bluuebunny/crossref_metadata_2025 huggingface dataset:
An evidence based approach to the management of salivary masses
Authors: Isa A.Y. , Hilmi O.J.
Published: September 2009

Background:  Salivary lumps are common and constitute 13.8% of all lumps assessed at the North Glasgow neck lump clinic. We present our management plan for these conditions.

Method:  Literature search using key words salivary lumps or glands or cancer or sialadenitis or sialalisthiasis in combination with diagnosis, management, investigation, treatment, intervention and surgery was performed in June 2009 using MEDLINE and Pubmed. Data from the North Glasgow neck lump clinic database are also presented.

Results:  Published literature on management of salivary lumps is level 2/3 evidence.

Conclusion:  The majority of salivary gland swellings can be adequately assessed with ultrasound and ultrasound guided FNA. The majority of patients with salivary gland tumours are likely to benefit from surgical excision. Due to the higher risk of malignancy in submandibular gland tumours surgical excision should be undertaken, unless there is significant co‐morbidity.
Fetal Liver Very Small Embryonic/Epiblast Like Stem Cells Follow Developmental Migratory Pathway of Hematopoietic Stem Cells
Authors: Zuba‐Surma Ewa K. , Kucia Magda , Rui Liu , Shin Dong‐Myung , Wojakowski Wojtek , Ratajczak Janina , Ratajczak Mariusz Z.
Published: September 2009

Fetal liver (FL) has been described as a source of both hematopoietic and nonhematopoietic stem cells. Recently we have purified from murine adult bone marrow (BM) a population of CXCR4+Oct‐4+SSEA‐1+Sca‐1+Lin−CD45− very small embryonic/epiblast‐like stem cells (VSELs). By employing several complementary imaging and molecular strategies, we report in this study that VSELs, like hematopoietic stem cells (HSCs), are highly enriched in murine FL during the second trimester of gestation. Subsequently, at the beginning of the third trimester of gestation their number decreases, which corresponds to the time when HSCs egress FL and follow the stromal derived factor‐1 (SDF‐1) gradient in order to colonize developing BM. Thus, our data support the hypothesis that VSELs are a mobile pool of primitive stem cells that respond to similar chemotactic gradients as HSCs and follow their developmental migratory route.
WNT Proteins: Environmental Factors Regulating HSC Fate in the Niche
Authors: Luis Tiago C. , Staal Frank J.T.
Published: September 2009

The Wnt signaling pathway has been implicated in regulation of hematopoiesis through a plethora of studies from many different laboratories. However, different inducible gain‐ and loss‐of‐function approaches retrieved controversial and sometimes contradictory results. Different levels of activation of the pathway, dosages of Wnt signaling required, and the interference by other signals in the context of Wnt activation collectively explain these controversies. Gain‐of‐function or in vitro exposure to WNT proteins and more specifically WNT3a was shown to enhance hematopoietic stem cell (HSC) activity, but its exact role was still not completely understood. In a recent study we analyzed the hematopoietic system of mice deficient for this specific Wnt gene. Wnt3a deficiency results in early embryonic lethality around embryonic day 12.5 (E12.5), precluding analysis in adult mice, but allowing hematopoiesis to be studied in fetal liver (FL) and in the just colonized thymic rudiment. Notably, we showed that long‐term HSCs and multipotent progenitors are reduced in FL and have severely reduced long‐term reconstitution capacity as observed in serial transplantation assays. Of interest, deficiency in Wnt3a leads to complete abolition of canonical Wnt signaling in FL hematopoietic stem and progenitor cells. This HSC deficiency is not explained by altered cell cycle or survival and is irreversible, since it cannot be restored by transplantation into Wnt3a‐competent mice. In addition, Wnt3a deficiency differentially affects myeloid and B‐lymphoid lineages, with myeloid cells being affected at the progenitor level, while B lymphopoiesis is apparently unaffected. Immature thymocytes, however, were reduced in cell numbers due to lack of Wnt3a production by the thymic microenvironment. Our results show that while in the thymus Wnt3a provides cytokine‐like, proliferative stimuli to developing thymocyte Wnt3a regulates cell fate decisions of FL HSC in a nonredundant way.
Hematopoietic Development from Human Induced Pluripotent Stem Cells
Authors: Lengerke Claudia , Grauer Matthias , Niebuhr Nina I. , Riedt Tamara , Kanz Lothar , Park In‐Hyun , Daley George Q.
Published: September 2009

A decade of research on human embryonic stem cells (ESC) has paved the way for the discovery of alternative approaches to generating pluripotent stem cells. Combinatorial overexpression of a limited number of proteins linked to pluripotency in ESC was recently found to reprogram differentiated somatic cells back to a pluripotent state, enabling the derivation of isogenic (patient‐specific) pluripotent stem cell lines. Current research is focusing on improving reprogramming protocols (e.g., circumventing the use of retroviral technology and oncoproteins), and on methods for differentiation into transplantable tissues of interest. In mouse ESC, we have previously shown that the embryonic morphogens BMP4 and Wnt3a direct blood formation via activation of Cdx and Hox genes. Ectopic expression of Cdx4 and HoxB4 enables the generation of mouse ESC‐derived hematopoietic stem cells (HSC) capable of multilineage reconstitution of lethally irradiated adult mice. Here, we explore hematopoietic development from human induced pluripotent stem (iPS) cells generated in our laboratory. Our data show robust differentiation of iPS cells to mesoderm and to blood lineages, as shown by generation of CD34+CD45+ cells, hematopoietic colony activity, and gene expression data, and suggest conservation of blood patterning pathways between mouse and human hematopoietic development.
Mesenchymal Stromal Cells
Authors: Bernardo Maria Ester , Locatelli Franco , Fibbe Willem E.
Published: September 2009

Mesenchymal stromal cells (MSCs) are multipotent cells that can be isolated from several human tissues and expanded ex vivo for clinical use. MSCs are identified by their adherent properties, immunephenotype, and differentiation potential. MSCs display immunological properties that have been demonstrated both in vitro and in vivo, in animal models and in humans, although the exact mechanisms underlying these effects remain largely unknown. MSCs preferentially home to damaged tissue and secrete paracrine factors with anti‐inflammatory properties. The immunomodulatory and reparative and anti‐inflammatory properties of MSCs have been tested in a variety of animal models and have been applied in specific clinical settings. Potential clinical applications of MSCs include prevention and treatment of therapy‐resistant acute graft‐versus‐host disease, prevention and treatment of rejection after either hematopoieitc stem cell and solid organ transplantation, tissue repair, and treatment of inborn errors and autoimmune diseases. This review focuses on recent advances that have broadened our understanding of the biological and functional properties of MSCs, which are increasingly attracting the attention of researchers involved in the optimization of approaches for reparative and regenerative cell therapy, as well as in the perspective of modulating immune response against alloantigens or, even, autoantigens.
In vitro Myogenic Differentiation of Human Bone Marrow–Derived Mesenchymal Stem Cells as a Potential Treatment for Urethral Sphincter Muscle Repair
Authors: Drost Adriana C. , Weng Sibylle , Feil Gerhard , Schäfer Jochen , Baumann Simon , Kanz Lothar , Sievert Karl‐Dietrich , Stenzl Arnulf , Möhle Robert
Published: September 2009

To explore a new treatment strategy for urinary incontinence, human bone marrow mesenchymal stem cells (MSC) of the first in vitro passage were exposed to 5‐azacytidine (AZA) to induce myogenic differentiation, and cultured for a total of six passages. Expression of stem cell surface antigens and intracellular α‐actin was examined by flow cytometry at the end of each passage and compared to that of native MSC (not exposed to AZA) cultured in parallel. To analyze differentiation into striated muscle, expression of the transcription factor MyoD1 and myosin heavy chain (MyHC) was examined by RT‐PCR. Both native and AZA‐exposed MSC of all passages were negative for the progenitor/endothelial antigen CD34, leukocytic CD45, and endothelial/monocytic CD31. In contrast, the MSC markers CD73, CD90, CD105, and intracellular actin were detected in both groups of MSC throughout the culture period. After an initial increase, the expression level of MSC antigens decreased over time particularly in AZA‐exposed MSC. Expression of smooth muscle α‐actin also declined, but was greater in AZA‐exposed MSC throughout the culture period. Varying percentages of MSC cultures expressed MyoD1 and MyHC mRNA. In late passages, AZA‐exposed MSC tended to be more frequently positive than native MSC. In pilot experiments, transplantation of MSC into the bladder neck tissue of athymic rats was feasible; long‐term analyses are pending. We conclude that independent of AZA exposure, MSC express smooth and striated muscle antigens. Treatment with AZA slightly increases myogenic differentiation, but may not be necessary in future studies of MSC as a treatment modality for urinary incontinence.
Disease Models from Pluripotent Stem Cells
Authors: Lengerke Claudia , Daley George Q.
Published: September 2009

Murine models of congenital and acquired diseases are invaluable yet often do not faithfully mirror human pathophysiology. Embryonic stem (ES) cells differentiated in vitro recapitulate aspects of early embryogenesis and differentiate into multiple somatic tissues, thereby serving as a powerful platform for developmental studies in the human. Analysis of genetically modified ES cells (by lentiviral gene transduction or derivation from embryos carrying genetic diseases, for example) offers the unprecedented opportunity to study in detail disease initiation and progression during embryonic development. ES cells and induced pluripotent stem (iPS) cells obtained by somatic cell reprogramming from patients affected by various disorders promise unique insights into the gradual pathogenesis of disease, moreover enabling development of customized cellular therapies by in vitro gene correction in autologous cells.
Functional Heterogeneity of the Bone Marrow Vascular Niche
Authors: Kopp Hans‐Georg , Hooper Andrea T. , Avecilla Scott T. , Rafii Shahin
Published: September 2009

Sinusoidal endothelial cells (SECs) comprise the platform where trafficking into and out of the BM occurs and where hematopoietic stem and progenitor cells (HSPC) harbor and receive cues for self‐renewal, survival, and differentiation. Therefore, SECs are referred to as a bone marrow vascular niche (BMVN). Hematopoietic regeneration has been shown to occur only with concurrent angiogenic regeneration. However, there are still not sufficient means to identify and isolate SECs, therefore the “niche endothelial cell” remains incompletely characterized. VEGF‐receptor‐3 (VEGFR3) is expressed exclusively by the SECs, while Sca1 and Tie2 are only expressed on the VEGFR3− arteriolar endothelium. We previously demonstrated the importance of vascular recovery in hematopoietic regeneration from myelosuppression due to cytotoxic agents or whole‐body irradiation. Therefore to establish the functional importance of SECs, the mechanisms underlying BMVN regeneration were examined utilizing a 5‐fluorouracil (5‐FU) myelosuppression model of vascular damage. Injection of antibodies against murine VEGFR‐1 and ‐2 had no significant effect on hemangiogenic recovery. However, when soluble VEGFR‐1, a decoy receptor for VEGF‐A and PlGF, was injected after 5‐FU, both angiogenic remodeling and regeneration of megakaryopoiesis were delayed. In conclusion, we show that the bone marrow vasculature comprises heterogeneous compartments. SECs are distinguished from arterioles by unique immunophenotypes. Regeneration of damaged SECs is the rate‐limiting step in hematopoietic regeneration from myelosuppressive therapy. Novel, high‐efficiency VEGF‐binding drugs in combination with chemotherapeutic agents may lead to cases of prolonged cytopenia.
Tenderness Perception of Poultry Major Pectoralis Muscle during Mastication
Authors: Lee Y.S. , Owens C.M. , Meullenet J.F.
Published: September 2009

ABSTRACT:  The relationship between textural perception of poultry meat and the masticatory activity and chewing behavior of 7 subjects were investigated. A total of 90 broilers were slaughtered at 7 wk of age and deboned at either 1.25, 4, or 24 h postmortem (PM). Sensory analysis on cooked meat was conducted by 7 trained meat descriptive panelists. Panelists were asked to evaluate initial hardness, hardness of mass, cohesiveness of mass, and number of chews related to meat tenderness. Tenderness of cooked meat was also predicted instrumentally by both the Meullenet–Owens razor shear (MORS) and Blunt–Meullenet–Owens razor shear (BMORS). Masticatory muscle (anterior‐temporalis and masseter) activities during chewing were measured by electromyography (EMG) and 19 parameters were used to characterize muscle activity during mastication. Jaw movement velocity and trajectory to characterize the chewing behavior was also recorded by electrognathography (EGN) during mastication. Significant differences among fillets deboned at various times PM were found in all sensory attributes. Significant differences in sensory attributes, muscle activities, and jaw movements among subjects were also observed. It was found that poultry meat texture was better predicted by muscle activity parameters (EMG) than by chewing behavior (EGN). Overall, EMG parameters calculated from mid and late chewing cycles were better predictors of poultry texture perception than initial cycles, indicating that comminuting of poultry meat is an important aspect of its texture perception.
Measurement of transepidermal water loss from clipped and unclipped anatomical sites on the dog
Authors: Oh W‐S , Oh T‐H
Published: September 2009

Objectives  To establish a standardised clipping method for the measurement of transepidermal water loss (TEWL) with a VapoMeter® in Beagle dogs and to identify the optimal anatomical site for TEWL measurement.

Procedure  TEWL values obtained from skin sites on five healthy Beagles clipped using two different blade angles (standard vs non‐standard) were compared. TEWL values for 48 h were also obtained from seven different anatomical sites that had differing hair density. The hair was clipped in the intensively haired anatomical sites (head, lower and upper back and tail), but not clipped in the sparsely haired sites (ear, inguinal region, footpad).

Results  The TEWL values for the standard and non‐standard clipping sites were 6.3 ± 1.31 and 27.2 ± 1.11 g/h/m2, respectively. We found the upper back among the clipped sites was the most appropriate site for TEWL measurement over 48 h after clipping, whereas among the unclipped sites the ear was the most appropriate, because the TEWL values from those anatomical sites had the least fluctuation and were less affected by movement.

Conclusion  The clipping method and anatomical site should be standardised in order to minimise the experimental variation in TEWL measurement in dogs.
Inhibition of hepatic stellate cells proliferation by mesenchymal stem cells and the possible mechanisms
Authors: Wang Jing , Bian Chunjing , Liao Lianming , Zhu Yashu , Li Jing , Zeng Lifen , Zhao Robert Chunhua
Published: September 2009

Aim: During fibrosis, hepatic stellate cells (HSCs) undergo a complex activation process characterized by increased proliferation and extracellular matrix deposition. Previous studies have suggested that mesenchymal stem cells (MSCs) may ameliorate fibrogenesis and represent a promising strategy for cell therapy. However, the underlying mechanisms are not fully understood.

Methods: Hepatic stellate cells were treated with or without MSCs. Then cell proliferation and cell cycle were analyzed. Production of soluble factors by MSCs and its relation with cell proliferation suppression was evaluated by transwell co‐culture and RNA interference. Effects of MSCs on the gene expression of collagen were also evaluated.

Results: MSCs induced G0/G1arrest of HSCs growth partly through secreting soluble factors TGF‐β3 and HGF, which resulted in up‐regulation of p21Cip1and p27Kip1expression and down‐regulation of cyclinD1. MSCs inhibited the phosphorylation of extracellular signal‐regulated kinase (ERK) 1/2 and reduced gene expression of collagen type I and III. MSCs did not reverse the proliferation and collagen type I gene expression of HSCs provoked by PDGF.

Conclusions: The growth inhibition of HSCs induced by MSCs through an arrest in the G0/G1phase of the cell cycle is partially mediated by secretion of TGF‐β3 and HGF. MSCs inhibit HSCs activation through decreasing phosphorylation of extracellular signal‐regulated kinase (ERK) 1/2. These results further support MSCs may be used as a novel therapy for treating fibrotic diseases in human.
Correlation of YMDD mutation and breakthrough hepatitis with hepatitis B virus DNA and serum ALT during lamivudine treatment
Authors: Kobayashi Mariko , Suzuki Fumitaka , Akuta Norio , Yatsuji Hiromi , Hosaka Tetsuya , Sezaki Hitomi , Kobayashi Masahiro , Kawamura Yusuke , Suzuki Yoshiyuki , Arase Yasuji , Ikeda Kenji , Mineta Rie , Iwasaki Satomi , Watahiki Sachiyo , Kumada Hiromitsu
Published: September 2009

Aim:  Continuous lamivudine treatment is associated with high frequency of drug resistance. We analyzed the incidence of tyrosine‐methionine‐aspartate‐aspartate (YMDD) motif mutant and breakthrough hepatitis (BTH) in hepatitis B virus (HBV) DNA positive patients receiving lamivudine for > 1 year and correlated it with HBV DNA and alanine aminotransferase (ALT) levels to evaluate if these measurements can provide a practical option for monitoring patients in clinical practice and define early switch from lamivudine therapy.

Methods:  Of the 929 patients receiving lamivudine for > 1 year, 359 patients who maintained an ALT level of ≤ 40 IU/L during the course of lamivudine treatment were stratified into two groups based on the duration of lamivudine treatment – one receiving lamivudine for < 3 years and the other for ≥ 3 years.

Results:  The incidence of YMDD motif in patients receiving lamivudine for < 3 years was 27% in patients with ALT ≤ 20 IU/L, 58% with ALT ≤ 30 IU/L, and 63% with ALT ≤ 40 IU/L, (P = 0.002). The corresponding incidence of BTH was 2%, 7%, and 48% (P < 0.001). The incidence of YMDD motif and BTH in these patients was 7% and 2% with HBV DNA < 2.6 (log copies/mL) and ALT ≤ 20 IU/L, while with ALT at 21–30, the YMDD motif mutant was 16% and BTH was 0%.

Conclusion:  Correlation of ALT and HBV DNA levels with YMDD motif mutant and BTH indicates that these measurements can be used in clinical practice for deciding early switch from lamivudine to other suitable antiviral therapies.
Development of HCC in patients receiving adefovir dipivoxil for lamivudine‐resistant hepatitis B virus mutants
Authors: Hosaka Tetsuya , Suzuki Fumitaka , Kobayashi Masahiro , Hirakawa Miharu , Kawamura Yusuke , Yastuji Hiromi , Sezaki Hitomi , Akuta Norio , Suzuki Yoshiyuki , Saitoh Satoshi , Arase Yasuji , Ikeda Kenji , Miyakawa Yuzo , Kumada Hiromitsu
Published: September 2009

Aim:  To identify factors for the development of hepatocellular carcinoma (HCC) in the patients who receive adefovir add‐on lamivudine for treatment of lamivudine‐resistant hepatitis B virus (HBV) mutants.

Methods:  A total of 247 patients who developed lamivudine‐resistant HBV mutants, with an increase of HBV DNA ≥ 1 log copies/mL, received adefovir dipivoxil 10 mg add‐on lamivudine 100 mg daily during a median of 115 weeks (range: 25–282 weeks). They were followed for the development of HCC by imaging modalities every 3−6 months.

Results:  HCC developed in 18 of the 247 (7.3%) patients. Eight factors were in significant association with the development of HCC by the univariate analysis. They included age, cirrhosis, platelet counts, levels of bilirubin, aspartate aminotransferase (AST), alanine aminotransferase and α‐fetoprotein, as well as YMDD mutants at the start of adefovir dipivoxil. By the multivariate analysis, AST levels, YIDD mutants, cirrhosis and age were independent factors for the development of HCC. By the Kaplan‐Meier analysis, AST levels ≥ 70 IU/L, YIDD mutants, cirrhosis and age ≥ 50 years increased the risk of HCC (P = 0.018, P = 0.035, P = 0.002 and P = 0.014, respectively). HCC developed more frequently in the patients with than without cirrhosis at the start of adefovir (10/59 [16.9%] vs. 8/188 [4.3%], P = 0.002).

Conclusion:  HCC can develop in cirrhotic patients receiving adefovir add‐on lamivudine. Hence, the patients with baseline AST ≥ 70 IU/L and YIDD mutants would need to be monitored closely for HCC.
Molecular targets for liver cancer therapy: From screening of target genes to clinical trials
Authors: Midorikawa Yutaka , Sugiyama Yasuyuki , Aburatani Hiroyuki
Published: September 2009

Cancer arises from the accumulation of genetic alterations, and the inactivation of oncogenes, or recovery of suppressor genes, are promising strategies for cancer treatment. Genome‐based drug research starts with identification of target genes and is accomplished by exploitation of target‐based drugs such as monoclonal antibodies, small molecules and antisense drugs. Recently, clinical trials for treatment of advanced hepatocellular carcinoma (HCC) have been performed, and the effectiveness of sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor and Ras kinase, has been demonstrated. In addition to known target genes, microarray technology has enabled us to constitute novel therapeutic targets, and many researchers have applied this technology in studies of HCC and have identified candidate target genes, validated to affect cell growth. In addition, promoter arrays for whole‐genome epigenetic aberration analysis, ChIP‐chip analysis using tiling arrays, and high‐throughput sequencing systems have been applied to drug discovery. To elucidate the status of therapeutic target genes in vivo, development of diagnostic markers for stratification of patients is a pressing need. Here, we review recent advances in microarray technology for liver cancer, discuss the innovations and approaches to therapeutic target discovery, and present data regarding the outcome of gene target therapy using monoclonal antibodies and molecular diagnostic markers in our laboratory.
Carbon Capture and Storage: How Green Can Black Be?
Authors: Haszeldine R. Stuart
Published: September 2009

The capture of carbon dioxide at the point of emission from coal- or gas-burning power plants is an attractive route to reducing carbon dioxide emissions into the atmosphere. To commercialize carbon capture, as well as transport of liquified carbon dioxide and its storage in exploited oil fields or saline formations, many technological, commercial, and political hurdles remain to be overcome. Urgent action is required if carbon capture and storage is to play a large role in limiting climate change.
One Size Fits All, After Tailoring

The Patent Crisis and How the Courts Can Solve It
by Dan L. Burk and Mark A. Lemley

University of Chicago Press, Chicago, 2009. 228 pp. $45, £31. ISBN 9780226080611.
Authors: Eisenberg Rebecca S.
Published: September 2009

Claiming that serious problems arise from current U.S. patent law applying the same set of rules across all industries, Burk and Lemley argue for giving the courts the power to interpret and apply the law so as to treat different types of businesses differently.
Amine Scrubbing for CO
2
Capture
Authors: Rochelle Gary T.
Published: September 2009

Amine scrubbing has been used to separate carbon dioxide (CO
2
) from natural gas and hydrogen since 1930. It is a robust technology and is ready to be tested and used on a larger scale for CO
2
capture from coal-fired power plants. The minimum work requirement to separate CO
2
from coal-fired flue gas and compress CO
2
to 150 bar is 0.11 megawatt-hours per metric ton of CO
2
. Process and solvent improvements should reduce the energy consumption to 0.2 megawatt-hour per ton of CO
2
. Other advanced technologies will not provide energy-efficient or timely solutions to CO
2
emission from conventional coal-fired power plants.
Oceanic Spawning Migration of the European Eel (
Anguilla anguilla
)
Authors: Aarestrup Kim , Økland Finn , Hansen Michael M. , Righton David , Gargan Patrik , Castonguay Martin , Bernatchez Louis , Howey Paul , Sparholt Henrik , Pedersen Michael I. , McKinley Robert S.
Published: September 2009

Satellite tracking technology has allowed scientists to map part of the migration route of the European eel.
Unraveling Traveling
Authors: Kyriacou Charalambos P.
Published: September 2009

The monarch butterfly uses a time-compensated clock in its antennae to calculate seasonal migration routes relative to the Sun's position.
Tin Takes Ethylene On—and Off
Authors: Sita Lawrence R.
Published: September 2009

A tin analog of acetylene can perform reactions normally forbidden to acetylene: It can bind two ethylene molecules in a reversible fashion.
Amyloid-β Dynamics Are Regulated by Orexin and the Sleep-Wake Cycle
Authors: Kang Jae-Eun , Lim Miranda M. , Bateman Randall J. , Lee James J. , Smyth Liam P. , Cirrito John R. , Fujiki Nobuhiro , Nishino Seiji , Holtzman David M.
Published: September 2009

Sleep and Alzheimer's Disease

Accumulation of amyloid-β (Aβ) in the brain is thought to be the initiating event in the pathogenesis of Alzheimer's disease (AD). Aβ is a peptide secreted in a soluble monomeric form predominantly by neurons and its aggregation into toxic forms is concentration dependent. Synaptic activity regulates the release of Aβ in vivo. However, how physiological and environmental processes are involved in regulation of Aβ levels is not understood.

Kang
et al.

(p.
1005
, published online 24 September), by performing sleep-wake studies in freely behaving animals concomitant with in vivo microdialysis, found that brain interstitial fluid levels of Aβ were significantly correlated with wakefulness and negatively correlated with sleep. Furthermore, relatively short-term (3 weeks) sleep deprivation markedly accelerated amyloid plaque deposition in amyloid precursor protein transgenic mice. Thus, sleep-wake behavior is linked to Aβ levels and abnormal sleep may be linked to AD pathogenesis.
Carbon Capture and Sequestration
Authors: Chu Steven
Published: September 2009

Overwhelming scientific evidence shows that CO
2
emissions from fossil fuels have caused the climate to change, and a dramatic reduction of these emissions is essential to reduce the risk of future devastating effects. On the other hand, access to energy is the basis of much of the current and future prosperity of the world. Eighty percent of this energy is derived from fossil fuel. The world has abundant fossil fuel reserves, particularly coal. The United States possesses one-quarter of the known coal supply, and the United States, Russia, China, and India account for two-thirds of the reserves. Coal accounts for roughly 25% of the world energy supply and 40% of the carbon emissions.
*
It is highly unlikely that any of these countries will turn their back on coal any time soon, and for this reason, the capture and storage of CO
2
emissions from fossil fuel power plants must be aggressively pursued.
A New Biology to Mend Society's Woes
Authors: Kaiser Jocelyn
Published: September 2009

Many science advocates were pleased last week when a National Academies panel called for a multidisciplinary initiative to address four major societal problems involving food, energy, the environment, and health.
The Force Behind North Korea's New Science University
Authors: Stone Richard
Published: September 2009

Last week, a ceremony in Pyongyang commemorated completion of the $35 million Pyongyang University of Science and Technology, which after 4 years of delays is expected to open in November to the crème de la crème of North Korea's science graduate students.
Who Will Pay for China's Planned X-ray Satellite?
Authors: Xin Hao
Published: September 2009

China's first space-based observatory, the Hard X-ray Modulation Telescope, is scheduled for launch next year, but
Science
has learned that no government agency has stepped forward to pay the estimated $146 million to build the satellite—putting the mission in jeopardy.
Exotic Telescopes Prepare to Probe Era of First Stars and Galaxies
Authors: Clery Daniel
Published: September 2009

Radio telescopes that substitute antenna arrays for dishes are gearing up to look back to the brink of the "dark ages" that followed the big bang.
Detection ofKRASmutations in colorectal cancer by high-resolution melting analysis
Authors: Ma E S K , Wong C L P , Law F B F , Chan W-K , Siu D
Published: September 2009

Aims:

Mutation of theKRASgene predicts the clinical response to the monoclonal antibody cetuximab in patients with advanced colorectal cancer (CRC). This study aimed to performKRASmutation detection on formalin-fixed paraffin-embedded (FFPE) tumour tissue by two different methods for comparison.

Methods:

The FFPE sample was microdissected to enrich for tumour cells.KRASexon 2 mutations were performed on 100 Chinese patients with CRC by direct nucleotide sequencing and high-resolution melting (HRM) analysis.

Results:

KRASexon 2 mutations were detected in a total of 62 patients with the two methods combined, comprising 11 different mutant alleles. Three common mutations p.Gly12Asp, p.Gly12Val and p.Gly13Asp accounted for approximately 70% of all cases. The concordant rate between the two methods was 95%. Four mutations not initially detected by direct sequencing were identified by HRM and confirmed by sequencing of the HRM amplicons. One mutation detected by direct sequencing was inadvertently grouped as a wild-type allele by HRM software, but this was readily rectified through manual review.

Conclusion:

HRM analysis is a sensitive method of detectingKRASmutation on FFPE tumour tissue to guide cetuximab treatment and is applicable to routine molecular diagnostic service. Utilisation of HRM to screen for mutations upfront economises the resource used in the sequencing reaction.
COSMOLOGICAL DISTANCE MEASURE CONSTRAINTS ON THE DECELERATION PARAMETER
Authors: XU LIXIN , LU JIANBO , ZHANG CHENGWU
Published: September 2009

Constraints on a parametrized deceleration parameter, q(a) = q0+ q1(1 - a), are investigated using cosmological observations of type Ia supernovae (SN Ia), baryon acoustic oscillations (BAOs) and cosmic microwave background (CMB) and observational Hubble data (OHD) which correspond to the cosmological distance measure. When a high redshift dataset of CMB is added in the SN + BAO + OHD case, a stronger constraint is obtained than for the lower redshift case, SN + BAO + OHD. The evolutions of the deceleration and Hubble parameters with respect to redshift z are reconstructed from cosmic observations. With cosmic observations as constraints, it is found that a smaller current deceleration parameter and a larger transition redshift are obtained in the SN + BAO + OHD case than in the SN + BAO + OHD + CMB case. In the SN + BAO + OHD + CMB case, slightly larger Hubble parameter values will be obtained than in the SN + BAO + OHD case.
CORRELATIONS AMONG FORWARD RETURNS IN THE NORDIC ELECTRICITY MARKET
Authors: FRESTAD DENNIS
Published: September 2009

I analyze empirical correlations of electricity forward returns from the perspective of a random field model that specifies the correlations in terms of the temporal separation between forward maturities. It turns out that temporal separation cannot fully account for the empirical forward return correlations. Specifically, the relation between correlations and temporal separation does not seem to be invariant across segments of the electricity forward market or trading periods.
THE VARIANCE SWAP CONTRACT UNDER THE CEV PROCESS
Authors: JORDAN RICHARD , TIER CHARLES
Published: September 2009

The problem of pricing the variance swap when the underlying asset follows the CEV process is considered. A hedging argument is used to replicate the variance swap in part using the log contract. The price of the log contract is shown in practice to provide a fast and accurate pricing method for the variance swap. An exact integral solution to the log contract price is derived along with simple exact and approximate formulas. Asymptotic methods are used to obtain the approximations. The situation when default is possible under the CEV process is considered. The shifted CEV model is introduced as an alternative if default can occur and asymptotic pricing formulas are constructed. The applicability and accuracy of the results are demonstrated numerically for the log contract and hence the variance swap.
SHARE REPURCHASES AND FIRM BEHAVIOR
Authors: DE RIDDER ADRI
Published: September 2009

Share repurchases have become an increasingly popular method for companies to distribute cash to its shareholders as many countries have removed restrictions related to this activity. By using a new and unique data set with complete information of each repurchase program, the long-run share price performance following actual share repurchases and whether managers trade strategically are examined for a sample of Swedish firms. I find that the announcement effect surrounding the first repurchase date is small but that repurchasing firms on average outperform several benchmarks during the first three years and thereby exhibit superior information of the stock price. Evidence of strategic trading is documented in small market cap firms. Finally, I document that Swedish firms repurchase more in the first half compared to the second half of the program and also that a higher completion rate is associated with high abnormal return.
MULTIAGENT LEARNING FOR BLACK BOX SYSTEM REWARD FUNCTIONS
Authors: TUMER KAGAN , AGOGINO ADRIAN
Published: September 2009

In large, distributed systems composed of adaptive and interactive components (agents), ensuring the coordination among the agents so that the system achieves certain performance objectives is a challenging proposition. The key difficulty to overcome in such systems is one of credit assignment: How to apportion credit (or blame) to a particular agent based on the performance of the entire system. In this paper, we show how this problem can be solved in general for a large class of reward functions whose analytical form may be unknown (hence "black box" reward). This method combines the salient features of global solutions (e.g. "team games") which are broadly applicable but provide poor solutions in large problems with those of local solutions (e.g. "difference rewards") which learn quickly, but can be computationally burdensome. We introduce two estimates for local rewards for a class of problems where the mapping from the agent actions to system reward functions can be decomposed into a linear combination of nonlinear functions of the agents' actions. We test our method's performance on a distributed marketing problem and an air traffic flow management problem and show a 44% performance improvement over team games and a speedup of order n for difference rewards (for an n agent system).
MULTI-MARKET MINORITY GAME: BREAKING THE SYMMETRY OF CHOICE
Authors: WAWRZYNIAK KAROL , WISLICKI WOJCIECH
Published: September 2009

Generalization of the minority game to more than one market is considered. At each time step, every agent chooses one of its strategies and acts on the market related to this strategy. If the payoff function allows for strong fluctuation of utility then market occupancies become inhomogeneous with preference given to this market where the fluctuation occurred first. There exists a critical size of agent population above which agents on bigger market behave collectively. In this regime, there always exists a history of decisions for which all agents on a bigger market react identically.
ECONOMIC NETWORKS: WHAT DO WE KNOW AND WHAT DO WE NEED TO KNOW?
Authors: SCHWEITZER FRANK , FAGIOLO GIORGIO , SORNETTE DIDIER , VEGA-REDONDO FERNANDO , WHITE DOUGLAS R.
Published: September 2009

We examine the emergent field of economic networks and explore its ability to shed light on the global and volatile economy where credit, ownership, innovation, investment, and virtually every other economic activity is carried at a scale and scope that respects no geographical, organizational, or political boundaries. In this context, the study of economic networks and their dynamics must reflect the vast complexity of the interaction patterns and integrate it with a realistic account of the incentives and information that govern agents' behavior. The interplay of both has been shown to produce metastabilities, system crashes, and emergent structures in ways that are yet only poorly understood. Meeting this exciting scientific challenge requires a combination of time-series analysis, complexity theory, and simulation with the analytical tools that have been developed by game theory, as well as graph and matrix theories. We argue that this will help achieving a better integration of theory and data models and provide a better understanding of the potentials and risks of modern economic systems.
FRACTAL CHARACTERIZATIONS OF MAX STATISTICAL DISTRIBUTION IN GENETIC ASSOCIATION STUDIES
Authors: LI WENTIAN , YANG YANING
Published: September 2009

Two noninteger parameters are defined for MAX statistics, which are maxima of d simpler test statistics. The first parameter, dMAX, is the fractional number of tests, representing the equivalent numbers of independent tests in MAX. If the d tests are dependent, dMAX< d. The second parameter is the fractional degrees of freedom k of the chi-square distribution [Formula: see text] that fits the MAX null distribution. These two parameters, dMAXand k, can be independently defined, and k can be noninteger even if dMAXis an integer. We illustrate these two parameters using the examples of MAX2 and MAX3 statistics in genetic case-control studies. We speculate that k is related to the amount of ambiguity of the model inferred by the test. In the case-control genetic association, tests with low k (e.g. k = 1) are able to provide definitive information about the disease model, as versus tests with high k (e.g. k = 2) that are completely uncertain about the disease model. Similar to Heisenberg's uncertain principle, the ability to infer disease model and the ability to detect significant association may not be simultaneously optimized, and k seems to measure the level of their balance.
SEARCH SIMILAR PROTEIN STRUCTURES WITH CLASSIFICATION, SEQUENCE AND 3D ALIGNMENTS
Authors: LU ZAIXIN , ZHAO ZHIYU , GARCIA SERGIO , KRISHNASWAMY KRISHNAKUMAR , FU BIN
Published: September 2009

We have developed an algorithm and web tool to search similar protein structures in the PDB (Protein Data Bank). The algorithm is a combination of a series of methods including protein classification, geometric feature extraction, sequence alignment, and 3D structure alignment. Given a protein structure, the tool can efficiently discover similar structures from hundreds of thousands of structures stored in the PDB. Our experimental results show that it is more accurate than other well-known protein search systems including PSI-BLAST, 3D-BLAST, and SSM in finding proteins that are structurally similar to the query protein, and its speed is also competitive with those systems. The algorithm has been fully implemented and is accessible online at the address , which is supported by a cluster of computers.
Multi-method chronometry of the Teletskoye graben and its basement, Siberian Altai Mountains: new insights on its thermo-tectonic evolution
Authors: De Grave Johan , Buslov Mikhail M. , Van Den Haute Peter , Metcalf James , Dehandschutter Boris , McWilliams Michael O.
Published: September 2009

The Altai Mountains form an intracontinental, transpressive deformation belt in the NW Central Asian orogenic system. Using a multi-method chronometric approach, the thermo-tectonic history of the basement underlying the Teletskoye graben area is constrained in more detail. The results provide new insights into the Siberian Altai basement evolution from the Early Palaeozoic to the present. Zircon SHRIMP (sensitive high-resolution ion microprobe) U–Pb ages (Late Ordovician–Early Silurian, 460–420 Ma) indicate an earlier crystallization age for the basement granitoids than previously thought (Late Devonian–Early Carboniferous, 370–350 Ma), while new multi-mineral
40
Ar/
39
Ar age spectra suggest continuous basement cooling throughout the Devonian–Carboniferous. Reactivation of long-lived Palaeozoic structures controls the Teletskoye graben formation since the Plio-Pleistocene as a distant effect of India–Eurasian convergence. Deformation is propagated through Central Asia and Siberia along an inherited structural network closely associated with its basement fabric. A similar reactivation affected the Altai during the Mesozoic. Modelled apatite fission-track data suggest Late Jurassic–Cretaceous (150–80 Ma) cooling, interpreted to be related to denudation and the tectonic reactivation that we link to the coeval Mongol–Okhotsk orogeny. From the Late Cretaceous until the Pliocene, the thermal history models indicate a period of stability. Roughly around 5 Ma ago renewed cooling is observed that possibly represents the denudation and growth of the present-day Altai, and provides the context for the Teletskoye graben formation. A modelled Late Cenozoic cooling can be a result of, or overemphasized by, a modelling artefact. Some caution should be taken not to overinterpret this cooling phase.
The effect of chemical etching on LA–ICP-MS analysis in determining uranium concentration for fission-track chronometry
Authors: Hasebe Noriko , Carter Andrew , Hurford Anthony J. , Arai Shoji
Published: September 2009

LA–ICP-MS (laser ablation–inductively coupled plasma-mass spectrometry) has the potential to measure uranium concentration for fission-track (FT) chronometry as an alternative to thermal neutron-induced fission of
235
U. This study examines the effect that chemical etching, required to reveal spontaneous fission tracks of
238
U, has upon LA–ICP-MS analyses. Uranium concentrations were measured before and after etching for six large gem-quality apatite crystals and six zircon samples – three large crystals and three FT age standards. Comparison of the results shows no significant difference in
238
U concentrations measured on the etched and unetched mineral surfaces. The
238
U concentrations determined by the LA–ICP-MS provide reasonable FT ages for the zircon age standards, which, with the previously reported LA–ICP-MS apatite FT results, promotes the use of the LA–ICP-MS for FT chronometry.
Reconstruction of palaeotopography from low-temperature thermochronological data
Authors: Wei Wang , Zuyi Zhou
Published: September 2009

Thermochronology can provide information on palaeotopography and its evolution. We present a new method to reconstruct the shape of the palaeotopography from the palaeoisotherm derived from low-temperature thermochronological data. While deriving palaeoisotherm and reconstructing palaeotopography, the exhumation rate may also be constrained. The proposed method is independent of the relationship between the ancient and modern topography; however, it requires that the palaeotopography maintains its shape and the subsurface thermal field is invariant with time during the period when a set of samples passed through the closure temperature. It is shown that the inherent uncertainties in sample age and the limited sampling density will inevitably induce errors in the reconstructed topography, and these errors can be reduced by eliminating the noise in the derived isotherm. Increasing the number of samples helps to reduce the noise, and if, before sampling, we can make rough estimates about the geothermal gradient, the exhumation rate, the uncertainties in sample age, and the wave components and the relief of the palaeotopography to be reconstructed, the number of samples can be tentatively decided. It is also shown that the reconstructed topography is sensitive to exhumation rate and geothermal gradient, and a concrete sensitivity analysis is needed for a given dataset. By reinterpreting the (U–Th)/He data from the Sierra Nevada, California, we show that our method can reveal palaeorelief as well as other valuable information on the palaeotopography of the studied area.
Alternative promoter and GATA5 transcripts in mouse
Authors: Chen Bohao , Yates Elena , Huang Yong , Kogut Paul , Ma Lan , Turner Jerrold R. , Tao Yun , Camoretti-Mercado Blanca , Lang Deborah , Svensson Eric C. , Garcia Joe G. N. , Gruber Peter J. , Morrisey Edward E. , Solway Julian
Published: September 2009

GATA5 is a member of the GATA zinc finger transcription factor family involved in tissue-specific transcriptional regulation during cell differentiation and embryogenesis. Previous reports indicate that null mutation of the zebrafish GATA5 gene results in embryonic lethality, whereas deletion of exon 1 from the mouse GATA5 gene causes only derangement of female urogenital development. Here, we have identified an alternate promoter within intron 1 of the mouse GATA5 gene that transcribes a 2.5-kb mRNA that lacks exon 1 entirely but includes 82 bp from intron 1 and all of exons 2–6. The alternative promoter was active during transient transfection in cultured airway myocytes and bronchial epithelial cells, and it drove reporter gene expression in gastric epithelial cells in transgenic mice. The 2.5-kb alternative transcript encodes an NH2-terminally truncated “short GATA5” comprising aa 226–404 with a single zinc finger, which retains ability to transactivate the atrial natriuretic factor promoter (albeit less efficiently than full-length GATA5). Another new GATA5 transcript contains all of exons 1–5 and the 5′ portion of exon 6 but lacks the terminal 1143 bp of the 3′-untranslated region from exon 6. These findings extend current understanding of the tissue distribution of GATA5 expression and suggests that GATA5 expression and function are more complex than previously appreciated.
Angiotensin II receptors are expressed and functional in human esophageal mucosa
Authors: Casselbrant Anna , Edebo Anders , Hallersund Peter , Spak Emma , Helander Herbert F. , Jönson Claes , Fändriks Lars
Published: September 2009

Only few studies have been devoted to the actions of the renin-angiotensin system (RAS) in the human gastrointestinal tract. The present study was undertaken to elucidate the expression and action of RAS in the human esophageal mucosa. Mucosal specimens with normal histological appearance were obtained from healthy subjects undergoing endoscopy and from patients undergoing esophagectomy due to neoplasm. Gene and protein expressions of angiotensin II (Ang II) receptor type 1 (AT1) and type 2 (AT2) and angiotensin-converting enzyme (ACE) were analyzed. In vivo functionality in healthy volunteers was reflected by assessing transmucosal potential difference (PD). Ussing chamber technique was used to analyze the different effects of Ang II on its AT1and AT2receptors. Immunoreactivity to AT1and AT2was localized to stratum superficiale and spinosum in the epithelium. ACE, AT1, and AT2were found in blood vessel walls. Transmucosal PD in vivo increased following administration of the AT1receptor antagonist candesartan. In Ussing preparations mean basal transmural PD was −6.4 mV, epithelial current ( Iep) 34 μA/cm2, and epithelial resistance ( Rep) 321 Ω·cm2. Serosal exposure to Ang II increased PD as a result of increased Iep, whereas Repwas constant. Ang II given together with the selective AT1-receptor antagonist losartan, or AT2agonist C21 given alone, resulted in a similar effect. Ang II given in presence of the AT2-receptor antagonist PD123319 did not influence PD, but Iepdecreased and Repincreased. In conclusion, Ang II receptors and ACE are expressed in the human esophageal epithelium. The results suggest that AT2-receptor stimulation increases epithelial ion transport, whereas the AT1receptor inhibits ion transport and increases Rep.