bluuebunny/crossref_metadata_2025 huggingface dataset:
β‐caryophyllene oxide inhibits constitutive and inducible STAT3 signaling pathway through induction of the SHP‐1 protein tyrosine phosphatase
Authors: Kim Chulwon , Cho Somi K. , Kapoor Shweta , Kumar Ansu , Vali Shireen , Abbasi Taher , Kim Sung‐Hoon , Sethi Gautam , Ahn Kwang Seok
Published: June 2013

Constitutive activation of STAT3 is frequently observed and closely linked with proliferation, survival, invasion, metastasis and angiogenesis in tumor cells. In the present study, we investigated whether β‐caryophyllene oxide (CPO), a sesquiterpene isolated primarily from the essential oils of medicinal plants such as guava (Psidium guajava), and oregano (Origanum vulgare L.), can mediate its effect through interference with the STAT3 activation pathway in cancer cells. The effect of CPO on STAT3 activation, associated protein kinases and phosphatase, STAT3‐regulated gene products and apoptosis was investigated using both functional proteomics tumor pathway technology platform and different tumor cell lines. We found that CPO suppressed constitutive STAT3 activation in multiple myeloma (MM), breast and prostate cancer cell lines, with a significant dose‐ and time‐dependent effects observed in MM cells. The suppression was mediated through the inhibition of activation of upstream kinases c‐Src and JAK1/2. Also, vanadate treatment reversed CPO‐induced down‐regulation of STAT3, suggesting the involvement of a tyrosine phosphatase. Indeed, we found that CPO induced the expression of tyrosine phosphatase SHP‐1 that correlated with the down‐regulation of constitutive STAT3 activation. Interestingly, deletion of SHP‐1 gene by siRNA abolished the ability of CPO to inhibit STAT3 activation. The inhibition of STAT3 activation by CPO inhibited proliferation, induced apoptosis and abrogated the invasive potential of tumor cells. Our results suggest for the first time that CPO is a novel blocker of STAT3 signaling cascade and thus has an enormous potential for the treatment of various cancers harboring constitutively activated STAT3. © 2013 Wiley Periodicals, Inc.
Wogonin reverses hypoxia resistance of human colon cancer HCT116 cells via downregulation of HIF‐1α and glycolysis, by inhibiting PI3K/Akt signaling pathway
Authors: Wang Hu , Zhao Li , Zhu Li‐Tao , Wang Yu , Pan Di , Yao Jing , You Qi‐Dong , Guo Qing‐Long
Published: June 2013

Hypoxia induced drug resistance is a major obstacle in the development of effective cancer therapy. In the present study, the reversal abilities of wogonin on the hypoxia resistance and the underlying mechanisms were discovered. MTT assay revealed that hypoxia increased maximal 1.71‐, 2.08‐, and 2.15‐fold of IC50 toward paclitaxel, ADM, and DDP in human colon cancer cell lines HCT116, respectively. Furthermore, wogonin showed strong reversal potency in HCT116 cells in hypoxia and the RF reached 2.05. hypoxia‐inducible factor‐1α (HIF‐1α) can activate the expression of target genes involved in glycolysis. Wogonin decreased the expression of glycolysis‐related proteins (HKII, PDHK1, LDHA), glucose uptake, and lactate generation in a dose‐dependent manner. Further, Western blot experiments exhibited that wogonin could down regulate HIF‐1α expression and glycolysis through inhibiting PI3K/Akt signaling pathway, which might be the mechanism of reversal resistance of wogonin. Also, wogonin could inhibit the growth of transplantable tumors and the expression of HIF‐1α, glycolysis‐related proteins and PI3K/Akt in vivo. In summary, wogonin could be a good candidate for the development of new multidrug resistance (MDR) reversal agent and its reversal mechanism probably is due to the suppression of HIF‐1α expression via inhibiting PI3K/Akt signaling pathway. © 2013 Wiley Periodicals, Inc.
Analysis of newton multilevel stabilized finite volume method for the three‐dimensional stationary Navier‐Stokes equations
Authors: Zhao Xin , Li Jian , Su Jian , Lei Gang
Published: June 2013

This article proposes and analyzes a multilevel stabilized finite volume method(FVM) for the three‐dimensional stationary Navier–Stokes equations approximated by the lowest equal‐order finite element pairs. The method combines the new stabilized FVM with the multilevel discretization under the assumption of the uniqueness condition. The multilevel stabilized FVM consists of solving the nonlinear problem on the coarsest mesh and then performs one Newton correction step on each subsequent mesh thus only solving one large linear systems. The error analysis shows that the multilevel‐stabilized FVM provides an approximate solution with the convergence rate of the same order as the usual stabilized finite element solution solving the stationary Navier–Stokes equations on a fine mesh for an appropriate choice of mesh widths: hj ∼ hj‐12, j = 1,…,J. Therefore, the multilevel stabilized FVM is more efficient than the standard one‐level‐stabilized FVM. © 2013 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2013
Bio‐inspired layer‐by‐layer assembled hybrid films for improvement of mechanical properties
Authors: Gu Changwei , Huang Xiancong , Shi Meiwu , Zhang Man , Wang Xin‐Ling , Zheng Zhen
Published: June 2013

Inspired by many strong, toughness, and stiffness materials in nature, we first present bio‐inspired structure hybrid films fabricated by layer‐by‐layer assembly technique based on low‐surface‐energy graphite micro‐sheets and styrenic block copolymers. Compared with pure polymer films, the mechanical properties of the hybrid films have been greatly modified in failure stress, elastic modulus, and failure energy due to the rigid bio‐inspired structure. After graphite micro‐sheets surface modified by dopamine, a better enhancement in mechanical properties was achieved with the assistance of dopamine surface modification in the almost same content of inorganic component. The layer‐by‐layer assembly method was improved by introducing the wet‐coating techniques that has been widely applied in industry. This improved method is more easily to fabricate large‐area hybrid films without destroying the bio‐inspired structure of the hybrid films. This improved method and bio‐inspired structure were first applied to reinforce elastomer in this work, while this bio‐inspired structure has shown great success when applied in the area of plastic. POLYM. COMPOS. 34:1261–1268, 2013. © 2013 Society of Plastics Engineers
How do we distinguish loss of vibration sensation due to neuropathy from that due to ageing?
Authors: Liu Yingqi , Brooks Belinda , McCosker Sarah , Molyneaux Lynda , Yue Dennis K
Published: June 2013

The aim of this study was to determine whether loss of sensation in the feet due to diabetic neuropathy can be distinguished from age‐related changes by testing sensation at more proximal sites.

Vibration perception threshold (VPT) was tested using a biothesiometer at the feet, mid‐tibia and knees on participants who had a VPT ≥50 volts. We studied: (i) diabetic patients with a history of neuropathic ulceration (N Ulcer+ve); (ii) elderly diabetic patients with no history of ulceration (E Ulcer−ve); and (iii) elderly non‐diabetic controls. The VPT of the N Ulcer+ve group dropped significantly at the level of mid‐tibia and knee and was significantly different from the E Ulcer−ve group at both sites and from the elderly controls at the knee (p ≤ 0.05). By contrast, the E Ulcer−ve group and the elderly controls tended to have poor vibration perception at all three sites.

The results of this study suggest that diabetic neuropathy is a predominantly distal disease, whereas ageing is associated with a more generalised loss of sensation. This observation may be used to grade more precisely the risk of ulceration in elderly diabetic patients. Copyright © 2013 John Wiley & Sons.
What proportion of patients fail NICE criteria for continuing GLP‐1 treatment beyond six months, and why?
Authors: Wessels L , Keigan S , O'Brien SV , Hardy KJ
Published: June 2013

Glucagon‐like peptide 1 (GLP‐1) agonist treatment in type 2 diabetes typically improves glycaemic control and results in weight loss. The National Institute for Health and Clinical Excellence (NICE) continuation criteria are that at six months patients must have achieved at least a 3% reduction in weight and an 11mmol/mol (1%) reduction in HbA1c. The St Helens Hospital diabetes team has provided a GLP‐1 service since 2007. As from August 2010, we implemented a new service structure to intensify support to patients, including monthly follow up for the first six months.

We assessed NICE continuation criteria in 43 patients who attended since the change in service structure, met NICE initiation criteria and received at least six months' treatment. Mean age was 56 years (SD 10), diabetes duration 10 years (SD 5), baseline median weight 118kg (range 78–152), BMI 41kg/m2 (range 31–60), and HbA1c 83mmol/mol (range 63–120; DCCT: 9.7% [7.9–13.1]).

Thirty (70%) patients met continuation criteria. After follow up of a median 8 months (range 6–12), these patients had a median weight loss of 7.8kg (range 3–21) and a median HbA1c fall of 24.2mmol/mol (range 11–34; DCCT: 2.2% [1–5.3]). Of those failing NICE continuation criteria, 38.5% failed on weight alone, 38.5% on HbA1c alone, and 23% on both. Baseline characteristics could not predict treatment failure. Median weight loss in those failing on HbA1c alone was 8.7kg (range 2.4–12.4). Median reduction in HbA1c in those failing on weight alone was 29.7mmol/mol (2.7%).

We conclude that in our clinic most patients can continue GLP‐1 treatment, but approximately 30% fail to meet NICE continuation criteria, despite clear treatment benefits. Copyright © 2013 John Wiley & Sons.
Patients' experience of admission to hospital with diabetic ketoacidosis and its psychological impact: an exploratory qualitative study
Authors: Moffett Matilda A , Buckingham Jocelyn C , Baker Christine R , Hawthorne Gillian , Leech Nicola J
Published: June 2013

The primary aim of this study was to better understand patients' experience of admission to hospital with diabetic ketoacidosis (DKA) and its psychological impact. The secondary aim was to improve our service provision for patients following an episode of DKA.

Forty patients who had been admitted to hospital with DKA were invited to participate. Four patients agreed to take part (three female, one male; mean age 34 years, range 21–49 years). All participants had type 1 diabetes. Participants completed a semi‐structured interview and psychometric questionnaires. Descriptive statistics were generated for demographic and questionnaire data. Interview transcripts were qualitatively analysed using thematic analysis.

The thematic analysis showed three important themes: Consequences of DKA; Recognising and Managing DKA; and Hospital Experience. The theme of Recognising and Managing DKA highlighted that only one participant recognised insufficient insulin as a trigger for DKA, and other people first recognised symptom severity in every case. The theme Hospital Experience seemed to support a number of studies that have found poor provision of care for those presenting with DKA.

It is important to note that there were only four participants who contributed, which limited the conclusions that can be drawn. It appeared some patients lack understanding of what DKA is. It seems that better provision of information on DKA needs to be given to both the individual and their family members. There was some evidence that an admission for DKA is a marker for follow‐up psychological assessment. Copyright © 2013 John Wiley & Sons.
Detection of adverse drug reactions using hospital databases—a nationwide study in Portugal
Authors: Miguel Ana , Bernardo Marques  , Freitas Alberto , Lopes Fernando , Azevedo Luís , Pereira Altamiro Costa
Published: June 2013

Purpose

This study aimed to detect and characterize adverse drug reactions (ADRs) that occurred during hospitalization (ADRIn) and ADRs associated with admission (ADRAd) in Portugal from 2000 to 2009. We also intended to compare the results of this methodology with spontaneous reporting.

Methods

We conducted a nationwide study using a hospital administrative database that included all acute care public hospitalizations in Portugal, from 2000 to 2009. We used International Classification of Diseases—9thRevision—Clinical Modification coding data for the detection of ADRs. Codes searched included “E” codes (E930 to E949.9, codes that exclude poisonings and errors) and five groups of diagnoses codes associated with high prevalence of ADR as found in a previous study: hypoglycemia, drug‐induced neutropenia, hepatitis unspecified, anaphylactic shock due to drugs, and shock due to anesthesia.

Results

From 9 271 122 hospitalizations within that period, 116 720 ADRs were detected through the database methodology, representing 1.26% from all hospitalizations. Of the ADRs, 97.3% occurred during hospitalization (ADRIn), whereas 2.7% were associated with admission. Age, female sex, and comorbidities such as pneumonia, heart failure, diabetes, and malignancies were associated with ADRs (all with differences statistically significant). There were 13 562 spontaneous reports from 2000 to 2009.

Conclusions

Several methods have been used for the detection of ADRs, but they are difficult to apply at a national level. Spontaneous reporting is widely used but grossly underestimates the frequency of ADRs. The database methodology can be very useful to estimate ADRs frequency and to perform a simple characterization of ADRs nationwide. Copyright © 2013 John Wiley & Sons, Ltd.
Estimating Spatial Differentials in Life Expectancy in Greece at Local Authority Level
Authors: Tsimbos Cleon , Kalogirou Stamatis , Verropoulou Georgia
Published: June 2013

The aims of this paper are to estimate, for the first time for Greece, life expectancy at birth by gender at local authority level and to explore spatial patterns. The data used in the analysis come from the vital registration system of Greece and the 2001 population census. For areas with male/female population 5,000 or more, representing 97% of the total, abridged life tables are constructed by employing the Chiang methodology. For local areas of less than 5,000, estimates of expectation of life at birth are obtained by employing regression models. Standard errors of life expectancy are estimated using the Chiang approximation as well as the Scherbov–Ediev reference tables. The results are presented in thematic as well as cluster maps; the latter are based on local Moran's I spatial autocorrelation statistics. Local populations are ranked by level of deprivation in three groups, low, medium, and high, and differences in mean life expectancies are assessed. The findings indicate that across localities, life expectancy ranges from 70.7 to 79.6 for men (8.9‐year difference) and from 76.1 to 82.5 for women (6.4‐year difference). More deprived areas exhibit lower life expectancy but greater sex difference. Comparatively high life expectancy is found in Crete, the Aegean and Ionian Islands, the Peloponnese, Central‐Western Greece and in Athens and Thessaloniki metropolitan areas; conditions are unfavourable in North‐Eastern Greece (particularly Thrace). Life expectancy standard errors, based on the two aforementioned procedures, are close, but Chiang approximation tends to underestimate to some extend standard errors particularly for populations 5,000–10,000. Copyright © 2013 John Wiley & Sons, Ltd.
Remediation of a Diffuse Trichloroethene Plume in an Urban Setting
Authors: Bienkowski Lee
Published: June 2013

During an environmental assessment of a former fleet vehicle maintenance facility located in Jacksonville, Florida, dissolved trichloroethene (TCE) concentrations exceeding the Florida groundwater standard (3 micrograms per liter) were detected at a depth of 40 feet (12 meters) below land surface (bls). A plume was delineated that measured approximately 600 feet (183 meters) by 150 feet (46 meters), extending across a major road and onto adjacent properties. Shaw Environmental, Inc., which was acquired by CB&I in February 2012, performed pilot tests with in situ oxygen curtain (iSOC), and the injection of Anaerobic Biochem Plus (ABC+), a mixture of lactates, a phosphate buffer, fatty acids, and zero‐valent iron. Based on the pilot‐test results, ABC+ appeared the more effective of the two methods and was selected for full‐scale implementation. In February 2011, Shaw Environmental, Inc. and a subcontractor used direct‐push technology to inject ABC+ in 120 borings. By September 2011, the treatment succeeded in lowering the concentrations of TCE to below the Florida standard in all impacted wells. Subsequent sampling events indicate that TCE concentrations have remained below the standard, but sampling continues for iron, which is decreasing but remains slightly elevated. © 2013 Wiley Periodicals, Inc.
Short‐Term Ethnography: Intense Routes to Knowing
Authors: Pink Sarah , Morgan Jennie
Published: June 2013

In this article, we explore how short‐term theoretically informed ethnography is emerging as an approach to doing research that is contemporary in both its subject matter and in its use for applied research projects designed to lead to informed interventions in the world. We argue that far from being a ‘quick and dirty’ route to doing qualitative research, short‐term ethnography is characterized by forms of intensity that lead to deep and valid ways of knowing.
Comparison of pneumatic jets and tabs for Active Aerodynamic Load Control
Authors: Blaylock Myra , Chow Raymond , Cooperman Aubryn , van Dam C. P.
Published: June 2013

A fast, efficient way to control loads on utility scale wind turbines is important for the growth of the wind industry. Microtabs and microjets are two Active Aerodynamic Load Control devices, which address this need. Both act perpendicular to the surface of the airfoil, and these actively controlled devices are used to mitigate changes in aerodynamic loading experienced by wind turbine rotors due to wind gusts, wind shear, or other atmospheric phenomena. This work explores the aerodynamic effects of microjets and then compares them to those of microtabs. Flow around an airfoil with an activated microjet at the trailing edge has been simulated using the Reynolds‐averaged Navier–Stokes solver OVERFLOW‐2. Using a Chimera overset grid topology, a microjet has been placed near the trailing edge of the lower surface of a NACA 0012 airfoil. For a jet velocity about half of the freestream velocity, the microjet can change the lift up to ΔCL = 0.2, but the amount of change varies with the momentum coefficient of the jet. The change in lift is not symmetric for positive and negative angles of attack due to changes in the boundary layer thickness with angle of attack. Increasing the Reynolds number reduces the effectiveness of the microjet only slightly. The effects of jet velocity, jet activation time, and airfoil angle of attack on airfoil lift, drag, and pitching moment are compared with previous work, which illustrates the deployment of a microtab at the 95% chord location of a NACA 0012 airfoil. This study shows that microjets and microtabs have very similar responses in lift and pitching moment, but the drag for the microjet is noticeably lower. Copyright © 2013 John Wiley & Sons, Ltd.
Dynamic response analysis of wind turbines under blade pitch system fault, grid loss, and shutdown events
Authors: Jiang Zhiyu , Karimirad Madjid , Moan Torgeir
Published: June 2013

This study focuses on the dynamic responses of land‐based and floating wind turbines under blade pitch system fault and emergency shutdown conditions. The NREL 5 MW turbine is studied. A hydraulic pitch system is considered, and the faults under study are events with a seized blade or a blade running out of control. Emergency shutdown is defined as a fast pitch‐to‐feather maneuver of the blades. Load cases with power production and grid fault with ensuing shutdown are also analysed for comparison. The fault scenarios and the blades' fast pitching activity are simulated using HAWC2 through external Dynamic Link Libraries. On the basis of the time‐domain simulations, the response characteristics of the land‐based and the floating turbines in the four design load cases are compared. The load effects from the fault conditions are compared with the operational cases. Strong system dynamics and resonant responses, such as the tower elastic mode and the yaw resonant response, are elicited during shutdown. If the pitch system has a fault and one blade is hindered from normal pitching, the uneven load distribution of the blades leads to large structural and motion responses. For both turbines, the response maxima vary cyclically with the instantaneous azimuth when the blades start pitching to feather. For the floating wind turbine, the interaction of waves and wind also affects the results. The effect of the pitch rate during shutdown is analysed. The responses of the land‐based turbine in grid loss and shutdown conditions are proportional to the pitch rate, whereas decreased sensitivity is found in the cases with pitch system faults. For the floating turbine, the effect of the pitch rate is small, and reduced pitch and yaw motion extremes are observed as the pitch rate increases. Copyright © 2013 John Wiley & Sons, Ltd.
Rsu1 contributes to regulation of cell adhesion and spreading by PINCH1‐dependent and ‐ independent mechanisms
Authors: Gonzalez‐Nieves Reyda , DeSantis Akiko Iwahari , Cutler Mary L.
Published: June 2013

Cell adhesion and migration are complex processes that require integrin activation, the formation and dissolution of focal adhesion (FAs), and linkage of actin cytoskeleton to the FAs. The IPP (ILK, PINCH, Parvin) complex regulates FA formation via binding of the adaptor protein ILK to β1 integrin, PINCH and parvin. The signaling protein Rsu1 is linked to the complex via binding PINCH1. The role of Rsu1 and PINCH1 in adhesion and migration was examined in non‐transformed mammary epithelial cells. Confocal microscopy revealed that the depletion of either Rsu1 or PINCH1 by siRNA in MCF10A cells decreased the number of focal adhesions and altered the distribution and localization of β1 integrin, vinculin, talin and paxillin without affecting the levels of FA protein expression. This correlated with reduced adhesion, failure to spread or migrate in response to EGF and a loss of actin stress fibers and caveolae. In addition, constitutive phosphorylation of actin regulatory proteins occurred in the absence of PINCH1. The depletion of Rsu1 caused significant reduction in PINCH1 implying that Rsu1 may function by regulating levels of PINCH1. However, while both Rsu1‐ or PINCH1‐depleted cells retained the ability to activate adhesion signaling in response to EGF stimulation, only Rsu1 was required for EGF‐induced p38 Map Kinase phosphorylation and ATF2 activation, suggesting an Rsu1 function independent from the IPP complex. Reconstitution of Rsu1‐depleted cells with an Rsu1 mutant that does not bind to PINCH1 failed to restore FAs or migration but did promote spreading and constitutive p38 activation. These data show that Rsu1‐PINCH1 association with ILK and the IPP complex is required for regulation of adhesion and migration but that Rsu1 has a critical role in linking integrin‐induced adhesion to activation of p38 Map kinase signaling and cell spreading. Moreover, it suggests that Rsu1 may regulate p38 signaling from the IPP complex affecting other functions including survival.
B cell translocation gene, a direct target of miR‐142‐5p, inhibits vascular smooth muscle cell proliferation by down‐regulating cell cycle progression
Authors: Kee Hae Jin , Park Sangha , Kwon Jin-Sook , Choe Nakwon , Ahn Youngkeun , Kook Hyun , Jeong Myung Ho
Published: June 2013

Vascular smooth muscle cell (VSMC) proliferation plays a key role in neointimal hyperplasia and restenosis. Here we report the role of the microRNA miR‐142‐5p and its downstream target genes on the proliferation of cultured VSMCs. miR‐142‐5p promoted VSMC proliferation by down‐regulating B cell translocation gene 3 (BTG3). We found that BTG3 inhibited the expression of cell cycle regulatory genes and cell growth. As shown by luciferase reporter assay, miR‐142‐5p bound directly to the 3′‐untranslated region of BTG3. Overexpression of miR‐142‐5p induced expression of cell cycle regulatory genes. Thus, BTG3, a novel, direct target of miR‐142‐5p, negatively regulates VSMC proliferation.
Small proline‐rich repeat protein 3 enhances the sensitivity of esophageal cancer cells in response to DNA damage‐induced apoptosis
Authors: Luo Aiping , Chen Hongyan , Ding Fang , Zhang Yu , Wang Mingrong , Xiao Zefen , Liu Zhihua
Published: June 2013

Small proline‐rich repeat protein 3 (SPRR3) has been linked with the altered chemoradiosensitivity, however the underlying molecular mechanisms remain elusive. Here, we report that ectopic overexpression of SPRR3 enhanced the sensitivity of cells in response to DNA damage‐induced apoptosis via loss of mitochondrial membrane potential (MMP), and increasing activation of caspase 3 in human esophageal cancer cell lines. Conversely, siRNA knockdown of SPRR3 reduced apoptosis. We found that SPRR3 was localized in mitochondria and interacted with Bcl‐2 in vivo, thus facilitating Bax mitochondrial translocation and the subsequent release of cytochrome c, and thereby enhancing cell sensitivity to DNA damage stimuli. In clinical samples, expression of SPRR3 was associated with the pathologic response (P = 0.007 in radiotherapy group, P = 0.035 in preoperative radiotherapy group) and good survival of patients with locally advanced esophageal squamous cell carcinoma (ESCC, P = 0.008). Taken together, our results implicate that SPRR3 might serve as a radiation‐sensitive predictor of ESCC.
Disgorging the Fruits of Historical Wrongdoing
Authors: GOODIN ROBERT E.
Published: June 2013

There are many different ways of responding to wrongdoing: person-centered or object-centered, victim-centered or perpetrator-centered, and fault-oriented or not. Among these approaches, requiring innocent beneficiaries to disgorge the fruits of historical wrongdoings of others is attractive because it is informationally the least demanding. Although that approach is perhaps not ideal, at least it is feasible where other responses are not, and doing something is better than doing nothing in response to grievous historical wrongdoing. Depending on circumstances, disgorgement can be in whole or in part, in kind or in cash. Even without the full information that disgorgement itself requires, general redistributive taxation might be justified as a tolerably close approximation.
NONTRIVIAL SOLUTIONS FOR STURM–LIOUVILLE SYSTEMS VIA A LOCAL MINIMUM THEOREM FOR FUNCTIONALS
Authors: BONANNO GABRIELE , HEIDARKHANI SHAPOUR , O’REGAN DONAL
Published: June 2013

In this paper, employing a very recent local minimum theorem for differentiable functionals, the existence of at least one nontrivial solution for a class of systems of $n$ second-order Sturm–Liouville equations is established.
A NEW UPPER BOUND FOR
Authors: TRUDGIAN TIMOTHY
Published: June 2013

It is known that $\zeta (1+ it)\ll \mathop{(\log t)}\nolimits ^{2/ 3} $ when $t\gg 1$. This paper provides a new explicit estimate $\vert \zeta (1+ it)\vert \leq \frac{3}{4} \log t$, for $t\geq 3$. This gives the best upper bound on $\vert \zeta (1+ it)\vert $ for $t\leq 1{0}^{2\cdot 1{0}^{5} } $.
Principals, Agents and Human Rights
Authors: Cingranelli David , Fajardo-Heyward Paola , Filippov Mikhail
Published: June 2013

This article argues that human rights could be improved by motivating politicians and bureaucrats to put more effort into protecting human rights. It conceptualizes the production of human rights practices as the outcome of two principal-agent relationships that constrain politicians and bureaucrats. Reliance on taxes is a non-electoral, fiscal factor that makes politicians more willing to protect human rights. Increased government revenue, no matter the source, raises bureaucratic compensation and helps create a more accountable bureaucracy. Thus both a higher reliance on taxes and larger state revenues lead to the better protection of human rights. Each fiscal factor promotes a different type of accountability, both of which independently contribute to good human rights practices.
Contracting with Nonfinancial Stakeholders and Corporate Capital Structure: The Case of Product Warranties
Authors: Kale Jayant R. , Meneghetti Costanza , Shahrur Husayn
Published: June 2013

We investigate the relation between a firm’s product warranty level and its leverage. We find that leverage relates negatively to the warranty level and that this relation is robust to controls for endogeneity and self-selection into offering warranties. The negative warranty-leverage relation obtains only in the subsample of firms in the manufacturing industries. We also show that firms with warranties have the lowest debt levels, firms without warranties but operating in industries where other firms offer warranties on average carry higher debt, and firms in industries where no firm offers a warranty have the highest debt levels.
Uncommon and rare causes of vocal fold paralysis detected via imaging
Authors: Sobrino-Guijarro B , Virk J S , Singh A , Lingam R K
Published: June 2013

Background:

Cross-sectional imaging can be used to trace the course of the vagus nerve and its laryngeal branches to detect many of the causes of vocal fold paralysis. The most frequent aetiologies are surgical injury and tumoural involvement of the recurrent laryngeal nerve anywhere along its course.

Method:

This review article focuses on the uncommon and rare causes of vocal fold paralysis that have been detected or diagnosed on cross-sectional imaging.

Results and conclusion:

Uncommon causes included a tortuous oesophagus, tracheal diverticulum, cervical osteophytes and cardiovocal syndrome. These examples are presented with clinical case histories and radiological appearances, and are discussed in the context of the current literature.
Are healthcare workers at higher risk of HIV infection than the general population in Burkina Faso?
Authors: KIRAKOYA-SAMADOULOUGOU F. , FAO P. , YARO S. , DEFER M.-C. , MEDA N. , ROBERT A. , NAGOT N.
Published: June 2013

In order to assess the HIV prevalence in healthcare workers (HCWs) in Burkina Faso, we conducted a national survey in 97 health facilities from urban and rural areas. Of 1570 HCWs who agreed to participate, 1013 (64·5%) provided a urine sample for HIV testing. The crude prevalence of HIV in HCWs was 3·5% (95% CI 2·3–4·6). HIV prevalence was 0·7% in students and trainees, 3·8% in nurses and midwives, 4·5% in administrative workers, and 4·6% in laboratory workers. After age and area standardization, men from the Demographic Health Survey (DHS) had a similar HIV prevalence (2·3%, 95% CI 1·4–2·9) as male HCWs (2·5%, 95% CI 1·1–4·0), while female HCWs were more infected (4·5%, 95% CI 2·5–6·0) than women from the DHS (2·1%, 95% CI 1·3–2·4). A voluntary counselling and testing (VCT) programme should be specifically implemented and adapted for female HCWs.
NEW TAXA OF CONVOLVULUS (CONVOLVULACEAE) FROM THE ARABIAN PENINSULA
Authors: Mill R. R.
Published: June 2013

Two new species of Convolvulus (Convolvulaceae), C. excelsus R.R.Mill and C. infantispinosus R.R.Mill, are described from Saudi Arabia. Convolvulus excelsus, an exceptionally tall species, has affinities with C. erinaceus Ledeb. but is phytogeographically disjunct from that and other allied species. Two new subspecies are also described: Convolvulus hystrix Vahl subsp. dhofarica R.R.Mill, from Oman, and C. oxyphyllus Boiss. subsp. sheilae R.R.Mill, from Saudi Arabia. Each novelty is given a provisional IUCN conservation assessment.
REDUNDANCY OR MISMEASUREMENT? A REAPPRAISAL OF MONEY
Authors: Hendrickson Joshua R.
Published: June 2013

The emerging consensus in monetary policy and business cycle analysis is that money aggregates are not useful as an intermediate target for monetary policy or as an information variable. The uselessness of money as an intermediate target is driven, at least in part, by empirical research that suggests that money demand is unstable. In addition, the informational quality of money has been called into question by empirical research that fails to identify a relationship between money growth and inflation, nominal income growth, and the output gap. Nevertheless, this research is potentially flawed by the use of simple sum money aggregates, which are not consistent with economic, aggregation, or index number theory. This paper therefore reexamines previous empirical evidence on money demand and the role of money as an information variable, using Divisia monetary aggregates. These aggregates have the advantage of being derived from microtheoretic foundations, as well as being consistent with aggregation and index number theory. The results of the reevaluation suggest that previous empirical work might be driven by mismeasurement.
The PathoChip, a functional gene array for assessing pathogenic properties of diverse microbial communities
Authors: Lee Yong-Jin , van Nostrand Joy D , Tu Qichao , Lu Zhenmei , Cheng Lei , Yuan Tong , Deng Ye , Carter Michelle Q , He Zhili , Wu Liyou , Yang Fang , Xu Jian , Zhou Jizhong
Published: June 2013

Pathogens present in the environment pose a serious threat to human, plant and animal health as evidenced by recent outbreaks. As many pathogens can survive and proliferate in the environment, it is important to understand their population dynamics and pathogenic potential in the environment. To assess pathogenic potential in diverse habitats, we developed a functional gene array, the PathoChip, constructed with key virulence genes related to major virulence factors, such as adherence, colonization, motility, invasion, toxin, immune evasion and iron uptake. A total of 3715 best probes were selected from 13 virulence factors, covering 7417 coding sequences from 1397 microbial species (2336 strains). The specificity of the PathoChip was computationally verified, and approximately 98% of the probes provided specificity at or below the species level, proving its excellent capability for the detection of target sequences with high discrimination power. We applied this array to community samples from soil, seawater and human saliva to assess the occurrence of virulence genes in natural environments. Both the abundance and diversity of virulence genes increased in stressed conditions compared with their corresponding controls, indicating a possible increase in abundance of pathogenic bacteria under environmental perturbations such as warming or oil spills. Statistical analyses showed that microbial communities harboring virulence genes were responsive to environmental perturbations, which drove changes in abundance and distribution of virulence genes. The PathoChip provides a useful tool to identify virulence genes in microbial populations, examine the dynamics of virulence genes in response to environmental perturbations and determine the pathogenic potential of microbial communities.
Evolutionarily conserved structural changes in phosphatidylinositol 5-phosphate 4-kinase (PI5P4K) isoforms are responsible for differences in enzyme activity and localization
Authors: Clarke Jonathan H. , Irvine Robin F.
Published: June 2013

Mammals have genes coding for three PI5P4Ks (PtdIns5P 4-kinases), and these have different cellular localizations, tissue distributions and lipid kinase activities. We describe in the present paper a detailed molecular exploration of human PI5P4Ks α, β and γ, as well as their fly and worm homologues, to understand how and why these differences came to be. The intrinsic ATPase activities of the three isoforms are very similar, and we show that differences in their G-loop regions can account for much of their wide differences in lipid kinase activity. We have also undertaken an extensive in silico evolutionary study of the PI5P4K family, and show experimentally that the single PI5P4K homologues from Caenorhabditis elegans and Drosophila melanogaster are as widely different in activity as the most divergent mammalian isoforms. Finally we show that the close association of PI5P4Ks α and γ is a true heterodimerization, and not a higher oligomer association of homodimers. We reveal that structural modelling is consistent with this and with the apparently random heterodimerization that we had earlier observed between PI5P4Kα and PI5P4Kβ [Wang, Bond, Letcher, Richardson, Lilley, Irvine and Clarke (2010), Biochem. J. 430, 215–221]. Overall the molecular diversity of mammalian PI5P4Ks explains much of their properties and behaviour, but their physiological functionality remains elusive.
Impact of PPAR-α induction on glucose homoeostasis in alcohol-fed mice
Authors: Lebrun Valérie , Molendi-Coste Olivier , Lanthier Nicolas , Sempoux Christine , Cani Patrice D. , van Rooijen Nico , Stärkel Peter , Horsmans Yves , Leclercq Isabelle A.
Published: June 2013

Alcohol consumption is a major cause of liver disease. It also associates with increased cardiovascular risk and Type 2 diabetes. ALD (alcoholic liver disease) and NAFLD (non-alcoholic fatty liver disease) share pathological features, pathogenic mechanisms and pattern of disease progression. In NAFLD, steatosis, lipotoxicity and liver inflammation participate to hepatic insulin resistance. The aim of the present study was to verify the effect of alcohol on hepatic insulin sensitivity and to evaluate the role of alcohol-induced steatosis and inflammation on glucose homoeostasis. C57BL/6J mice were fed for 20 days a modified Lieber–DeCarli diet in which the alcohol concentration was gradually increased up to 35% of daily caloric intake. OH (alcohol liquid diet)-fed mice had liver steatosis and inflammatory infiltration. In addition, these mice developed insulin resistance in the liver, but not in muscles, as demonstrated by euglycaemic–hyperinsulinaemic clamp and analysis of the insulin signalling cascade. Treatment with the PPAR-α (peroxisome-proliferator-activated receptor-α) agonist Wy14,643 protected against OH-induced steatosis and KC (Kupffer cell) activation and almost abolished OH-induced insulin resistance. As KC activation may modulate insulin sensitivity, we repeated the clamp studies in mice depleted in KC to decipher the role of macrophages. Depletion of KC using liposomes-encapsuled clodronate in OH-fed mice failed both to improve hepatic steatosis and to restore insulin sensitivity as assessed by clamp. Our study shows that chronic alcohol consumption induces steatosis, KC activation and hepatic insulin resistance in mice. PPAR-α agonist treatment that prevents steatosis and dampens hepatic inflammation also prevents alcohol-induced hepatic insulin resistance. However, KC depletion has little impact on OH-induced metabolic disturbances.
Effect of fluorocarbon self-assembled monolayer films on sidewall adhesion and friction of surface micromachines with impacting and sliding contact interfaces
Authors: Xiang H. , Komvopoulos K.
Published: June 2013

A self-assembled monolayer film consisting of fluoro-octyltrichlorosilane (FOTS) was vapor-phase deposited on Si(100) substrates and polycrystalline silicon (polysilicon) surface micromachines. The hydrophobic behavior and structural composition of the FOTS film deposited on Si(100) were investigated by goniometry and X-ray photoelectron spectroscopy, respectively. The effects of contact pressure, relative humidity, temperature, and impact/sliding cycles on the adhesive and friction behavior of uncoated and FOTS-coated polysilicon micromachines (referred to as the Si and FOTS/Si micromachines, respectively) were investigated under controlled loading and environmental conditions. FOTS/Si micromachines demonstrated much lower and stable adhesion than Si micromachines due to the highly hydrophobic and conformal FOTS film. Contrary to Si micromachines, sidewall adhesion of FOTS/Si micromachines demonstrated a weak dependence on relative humidity, temperature, and impact cycles. In addition, FOTS/Si micromachines showed low and stable adhesion and low static friction for significantly more sliding cycles than Si micromachines. The adhesive and static friction characteristics of Si and FOTS/Si micromachines are interpreted in the context of physicochemical surface changes, resulting in the increase of the real area of contact and a hydrophobic-to-hydrophilic transition of the surface chemical characteristics caused by nanoscale surface smoothening and the removal of the organic residue (Si micromachines) or the FOTS film (FOTS/Si micromachines) during repetitive impact and oscillatory sliding of the sidewall surfaces.
On Baxter's Q operator of the higher spin XXZ chain at the Razumov-Stroganov point
Authors: Motegi Kohei
Published: June 2013

Based on the conjecture for the exact eigenvalue of the transfer matrix of the higher half-integer spin XXZ chain at the Razumov-Stroganov point, we evaluate the corresponding Baxter's Q operator in closed form by solving the TQ equation. The combination of the Q operators on the “right side” and the “wrong side” is shown to produce the hierarchy of functional relations.
Correlated one-body potential from second-order Møller-Plesset perturbation theory: Alternative to orbital-optimized MP2 method
Authors: Lan Tran Nguyen , Yanai Takeshi
Published: June 2013

A mean-field (or one-particle) theory to represent electron correlation at the level of the second-order Møller-Plesset perturbation (MP2) theory is presented. Orbitals and associated energy levels are given as eigenfunctions and eigenvalues of the resulting one-body (or Fock-like) MP2 Hamiltonian, respectively. They are optimized in the presence of MP2-level correlation with the self-consistent field procedure and used to update the MP1 amplitudes including their denominators. Numerical performance is illustrated in molecular applications for computing reaction energies, applying Koopmans’ theorem, and examining the effects of dynamic correlation on energy levels of metal complexes.
Development of a confocal rheometer for soft and biological materials
Authors: Dutta S. K. , Mbi A. , Arevalo Richard C. , Blair Daniel L.
Published: June 2013

We discuss the design and operation of a confocal rheometer, formed by integrating an Anton Paar MCR301 stress-controlled rheometer with a Leica SP5 laser scanning confocal microscope. Combining two commercial instruments results in a system which is straightforward to assemble that preserves the performance of each component with virtually no impact on the precision of either device. The instruments are configured so that the microscope can acquire time-resolved, three-dimensional volumes of a sample whose bulk viscoelastic properties are being measured simultaneously. We describe several aspects of the design and, to demonstrate the system's capabilities, present the results of a few common measurements in the study of soft materials.
Towards a whole-cell modeling approach for synthetic biology
Authors: Purcell Oliver , Jain Bonny , Karr Jonathan R. , Covert Markus W. , Lu Timothy K.
Published: June 2013

Despite rapid advances over the last decade, synthetic biology lacks the predictive tools needed to enable rational design. Unlike established engineering disciplines, the engineering of synthetic gene circuits still relies heavily on experimental trial-and-error, a time-consuming and inefficient process that slows down the biological design cycle. This reliance on experimental tuning is because current modeling approaches are unable to make reliable predictions about the in vivo behavior of synthetic circuits. A major reason for this lack of predictability is that current models view circuits in isolation, ignoring the vast number of complex cellular processes that impinge on the dynamics of the synthetic circuit and vice versa. To address this problem, we present a modeling approach for the design of synthetic circuits in the context of cellular networks. Using the recently published whole-cell model of Mycoplasma genitalium, we examined the effect of adding genes into the host genome. We also investigated how codon usage correlates with gene expression and find agreement with existing experimental results. Finally, we successfully implemented a synthetic Goodwin oscillator in the whole-cell model. We provide an updated software framework for the whole-cell model that lays the foundation for the integration of whole-cell models with synthetic gene circuit models. This software framework is made freely available to the community to enable future extensions. We envision that this approach will be critical to transforming the field of synthetic biology into a rational and predictive engineering discipline.
Two dimensional barcode-inspired automatic analysis for arrayed microfluidic immunoassays
Authors: Zhang Yi , Qiao Lingbo , Ren Yunke , Wang Xuwei , Gao Ming , Tang Yunfang , Jeff Xi Jianzhong , Fu Tzung-May , Jiang Xingyu
Published: June 2013

The usability of many high-throughput lab-on-a-chip devices in point-of-care applications is currently limited by the manual data acquisition and analysis process, which are labor intensive and time consuming. Based on our original design in the biochemical reactions, we proposed here a universal approach to perform automatic, fast, and robust analysis for high-throughput array-based microfluidic immunoassays. Inspired by two-dimensional (2D) barcodes, we incorporated asymmetric function patterns into a microfluidic array. These function patterns provide quantitative information on the characteristic dimensions of the microfluidic array, as well as mark its orientation and origin of coordinates. We used a computer program to perform automatic analysis for a high-throughput antigen/antibody interaction experiment in 10 s, which was more than 500 times faster than conventional manual processing. Our method is broadly applicable to many other microchannel-based immunoassays.
Mitochondrial calcium uptake
Authors: Williams George S. B. , Boyman Liron , Chikando Aristide C. , Khairallah Ramzi J. , Lederer W. J.
Published: June 2013

Calcium (Ca
2+
) uptake into the mitochondrial matrix is critically important to cellular function. As a regulator of matrix Ca
2+
levels, this flux influences energy production and can initiate cell death. If large, this flux could potentially alter intracellular Ca
2+
([Ca
2+
]
i
) signals. Despite years of study, fundamental disagreements on the extent and speed of mitochondrial Ca
2+
uptake still exist. Here, we review and quantitatively analyze mitochondrial Ca
2+
uptake fluxes from different tissues and interpret the results with respect to the recently proposed mitochondrial Ca
2+
uniporter (MCU) candidate. This quantitative analysis yields four clear results: (
i
) under physiological conditions, Ca
2+
influx into the mitochondria via the MCU is small relative to other cytosolic Ca
2+
extrusion pathways; (
ii
) single MCU conductance is ∼6–7 pS (105 mM [Ca
2+
]), and MCU flux appears to be modulated by [Ca
2+
]
i
, suggesting Ca
2+
regulation of MCU open probability (
P

O

); (
iii
) in the heart, two features are clear: the number of MCU channels per mitochondrion can be calculated, and MCU probability is low under normal conditions; and (
iv
) in skeletal muscle and liver cells, uptake per mitochondrion varies in magnitude but total uptake per cell still appears to be modest. Based on our analysis of available quantitative data, we conclude that although Ca
2+
critically regulates mitochondrial function, the mitochondria do not act as a significant dynamic buffer of cytosolic Ca
2+
under physiological conditions. Nevertheless, with prolonged (superphysiological) elevations of [Ca
2+
]
i
, mitochondrial Ca
2+
uptake can increase 10- to 1,000-fold and begin to shape [Ca
2+
]
i
dynamics.