bluuebunny/crossref_metadata_2025 huggingface dataset:
The Exposome – Exciting Opportunities for Discoveries in Reproductive and Perinatal Epidemiology
Authors: Buck Louis Germaine M. , Yeung Edwina , Sundaram Rajeshwari , Laughon S. Katherine , Zhang Cuilin
Published: January 2013

Understanding the mechanisms that underlie successful human reproduction and development is an ambitious goal, given the many unique methodological challenges surrounding such study. These challenges are well understood by reproductive and perinatal epidemiologists and include its conditional nature, unobservable yet informative outcomes such as conception, multi‐scale missing data, correlated or non‐independent outcomes, interval censoring and a hierarchical data structure. Novel methodologies for overcoming these challenges and for answering critical data gaps are needed if we are to better understand the inefficiency that currently characterises human reproduction with the goal of improving population health. The exposome is an emerging paradigm that offers promise for understanding the natural history of human reproduction and development, and its many associated impairments that develop later in child‐ or adulthood. This novel paradigm recognises the need to identify and measure the totality of environmental (non‐genetic) exposures from preconception through sensitive windows, and to identify patterns associated with healthy and adverse outcomes. The exposome accommodates research focusing on unique subpopulations, such as couples undergoing assisted reproductive technologies, so that methodological limitations such as unobservable and conditional outcomes can be better addressed. Reproductive and perinatal epidemiology is uniquely suited for proof‐of‐concept exposome research, given the intricate relations between fecundity, gravid health and later onset disease and the narrow and interrelated sensitive windows that characterise the conditional nature of human reproduction and development. Bold new conceptual frameworks such as the exposome are needed for designing research that may lead to discovery and improve population health.
Tuberculosis screening in immigrants from high‐prevalence countries: Interview first or chest radiograph first? A pro/con debate
Authors: Mor Zohar , Leventhal Alex , Diacon Andreas H. , Finger Rebekka , Schoch Otto D.
Published: January 2013

Immigration from high tuberculosis (TB) prevalence countries has a substantial impact on the epidemiology of TB in receiving countries with low TB incidence. Cross‐border migration offers an ideal opportunity for active case finding that will result in a lower caseload in the host country and a reduced spread of disease to both the indigenous and migrant populations. Screening strategies can start ‘offshore’, thereby indirectly assisting and empowering public health systems in the source countries, or be performed at ports of entry with or without long‐term engagement of ‘onshore’ facilities and systems to provide either preventive therapy or surveillance for reactivation of latent TB. The chest radiograph seems to be playing a key role in this process, but questions remain regarding when, where and in whom radiographs are best done for optimal yield and cost‐effectiveness, and with what other tests they might best be combined to further increase the usefulness of transborder TB control.
Export Destination, Product Quality and Wages in a Middle‐Income Country. The Case of South Africa
Authors: Rankin Neil , Schöer Volker
Published: January 2013

A robust finding in the firm‐level literature is that exporting firms pay higher wages. Using South African data this paper investigates the relationship between export destination and wages at a worker level. South Africa, a middle‐income country, has two distinct main export markets—a regional market where per capita incomes are lower than at home, and an international market with higher per capita incomes. Our estimates show that workers in firms that export to the region earn less than those that produce for the domestic market. Those in firms that export outside the region earn more than either domestic producers or region‐only exporters. Much of this difference in wages can be explained by the premium the different types of exporters pay for skills. These results support previous studies which suggest that export destination is related to product quality which in turn is related to worker quality and therefore wages.
Wage Discrimination in India's Informal Labor Markets: Exploring the Impact of Caste and Gender
Authors: Deininger Klaus , Jin Songqing , Nagarajan Hari
Published: January 2013

Although there has been considerable interest in wage discrimination in India, available studies have largely dealt with formal rather than informal markets that are of little relevance for the poorest people. Focusing on India's informal labor markets leads to three findings of interest. First, gender wage discrimination is larger in informal than in formal labor markets, resulting in losses that are larger than receipts from one of the country's most important safety‐net programs. Second, economic growth will not make gender discrimination in wage labor markets disappear. Finally, contrary to what is found for gender, the hypothesis of no significant wage discrimination based on caste cannot be rejected.
Assessment of the quality of hospital care for children in Indonesia
Authors: Sidik Nurul A. , Lazuardi Lilliana , Agung Fransisca H. , Pritasari Kirana , Roespandi Hanny , Setiawan Tini , Pawitro Udjiani , Nurhamzah Waldi , Weber Martin W. ,   The Indonesian Paediatric Hospital Assessment Group
Published: January 2013

Objectives

To obtain an overview of the quality of care for children in Indonesia, by assessing hospitals with a view to proceed to a quality improvement mechanism for child care.

Methods

Stratified two‐stage random sampling in six regions identified 18 hospitals (provinces Jambi, East Java, Central Kalimantan, South–East Sulawesi, East Nusa Tenggara, North Maluku). Three randomly selected hospitals in each province were visited by trained assessors who scored each assessed service (expressed as a percentage of achievement) and grouped into good (≥ 80%), requiring improvement (60–79%) and urgently requiring improvement (< 60%).

Results

The overall median result score across all areas was 43% (IQR 28%–53%). Case management for common childhood illnesses had a median score of 37% (IQR18–43%), neonatal care 46% (IQR 26–57%) and patient monitoring 40% (IQR 30–50%), all indicating an urgent need for improvement. Qualitative data showed as main problems inadequate use of standard treatment guidelines, irrational prescribing of antibiotics, poor progress monitoring and poor supportive care.

Conclusion

We found serious shortcomings in the quality of hospital care for children. Finding and documenting those is the first step in a quality improvement process. Work is needed to start an improvement cycle for hospital care.
Natural Resources, Wage Growth and Institutions – a Panel Approach
Authors: Torres Nuno , Afonso Oscar , Soares Isabel
Published: January 2013

This paper exam,ines the effect of nat,u,ral resource export depen,dence and fis,cal respon,si,bil,ity on wage growth, which is derived from the labour first‐order con,di,tion and esti,mated using a panel growth‐account,ing frame,work. Using annual data, the study accounts for the var,i,abil,ity of resource rev,e,nues, one of the major dif,fi,cul,ties of man,ag,ing these resources. The con,trol vari,ables include the most cru,cial growth fac,tors. Due to insuf,fi,cient annual data, human cap,i,tal is only con,sid,ered inside wages as in many endog,e,nous growth mod,els. We esti,mate the influ,ence on real wage growth aris,ing from the growth‐impacts of nat,u,ral resources through labour and cap,i,tal effi,ciency while con,trol,ling for fis,cal respon,si,bil,ity, which proves a suit,able proxy for pol,i,cies and insti,tu,tions in a sin,gle‐panel case. The results show that respon,si,ble fis,cal pol,icy, assessed by the bud,get bal,ance, pre,vents (var,i,able) dif,fuse and point‐source resources from hin,der,ing real wage growth (through labour effi,ciency), a result also sig,nif,i,cant in a sub‐sam,ple of un‐free coun,tries. The hypoth,e,sis of a resource curse work,ing through insti,tu,tions and reflected on real wage growth holds for resource export shares, but not adjust,ing for re‐expor,ta,tion. Over,all, resource effects are jointly insig,nif,i,cant, even though point‐source resources show a positive impact through cap,i,tal effi,ciency.
Taste responses in mice lacking taste receptor subunit T1R1
Authors: Kusuhara Yoko , Yoshida Ryusuke , Ohkuri Tadahiro , Yasumatsu Keiko , Voigt Anja , Hübner Sandra , Maeda Katsumasa , Boehm Ulrich , Meyerhof Wolfgang , Ninomiya Yuzo
Published: January 2013

Key points

The taste receptor heterodimer T1R1 + T1R3, metabotropic glutamate receptors (mGluRs) and/or their variants may function as umami taste receptors.

Here, we used newly developed T1R1−/− mice and examined the role of T1R1 and mGluRs in taste detection.

The T1R1−/− mice exhibited seriously diminished synergistic responses to glutamate and inosine monophosphate but not to glutamate alone and significantly smaller responses to sweeteners.

Addition of mGluR antagonists significantly inhibited responses to glutamate in both T1R1−/− and heterozygous T1R1+/− mice.

Taken together, these results suggest that T1R1 mainly contributes to umami taste synergism and partly to sweet sensitivity, while mGluRs are involved in the detection of umami compounds.

Abstract  The T1R1 receptor subunit acts as an umami taste receptor in combination with its partner, T1R3. In addition, metabotropic glutamate receptors (brain and taste variants of mGluR1 and mGluR4) are thought to function as umami taste receptors. To elucidate the function of T1R1 and the contribution of mGluRs to umami taste detection in vivo, we used newly developed knock‐out (T1R1−/−) mice, which lack the entire coding region of the Tas1r1 gene and express mCherry in T1R1‐expressing cells. Gustatory nerve recordings demonstrated that T1R1−/− mice exhibited a serious deficit in inosine monophosphate‐elicited synergy but substantial residual responses to glutamate alone in both chorda tympani and glossopharyngeal nerves. Interestingly, chorda tympani nerve responses to sweeteners were smaller in T1R1−/− mice. Taste cell recordings demonstrated that many mCherry‐expressing taste cells in T1R1+/− mice responded to sweet and umami compounds, whereas those in T1R1−/− mice responded to sweet stimuli. The proportion of sweet‐responsive cells was smaller in T1R1−/− than in T1R1+/− mice. Single‐cell RT‐PCR demonstrated that some single mCherry‐expressing cells expressed all three T1R subunits. Chorda tympani and glossopharyngeal nerve responses to glutamate were significantly inhibited by addition of mGluR antagonists in both T1R1−/− and T1R1+/− mice. Conditioned taste aversion tests demonstrated that both T1R1−/− and T1R1+/− mice were equally capable of discriminating glutamate from other basic taste stimuli. Avoidance conditioned to glutamate was significantly reduced by addition of mGluR antagonists. These results suggest that T1R1‐expressing cells mainly contribute to umami taste synergism and partly to sweet sensitivity and that mGluRs are involved in the detection of umami compounds.
Interactions between spinal interneurons and ventral spinocerebellar tract neurons
Authors: Jankowska Elzbieta , Hammar Ingela
Published: January 2013

Abstract Recent evidence indicates that ventral spinocerebellar tract (VSCT) neurons do not merely receive information provided by spinal interneurons but may also modulate the activity of these interneurons. Hence, interactions between them may be mutual. However, while it is well established that spinal interneurons may provide both excitatory and inhibitory input to ascending tract neurons, the functional consequences of the almost exclusively inhibitory input from premotor interneurons to subpopulations of VSCT neurons were only recently addressed. These are discussed in the first part of this review. The second part of the review summarizes evidence that some VSCT neurons may operate both as projection neurons and as spinal interneurons and play a role in spinal circuitry. It outlines the evidence that initial axon collaterals of VSCT neurons target premotor inhibitory interneurons in disynaptic reflex pathways from tendon organs and muscle spindles (group Ia, Ib and/or II muscle afferents) to motoneurons. By activating these interneurons VSCT neurons may evoke disynaptic IPSPs in motoneurons and thus facilitate inhibitory actions of contralateral muscle afferents on motoneurons. In this way they may contribute to the coordination between neuronal networks on both sides of the spinal cord in advance of modulatory actions evoked via the cerebellar control systems.
Sonic Hedgehog Mediates Pathogen-Specific Response
Authors: VanHook Annalisa M.
Published: January 2013

Sonic hedgehog signaling modulates the immune response to
Mycobacterium bovis
.
Controlling the Allergic Reaction
Authors: Ferrarelli Leslie K.
Published: January 2013

The alarmins Mrp8 and Mrp14 function as both activators and inhibitors of the immune response.
Driver obesity and the risk of fatal injury during traffic collisions
Authors: Rice Thomas M , Zhu Motao
Published: January 2013

Background

Few studies have looked at how obesity affects injury outcomes among vehicle occupants involved in traffic collisions.

Objective

To estimate the association of obesity with death risk among drivers of passenger vehicles aged ≥16 and to examine effect modification by driver sex, driver seat belt use, vehicle type and collision type.

Methods

We conducted a matched-pair cohort study using data from the Fatality Analysis Reporting System. WHO body mass index (BMI) categories were calculated. Data were analysed using conditional Poisson regression.

Results

Estimated risk ratios (RRs) were slightly raised for underweight drivers (RR=1.19, 95% CI 0.86 to 1.63). RR increased with higher BMI categories and were 1.21 (0.98 to 1.49) for BMI 30–34.9, 1.51 (1.10 to 2.08) for BMI 35–39.9 and 1.80 (1.15 to 2.84) for BMI ≥40. Estimated BMI effects varied by gender. We found no meaningful variation across levels of vehicle type, collision type or seat belt use.

Conclusions

Findings from this study suggest that obese vehicle drivers are more likely to die from traffic collision-related injuries than non-obese occupants involved in the same collision. Education is needed to improve seat belt use among obese people, as is research to understand the potential role of comorbidities in injury outcomes.
Republished: Developing capable quality improvement leaders
Authors: Kaminski Geraldine M , Britto Maria T , Schoettker Pamela J , Farber Stacey L , Muething Stephen , Kotagal Uma R
Published: January 2013

Background/objective

Cincinnati Children's Hospital Medical Center created the Intermediate Improvement Science Series (I2S2) training course to develop organisational leaders to do improvement, lead improvement and get results on specific projects.

Design methods

Each multidisciplinary class consists of 25–30 participants and 12 in-class training days over 6 months. Instructional methods include lectures, case studies, interactive application exercises and dialogue, participant reports and assigned readings. Participants demonstrate competence in improvement science by completing a project with improvement in outcome and/or process measures. They present on their projects and receive feedback during each session and one-on-one coaching between sessions.

Results

Since 2006, 279 participants in 11 classes have completed the I2S2 course. Participant evaluations have consistently rated satisfaction, learning, application, impact and value very high. Large and statistically significant changes were observed in pre-course to post-course self-assessment of knowledge of five quality improvement topics. Approximately 85% of the projects demonstrated measurable improvement. At follow-up, 72% of improvement projects were completed and made a part of everyday operations in the participant's unit or were the focus of continuing improvement work. Many changes were spread to other units or programmes. Most (88%) responding graduates continued to participate in formal quality improvement efforts and many led other improvement projects. Nearly half of the respondents presented their results at one or more professional conference.

Conclusions

Through the I2S2 course, the authors are developing improvement leaders, accelerating the shift in the culture from a traditional academic medical centre to an improvement-focused culture, and building cross-silo relationships by developing leaders who understand the organisation as a large system of interdependent subsystems focused on improving health.
Holocene sediments from a coastal lake on northern Devon Island, Nunavut, Canada
Authors: Courtney Mustaphi Colin J. , Gajewski Konrad
Published: January 2013

Sediment cores from Lake DV09, northern Devon Island, Nunavut, Canada (75°34′34″N, 89°18′55″W), were studied to reconstruct the lake ontogeny through analysis and interpretation of the sediment stratigraphy. The lake was uplifted from marine inundation ∼7600 cal BP. After a millennium of rapid sediment accumulation, which coincided with the Holocene Thermal Maximum in the region, accumulation rates decreased over the past 6000 years as the Arctic became colder. This resulted in the deposition of very fine laminae that were interpreted as varves. The uppermost laminated sediments provided a ∼1600 year history of annual sediment transport and deposition into the lake. During periods of warmer temperatures, such as between 6000 and 7500 cal BP and during the Medieval Climate Anomaly (∼950–1300 CE; CE, Christian Era), hydroclimatic and permafrost slope processes increased sedimentation rates into the basin.
HADAMARD STATES FOR THE VECTOR POTENTIAL ON ASYMPTOTICALLY FLAT SPACETIMES
Authors: DAPPIAGGI CLAUDIO , SIEMSSEN DANIEL
Published: January 2013

We develop a quantization scheme for the vector potential on globally hyperbolic spacetimes which realizes it as a locally covariant conformal quantum field theory. This result allows us to employ on a large class of backgrounds, which are asymptotically flat at null infinity, a bulk-to-boundary correspondence procedure in order to identify for the underlying field algebra a distinguished ground state which is of Hadamard form.
Acupuncture for Chronic Low Back Pain in Long-Term Follow-Up: A Meta-Analysis of 13 Randomized Controlled Trials
Authors: Xu Mai , Yan Shi , Yin Xu , Li Xiuyang , Gao Shuguang , Han Rui , Wei Licheng , Luo Wei , Lei Guanghua
Published: January 2013

Chronic low back pain is one of the most common reasons that people seek medical treatment, and the consequent disability creates a great financial burden on individuals and society. The etiology of chronic low back pain is not clear, which means it is often refractory to treatment. Acupuncture has been reported to be effective in providing symptomatic relief of chronic low back pain. However, it is not known whether the effects of acupuncture are due to the needling itself or nonspecific effects arising from the manipulation. To determine the effectiveness of acupuncture therapy, a meta-analysis was performed to compare acupuncture with sham acupuncture and other treatments. Overall, 2678 patients were identified from thirteen randomized controlled trials. The meta-analysis was performed by a random model (Cohen's test), using the I-square test for heterogeneity and Begg's test to assess for publication bias. Clinical outcomes were evaluated by pain intensity, disability, spinal flexion, and quality of life. Compared with no treatment, acupuncture achieved better outcomes in terms of pain relief, disability recovery and better quality of life, but these effects were not observed when compared to sham acupuncture. Acupuncture achieved better outcomes when compared with other treatments. No publication bias was detected. Acupuncture is an effective treatment for chronic low back pain, but this effect is likely to be produced by the nonspecific effects of manipulation.
A Prospective Multicenter Clinical Trial of Chinese Herbal Formula JZQG (Jiangzhuoqinggan) for Hypertension
Authors: Tong Xiao-Lin , Lian Feng-Mei , Zhou Qiang , Xu Li-Peng , Ji Hang-Yu , Xu Gui-Cheng , Hu Yuan-Hui , Zhao Lin-Hua , Xia Le , Wang Jia , Chen Xin-Yan , Chan Man-Hon , Zhang Lan-Lan , Gao Wen , Zhen Zhong , Zhou Shui-Ping , Chang Bai
Published: January 2013

A prospective multicenter clinical trial was conducted to compare the beneficial effects of a Chinese herbal medicine formula Jiangzhuoqinggan (JZQG) and western antihypertension drug irbesartan. JZQG is mainly composed of rhubarb, coptis, cassia, and uncaria. A total of 240 patients with mild to moderate hypertension were enrolled in the trial. Patients were assigned into two groups after screening: JZQG group and the irbesartan group. After four weeks of treatment, we compared the changes in routine blood pressure, 24 h ambulatory blood pressure, and waist circumference. There was a significant reduction in systolic blood pressure and diastolic blood pressure in the JZQG group (both p < 0.01). There were no significant differences between the reduction of systolic and diastolic blood pressures in the two treatment groups. From the 24 h ambulatory blood pressure measurement, the JZQG group showed a greater reduction in both systolic and diastolic blood pressures (in both daytime and nighttime) than the irbesartan group. Furthermore, there was a significant difference in waist circumference in the JZQG group (1.51 cm reduction; P < 0.05) but not the irbesartan group (0.42 cm). Thus, the JZQG formula may have therapeutic value in patients with both hypertension and metabolic syndrome.
Poria cocosInhibits High Glucose-Induced Proliferation of Rat Mesangial Cells
Authors: Yoon Jung Joo , Lee Yun Jung , Lee So Min , Jin Song Nan , Kang Dae Gill , Lee Ho Sub
Published: January 2013

Mesangial cell proliferation is correlated with the progression of renal failure. The purpose of this study was to determine whether a water extract of Poria cocos Wolf (WPC), a well-known medicinal plant, regulates rat mesangial cell proliferation in the presence of high glucose (HG). HG significantly accelerated [3H]-thymidine incorporation, which was inhibited by WPC (1–50 μg/mL) in a dose-dependent manner. Cell migration and fibronectin mRNA expression data also supported the anti-proliferative effect of WPC. Western blot analysis revealed that pretreatment with WPC decreased the expression of cyclins and cyclin-dependent kinases (CDKs) and promoted the expression of p21waf1/cip1and p27kip1. WPC also suppressed HG-induced p38 mitogen-activated protein kinase (p38 MAPK) and extracellular-signal-regulated kinase 1/2 (ERK 1/2) phosphorylation. Furthermore, WPC inhibited HG-induced production of dichlorofluorescein (DCF)-sensitive intracellular reactive oxygen species (ROS). In conclusion, HG promoted mesangial cell proliferation, and WPC inhibited this activity, at least in part, via induction of cell cycle arrest and activation of anti-oxidant properties. Taken together, these results suggest that P. cocos may be a potent regulator of HG-induced proliferation.
Prunellae Spica Extract Contains Antagonists for Human Endothelin Receptors
Authors: Chen Chih-Ying , Ho Low-Tone , Yang Feng-Yuan , Juan Chi-Chang , Au Lo-Chun
Published: January 2013

Endothelin-1 (ET-1) is a powerful vasoconstrictor that contributes to blood pressure elevation. The biological effects of ETs are mediated by two receptors, namely, endothelin type A receptor (ETAR) and endothelin type B receptor (ETBR). Chinese herbal medicines (CHM) with antagonist activity for these two receptors were screened by establishing stable clones of CHO-K1 cells expressing high levels of human ETAR and ETBR, namely CHO-ETAR and CHO-ETBR.The aqueous extract of Prunellae Spica (P1) inhibited the binding of 125I-ET-1 to ETAR and ETBR in CHO-ETAR and CHO-ETBR cells, respectively. P1 suppressed the ET-1-induced mobilization of intracellular Ca2+ . Through the alcohol fractionation of P1, the antagonists of human ETAR and ETBR were found to belong to different, separable ingredients and the antagonist of ETAR is more soluble in alcohol. The two antagonists were also effective in the test on human primary cells, HASMC and HUVEC. P1 successfully prevented the development of ET-1-associated hypertension in rats without further purification. These results indicate the presence of anti-hypertensive ingredients in P. Spica extract, at least through the inactivation of ETAR and/or ETBR.
Anti-Hepatitis B Virus Effects of Dehydrocheilanthifoline fromCorydalis saxicola
Authors: Zeng Fan-Li , Xiang Yang-Fei , Liang Zhen-Ran , Wang Xiao , Huang Dan-e , Zhu Sui-Nan , Li Min-Min , Yang De-Po , Wang Dong-Mei , Wang Yi-Fei
Published: January 2013

In this report, the anti-hepatitis B virus (HBV) activity of dehydrocheilanthifoline (DHCH), a quaternary ammonium alkaloid isolated from the traditional Chinese medicine Corydalis saxicola Bunting (Papaveraceae), was determined in vitro. Following six days of treatment, DHCH efficiently suppressed the secretions of HBsAg and HBeAg in HepG2.2.15 cell cultures, with a half-maximal inhibitory concentration (IC50) of 15.84 and 17.12 μM, and with a therapeutic index (TI) of 7.32 and 6.77, respectively. Further studies revealed that DHCH reduced the levels of extracellular DNA, intracellular DNA and covalently closed circular DNA (cccDNA) of HBV in a dose-dependent and time-dependent manner, with IC50values of 15.08, 7.62 and 8.25 μM, respectively after six days of treatment. In contrast, the level of viral pre-genomic RNA (pgRNA) increased 6.13-fold after treatment with DHCH. Together, it was demonstrated for the first time that DHCH could significantly inhibit the replication of HBV, which warrants further studies on the antiviral mechanisms of DHCH, and suggests that it may be a promising candidate in the therapy of HBV infection.
Oridonin Induces Apoptosis, Inhibits Migration and Invasion on Highly-Metastatic Human Breast Cancer Cells
Authors: Wang Shengpeng , Zhong Zhangfeng , Wan Jianbo , Tan Wen , Wu Guosheng , Chen Meiwan , Wang Yitao
Published: January 2013

Oridonin, a natural tetracycline diterpenoid isolated from Chinese herb Rabdosia rubescens, has been reported to be a potent cytotoxic agent against a wide variety of tumors. However, its effect on highly metastatic breast cancer cells has not been addressed. In this study, we investigated the effects of oridonin on growth, migration and invasion of highly-metastatic human breast cancer cells. Our results showed that oridonin induced potent growth inhibition on human breast cancer cells MCF-7 and MDA-MB-231 in a time- and dose-dependent manner. According to the flow cytometric analysis, oridonin suppressed MCF-7 cell growth by cell cycle arrest at the G2/M phase and caused accumulation of MDA-MB-231 cells in the Sub-G1 phase. The induced apoptotic effect of oridonin was further confirmed by a morphologic characteristics assay and TUNEL assay. Oridonin triggered the reduction of Bcl-2/Bax ratio, caspase-8, NF-κB (p65), IKKα, IKKβ, phospho-mTOR, and increased expression level of cleaved PARP, Fas and PPARγ in a time-dependent manner. Immunofluorescent analysis showed that γH2AX-containing nuclear foci were significant in oridonin-treated MDA-MB-231 cells. Meanwhile, oridonin significantly suppressed MDA-MB-231 cell migration and invasion, decreased MMP-2/MMP-9 activation and inhibited the expression of Integrin β1 and FAK. In conclusion, oridonin inhibited the growth and induced apoptosis in breast cancer cells, which might be related to DNA damage and activation of intrinsic or extrinsic apoptotic pathways. Moreover, oridonin also inhibited tumor invasion and metastasis in vitro possibly via decreasing the expression of MMPs and regulating the Integrin β1/FAK pathway in MDA-MB-231 cells.
Novel Microemulsion of Tanshinone IIA, Isolated from Salvia miltiorrhiza Bunge, Exerts Anticancer Activity Through Inducing Apoptosis in Hepatoma Cells
Authors: Ma Hui , Fan Qing , Yu Jia , Xin Jile , Zhang Ce
Published: January 2013

Natural product Tanshinone IIA (TanIIA) induces apoptosis and differentiation in hepatocellular carcinoma (HCC) cells, but its clinical use is limited due to poor water solubility and lack of appropriate formulations for drug delivery. In this study, we capsulated TanIIA into a microemulsion (ME) that was composed of phospholipid, ethyl oleate, glycerol and pluronic F68. We then determined the anticancer effects and mechanisms of action for TanIIA ME with in vitro and in vivo HCC models. The mRNA and protein levels of apoptosis-related molecules (Bcl-2, Bax and caspase-3) were analyzed in murine hepatoma H22 cells and H22 tumor-bearing mice by flow cytometry, RT-PCR and immunofluorescence staining. Compared with the groups treated with empty ME and drug solution, the mRNA levels of Bax and caspase-3 were up-regulated, and the mRNA and protein levels of Bcl-2 were down-regulated in H22 cells treated with TanIIA ME in a dose-dependent manner. The mRNA and protein levels of Bax and caspase-3 were up-regulated and the Bcl-2 levels were also down-regulated in animals treated with TanIIA ME in a dose-dependent manner. Our results suggest that as a novel drug delivery system, microemulsion enhances the antitumor effects of TanIIA.
Simultaneous Quantitative Determination of Nine Active Chemical Compositions in Traditional Chinese Medicine Glycyrrhiza by RP-HPLC with Full-Time Five-Wavelength Fusion Method
Authors: Wu Yin-Ping , Meng Xian-Sheng , Bao Yong-Rui , Wang Shuai , Kang Ting-Guo
Published: January 2013

A new, simple, accurate and reliable full-time five-wavelength fusion method for the simultaneous separation and determination of nine active chemical compositions (liquiritin apioside, liquiritin, isoliquiritin apioside, ononin, isoliquiritin, liquiritigenin, calycosin, isoliquiritigenin, Glycyrrhizic acid monoammonium salt) in traditional Chinese medicine Glycyrrhiza was developed using reverse phase high-performance liquid chromatography (RP-HPLC) coupled with a diode-array detector (DAD). The chromatographic separation was performed on an Agilent TC-C18 column with gradient elution using 0.04% methanoic acid (A) and acetonitrile (B) at a flow rate of 1.0 mL min-1 and UV detection at 248 nm, 250 nm, 276 nm, 362 nm, 370 nm. The standard curves were linear over the range of 2.1379–12.8272 μg for liquiritin apioside, 3.9299–23.5794 μg for liquiritin, 1.0432–6.2592 μg for isoliquiritin apioside, 0.8764–5.8584 μg for ononin, 1.0701–6.4205 μg for isoliquiritin, 1.3685–8.2111 μg for liquiritigenin, 0.3927–2.3563 μg for calycosin, 0.2498– 1.4986 μg for isoliquiritigenin, 2.0094–12.0564 μg for Glycyrrhizic acid monoammonium salt, respectively (r2 > 0.9997). The recoveries and relative standard deviation (RSD) varied from 95.09% to 103.54% and 1.09% to 2.36%, respectively. The precision for all the analytes was less than 2.52%. The method indicated good performance in terms of precision, accuracy and linearity. The method enabled the simultaneous determination of nine active chemical compositions for quality control of Glycyrrhiza.
RESIDUE-WEIGHTED NUMBER CONVERSION FOR MODULI SET {2n-1, 2n + 1, 22n + 1, 2n} USING SIGNED-DIGIT NUMBER
Authors: JIANG CHANGJUN , WEI SHUGANG
Published: January 2013

Signed-digit number systems support carry-free, constant time addition. By introducing the signed-digit number arithmetic into a residue number system (RNS), arithmetic operations can be performed efficiently. In this paper, a new algorithm for residue-to-binary conversion for four moduli set {2n-1, 2n + 1, 22n + 1, 2n} that only requires modulo 24n - 1 SD number addition is proposed. This moduli set has 5n-bit dynamic range. Based on the proposed algorithm, the converters are designed with a two-level binary tree structure formed by the modulo 24n - 1 SD number residue adders. Moreover, we simplify the residue adders in converters to obtain more area and time efficiency. The comparison of the converters proposed with the converter using binary arithmetic using 0.18 μm CMOS gate array technology yields reductions in delays of 44%, 60% and 75% for n = 4, n = 8 and n = 16, respectively.
A NEW CURRENT-MODE SQUARE-ROOT-DOMAIN GENERAL NOTCH FILTER
Authors: KIRCAY ALI , KESERLIOGLU M. SERHAT , CAM UGUR
Published: January 2013

In this paper, a new current-mode second-order square-root-domain general notch filter is proposed. The design is based on the state-space synthesis method with two subcircuit; square-root and squarer/divider circuits. In the circuit, the input and the output values, and dominant variables are all currents. Only MOS transistors and grounded capacitors are required to realize the filter circuit. Three cases of the second-order notch filter were obtained. The regular notch was obtained when ωn = ωp, the lowpass notch was obtained when ωn > ωp, and the highpass notch was obtained when ωn < ωp. The center frequency, and the notch frequency of the filter can be electronically tuned by changing external currents. Time and frequency domain simulations are performed using PSPICE program for the filter to verify the theory and to show the performance of it. For this purpose, the filter is simulated by using TSMC 0.35 μm Level 3 CMOS process parameters.
Vectorization technology to improve interpreter performance
Authors: Rohou Erven , Williams Kevin , Yuste David
Published: January 2013

In the present computing landscape, interpreters are in use in a wide range of systems. Recent trends in consumer electronics have created a new category of portable, lightweight software applications. Typically, these applications have fast development cycles and short life spans. They run on a wide range of systems and are deployed in a target independent bytecode format over Internet and cellular networks. Their authors are untrusted third-party vendors, and they are executed in secure managed runtimes or virtual machines. Furthermore, due to security policies or development time constraints, these virtual machines often lack just-in-time compilers and rely on interpreted execution. At the other end of the spectrum, interpreters are also a reality in the field of high-performance computations because of the flexibility they provide.

The main performance penalty in interpreters arises from instruction dispatch. Each bytecode requires a minimum number of machine instructions to be executed. In this work, we introduce a novel approach for interpreter optimization that reduces instruction dispatch thanks to vectorization technology. We extend the split compilation paradigm to interpreters, thus guaranteeing that our approach exhibits almost no overhead at runtime. We take advantage of the vast research in vectorization and its presence in modern compilers. Complex analyses are performed ahead of time, and their results are conveyed to the executable bytecode. At runtime, the interpreter retrieves this additional information to build the SIMD IR (intermediate representation) instructions that carry the vector semantics. The bytecode language remains unmodified, making this representation compatible with legacy interpreters and previously proposed JIT compilers.

We show that this approach drastically reduces the number of instructions to interpret and decreases execution time of vectorizable applications. Moreover, we map SIMD IR instructions to hardware SIMD instructions when available, with a substantial additional improvement. Finally, we finely analyze the impact of our extension on the behavior of the caches and branch predictors.
Fast asymmetric thread synchronization
Authors: Cleary Jimmy , Callanan Owen , Purcell Mark , Gregg David
Published: January 2013

For most multi-threaded applications, data structures must be shared between threads. Ensuring thread safety on these data structures incurs overhead in the form of locking and other synchronization mechanisms. Where data is shared among multiple threads these costs are unavoidable. However, a common access pattern is that data is accessed primarily by one dominant thread, and only very rarely by the other, non-dominant threads. Previous research has proposed biased locks, which are optimized for a single dominant thread, at the cost of greater overheads for non-dominant threads. In this article we propose a new family of biased synchronization mechanisms that, using a modified interface, push accesses to shared data from the non-dominant threads to the dominant one, via a novel set of message passing mechanisms. We present mechanisms for protecting critical sections, for queueing work, for caching shared data in registers where it is safe to do so, and for asynchronous critical section accesses. We present results for the conventional Intel® Sandy Bridge processor and for the emerging network-optimized many-core IBM® PowerEN™ processor. We find that our algorithms compete well with existing biased locking algorithms, and, in particular, perform better than existing algorithms as accesses from non-dominant threads increase.
Understanding fundamental design choices in single-ISA heterogeneous multicore architectures
Authors: Van Craeynest Kenzo , Eeckhout Lieven
Published: January 2013

Single-ISA heterogeneous multicore processors have gained substantial interest over the past few years because of their power efficiency, as they offer the potential for high overall chip throughput within a given power budget. Prior work in heterogeneous architectures has mainly focused on how heterogeneity can improve overall system throughput. To what extent heterogeneity affects per-program performance has remained largely unanswered. In this article, we aim at understanding how heterogeneity affects both chip throughput and per-program performance; how heterogeneous architectures compare to homogeneous architectures under both performance metrics; and how fundamental design choices, such as core type, cache size, and off-chip bandwidth, affect performance.

We use analytical modeling to explore a large space of single-ISA heterogeneous architectures. The analytical model has linear-time complexity in the number of core types and programs of interest, and offers a unique opportunity for exploring the large space of both homogeneous and heterogeneous multicore processors in limited time. Our analysis provides several interesting insights: While it is true that heterogeneity can improve system throughput, it fundamentally trades per-program performance for chip throughput; although some heterogeneous configurations yield better throughput and per-program performance than homogeneous designs, some homogeneous configurations are optimal for particular throughput versus per-program performance trade-offs. Two core types provide most of the benefits from heterogeneity and a larger number of core types does not contribute much; job-to-core mapping is both important and challenging for heterogeneous multicore processors to achieve optimum performance. Limited off-chip bandwidth does alter some of the fundamental design choices in heterogeneous multicore architectures, such as the need for large on-chip caches for achieving high throughput, and per-program performance degrading more relative to throughput under constrained off-chip bandwidth.
The CRNS framework and its application to programmable and reconfigurable cryptography
Authors: Antão Samuel , Sousa Leonel
Published: January 2013

This article proposes the Computing with the ResidueNumber System (CRNS) framework, which aims at the design automation of accelerators for Modular Arithmetic (MA). The framework provides a comprehensive set of tools ranging from a programming language and respective compiler to back-ends targeting parallel computation platforms such as Graphical Processing Units (GPUs) and reconfigurable hardware. Given an input algorithm described with a high-level programming language, the CRNS can be used to obtain in a few seconds the corresponding optimized Parallel Thread Execution (PTX) program ready to be run on GPUs or the Hardware Description Language (HDL) specification of a fully functional accelerator suitable for reconfigurable hardware and embedded systems. The resulting framework's implementations benefit from the Residue Number System (RNS) arithmetic's parallelization properties in a fully automated way. Designers do not need to be familiar with the mathematical details concerning the employed arithmetic, namely the RNS representation. In order to thoroughly describe and evaluate the proposed framework, experimental results obtained for the supported back-ends (GPU and HDL) are presented targeting the implementation of the modular exponentiation used in the Rivest-Shamir-Adleman (RSA) algorithm and Elliptic Curve (EC) point multiplication. Results suggest competitive latency and throughput with minimum design effort and overcoming all the development issues that arise in the specification and verification of dedicated solutions.
LIGERO
Authors: Abad Pablo , Puente Valentin , Gregorio Jose-Angel
Published: January 2013

Although abstraction is the best approach to deal with computing system complexity, sometimes implementation details should be considered. Considering on-chip interconnection networks in particular, underestimating the underlying system specificity could have nonnegligible impact on performance, cost, or correctness. This article presents a very efficient router that has been devised to deal with cache-coherent chip multiprocessor particularities in a balanced way. Employing the same principles of packet rotation structures as in the rotary router, we present a router configuration with the following novel features: (1) reduced buffering requirements, (2) optimized pipeline under contentionless conditions, (3) more efficient deadlock avoidance mechanism, and (4) optimized in-order delivery guarantee. Putting it all together, our proposal provides a set of features that no other router, to the best of our knowledge, has achieved previously. These are: (1') low implementation cost, (2') low pass-through latency under low load, (3') improved resource utilization through adaptive routing and a buffering scheme free of head-of-line blocking, (4') guarantee of coherence protocol correctness via end-to-end deadlock avoidance and in-order delivery, and (5') improvement of coherence protocol responsiveness through adaptive in-network multicast support. We conduct a thorough evaluation that includes hardware cost estimation and performance evaluation under a wide spectrum of realistic workloads and coherence protocols. Comparing our proposal with VCTM, an optimized state-of-the-art wormhole router, it requires 50% less area, reduces on-chip cache hierarchy energy delay product on average by 20%, and improves the cache-coherency chip multiprocessor performance under realistic working conditions by up to 20%.
ADAPT
Authors: Kumar Pusukuri Kishore , Gupta Rajiv , Bhuyan Laxmi N.
Published: January 2013

Since multicore systems offer greater performance via parallelism, future computing is progressing towards use of multicore machines with large number of cores. However, the performance of emerging multithreaded programs often does not scale to fully utilize the available cores. Therefore, simultaneously running multiple multithreaded applications becomes inevitable to fully exploit the computing potential of such machines. However, maximizing the performance and throughput on multicore machines in the presence of multiple multithreaded programs is a challenge for the OS. We have observed that the state-of-the-art contention management algorithms fail to effectively coschedule multithreaded programs on multicore machines. To address the above challenge, we present ADAPT, a scheduling framework that continuously monitors the resource usage of multithreaded programs and adaptively coschedules them such that they interfere with each other's performance as little as possible. In addition, ADAPT selects appropriate memory allocation and scheduling policies according to the workload characteristics. We have implemented ADAPT on a 64-core Supermicro server running Solaris 11 and evaluated it using 26 multithreaded programs including the TATP database application, SPECjbb2005, and programs from Phoenix, PARSEC, and SPEC OMP suites. The experimental results show that ADAPT substantially improves total turnaround time and system utilization relative to the default Solaris 11 scheduler.
Continuous learning of compiler heuristics
Authors: Tartara Michele , Crespi Reghizzi Stefano
Published: January 2013

Optimizing programs to exploit the underlying hardware architecture is an important task. Much research has been done on enabling compilers to find the best set of code optimizations that can build the fastest and less resource-hungry executable for a given program. A common approach is iterative compilation, sometimes enriched by machine learning techniques. This provides good results, but requires extremely long compilation times and an initial training phase lasting even for days or weeks.

We present long-term learning, a new algorithm that allows the compiler user to improve the performance of compiled programs with reduced compilation times with respect to iterative compilation, and without an initial training phase. Our algorithm does not just build good programs: it acquires knowledge every time a program is compiled and it uses such knowledge to learn compiler heuristics, without the need for an expert to manually define them. The heuristics are evolved during every compilation, by evaluating their effect on the generated programs. We present implementations of long-term learning on top of two different compilers, and experimental data gathered on multiple hardware configurations showing its effectiveness.
Significantly reducing MPI intercommunication latency and power overhead in both embedded and HPC systems
Authors: Mattheakis Pavlos M. , Papaefstathiou Ioannis
Published: January 2013

Highly parallel systems are becoming mainstream in a wide range of sectors ranging from their traditional stronghold high-performance computing, to data centers and even embedded systems. However, despite the quantum leaps of improvements in cost and performance of individual components over the last decade (e.g., processor speeds, memory/interconnection bandwidth, etc.), system manufacturers are still struggling to deliver low-latency, highly scalable solutions. One of the main reasons is that the intercommunication latency grows significantly with the number of processor nodes. This article presents a novel way to reduce this intercommunication delay by implementing, in custom hardware, certain communication tasks. In particular, the proposed novel device implements the two most widely used procedures of the most popular communication protocol in parallel systems the Message Passing Interface (MPI). Our novel approach has initially been simulated within a pioneering parallel systems simulation framework and then synthesized directly from a high-level description language (i.e., SystemC) using a state-of-the-art synthesis tool. To the best of our knowledge, this is the first article presenting the complete hardware implementation of such a system. The proposed novel approach triggers a speedup from one to four orders of magnitude when compared with conventional software-based solutions and from one to three orders of magnitude when compared with a sophisticated software-based approach. Moreover, the performance of our system is from one to two orders of magnitude higher than the simulated performance of a similar but, relatively simpler hardware architecture; at the same time the power consumption of our device is about two orders of magnitude lower than that of a low-power CPU when executing the exact same intercommunication tasks.