bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Determination of Material Creep Constants Using Miniature Creep Test Specimens
Authors: Hyde Tom H. , Ali Balhassn S. M. , Sun Wei
Published: January 2014

Full size creep test specimens, i.e., conventional uniaxial creep test specimen and Bridgman notch specimens are usually used to determine the full set of material constants for any creep model. However, in many situations, sufficient material is not available for theses specimens to be manufactured from it. Therefore, small creep test specimens have been introduced and used to determine (i) creep constants and (ii) the remaining life time for engineering components. Two commonly used small creep specimen types, i.e., the impression and the small ring creep tests, are used in this paper to determine the steady state creep constants. However, these specimen types are limited for use in determining the secondary creep properties, i.e., they are unable to determine the full set of material creep constants for creep damage models. In this paper the recently developed small two-bar creep test specimen and the newly developed small notched specimen test are described and used to determine a full set of material constants for Kachanov and Liu-Murakami creep damage models. The small notched specimen manufacturing, loading and testing procedures are described in this paper. P91 steel at 600 °C and (Bar-257) P91 steel at 650 °C have been used to compare the material constants obtained from the small two-bar and the small notched creep test specimens with those obtained from the conventional uniaxial creep test specimens and Bridgman notch specimens. The results show remarkably good agreement between the two sets of results.
Co-registration of speech production datasets from electromagnetic articulography and real-time magnetic resonance imaging
Authors: Kim Jangwon , Lammert Adam C. , Kumar Ghosh Prasanta , Narayanan Shrikanth S.
Published: January 2014

This paper describes a spatio-temporal registration approach for speech articulation data obtained from electromagnetic articulography (EMA) and real-time Magnetic Resonance Imaging (rtMRI). This is motivated by the potential for combining the complementary advantages of both types of data. The registration method is validated on EMA and rtMRI datasets obtained at different times, but using the same stimuli. The aligned corpus offers the advantages of high temporal resolution (from EMA) and a complete mid-sagittal view (from rtMRI). The co-registration also yields optimum placement of EMA sensors as articulatory landmarks on the magnetic resonance images, thus providing richer spatio-temporal information about articulatory dynamics.
STAT3 Induction of miR-146b Forms a Feedback Loop to Inhibit the NF-κB to IL-6 Signaling Axis and STAT3-Driven Cancer Phenotypes
Authors: Xiang Michael , Birkbak Nicolai J. , Vafaizadeh Vida , Walker Sarah R. , Yeh Jennifer E. , Liu Suhu , Kroll Yasmin , Boldin Mark , Taganov Konstantin , Groner Bernd , Richardson Andrea L. , Frank David A.
Published: January 2014

An epigenetic modification prevents the production of a tumor-suppressing and anti-inflammatory microRNA in receptor-negative breast cancers.
Biasing GPCR Signaling from Inside
Authors: Shukla Arun K.
Published: January 2014

Strategies that target the intracellular domain of G protein–coupled receptors may enable development of new intracellular biased signaling modulators.
Crystal Structure of Carbapenemase OXA-58 from Acinetobacter baumannii
Authors: Smith Clyde A. , Antunes Nuno Tiago , Toth Marta , Vakulenko Sergei B.
Published: January 2014

Class D β-lactamases capable of hydrolyzing last-resort carbapenem antibiotics represent a major challenge for treatment of bacterial infections. Wide dissemination of these enzymes in
Acinetobacter baumannii
elevated this pathogen to the category of most deadly and difficult to treat. We present here the structure of the OXA-58 β-lactamase, a major class D carbapenemase of
A. baumannii
, determined to 1.30-Å resolution. Unlike two other
Acinetobacter
carbapenemases, OXA23 and OXA-24, the OXA-58 enzyme lacks the characteristic hydrophobic bridge over the active site, despite conservation of the residues which participate in its formation. The active-site residues in OXA-58 are spatially conserved in comparison to those in other class D β-lactamases. Lys86, which activates water molecules during the acylation and deacylation steps, is fully carboxylated in the OXA-58 structure. In the absence of a substrate, a water molecule is observed in the active site of the enzyme and is positioned in the pocket that is usually occupied by the 6α-hydroxyethyl moiety of carbapenems. A water molecule in this location would efficiently deacylate good substrates, such as the penicillins, but in the case of carbapenems, it would be expelled by the 6α-hydroxyethyl moiety of the antibiotics and a water from the surrounding medium would find its way to the vicinity of the carboxylated Lys86 to perform deacylation. Subtle differences in the position of this water in the acyl-enzyme complexes of class D β-lactamases could ultimately be responsible for differences in the catalytic efficiencies of these enzymes against last-resort carbapenem antibiotics.
Phase I, Open-Label, Safety and Pharmacokinetic Study To Assess Bronchopulmonary Disposition of Intravenous Eravacycline in Healthy Men and Women
Authors: Connors Kevin P. , Housman Seth T. , Pope J. Samuel , Russomanno John , Salerno Edward , Shore Eric , Redican Susan , Nicolau David P.
Published: January 2014

This study evaluated the pulmonary disposition of eravacycline in 20 healthy adult volunteers receiving 1.0 mg of eravacycline/kg intravenously every 12 h for a total of seven doses over 4 days. Plasma samples were collected at 0, 1, 2, 4, 6, and 12 h on day 4, with each subject randomized to undergo a single bronchoalveolar lavage (BAL) at 2, 4, 6, or 12 h. Drug concentrations in plasma, BAL fluid, and alveolar macrophages (AM) were determined by liquid chromatography-tandem mass spectrometry, and the urea correction method was used to calculate epithelial lining fluid (ELF) concentrations. Pharmacokinetic parameters were estimated by noncompartmental methods. Penetration for ELF and AM was calculated by using a ratio of the area under the concentration time curve (AUC
0–12
) for each respective parameter against free drug AUC (
f
AUC
0–12
) in plasma. The total AUC
0–12
in plasma was 4.56 ± 0.94 μg·h/ml with a mean
f
AUC
0–12
of 0.77 ± 0.14 μg·h/ml. The eravacycline concentrations in ELF and AM at 2, 4, 6, and 12 h were means ± the standard deviations (μg/ml) of 0.70 ± 0.30, 0.57 ± 0.20, 0.34 ± 0.16, and 0.25 ± 0.13 with a penetration ratio of 6.44 and 8.25 ± 4.55, 5.15 ± 1.25, 1.77 ± 0.64, and 1.42 ± 1.45 with a penetration ratio of 51.63, respectively. The eravacycline concentrations in the ELF and AM achieved greater levels than plasma by 6- and 50-fold, respectively, supporting further study of eravacycline for patients with respiratory infections.
Disuccinyl Betulin Triggers Metacaspase-Dependent Endonuclease G-Mediated Cell Death in Unicellular Protozoan Parasite Leishmania donovani
Authors: Chowdhury Sayan , Mukherjee Tulika , Chowdhury Somenath Roy , Sengupta Souvik , Mukhopadhyay Sibabrata , Jaisankar Parasuraman , Majumder Hemanta K.
Published: January 2014

The unicellular organism
Leishmania
undergoes apoptosis-like cell death in response to external stress or exposure to antileishmanial agents. Here, we showed that 3-
O
,28-
O
-disuccinyl betulin (DiSB), a potent topoisomerase type IB inhibitor, induced parasitic cell death by generating oxidative stress. The characteristic feature of the death process resembled the programmed cell death (PCD) seen in higher eukaryotes. In the current study, the generation of reactive oxygen species (ROS), followed by the depolarization of mitochondrial membrane potential (ΔΨ
m
), caused a loss in ATP production in
Leishmania
parasites. This further gave positive feedback to produce a large amount of ROS, which in turn caused oxidative DNA lesions and genomic DNA fragmentation. The treatment of promastigotes with DiSB induced high expression levels of metacaspase protein that led to cell death in this unicellular organism. The PCD was insensitive to benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk), suggesting that the death process was not associated with the activation of caspases. DiSB treatment translocated
Leishmania donovani
endonuclease G (LdEndoG) from mitochondria to the nucleus, which was responsible for the DNA degradation process. Conditional antisense knockdown of
L. donovani
metacaspase (LdMC), as well as EndoG, -subverted death of the parasite and rescued cell cycle arrest in G
1
phase. The present study on the effector molecules associated with the PCD pathway of the parasite should help to manifest the mechanisms of PCD and also might be exploited in antileishmanial chemotherapy.
An Altered Mycobacterium tuberculosis Metabolome Induced by
katG
Mutations Resulting in Isoniazid Resistance
Authors: Loots Du Toit
Published: January 2014

The most common form of drug resistance found in tuberculosis (TB)-positive clinical samples is monoresistance to isoniazid. Various genomics and proteomics studies to date have investigated this phenomenon; however, the exact mechanisms relating to how this occurs, as well as the implications of this on the TB-causing organisms function and structure, are only partly understood. Considering this, we followed a metabolomics research approach to identify potential new metabolic pathways and metabolite markers, which when interpreted in context would give a holistic explanation for many of the phenotypic characteristics associated with a
katG
mutation and the resulting isoniazid resistance in
Mycobacterium tuberculosis
. In order to achieve these objectives, gas chromatography-time of flight mass spectrometry (GCxGC-TOFMS)-generated metabolite profiles from two isoniazid-resistant strains were compared to a wild-type parent strain. Principal component analyses showed clear differentiation between the groups, and the metabolites best describing the separation between these groups were identified. It is clear from the data that due to a mutation in the
katG
gene encoding catalase, the isoniazid-resistant strains experience increased susceptibility to oxidative stress and have consequently adapted to this by upregulating the synthesis of a number of compounds involved in (i) increased uptake and use of alkanes and fatty acids as a source of carbon and energy and (ii) the synthesis of a number of compounds directly involved in reducing oxidative stress, including an ascorbic acid degradation pathway, which to date hasn't been proposed to exist in these organisms.
OXA-48 Carbapenemase-Producing Salmonella enterica Serovar Kentucky Isolate of Sequence Type 198 in a Patient Transferred from Libya to Switzerland
Authors: Seiffert Salome N. , Perreten Vincent , Johannes Sönke , Droz Sara , Bodmer Thomas , Endimiani Andrea
Published: January 2014

Here, we report a case of OXA-48-producing
Salmonella enterica
serovar Kentucky of sequence type 198 (ST198) from perianal screening cultures of a patient transferred from Libya to Switzerland. The
bla
OXA-48
gene was carried by Tn
1999.2
and located on an ∼60-kb IncL/M plasmid. This
Salmonella
strain also possessed the
bla
VEB-8
,
aac
(
6
)-
Ib
,
tet
(A),
sul1
, and
mphA
resistance genes and substitutions in GyrA (Ser83Phe and Asp87Asn) and ParC (Ser80Ile). This finding emphasizes that prompt screening strategies are essential to prevent the dissemination of carbapenemase producers imported from countries where they are endemic.
Defect of CARD9 Leads to Impaired Accumulation of Gamma Interferon-Producing Memory Phenotype T Cells in Lungs and Increased Susceptibility to Pulmonary Infection with Cryptococcus neoformans
Authors: Yamamoto Hideki , Nakamura Yuri , Sato Ko , Takahashi Yurie , Nomura Toshiki , Miyasaka Tomomitsu , Ishii Keiko , Hara Hiromitsu , Yamamoto Natsuo , Kanno Emi , Iwakura Yoichiro , Kawakami Kazuyoshi
Published: January 2014

Caspase recruitment domain-containing protein 9 (CARD9) is an adaptor molecule signal that is critical for NF-κB activation and is triggered through C-type lectin receptors (CLRs), which are pattern recognition receptors that recognize carbohydrate structures. Previous studies have reported thatCryptococcus neoformans, a fungal pathogen that causes meningoencephalitis in AIDS patients, is recognized through some CLRs, such as mannose receptors or DC-SIGN. However, the role of CARD9 in the host defense against cryptococcal infection remains to be elucidated. In the present study, we analyzed the role of CARD9 in the host defense against pulmonary infection withC. neoformans. CARD9 gene-disrupted (knockout [KO]) mice were highly susceptible to this infection, as shown by the reduced fungal clearance in the infected lungs of CARD9 KO mice, compared to that in wild-type (WT) mice. Gamma interferon (IFN-γ) production was strongly reduced in CARD9 KO mice during the innate-immunity phase of infection. Reduced IFN-γ synthesis was due to impaired accumulation of NK and memory phenotype T cells, which are major sources of IFN-γ innate-immunity-phase production; a reduction in the accumulation of these cells was correlated with reduced CCL4, CCL5, CXCL9, and CXCL10 synthesis. However, differentiation of Th17 cells, but not of Th1 cells, was impaired at the adaptive-immunity phase in CARD9 KO mice compared to WT mice, although there was no significant difference in the infection susceptibility between interleukin 17A (IL-17A) KO and WT mice. These results suggest that CARD9 KO mice are susceptible toC. neoformansinfection probably due to the reduced accumulation of IFN-γ-expressing NK and memory phenotype T cells at the early stage of infection.
Elucidating the Genetic Basis of Crystalline Biofilm Formation in Proteus mirabilis
Authors: Holling N. , Lednor D. , Tsang S. , Bissell A. , Campbell L. , Nzakizwanayo J. , Dedi C. , Hawthorne J. A. , Hanlon G. , Ogilvie L. A. , Salvage J. P. , Patel B. A. , Barnes L. M. , Jones B. V.
Published: January 2014

Proteus mirabilis
forms extensive crystalline biofilms on urethral catheters that occlude urine flow and frequently complicate the management of long-term-catheterized patients. Here, using random transposon mutagenesis in conjunction with
in vitro
models of the catheterized urinary tract, we elucidate the mechanisms underpinning the formation of crystalline biofilms by
P. mirabilis
. Mutants identified as defective in blockage of urethral catheters had disruptions in genes involved in nitrogen metabolism and efflux systems but were unaffected in general growth, survival in bladder model systems, or the ability to elevate urinary pH. Imaging of biofilms directly on catheter surfaces, along with quantification of levels of encrustation and biomass, confirmed that the mutants were attenuated specifically in the ability to form crystalline biofilms compared with that of the wild type. However, the biofilm-deficient phenotype of these mutants was not due to deficiencies in attachment to catheter biomaterials, and defects in later stages of biofilm development were indicated. For one blocking-deficient mutant, the disrupted gene (encoding a putative multidrug efflux pump) was also found to be associated with susceptibility to fosfomycin, and loss of this system or general inhibition of efflux pumps increased sensitivity to this antibiotic. Furthermore, homologues of this system were found to be widely distributed among other common pathogens of the catheterized urinary tract. Overall, our findings provide fundamental new insight into crystalline biofilm formation by
P. mirabilis
, including the link between biofilm formation and antibiotic resistance in this organism, and indicate a potential role for efflux pump inhibitors in the treatment or prevention of
P. mirabilis
crystalline biofilms.
Management of internal resorption of central incisor using hybrid technique
Authors: Gayathri Prabakaran , Pandey Ramesh Kumar , Jain Eesha
Published: January 2014

Internal inflammatory root resorption is characterised by progressive destruction of intraradicular dentin and dentinal tubules along the root canal wall. A number of theories have been proposed as a possible cause for internal resorption. It is usually asymptomatic and detected during routine radiographic investigations. Prompt diagnosis and early management of such defects is essential to maintain the integrity of the tooth. Non-surgical and surgical methods are the two main strategies involved in the management of internal resorption. The non-surgical method is usually preferred, but in cases of extensive resorption with external root perforation, surgical intervention has been advocated. The present case illustrates repair of perforating internal resorption by hybrid method, using mineral trioxide aggregate and gutta-percha, following surgical exposure. After a 10-month follow-up, no clinical and radiographic abnormalities were observed. Additionally, there was also marked reduction in periodontal pocket depth.
An extraordinary survival at the age of 67 years in an unoperated case tetralogy of Fallot presenting as systemic hypertension despite RV dysfunction
Authors: Prakash Sadashivappa Surhonne , Sharma Rajni , Agrawal Navin , Shankar Somanna
Published: January 2014

Tetralogy of Fallot is a cyanotic congenital heart disease characterised by a tetrad of four anomalies including ventricular septal defect, pulmonary stenosis, over-riding of aorta and right ventricular hypertrophy with high incidence of infant and early childhood mortality with middle age survival less than 5%. Most cases require treatment in infancy and are symptomatic early on. Rare cases of survival to middle age have been reported especially after the fourth decade. We report an unoperated case of tetralogy of Fallot diagnosed at the age of 67 which is one of the longest time periods of diagnosis of a life-threatening congenital heart disease. Despite tetralogy and having right ventricular dysfunction manifested in the form of congestive symptoms, this patient presented with systemic hypertension along with cyanosis and clubbing which is considered to be a relatively rare presentation in this syndrome. The patient wished to be managed conservatively.
Stratified medicine in European Medicines Agency licensing: a systematic review of predictive biomarkers
Authors: Malottki Kinga , Biswas Mousumi , Deeks Jonathan J , Riley Richard D , Craddock Charles , Johnson Philip , Billingham Lucinda
Published: January 2014

Objectives

Stratified medicine is often heralded as the future of clinical practice. Key part of stratified medicine is the use of predictive biomarkers, which identify patient subgroups most likely to benefit (or least likely to experience harm) from an intervention. We investigated how many and what predictive biomarkers are currently included in European Medicines Agency (EMA) licensing.

Setting

EMA licensing.

Participants

Indications and contraindications of all drugs considered by the EMA and published in 883 European Public Assessment Reports and Pending Decisions.

Primary and secondary outcome measures

Data were collected on: the type of the biomarker, whether it selected a subgroup of patients based on efficacy or toxicity, therapeutic area, marketing status, date of licensing decision, date of inclusion of the biomarker in the indication or contraindication and on orphan designation.

Results

49 biomarker–indication–drug (B-I-D) combinations were identified over 16 years, which included 37 biomarkers and 41 different drugs. All identified biomarkers were molecular. Six drugs (relating to 10 B-I-D combinations) had an orphan designation at the time of licensing. The identified B-I-D combinations were mainly used in cancer and HIV treatment, and also in hepatitis C and three other indications (cystic fibrosis, hyperlipoproteinaemia type I and methemoglobinaemia). In 45 B-I-D combinations, biomarkers were used as predictive of drug efficacy and in four of drug toxicity. It appeared that there was an increase in the number of B-I-D combinations introduced each year; however, the numbers were too small to identify any trends.

Conclusions

Given the large body of literature documenting research into potential predictive biomarkers and extensive investment into stratified medicine, we identified relatively few predictive biomarkers included in licensing. These were also limited to a small number of clinical areas. This might suggest a need for improvement in methods of translation from laboratory findings to clinical practice.
An analysis of the learning curve to achieve competency at colonoscopy using the JETS database
Authors: Ward Stephen Thomas , Mohammed Mohammed A , Walt Robert , Valori Roland , Ismail Tariq , Dunckley Paul
Published: January 2014

Objective

The number of colonoscopies required to reach competency is not well established. The primary aim of this study was to determine the number of colonoscopies trainees need to perform to attain competency, defined by a caecal intubation rate (CIR) ≥90%. As competency depends on completion, we also investigated trainee factors that were associated with colonoscopy completion.

Design

The Joint Advisory Group on GI Endoscopy in the UK has developed a trainee e-portfolio from which colonoscopy data were retrieved. Inclusion criteria were all trainees who had performed a total of ≥20 colonoscopies and had performed ≤50 colonoscopies prior to submission of data to the e-portfolio. The primary outcome measure was colonoscopy completion. The number of colonoscopies required to achieve CIR ≥90% was calculated by the moving average method and learning curve cumulative summation (LC-Cusum) analysis. To determine factors which determine colonoscopy completion, a mixed effect logistic regression model was developed which allowed for nesting of patients within trainees and nesting of patients within hospitals, with various patient, trainee and training factors entered as fixed effects.

Results

297 trainees undertook 36 730 colonoscopies. By moving average analysis, the cohort of trainees reached a CIR of 90% at 233 procedures. By LC-Cusum analysis, 41% of trainees were competent after 200 procedures. Of the trainee factors, the number of colonoscopies, intensity of training and previous flexible sigmoidoscopy experience were significant factors associated with colonoscopy completion.

Conclusions

This is the largest study to date investigating the number of procedures required to achieve competency in colonoscopy. The current training certification benchmark in the UK of 200 procedures does not appear to be an inappropriate minimum requirement. The LC-Cusum chart provides real time feedback on individual learning curves for trainees. The association of training intensity and flexible sigmoidoscopy experience with colonoscopy completion could be exploited in training programmes.
The first substantive evidence of Utatsusaurus (Ichthyopterygia) from the Sulphur Mountain Formation (Lower–Middle Triassic) of British Columbia, Canada: a skull roof description in comparison with other early taxa
Authors: Cuthbertson Robin S. , Russell Anthony P. , Anderson Jason S.
Published: January 2014

We describe the skull roof anatomy of PRPRC 2007.08.81, a new specimen of late Olenekian (Spathian) ichthyopterygian from the Vega-Phroso Siltstone Member of the Sulphur Mountain Formation of British Columbia, Canada. Based on the presence of a well-developed anterolateral prefrontal process, parietal that is deeply excavated along its posteromedial margin, and skull roof sutural patterns, PRPRC 2007.08.81 closely resembles other Olenekian forms such as Utatsusaurus, Grippia, Chaohusaurus, and Gulosaurus (a new taxon recently described from British Columbia, Canada). However, due to their shared apomorphic supratemporal terrace morphology, PRPRC 2007.08.81 is identified as Utatsusaurus sp. With the only other known conclusive Utatsusaurus material retrieved from the Osawa Formation (Lower Triassic) of Japan, the broad palaeogeographic distribution of this taxon suggests a radiation event for Ichthyopterygia occurring prior to the latter part of the Olenekian. However, despite this inference, the palaeogeographic origin of Ichthyopterygia continues to be unclear; only the acquisition and interpretation of additional chronologically early ichthyopterygian material will resolve the early evolutionary history of this group.
Medicinal Herbs in the Prevention and Treatment of Osteoporosis
Authors: Li Chenrui , Li Qiang , Liu Ruijun , Niu Yinbo , Pan Yalei , Zhai Yuankun , Mei Qibing
Published: January 2014

Osteoporosis is a common disease with wide prevalence, especially in the elderly population. Osteoporosis induced fractures not only decrease the patient's life quality, but also cause heavy financial burden to the society. Although current medications for osteoporosis are effective, numerous adverse effects have been observed accompanying their clinical applications. Effective prevention and therapy strategies with high safety are critical, which benefit both individual patients and the whole society. Traditional Chinese medicines have been used for thousands of years to treat bone related diseases in China and a number of modern preparations have been developed that are currently commercially available. In addition, several medicinal herbs demonstrated therapeutic effects against osteoporosis in animal models. This paper reviewed the anti-osteoporotic effects of traditional Chinese formulas, medicinal herbs and bioactive constituents based on clinical trials and in vivo animal studies. Due to the lack of rigorous studies to compare the effectiveness with conventional interventions, traditional formulas are recommended as alternative medications or supplements to treat osteoporosis at the current stage. Although there are abundant natural resources with anti-osteoporotic effects, either in the form of medicinal herbs or bioactive components, much work need to be accomplished before they are developed into potential drugs.
Phytochemistry and Biology of Loranthus parasiticus Merr, a Commonly Used Herbal Medicine
Authors: Moghadamtousi Soheil Zorofchian , Kamarudin Muhamad Noor Alfarizal , Chan Chim Kei , Goh Bey Hing , Kadir Habsah Abdul
Published: January 2014

Loranthus parasiticus Merr (L. parasiticus) is a member of Loranthaceae family and is an important medicinal plant with a long history of Chinese traditional use. L. parasiticus, also known as Sang Ji Sheng (in Chinese), benalu teh (in Malay) and baso-kisei (in Japanese), is a semiparasitic plant, which is mostly distributed in the southern and southwestern regions of China. This review aims to provide a comprehensive overview of the ethnomedicinal use, phytochemistry and pharmacological activity of L. parasiticus and to highlight the needs for further investigation and greater global development of the plant's medicinal properties. To date, pharmacological studies have demonstrated significant biological activities, which support the traditional use of the plant as a neuroprotective, tranquilizing, anticancer, immunomodulatory, antiviral, diuretic and hypotensive agent. In addition, studies have identified antioxidative, antimutagenic, antiviral, antihepatotoxic and antinephrotoxic activity. The key bioactive constituents in L. parasiticus include coriaria lactone comprised of sesquiterpene lactones: coriamyrtin, tutin, corianin, and coriatin. In addition, two proanthocyanidins, namely, AC trimer and (+)-catechin, have been recently discovered as novel to L. parasiticus. L. parasiticus usefulness as a medicinal plant with current widespread traditional use warrants further research, clinical trials and product development to fully exploit its medicinal value.
Therapeutic Angiogenesis after Ischemic Stroke: Chinese Medicines, Bone Marrow Stromal Cells (BMSCs) and their Combinational Treatment
Authors: Zhang Qian , Zhao Yong-Hua
Published: January 2014

Ischemic stroke is a clinical acute disease which causes neurological dysfunction and threatens a patient's life. Because the mechanism of pathology is complicated and most patients miss the best therapeutic window time, the effect of the treatment is not satisfied at present. Numerous studies indicated new vessels not only recuperated blood flow in the ischemic boundary zone, but also facilitated endogenous neurogenesis and improved neurological function after ischemic stroke. Therefore, angiogenesis has been an important research field in neurovascular regeneration. Recently, some Chinese medicines, bone marrow stromal cells (BMSCs) and their combination treatment were demonstrated to have beneficial effects in promoting angiogenesis both in vitro and in vivo. In this review, we summarized the effective mechanisms of Chinese medicines and BMSCs, as well as BMSCs in combination with Chinese medicines on angiogenesis post-stroke.
Phosphatase-Mediated Intracellular Signaling Contributes to Neuroprotection by Flavonoids of Iris tenuifolia
Authors: Jalsrai Aldarmaa , Numakawa Tadahiro , Ooshima Yoshiko , Adachi Naoki , Kunugi Hiroshi
Published: January 2014

A variety of flavonoids are suggested to be useful for the treatment of brain-related disorders, including dementia and depression. An investigation on the characteristics of the extracted compounds of Iris tenuifolia Pall. (IT) is of much interest, as this plant has been used as a traditional medicine. In the present study, we examined the effect of total flavonoids obtained from IT on cultured cortical neurons under oxidative-stress and found that pretreatment with IT flavonoids significantly inhibited H 2 O 2-induced cell death in cortical neurons. Such a survival-promoting effect by IT flavonoids was partially blocked by inhibitors for extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase/Akt (PI3K/Akt) cascades, both of which are known as survival-promoting signaling molecules. Furthermore, the phosphorylation of Src homology-2 (SH2) domain-containing phosphatase2 (Shp2) was induced by IT flavonoids, and the protective effect of IT flavonoids was abolished by NSC87877, an inhibitor for Shp2, suggesting the involvement of Shp2-mediated intracellular signaling in flavonoid-dependent neuroprotection.
Effects of Carnosine on Cyclophosphamide-Induced Hematopoietic Suppression in Mice
Authors: Xu Meng , He Rong-Rong , Zhai Yu-Jia , Abe Keiichi , Kurihara Hiroshi
Published: January 2014

Cyclophosphamide is one of the most widely used chemotherapeutic agents in treating cancers. Chemotherapy drug-induced oxidative stress produces side effects. The severity of myelosuppression increases with a high dose of cyclophosphamide. Chicken soup or chicken essence, a traditional Chinese aliment, is a popular health supplement for patients with cancers or other diseases in Asia. As a major functional component of chicken meat extract, carnosine (beta-alanyl-L-histidine), a dipeptide of the amino acids beta-alanine and histidine, has been shown to have strong antioxidant activities. In the present study, we investigated the effects of carnosine on hematopoietic suppression in mice treated with cyclophosphamide. As expected, we found that cyclophosphamide administration (with a single dose of 150 mg/kg) induced a rapid (within 24 hours) and severe hematopoietic suppression in mice. We further showed that carnosine administration (100 mg/kg/day or 200 mg/kg/day for continuous seven days) could substantially improve suppressed hematopoietic functions and accelerate the recovery of leukocyte counts, bone marrow spontaneous proliferation, colony stimulating activity (CSA) in serum, and production of endogenous cytokines such as interleukin-3 (IL-3) and stem cell factor (SCF). These results indicate that carnosine has the potential to promote the recovery from hematopoietic suppression induced by cyclophosphamide. Our data suggest that carnosine holds a potential in clinical application to minimize the side effects induced by chemotherapeutic agents such as cyclophosphamide and thus will substantially improve the overall anti-tumor effects of the standard chemotherapies.
Du-Zhong (Eucommia ulmoides) Prevents Disuse-Induced Osteoporosis in Hind Limb Suspension Rats
Authors: Pan Yalei , Niu Yinbo , Li Chenrui , Zhai Yuankun , Zhang Rong , Guo Xin , Mei Qibing
Published: January 2014

Du-Zhong has a long history of being used in traditional Chinese formulas to treat bone related diseases. The objective of the present study is to systematically investigate the effects of Du-Zhong cortex extract (DZCE) on disuse-induced osteoporosis. Rats were randomly divided into four groups, and three groups were treated with hind limb suspension (HLS). Control and HLS group received deionized distilled water, while the other two groups received alendronate (2.0 mg/kg/day) and DZCE (300 mg/kg/day) respectively by intragastric gavage for six weeks (two weeks prior to and during the four weeks of HLS). Dual-energy X-ray absorptiometry, assay of biochemical markers, and three-point bending test were employed to determine the effect of various treatments on bone mass, turnover, and strength. The trabecular bone microarchitecture was assessed by microCT analysis. DZCE could effectively prevent the bone loss induced by HLS, which was indicated by decreased levels of bone turnover markers as well as the changes in urinary calcium and phosphorus. The DZCE treatment also enhanced the biomechanical strength of bone and prevented the deterioration of trabecular bone microarchitecture. DZCE administration was able to prevent disuse-induced osteoporosis by regulating the bone metabolism, suggesting that DZCE could be used as an alternative therapy for the prevention of disuse-induced osteoporosis.
Induction of Nrf2 and Metallothionein as a Common Mechanism of Hepatoprotective Medicinal Herbs
Authors: Wu Qin , Zhang Dan , Tao Na , Zhu Qiong-Ni , Jin Tao , Shi Jing-Shan , Liu Jie
Published: January 2014

Many Chinese medicines have the potential to be hepatoprotective and therefore can be used to treat acute and chronic liver diseases. The challenge is to identify the molecular target for their protective mechanism. This study investigated the induction of nuclear factor-erythroid 2(NF-E2)-related factor 2 (Nrf2) antioxidant genes and metallothionein as a common mechanism of hepatoprotective effects of Chinese medicines such as Piper puberulum. Mice were pretreated with Piper puberulum extract (PPE, 500 mg/kg, po) or vehicles for seven days, followed by intoxication with CCl4(25 μl/kg, ip for 16 h), D-galactosamine (800 mg/kg, ip for 8 h), or acetaminophen (400 mg/kg, ip for 8 h). Hepatotoprotection was evaluated by serum enzyme activities and histopathology. To determine the mechanism of protection, mice were given PPE (250–1000 mg/kg, po for seven days) and livers were collected to quantify the expression of Nrf2-targeted genes and metallothionein. Nrf2-null mice were also used to determine the role of Nrf2 in PPE-mediated hepatoprotection.PPE pretreatment protected against the hepatotoxicity produced by CCl4, D-galactosamine, and acetaminophen, as evidenced by decreased serum enzyme activities and ameliorated liver lesions. PPE treatment increased the expression of hepatic Nrf2, NAD(P)H:quinone oxidoreductase1 (Nqo1), heme oxygenase-1 (Ho-1), glutamate–cysteine ligases (Gclc), and metallothionein (MT), at both transcripts and protein levels. PPE protected wild-type mice from CCl4and acetaminophen hepatotoxicity, but not Nrf2-null mice, fortifying the Nrf2-dependent protection. In conclusion, induction of the Nrf2 antioxidant pathways and metallothionein appears to be a common mechanism for hepatoprotective herbs such as PPE.
Antinociceptive and Anti-Inflammatory Activities ofCuscuta chinensisSeeds in Mice
Authors: Liao Jung-Chun , Chang Wen-Te , Lee Meng-Shiou , Chiu Yung-Jia , Chao Wei-Kai , Lin Ying-Chih , Lin Ming-Kuem , Peng Wen-Huang
Published: January 2014

The seeds of Cuscuta chinensis, Cuscutae Semen, are commonly used as a medicinal material for treating the aching and weakness of the loins and knees, tonifying the defects of the liver and the kidney, and treating the diarrhea due to hypofunction of the kidney and the spleen. Since aching and inflammation are highly correlated with such diseases, the aim of this study is to investigate the possible antinociceptive and anti-inflammatory mechanisms of the seeds of C. chinensis. The antinociceptive effect of the seeds of C. chinensis was evaluated via the acetic acid-induced writhing response and formalin-induced paw licking methods. The anti-inflammatory effect was evaluated via the λ-carrageenan induced mouse paw edema method. The results found that 100 and 500 mg/kg of the methanol extract of the seeds of C. chinensis( CCMeOH) significantly decreased (p < 0.01 and p < 0.001, respectively) the writhing response in the acetic acid assay. Additionally, 20–500 mg/kg of CCMeOHsignificantly decreased licking time at the early (20 and 100 mg/kg, p < 0.001) and late phases (100 mg/kg, p < 0.01; 500 mg/kg, p < 0.001) of the formalin test, respectively. Furthermore, CCMeOH(100 and 500 mg/kg) significantly decreased (p < 0.01 and p < 0.001, respectively) edema paw volume four hours after λ-carrageenan had been injected. The results in the following study also revealed that the anti-inflammatory mechanism of CCMeOHmay be due to declined levels of NO and MDA in the edema paw by increasing the activities of SOD, GPx and GRd in the liver. In addition, CCMeOHalso decreased IL-1β, IL-6, NF-κB, TNF-α, and COX-2 levels. This is the first study to demonstrate the possible mechanisms for the antinociceptive and anti-inflammatory effects of CCMeOHin vivo. Thus, it provides evidence for the treatment of Cuscutae Semen in inflammatory diseases.
THE MoEDAL EXPERIMENT AT THE LHC — A NEW LIGHT ON THE HIGH ENERGY FRONTIER
Authors: PINFOLD JAMES L.
Published: January 2014

In 2010, the CERN (European Centre for Particle Physics Research) Research Board unanimously approved MoEDAL, the seventh international experiment at the Large Hadron Collider (LHC), which is designed to search for avatars of new physics signified by highly ionizing particles. A MoEDAL discovery would have revolutionary implications for our understanding of the microcosm, providing insights into such fundamental questions as: do magnetic monopoles exist, are there extra dimensions or new symmetries of nature; what is the mechanism for the generation of mass; what is the nature of dark matter and how did the big bang unfurl at the earliest times.
PARTIALLY PUMPED RANDOM LASERS
Authors: ANDREASEN JONATHAN , BACHELARD NICOLAS , BHAKTHA SHIVAKIRAN B. N. , CAO HUI , SEBBAH PATRICK , VANNESTE CHRISTIAN
Published: January 2014

Conventional lasers consist of two components: a gain material that is pumped in order to provide amplification of light and a cavity to provide feedback. Random lasers replace the traditional laser cavity with a random, multiple-scattering medium. This can give rise to complex lasing behavior, such as unpredictable multidirectional and multifrequency output. Controlling these systems has proved difficult and, until now, has consisted of material and structural manipulations. In random lasers, the most common pumping mechanism is an optical field, which can be applied uniformly or partially across the scattering medium. Partial pumping, referring to the restricted spatial extent of the pump applied to the gain material, is therefore quite ubiquitous in such systems. In contrast to conventional lasers, however, the impact of partial pumping can be significant in random lasers as a subset of the scattering medium is probed. In this review, we discuss state-of-the-art investigations of partially pumped random lasers. Numerical and experimental investigations of how even a simple spot profile of the pump can dramatically alter random laser output are presented. First, the simple case of partial pumping in strongly scattering systems where laser modes are spatially confined is described. Then the most common but more difficult case of weakly scattering random lasers is considered. Here, modes are spatially extended, forcing greater mode interaction and making the random laser output more difficult to predict. Finally, we review recent works that show how the pumping degree of freedom allows a general increase in control over random lasers.
OPTICAL PROPERTIES OF AGaAsPYRAMID QUANTUM DOT: SECOND- AND THIRD-HARMONIC GENERATION
Authors: BAHRAMIYAN H. , KHORDAD R.
Published: January 2014

In the present work, we have studied the second-harmonic generation (SHG) and third-harmonic generation (THG) in a pyramid quantum dot. For this purpose, we first obtain the energy levels and wavefunctions of this system. Then, we have used an analytic expression for the SHG and THG by a compact density matrix approach and an iterative procedure. The SHG and THG enhance and shift to lower energies by increasing the height (h) and vertex angle (φ). According to the results, it is found that the structural parameters have great influence on the SHG and THG of a pyramid quantum dot.
Foreign Direct Investment in China and India: Diasporas in Homeland Reform
Authors: YE Min
Published: January 2014

China and India have drawn on transnational diasporas to implement past reforms. Entrepreneurial diasporas were the bedrock of China's foreign direct investment and exports. Professional diasporas were key policy advisors in India. Both countries presently have diasporas to carry out social reform in China and to spur entrepeneurship in India. Whether diasporas can play such roles in the future depends on the leadership and vision of their home states.
China's Shadow Banking in Spotlight
Authors: YANG Mu , YAO Jielu
Published: January 2014

Shadow banking in China encompasses informal financing activities including both underground lending and the banks' off-balance-sheet credit. The lack of formal credit access prompted the development of China's underground lending. Banks' off-balance-sheet credit refers to various contingent liabilities of commercial banks. Though the Chinese government has taken measures to lower risks posed by shadow banking, it needs to move towards more market-determined interest rates and lower entry barriers to the banking sector.
Nansha New District in Guangdong: State Initiatives and Perspectives
Authors: YU Hong
Published: January 2014

The Chinese central government mapped out a new national development area and new blueprint for Nansha New Area of Guangzhou in September 2012. Central and local governments expect that the development of Nansha would help speed up the industrial upgrading of Guangdong. However, the current institutional framework reflects that the Nansha government lacks the authority to exercise real autonomy over local development, implement reform initiatives or achieve reform breakthroughs.
Fracture analysis in the Amellago outcrop and permeability predictions
Authors: Malinouskaya Iryna , Thovert Jean-François , Mourzenko Valeri V. , Adler Pierre M. , Shekhar Ravi , Agar Susan , Rosero Enrique , Tsenn Michael
Published: January 2014

Field observations from several outcrops in the Eastern High Atlas Mountains, near Amellago (Morocco), are used to determine fracture-network model parameters, such as the aspect ratio of the fractures represented as rectangles whose longer side is horizontal, the volumetric area of fracture surfaces, the fracture mean size and the fracture density. The fracture orientations can be roughly approximated by Fisher distributions, where the parameters are determined by outcrop measurements. The permeability of the fracture networks can be calculated by application of the Snow equation for infinite fractures or by numerical resolution of the flow equation for fracture networks generated with the parameters deduced from the outcrop measurements. These two permeability estimations are shown to be in good agreement, which suggests that theoretical or semi-empirical solutions may provide reasonable approximations of fracture-network permeability in some carbonate reservoirs when conditioned to appropriate outcrop and subsurface data.
Interaction of stratigraphic and sedimentological heterogeneities with flow in carbonate ramp reservoirs: impact of fluid properties and production strategy
Authors: Fitch P. J. R. , Jackson M. D. , Hampson G. J. , John C. M.
Published: January 2014

It is well known that heterogeneities in carbonate reservoirs impact fluid flow during production. However, few studies have examined the impact of the same heterogeneities on flow behaviour with different fluid properties and production scenarios. We use integrated flow simulation and experimental design techniques to investigate the relative, first-order impact of stratigraphic and sedimentological heterogeneities on simulated recovery in carbonate ramp reservoirs. Two production strategies are compared, which promote dominance of either horizontal or vertical flow.

We find that the modelled geology is more important than the simulated fluid properties and production scenarios over the ranges tested. Of the heterogeneities modelled here, rock properties and stratigraphic heterogeneities that control reservoir architecture and the spatial distribution of environment of deposition (EOD) belts are important controls on recovery regardless of the production strategy. The presence of cemented hardground surfaces becomes the key control on oil recovery in displacements dominated by vertical flow. Permeability anisotropy is of low importance for all production strategies. The impacts of stratigraphic heterogeneities on recovery factor and water breakthrough are more strongly influenced by fluid properties and well spacing in displacements dominated by vertical flow. These results help to streamline the reservoir modelling process, by identifying key heterogeneities, and to optimize production strategies.
Effect of strain geometry on the petrophysical properties of plastically deformed aggregates: experiments on Solnhofen limestone
Authors: Llana-Fúnez Sergio , Rutter Ernest H.
Published: January 2014

Specimens of Solnhofen limestone were deformed under conditions where calcite deforms plastically using four experimental configurations: extension, torsion, direct shear and axisymmetric shortening. All experiments were run on dry specimens at the same temperature (600 °C), confining pressure (200 MPa) and comparable strain rates (
c.
10
−4
s
−1
). The different experimental settings and the heterogeneity of deformation within some of the specimens provided a large range of strain geometries. They allowed locally imposed strain geometries to be related to the crystallographic preferred orientation (CPO) patterns of calcite and the orientation of the shape fabric of calcite grains. CPO in calcite was measured using electron back-scattered diffraction (EBSD) in scanning electron microscopy. The development of CPO during deformation under the dominance of intracrystalline plasticity contains information about the strain geometry accumulated in rocks in 3D, although in nature the strain geometry can be modified by dynamic recrystallization that was not seen in the experiments. The different CPO patterns have a significant effect on the velocity structure of the deformed aggregates. Seismic properties inferred from CPO show that the orientation of the fastest
V

p

wave aligns with principal strain directions that are not equivalent in different strain geometries.
Computation takes time, but how much?
Authors: Wilhelm Reinhard , Grund Daniel
Published: January 2014

Timing analysis for hard real-time systems.