, can be used to obtain the same results as calculated in a more conventional way but significantly more quickly. Specially, when the parameters of scaling law optimized, we found that a previously proposed scaling form for the breakthrough time distribution when applied to a real oil field is in good agreement with more time consuming simulation results. Consequently, these methods can be used in practical engineering circumstances to aid decision making for real field problems.
Rare Earth Elements in No. 2 Coal of Huangling Mine, Huanglong Coalfield, China
Authors: Zhao Cunliang , Duan Dujuan , Li Yanheng , Zhang Jianya
Published: October 2012

Rare earth elements (REEs) can provide lots of information relevant to the evolution of source rocks, depositional environment, and epigenetic tectonic activity. In this study, 14 bench samples (including 11 coals, 1parting, 1roof and 1floor) of the No. 2 coal seam from Huangling Mine, Huanglong Coalfield, Ordos Basin, China were collected to study the REE geochemistry. The average concentration of REEs is 44.03 μg/g, and it is lower than those in coals of the Chinese and world coal. The coals are enriched in light REEs and the LREEs-HREEs have been highly fractionated, with an average (La/Yb) N of 11.38. The values of Ce/Ce* are more or less than 1 (with an average 0.92) and indicates that the anomaly of Ce is very slight. However, the values of Eu/Eu* (with an average 7.69 of coal) are distinctly higher than reported data of coals. The extremely high contents of Ba caused the geochemical anomaly of REEs. The Ba2+ was origin from the barium metallogenic belt in Qinling Old-upland.
Distribution of Uranium in the Main Coalfields of China
Authors: Huang Wenhui , Wan Huan , Finkelman Robert B. , Tang Xiuyi , Zhao Zhigen
Published: October 2012

In China, the world's largest producer of coal, the mean value of uranium in coal is 3 mg/kg, which is near the published value for uranium in coal in the United States and the world coal average. There are a few examples of Chinese coal that have exceptionally high concentrations of uranium and may be considered as a uranium source. In Hubei province in southern China a special type of stone-coal from the lower Silurian has a uranium concentration of 180 to 280 mg/kg in the coal ash. A few samples from Jurassic coal in Xinjiang of northwest China have more than 200 mg/kg uranium. The uranium in coal is mainly associated with organic matter in low rank coal. In high rank coal the uranium probably occurs in the minerals. In nature, the uranium-rich deposit is rare, and usually small in scale. Uranium abundance and occurrence in different places and strata, especially in coal stone in the South China and in marine shale, have potential hazards on the environment.
A Logarithmic Method for Reducing Binary Variables and Inequality Constraints in Solving Task Assignment Problems
Authors: Li Han-Lin , Huang Yao-Huei , Fang Shu-Cherng
Published: October 2012

This paper studies the classical task assignment problem (TAP) in which M unbreakable tasks are assigned to N agents with the objective to minimize the communication and process costs subject to each agent's capacity constraint. Because a large-size TAP involves many binary variables, most, if not all, traditional methods experience the difficulty in solving the problem within a reasonable time period. Recent works present a logarithmic approach to reduce the number of binary variables in problems with mixed-integer variables. This study proposes a new logarithmic method that significantly reduces the numbers of binary variables and inequality constraints in solving task assignment problems. Our numerical experiments demonstrate that the proposed method is superior to other known methods of this kind for solving large-size TAPs.
Zigzag Search for Continuous Multiobjective Optimization
Authors: Wang Honggang
Published: October 2012

A new method is proposed using a gradient-based zigzag search approach for multiobjective optimization (MOO) or vector optimization problems. The key idea of this method is searching around the Pareto front by applying an efficient local search procedure using the gradients of the objective functions. This local search zigzags along the Pareto surface guided by the gradients and iteratively returns the visited Pareto optima. Many continuous MOO problems have smooth objective functions and the set of the nondominated objective function values forms a regular surface in the image space. This fact motivates developing the zigzag search method for such relatively well-posed MOO problems. A simple implementation of this method, z-algorithm, is presented particularly for continuous bi-objective optimization (BOO) problems with well-connected Pareto optimal solutions. The efficiency of the z-algorithm is studied with a set of BOO problems and the algorithm performances are compared to those of a recently developed MOO algorithm, Pareto front approximation with adaptive weighted sum method.
Tafluprost: The First Preservative-Free Prostaglandin to Treat Open-Angle Glaucoma and Ocular Hypertension
Authors: Swymer Cory , Neville Michael W
Published: October 2012

OBJECTIVE:

To review the pharmacology, pharmacokinetics, clinical trial data, efficacy data, and adverse effect incidence of tafluprost.

DATA SOURCES:

A literature search was completed using PubMed, Web of Science, and Google Scholar. Tafluprost was the primary search term. Articles published between January 2008 and April 2012 were included in this review. Additional limits placed on the searches were “human” and “English.” Citations in which tafluprost appeared in the title were 36, 29, and more than 300 in PubMed, Web of Science, and Google Scholar, respectively.

STUDY SELECTION AND DATA EXTRACTION:

Three clinical trials were included in this review. One trial enrolled more than 500 subjects in a randomized fashion. Another also enrolled more than 500 subjects, although the study design was not randomized. The third trial evaluated the effects of tafluprost on subjects who had recently discontinued use of latanoprost, another prostaglandin that is approved to treat glaucoma and ocular hypertension. The duration of all 3 trials was 12 weeks.

DATA SYNTHESIS:

Tafluprost 0.0015% is the first topical prostaglandin approved by the Food and Drug Administration for treatment of open-angle glaucoma and ocular hypertension that does not contain the widely used preservative, benzalkonium chloride (BAK). Although some controversy surrounds the long-term safety of exposure to BAK, clinical trial data are inconclusive. Tafluprost, like other prostaglandin analogues, exerts its effects on prostaglandin F receptors to reduce intraocular pressure (IOP). Results from 1 trial demonstrated significant reductions in IOP when monotherapy was switched to tafluprost monotherapy. Reductions in IOP with tafluprost use were compared with those seen with use of timolol and latanoprost in 2 trials, and noninferiority was observed. Significant reductions in tear osmolarity were noted in subjects who changed from latanoprost, another prostaglandin analogue, to tafluprost therapy. Conjunctival hyperemia is the most common adverse effect seen in patients receiving drugs from this class. Many have also reported stinging, ocular pruritus, increased darkening or growth of eyelashes, and darkening of eyelids, as well as irreversible brown pigmentation of the iris.

CONCLUSIONS:

Clinical trial data suggest that tafluprost is as efficacious as other agents used in the management of ocular hypertension and glaucoma. Its use may be especially advantageous in people with allergies, sensitivities to preservatives, or dry or sensitive eyes.
Changes in Neural Connectivity Underlie Decision Threshold Modulation for Reward Maximization
Authors: Green Nikos , Biele Guido P. , Heekeren Hauke R.
Published: October 2012

Using neuroimaging in combination with computational modeling, this study shows that decision threshold modulation for reward maximization is accompanied by a change in effective connectivity within corticostriatal and cerebellar–striatal brain systems. Research on perceptual decision making suggests that people make decisions by accumulating sensory evidence until a decision threshold is crossed. This threshold can be adjusted to changing circumstances, to maximize rewards. Decision making thus requires effectively managing the amount of accumulated evidence versus the amount of available time. Importantly, the neural substrate of this decision threshold modulation is unknown. Participants performed a perceptual decision-making task in blocks with identical duration but different reward schedules. Behavioral and modeling results indicate that human subjects modulated their decision threshold to maximize net reward. Neuroimaging results indicate that decision threshold modulation was achieved by adjusting effective connectivity within corticostriatal and cerebellar–striatal brain systems, the former being responsible for processing of accumulated sensory evidence and the latter being responsible for automatic, subsecond temporal processing. Participants who adjusted their threshold to a greater extent (and gained more net reward) also showed a greater modulation of effective connectivity. These results reveal a neural mechanism that underlies decision makers' abilities to adjust to changing circumstances to maximize reward.
Ric-8a, a Guanine Nucleotide Exchange Factor for Heterotrimeric G Proteins, Regulates Bergmann Glia-Basement Membrane Adhesion during Cerebellar Foliation
Authors: Ma Shang , Kwon Hyo Jun , Huang Zhen
Published: October 2012

The cerebellum consists of an intricate array of lobules that arises during the process of foliation. Foliation not only increases surface area, but may also facilitate organization of cerebellar neural circuitry. Defects in cerebellar foliation are associated with a number of diseases. Yet, little is known about how foliation, a process involving large-scale and simultaneous movement of several different cell types, is coordinated by cell–cell signaling at the molecular level. Here we show that Ric-8a, a guanine nucleotide exchange factor in the G-protein-coupled receptor pathway, is specifically required in Bergmann glia during cerebellar foliation. We find thatric-8amutation in mice results in disorganized Bergmann glial scaffolding, defective granule cell migration, and disrupted Purkinje cell positioning. These abnormalities result from primary defects in Bergmann glia since mutations in granule cells do not show similar effects. They first arise during late embryogenesis, at the onset of foliation, whenric-8amutant Bergmann glia fail to maintain adhesion to the basement membrane specifically at emerging fissures. This suggests that Ric-8a is essential for the enhanced Bergmann glia-basement membrane adhesion required for fissure formation. Indeed, we find thatric-8a-deficient cerebellar glia show decreased affinity for basement membrane components. We also find that weakening Bergmann glia-basement membrane interaction by β1 integrin deletion results in a similar phenotype. These results thus reveal a novel role of Ric-8a in modulating Bergmann glia-basement membrane adhesion during foliation, and provide new insights into the signaling pathways that coordinate cellular movement during cerebellar morphogenesis.
Metalloproteinases and Their Associated Genes Contribute to the Functional Integrity and Noise-Induced Damage in the Cochlear Sensory Epithelium
Authors: Hu Bo Hua , Cai Qunfeng , Hu Zihua , Patel Minal , Bard Jonathan , Jamison Jennifer , Coling Donald
Published: October 2012

Matrix metalloproteinases (MMPs) and their related gene products regulate essential cellular functions. An imbalance in MMPs has been implicated in various neurological disorders, including traumatic injuries. Here, we report a role for MMPs and their related gene products in the modulation of cochlear responses to acoustic trauma in rats. The normal cochlea was shown to be enriched in MMP enzymatic activity, and this activity was reduced in a time-dependent manner after traumatic noise injury. The analysis of gene expression by RNA sequencing and qRT-PCR revealed the differential expression of MMPs and their related genes between functionally specialized regions of the sensory epithelium. The expression of these genes was dynamically regulated between the acute and chronic phases of noise-induced hearing loss. Moreover, noise-induced expression changes in two endogenous MMP inhibitors, Timp1 and Timp2, in sensory cells were dependent on the stage of nuclear condensation, suggesting a specific role for MMP activity in sensory cell apoptosis. A short-term application of doxycycline, a broad-spectrum inhibitor of MMPs, before noise exposure reduced noise-induced hearing loss and sensory cell death. In contrast, a 7 d treatment compromised hearing sensitivity and potentiated noise-induced hearing loss. This detrimental effect of the long-term inhibition of MMPs on noise-induced hearing loss was further confirmed using targeted Mmp7 knock-out mice. Together, these observations suggest that MMPs and their related genes participate in the regulation of cochlear responses to acoustic overstimulation and that the modulation of MMP activity can serve as a novel therapeutic target for the reduction of noise-induced cochlear damage.
Hair Cell Replacement in Adult Mouse Utricles after Targeted Ablation of Hair Cells with Diphtheria Toxin
Authors: Golub Justin S. , Tong Ling , Ngyuen Tot B. , Hume Cliff R. , Palmiter Richard D. , Rubel Edwin W. , Stone Jennifer S.
Published: October 2012

We developed a transgenic mouse to permit conditional and selective ablation of hair cells in the adult mouse utricle by inserting the humandiphtheria toxin receptor(DTR) gene into thePou4f3gene, which encodes a hair cell-specific transcription factor. In adult wild-type mice, administration of diphtheria toxin (DT) caused no significant hair cell loss. In adultPou4f3+/DTRmice, DT treatment reduced hair cell numbers to 6% of normal by 14 days post-DT. Remaining hair cells were located primarily in the lateral extrastriola. Over time, hair cell numbers increased in these regions, reaching 17% of untreatedPou4f3+/DTRmice by 60 days post-DT. Replacement hair cells were morphologically distinct, with multiple cytoplasmic processes, and displayed evidence for active mechanotransduction channels and synapses characteristic of type II hair cells. Three lines of evidence suggest replacement hair cells were derived via direct (nonmitotic) transdifferentiation of supporting cells: new hair cells did not incorporate BrdU, supporting cells upregulated the pro-hair cell geneAtoh1, and supporting cell numbers decreased over time. This study introduces a new method for efficient conditional hair cell ablation in adult mouse utricles and demonstrates that hair cells are spontaneously regeneratedin vivoin regions where there may be ongoing hair cell turnover.
Pain and Plasticity: Is Chronic Pain Always Associated with Somatosensory Cortex Activity and Reorganization?
Authors: Gustin Sylvia M. , Peck Chris C. , Cheney Lukas B. , Macey Paul M. , Murray Greg M. , Henderson Luke A.
Published: October 2012

The somatosensory cortex remodels in response to sensory deprivation, with regions deprived of input invaded by neighboring representations. The degree of cortical reorganization is correlated with ongoing pain intensity, which has led to the assumption that chronic pain conditions are invariably associated with somatosensory cortex reorganization. Because the presentation and etiology of chronic pain vary, we determined whether cortical changes in human subjects are similar for differing pain types. Using functional and anatomical magnetic resonance imaging, we found that, while human patients with neuropathic pain displayed cortical reorganization and changes in somatosensory cortex activity, patients with non-neuropathic chronic pain did not. Furthermore, cortical reorganization in neuropathic pain patients was associated with changes in regional anatomy. These data, by showing that pain per se is not associated with cortical plasticity, suggest that treatments aimed at reversing cortical reorganization should only be considered for use in patients with certain types of chronic pain.
Psychophysical Chromatic Mechanisms in Macaque Monkey
Authors: Stoughton Cleo M. , Lafer-Sousa Rosa , Gagin Galina , Conway Bevil R.
Published: October 2012

Chromatic mechanisms have been studied extensively with psychophysical techniques in humans, but the number and nature of the mechanisms are still controversial. Appeals to monkey neurophysiology are often used to sort out the competing claims and to test hypotheses arising from the experiments in humans, but psychophysical chromatic mechanisms have never been assessed in monkeys. Here we address this issue by measuring color-detection thresholds in monkeys before and after chromatic adaptation, employing a standard approach used to determine chromatic mechanisms in humans. We conducted separate experiments using adaptation configured as either flickering full-field colors or heterochromatic gratings. Full-field colors would favor activity within the visual system at or before the arrival of retinal signals to V1, before the spatial transformation of color signals by the cortex. Conversely, gratings would favor activity within the cortex where neurons are often sensitive to spatial chromatic structure. Detection thresholds were selectively elevated for the colors of full-field adaptation when it modulated along either of the two cardinal chromatic axes that define cone-opponent color space [L vs M or S vs (L + M)], providing evidence for two privileged cardinal chromatic mechanisms implemented early in the visual-processing hierarchy. Adaptation with gratings produced elevated thresholds for colors of the adaptation regardless of its chromatic makeup, suggesting a cortical representation comprised of multiple higher-order mechanisms each selective for a different direction in color space. The results suggest that color is represented by two cardinal channels early in the processing hierarchy and many chromatic channels in brain regions closer to perceptual readout.