bluuebunny/crossref_metadata_2025 huggingface dataset:
A PROPOSED FORMULA FOR HORIZONTAL REVENUE ALLOCATION IN NIGERIA
Authors: EKHOSUEHI VIRTUE U. , OSAGIEDE AUGUSTINE A.
Published: January 2013

In this study, we have applied optimal control theory to determine the optimum value of tax revenues accruing to a state given the range of budgeted expenditure on enforcing tax laws and awareness creation on the payment of the correct tax. This is achieved by maximizing the state's net tax revenue over a fixed time interval subject to certain constraints. By assuming that the satisfaction derived by the Federal Government of Nigeria on the ability of the individual states to generate tax revenue which is as near as the optimum tax revenue (via the state's control problem) is described by the logarithmic form of the Cobb–Douglas utility function, a formula for horizontal revenue allocation in Nigeria in its raw form is derived. Afterwards, we illustrate the use of the proposed horizontal revenue allocation formula using hypothetical data.
NONEQUILIBRIUM TRANSPORT AND THE BERNOULLI EFFECT OF ELECTRONS IN A TWO-DIMENSIONAL ELECTRON GAS
Authors: KAYA İSMET İ.
Published: January 2013

Nonequilibrium transport of charged carriers in a two-dimensional electron gas is summarized from an experimental point of view. The transport regime in which the electron–electron interactions are enhanced at high bias leads to a range of striking effects in a two-dimensional electron gas. This regime of transport is quite different than the ballistic transport in which particles propagate coherently with no intercarrier energy transfer and the diffusive transport in which the momentum of the electron system is lost with the involvement of the phonons. Quite a few hydrodynamic phenomena observed in classical gasses have the electrical analogs in the current flow. When intercarrier scattering events dominate the transport, the momentum sharing via narrow angle scattering among the hot and cold electrons lead to negative resistance and electron pumping which can be viewed as the analog of the Bernoulli–Venturi effect observed classical gasses. The recent experimental findings and the background work in the field are reviewed.
PLANE CURVES IN AN IMMERSED GRAPH IN ℝ2
Authors: SAKAMOTO MARISA , TANIYAMA KOUKI
Published: January 2013

For any chord diagram on a circle there exists a complete graph on sufficiently many vertices such that any generic immersion of it to the plane contains a plane-closed curve whose chord diagram contains the given chord diagram as a sub-chord diagram. For any generic immersion of the complete graph on six vertices to the plane, the sum of averaged invariants of all Hamiltonian plane curves in it is congruent to one quarter modulo one-half.
OCCLUSION ROBUST FACE RECOGNITION WITH SCATTERING OPERATOR IN GRADIENT DOMAIN
Authors: XU BIN , SHANG ZHAO WEI , TANG YUAN YAN , FANG BIN , ZHANG TAI PING
Published: January 2013

In this paper, we propose a novel occlusion robust face recognition algorithm in gradient direction domain (GDD) using scattering operator. The proposed algorithm transforms image into the GDD to remove pseudo-edges, then scattering operator is used to extract face feature from face image in GDD. Since scattering operators can effectively extract the structural information in face owing to locally translation invariant and deformation stability, the proposed approach is robust to occlusion and varying expression. Our scheme has demonstrated the state-of-the-art performance on several datasets. Especially, our method on the sunglasses images and the scarf in AR database achieves a recognition rate of 100 and 95% respectively, which significantly outperforms most existing methods.
Situation-Specific Models of Color Differentiation
Authors: Flatla David R. , Gutwin Carl
Published: January 2013

Color is commonly used to represent categories and values in computer applications, but users with Color-Vision Deficiencies (CVD) often have difficulty differentiating these colors. Recoloring tools have been developed to address the problem, but current recolorers are limited in that they work from a model of only one type of congenital CVD (i.e., dichromatism). This model does not adequately describe many other forms of CVD (e.g., more common congenital deficiencies such as anomalous trichromacy, acquired deficiencies such as cataracts or age-related yellowing of the lens, or temporary deficiencies such as wearing tinted glasses or working in bright sunlight), and so standard recolorers work poorly in many situations. In this article we describe an alternate approach that can address these limitations. The new approach, called Situation-Specific Modeling (SSM), constructs a model of a specific user’s color differentiation abilities in a specific situation, and uses that model as the basis for recoloring digital presentations. As a result, SSM can inherently handle all types of CVD, whether congenital, acquired, or environmental. In this article we describe and evaluate several models that are based on the SSM approach. Our first model of individual color differentiation (called ICD-1) works in RGB color space, and a user study showed it to be accurate and robust (both for users with and without congenital CVD). However, three aspects of ICD-1 were identified as needing improvement: the calibration step needed to build the situation-specific model, and the prediction steps used in recoloring were too slow for real-world use; and the results of the model’s predictions were too coarse for some uses. We therefore developed three further techniques: ICD-2 reduces the time needed to calibrate the model; ICD-3 reduces the time needed to make predictions with the model; and ICD-4 provides additional information about the degree of differentiability in a prediction. Our final result is a model of the user’s color perception that handles any type of CVD, can be calibrated in two minutes, and can find replacement colors in near-real time (
~
1 second for a 64-color image). The ICD models provide a tool that can greatly improve the perceptibility of digital color for many different types of CVD users, and also demonstrates situation-specific modeling as a new approach that can broaden the applicability of assistive technology.
The pledge of the computing professional
Authors: Albrecht Bill , Christensen Ken , Dasigi Venu , Huggins Jim , Paul Jody
Published: January 2013

All of us in the computing community understand the importance of recognizing and promoting ethical behavior in our profession. Instruction in ethics is rapidly becoming a part of most computing-related curricula, whether as a stand-alone course or infused into existing courses. Both Computing Curricula 2005 and the current discussions on Computing Curricula 2013 recognize the significance of ethics, generally considering it a core topic across the various computing disciplines. Additionally, in their criteria for the accreditation of computing programs, ABET specifies that a student must attain by the time of graduation an understanding of ethical issues and responsibilities. What has been missing is a formal rite-of-passage ceremony to prompt student recognition and self-reflection on the transition from being a student to a computing professional. In 2009, seventeen faculty members and industry representatives from a wide range of institutions began to address this open problem by forming
The Pledge of the Computing Professional
[1], [2]. The Pledge exists to promote and recognize the ethical and moral behavior and responsibilities in graduates of computing-related degree programs as they transition to careers of service to society. The Pledge does not seek to define or enforce ethics --- this is the role of other organizations. Specifically, The Pledge is modeled after the Order of the Engineer [3] and provides a rite-of-passage ceremony at the time of graduation.
Using moral rules to address truth in transition and the demise facts
Authors: Gotterbarn Don
Published: January 2013

Many elements in current social media have led to the technological devolving of the concept of truth. It is argued that some of these problems can be mitigated by the application of moral "Rules".
Social responsibility in the information society
Authors: Taylor Richard
Published: January 2013

The technical advances that have enabled the development of "the cloud" have resulted in an exponential increase in the speed of information dissemination. Policy makers, sponsors of IT infrastructure and users of information and communication technologies, while being aware of the benefits of "the Cloud" as a mechanism to facilitate more efficient access to information, do not always appreciate that these developments may not always have the positive outcomes intended.

University courses such as those in Social Informatics have managed to keep pace with this rapid evolution of information and communication technologies and their societal impacts, but within the secondary education sector this has not always been possible, potentially creating a knowledge gap for tomorrow's policy makers.
Flow in Foams and Flowing Foams
Authors: Cohen-Addad Sylvie , Höhler Reinhard , Pitois Olivier
Published: January 2013

Aqueous foams are complex fluids composed of gas bubbles tightly packed in a surfactant solution. Even though they generally consist only of Newtonian fluids, foam flow obeys nonlinear laws. This can result from nonaffine deformations of the disordered bubble packing as well as from a coupling between the surface flow in the surfactant monolayers and the bulk liquid flow in the films, channels, and nodes. A similar coupling governs the permeation of liquid through the bubble packing that is observed when foams drain due to gravity. We review the experimental state of the art as well as recent models that describe the interplay of the processes at multiple length scales involved in foam drainage and rheology.
Aldosterone mediates its rapid effects in vascular endothelial cells through GPER activation
Authors: Gros Robert , Ding Qingming , Liu Bonan , Chorazyczewski Jozef , Feldman Ross D.
Published: January 2013

The importance of the rapid vascular effects of aldosterone is increasingly appreciated. Through these rapid pathways, aldosterone has been shown to regulate vascular contractility, cell growth, and apoptosis. In our most recent studies, we demonstrated the effects of aldosterone on cell growth and contractility in vascular smooth muscle cells. We showed that these effects could occur via activation of the classic mineralocorticoid receptor, as well the recently characterized G protein-coupled estrogen receptor (GPER), initially characterized as an estrogen-specific receptor. However, the mechanisms underlying aldosterone's endothelium-dependent actions are unknown. Furthermore, the ERK regulatory and proapoptotic effects of aldosterone mediated by GPER activation in cultured vascular smooth muscle cells were only apparent when GPER was reintroduced into these cells by gene transfer. Whether GPER activation via aldosterone might be an important regulator in native vascular cells has been questioned. Therefore, to determine the role of GPER in mediating aldosterone's effects on cell growth and vascular reactivity in native cells, we examined rat aortic vascular endothelial cells, a model characterized by persistent robust expression of GPER, but without detectable mineralocorticoid receptor expression. In these endothelial cells, the GPER agonist G1 mediates a rapid increase in ERK phosphorylation that is wholly GPER-dependent, paralleling the actions of aldosterone. The effects of G1 and aldosterone to stimulate ERK phosphorylation paralleled their proapoptotic and antiproliferative effects. In previous studies, we reported that aldosterone mediates a rapid endothelium-dependent vasodilatory effect, antagonistic to its direct vasoconstrictor effect in endothelium-denuded preparations. Using a rat aortic ring/organ bath preparation to determine the GPER dependence of aldosterone's endothelium-dependent vasodilator effects, we demonstrate that aldosterone inhibits phenylephrine-mediated contraction. This vasodilator effect parallels the actions of the GPER agonist G1. Furthermore, the effects of aldosterone were completely ablated by the GPER antagonist G15. These data support an important role of GPER activation in aldosterone-mediated regulation of endothelial cell growth, as well as in aldosterone's endothelium-mediated regulation of vasoreactivity.
Intracellular two-phase Ca2+ release and apoptosis controlled by TRP-ML1 channel activity in coronary arterial myocytes
Authors: Xu Ming , Li Xiaoxue , Walsh Scott W. , Zhang Yang , Abais Justine M. , Boini Krishna M. , Li Pin-Lan
Published: January 2013

Activation of the death receptor Fas has been reported to produce a two-phase intracellular Ca2+ release response in coronary arterial myocytes (CAMs), which consists of local Ca2+ bursts via lysosomal transient potential receptor-mucolipin 1 (TRP-ML1) channels and consequent Ca2+ release from the sarcoplasmic reticulum (SR). The present study was designed to explore the molecular mechanism by which lysosomal Ca2+ bursts are coupled with SR Ca2+ release in mouse CAMs and to determine the functional relevance of this lysosome-associated two-phase Ca2+ release to apoptosis, a common action of Fas activation with Fas ligand (FasL). By confocal microscopy, we found that transfection of CAMs with TRP-ML1 small interfering (si)RNA substantially inhibited FasL (10 ng/ml)-induced lysosome Ca2+ bursts and consequent SR Ca2+ release. In contrast, transfection of CAMs with plasmids containing a full-length TRP-ML1 gene enhanced FasL-induced two-phase Ca2+ release. We further demonstrated that FasL significantly increased the colocalization of the lysosomal marker Lamp1 with ryanodine receptor 3 and enhanced a dynamic trafficking of lysosomes to the SR. When CAMs were treated with TRP-ML1 siRNA, FasL-induced interactions between the lysosomes and SR were substantially blocked. Functionally, FasL-induced apoptosis and activation of calpain and calcineurin, the Ca2+ sensitive proteins that mediate apoptosis, were significantly attenuated by silencing TRP-ML1 gene but enhanced by overexpression of TRP-ML1 gene. These results suggest that TRP-ML1 channel-mediated lysosomal Ca2+ bursts upon FasL stimulation promote lysosome trafficking and interactions with the SR, leading to apoptosis of CAMs via a Ca2+-dependent mechanism.
Angiotensin II contributes to glomerular hyperfiltration in diabetic rats independently of adenosine type I receptors
Authors: Patinha Daniela , Fasching Angelica , Pinho Dora , Albino-Teixeira António , Morato Manuela , Palm Fredrik
Published: January 2013

Increased angiotensin II (ANG II) or adenosine can potentiate each other in the regulation of renal hemodynamics and tubular function. Diabetes is characterized by hyperfiltration, yet the roles of ANG II and adenosine receptors for controlling baseline renal blood flow (RBF) or tubular Na+handling in diabetes is presently unknown. Accordingly, the changes in their functions were investigated in control and 2-wk streptozotocin-diabetic rats after intrarenal infusion of the ANG II AT1receptor antagonist candesartan, the adenosine A1receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), or their combination. Compared with controls, the baseline blood pressure, RBF, and renal vascular resistance (RVR) were similar in diabetics, whereas the glomerular filtration rate (GFR) and filtration fraction (FF) were increased. Candesartan, DPCPX, or the combination increased RBF and decreased RVR similarly in all groups. In controls, the GFR was increased by DPCPX, but in diabetics, it was decreased by candesartan. The FF was decreased by candesartan and DPCPX, independently. DPCPX caused the most pronounced increase in fractional Na+excretion in both controls and diabetics, whereas candesartan or the combination only affected fractional Li+excretion in diabetics. These results suggest that RBF, via a unifying mechanism, and tubular function are under strict tonic control of both ANG II and adenosine in both control and diabetic kidneys. Furthermore, increased vascular AT1receptor activity is a contribution to diabetes-induced hyperfiltration independent of any effect of adenosine A1receptors.
Neural pathways involved in sacral neuromodulation of reflex bladder activity in cats
Authors: Zhang Fan , Zhao Shouguo , Shen Bing , Wang Jicheng , Nelson Dwight E. , Roppolo James R. , de Groat William C. , Tai Changfeng
Published: January 2013

This study examined the mechanisms underlying the effects of sacral neuromodulation on reflex bladder activity in chloralose-anesthetized cats. Bladder activity was recorded during cystometrograms (CMGs) or under isovolumetric conditions. An S1–S3 dorsal (DRT) or ventral root (VRT) was electrically stimulated at a range of frequencies (1–30 Hz) and at intensities relative to threshold (0.25–2T) for evoking anal/toe twitches. Stimulation of DRTs but not VRTs at 1T intensity and frequencies of 1–30 Hz inhibited isovolumetric rhythmic bladder contractions. A 5-Hz DRT stimulation during CMGs was optimal for increasing ( P < 0.05) bladder capacity (BC), but stimulation at 15 and 30 Hz was ineffective. Stimulation of the S1 DRT was more effective (increases BC to 144% and 164% of control at 1T and 2T, respectively) than S2 DRT stimulation (increases BC to 132% and 150% of control). Bilateral transection of the hypogastric or pudendal nerves did not change the inhibitory effect induced by S1 DRT stimulation. Repeated stimulation of S1 and S2 DRTs during multiple CMGs elicited a significant ( P < 0.05) increase in BC (to 155 ± 11% of control) that persisted after termination of the stimulation. These results in cats suggest that the inhibition of reflex bladder activity by sacral neuromodulation occurs primarily in the central nervous system by inhibiting the ascending or descending pathways of the spinobulbospinal micturition reflex.
Uric acid-induced phenotypic transition of renal tubular cells as a novel mechanism of chronic kidney disease
Authors: Ryu Eun-Sun , Kim Mi Jin , Shin Hyun-Soo , Jang Yang-Hee , Choi Hack Sun , Jo Inho , Johnson Richard J. , Kang Duk-Hee
Published: January 2013

Recent experimental and clinical studies suggest a causal role of uric acid in the development of chronic kidney disease. Most studies have focused on uric acid-induced endothelial dysfunction, oxidative stress, and inflammation in the kidney. The direct effects of uric acid on tubular cells have not been studied in detail, and whether uric acid can mediate phenotypic transition of renal tubular cells such as epithelial-to-mesenchymal transition (EMT) is not known. We therefore investigated whether uric acid could alter E-cadherin expression and EMT in the kidney of hyperuricemic rats and in cultured renal tubular cells (NRK cells). Experimental hyperuricemia was associated with evidence of EMT before the development of significant tubulointerstitial fibrosis at 4 wk, as shown by decreased E-cadherin expression and an increased α-smooth muscle actin (α-SMA). Allopurinol significantly inhibited uric acid-induced changes in E-cadherin and α-SMA with an amelioration of renal fibrosis at 6 wk. In cultured NRK cells, uric acid induced EMT, which was blocked by the organic anion transport inhibitor probenecid. Uric acid increased expression of transcriptional factors associated with decreased synthesis of E-cadherin (Snail and Slug). Uric acid also increased the degradation of E-cadherin via ubiquitination, which is of importance since downregulation of E-cadherin is considered to be a triggering mechanism for EMT. In conclusion, uric acid induces EMT of renal tubular cells decreasing E-cadherin synthesis via an activation of Snail and Slug as well as increasing the degradation of E-cadherin.
An Overview of HIV Prevention Interventions for People Who Inject Drugs in Tanzania
Authors: Ratliff Eric A. , McCurdy Sheryl A. , Mbwambo Jessie K. K. , Lambdin Barrot H. , Voets Ancella , Pont Sandrine , Maruyama Haruka , Kilonzo Gad P.
Published: January 2013

In the past decade, Tanzania has seen a rapid rise in the number of people who inject drugs (PWID), specifically heroin. While the overall HIV prevalence in Tanzania has declined recently to 5.6%, in 2009, the HIV prevalence among PWID remains alarmingly high at 35%. In this paper, we describe how the Tanzania AIDS Prevention Program (TAPP), Médecins du Monde France (MdM-F), and other organisations have been at the forefront of addressing this public health issue in Africa, implementing a wide array of harm reduction interventions including medication-assisted treatment (MAT), needle and syringe programs (NSP), and “sober houses” for residential treatment in the capital, Dar es Salaam, and in Zanzibar. Looking toward the future, we discuss the need to (1)extendexisting services and programs to reach more PWID and others at risk for HIV, (2)developadditional programs to strengthen existing programs, and (3)expandactivities to include structural interventions to address vulnerabilities that increase HIV risk for all Tanzanians.
Clinical Features and Prognosis of CD20 Negative Aggressive B-Cell Non-Hodgkins Lymphoma
Authors: Gaur Sumit , Padilla Osvaldo , Nahleh Zeina
Published: January 2013

Cluster designation (CD) 20 antigen is expressed on most B-cell lymphomas and serves as a therapeutic target for rituximab. A small minority of aggressive B-cell lymphomas, predominantly plasmablastic variants, do not express CD 20. We systematically reviewed all cases of aggressive B-cell lymphomas diagnosed at our institution over a period of 13 years. Of the 232 cases, 7 did not express CD 20. Five of these were plasmablastic lymphomas while two were unclassifiable B-cell lymphomas. While most of the plasmablastic lymphomas responded to chemotherapy, patients with unclassifiable lymphomas were primarily refractory or relapsed soon after chemotherapy.
Design of Satellite Attitude Control Algorithm Based on the SDRE Method Using Gas Jets and Reaction Wheels
Authors: de Souza Luiz C. G. , Arena Victor M. R.
Published: January 2013

An experimental attitude control algorithm design using prototypes can minimize space mission costs by reducing the number of errors transmitted to the next phase of the project. The Space Mechanics and Control Division (DMC) of INPE is constructing a 3D simulator to supply the conditions for implementing and testing satellite control hardware and software. Satellite large angle maneuver makes the plant highly nonlinear and if the parameters of the system are not well determined, the plant can also present some level of uncertainty. As a result, controller designed by a linear control technique can have its performance and robustness degraded. In this paper the standard LQR linear controller and the SDRE controller associated with an SDRE filter are applied to design a controller for a nonlinear plant. The plant is similar to the DMC 3D satellite simulator where the unstructured uncertainties of the system are represented by process and measurements noise. In the sequel the State-Dependent Riccati Equation (SDRE) method is used to design and test an attitude control algorithm based on gas jets and reaction wheel torques to perform large angle maneuver in three axes. The SDRE controller design takes into account the effects of the plant nonlinearities and system noise which represents uncertainty. The SDRE controller performance and robustness are tested during the transition phase from angular velocity reductions to normal mode of operation with stringent pointing accuracy using a switching control algorithm based on minimum system energy. This work serves to validate the numerical simulator model and to verify the functionality of the control algorithm designed by the SDRE method.
Rapid and Efficient Synthesis of Hydroxytriarylmethanes under Ultra Sonic Irradiation Using Keggin Heteropolyacids and Preyssler Catalysts in Green Conditions
Authors: Hamidian Hooshang
Published: January 2013

A new synthesis of hydroxytriarylmethane derived from the reaction of 2-sulfobenzoic anhydride and phenols in the presence of heteropolyacids as green, reusable, and efficient catalyst (using catalytic amount) under ultrasonic irradiation is reported in this paper.
t(17;19) in Children with Acute Lymphocytic Leukemia: A Report of 3 Cases and a Review of the Literature
Authors: Minson Katherine A. , Prasad Pinki , Vear Susan , Borinstein Scott , Ho Richard , Domm Jennifer , Frangoul Haydar
Published: January 2013

Several cytogenetic abnormalities identified in patients with childhood acute lymphocytic leukemia (ALL) have been associated with a poor prognosis. There are several case reports in the literature describing t(17;19) in children with ALL. This translocation has been associated with hypercalcemia, coagulopathy, and poor outcome. We present three cases of ALL with t(17;19) treated at our institution and review the outcome of children reported in the medical literature.
Prevalence and Risk Factors of Hepatitis B and Hepatitis C Virus Infections among Patients with Chronic Liver Diseases in Public Hospitals in Addis Ababa, Ethiopia
Authors: Ayele Abel Girma , Gebre-Selassie Solomon
Published: January 2013

Background and Aims. Hepatitis B and hepatitis C viruses are major public health problems worldwide. The aim of this study was to determine the prevalence and risk factors of hepatitis B and C virus infections in patients with chronic liver diseases in three public hospitals in Addis Ababa City, Ethiopia.Methods. The study was conducted on 120 clinically diagnosed chronic liver disease patients. Possible associated factors with infections by the viruses were collected from patient using questionnaire. Serum was screened for the presence of hepatitis B surface antigen and antihepatitis C virus antibodies using qualitative immunochromatographic method.Results. Hepatitis B surface antigen was detected in 43 (35.8%) and anti-HCV antibody 27 (22.5%) patients clinically diagnosed to have chronic liver diseases. Hepatitis B virus infection was higher in males 29/76 (38.2%) compared to 14/44 (31.8%) females, while antihepatitis C virus antibody was higher in females 13/44 (29.5%) compared to 14/76 (18.4%) males. Of the study participants, 3 (2.5%) had dual hepatitis B and C virus coinfection.Conclusion. The prevalence of hepatitis B surface antigen and anti-HCV antibody was high in patients below 50 years of age. Dental extraction procedure at health facility was associated with hepatitis C virus infection (OR, 2.95; 95% CI, 1.21–7.17, ).
Energy Analysis and Performance Evaluation of the Adsorption Refrigeration System
Authors: Hassan H. Z.
Published: January 2013

A complete steady state thermodynamic differential analysis is developed for the adsorption-based refrigeration systems. The introduced thermodynamic model accurately represents the behaviour of adsorption cooling systems, based on a precise, reasonable, and clear fundamental approach. Based on the energy conservation principle, all components and processes in the system are analyzed. The dynamics of adsorption is expressed by the Dubinin-Astakhov adsorption equilibrium model. All types of energy interactions are evaluated in order to determine the theoretical performance and the operating parameters of the system. Moreover, the actual thermodynamic properties of the refrigerant are considered in developing the model. The case studied is an ice maker which uses activated carbon-methanol as the working pair.
Numerical Tools for Composite Woven Fabric Preforming
Authors: Cherouat Abel , Bourouchaki Houman
Published: January 2013

An important step in the manufacturing processes of thin composite components is the layingup of the reinforcement onto the mould surface. The prediction of the angular distortion of the reinforcement during draping and the changes in fibre orientation are essential for the understanding of the manufacture process and the evaluation of the mechanical properties of the composite structures. This paper presents an optimization-based method for the simulation of the forming processes of woven fabric reinforced composites. Two different approaches are proposed for the simulation of the draping of woven fabric onto complex geometries: geometrical and mechanical approaches. The geometrical approach is based on a fishnet model. It is well adapted to predimensioning fabrics and to give a suitable quantification of the resulting flat patterns. The mechanical approach is based on a mesostructural model. It allows us to take into account the mechanical properties of fibres and resin and the various dominating mode of deformation of woven fabrics during the forming process. Some numerical simulations of the forming process are proposed and compared with the experimental results in order to demonstrate the efficiency of our approaches.
Characterization of CD8+T-Cell Responses in the Peripheral Blood and Skin Injection Sites of Melanoma Patients Treated with mRNA Electroporated Autologous Dendritic Cells (TriMixDC-MEL)
Authors: Benteyn Daphné , Van Nuffel An M. T. , Wilgenhof Sofie , Corthals Jurgen , Heirman Carlo , Neyns Bart , Thielemans Kris , Bonehill Aude
Published: January 2013

Treatment of melanoma patients with mRNA electroporated dendritic cells (TriMixDC-MEL) stimulates T-cell responses against the presented tumor-associated antigens (TAAs). In the current clinical trials, melanoma patients with systemic metastases are treated, requiring priming and/or expansion of preexisting TAA-specific T cells that are able to migrate to both the skin and internal organs. We monitored the presence of TAA-specific CD8+T cells infiltrating the skin at sites of intradermal TriMixDC-MEL injection (SKILs) and within the circulation of melanoma patients treated in two clinical trials. In 10 out of fourteen (71%) patients screened, CD8+T cells recognizing any of the four TAA presented by TriMixDC-MEL cellular vaccine were found in both compartments. In total, 30 TAA-specific T-cell responses were detected among the SKILs and 29 among peripheral blood T cells, of which 24 in common. A detailed characterization of the antigen specificity of CD8+T-cell populations in four patients indicates that the majority of the epitopes detected were only recognized by CD8+T cells derived from either skin biopsies or peripheral blood, indicating that some compartmentalization occurs after TriMix-DC therapy. To conclude, functional TAA-specific CD8+T cells distribute both to the skin and peripheral blood of patients after TriMixDC-MEL therapy.
Chloroquine in Cancer Therapy: A Double-Edged Sword of Autophagy
Authors: Kimura Tomonori , Takabatake Yoshitsugu , Takahashi Atsushi , Isaka Yoshitaka
Published: January 2013

Autophagy is a homeostatic cellular recycling system that is responsible for degrading damaged or unnecessary cellular organelles and proteins. Cancer cells are thought to use autophagy as a source of energy in the unfavorable metastatic environment, and a number of clinical trials are now revealing the promising role of chloroquine, an autophagy inhibitor, as a novel antitumor drug. On the other hand, however, the kidneys are highly vulnerable to chemotherapeutic agents. Recent studies have shown that autophagy plays a protective role against acute kidney injury, including cisplatin-induced kidney injury, and thus, we suspect that the use of chloroquine in combination with anticancer drugs may exacerbate kidney damage. Moreover, organs in which autophagy also plays a homeostatic role, such as the neurons, liver, hematopoietic stem cells, and heart, may be sensitive to the combined use of chloroquine and anticancer drugs. Here, we summarize the functions of autophagy in cancer and kidney injury, especially focusing on the use of chloroquine to treat cancer, and address the possible side effects in the combined use of chloroquine and anticancer drugs. Cancer Res; 73(1); 3–7. ©2012 AACR.
Crucial Role for Ca
2+
/Calmodulin-Dependent Protein Kinase-II in Regulating Diastolic Stress of Normal and Failing Hearts via Titin Phosphorylation
Authors: Hamdani Nazha , Krysiak Judith , Kreusser Michael M. , Neef Stefan , dos Remedios Cristobal G. , Maier Lars S. , Krüger Markus , Backs Johannes , Linke Wolfgang A.
Published: January 2013

Rationale:

Myocardial diastolic stiffness and cardiomyocyte passive force (F
passive
) depend in part on titin isoform composition and phosphorylation. Ca
2+
/calmodulin-dependent protein kinase-II (CaMKII) phosphorylates ion channels, Ca
2+
-handling proteins, and chromatin-modifying enzymes in the heart, but has not been known to target titin.

Objective:

To elucidate whether CaMKII phosphorylates titin and modulates F
passive
in normal and failing myocardium.

Methods and Results:

Titin phosphorylation was assessed in CaMKIIδ/γ double-knockout (DKO) mouse, transgenic CaMKIIδC-overexpressing mouse, and human hearts, by Pro-Q-Diamond/Sypro-Ruby staining, autoradiography, and immunoblotting using phosphoserine-specific titin-antibodies. CaMKII-dependent site-specific titin phosphorylation was quantified in vivo by mass spectrometry using s
table
isotope labeling by amino acids in cell culture mouse heart mixed with wild-type (WT) or DKO heart. F
passive
of single permeabilized cardiomyocytes was recorded before and after CaMKII-administration. All-titin phosphorylation was reduced by >50% in DKO but increased by up to ≈100% in transgenic versus WT hearts. Conserved CaMKII-dependent phosphosites were identified within the PEVK-domain of titin by quantitative mass spectrometry and confirmed in recombinant human PEVK-fragments. CaMKII also phosphorylated the cardiac titin N2B-unique sequence. Phosphorylation at specific PEVK/titin N2B-unique sequence sites was decreased in DKO and amplified in transgenic versus WT hearts. F
passive
was elevated in DKO and reduced in transgenic compared with WT cardiomyocytes. CaMKII-administration lowered F
passive
of WT and DKO cardiomyocytes, an effect blunted by titin antibody pretreatment. Human end-stage failing hearts revealed higher CaMKII expression/activity and phosphorylation at PEVK/titin N2B-unique sequence sites than nonfailing donor hearts.

Conclusions:

CaMKII phosphorylates the titin springs at conserved serines/threonines, thereby lowering F
passive
. Deranged CaMKII-dependent titin phosphorylation occurs in heart failure and contributes to altered diastolic stress.
Trapping Cardiac Recessive Mutants via Expression-Based Insertional Mutagenesis Screening
Authors: Ding Yonghe , Liu Weibin , Deng Yun , Jomok Beninio , Yang Jingchun , Huang Wei , Clark Karl J. , Zhong Tao P. , Lin Xueying , Ekker Stephen C. , Xu Xiaolei
Published: January 2013

Rationale:

Mutagenesis screening is a powerful genetic tool for probing biological mechanisms underlying vertebrate development and human diseases. However, the increased colony management efforts in vertebrates impose a significant challenge for identifying genes affecting a particular organ, such as the heart, especially those exhibiting adult phenotypes on depletion.

Objective:

We aim to develop a facile approach that streamlines colony management efforts via enriching cardiac mutants, which enables us to screen for adult phenotypes.

Methods and Results:

The transparency of the zebrafish embryos enabled us to score 67 stable transgenic lines generated from an insertional mutagenesis screen using a transposon-based protein trapping vector. Fifteen lines with cardiac monomeric red fluorescent protein reporter expression were identified. We defined the molecular nature for 10 lines and bred them to homozygosity, which led to the identification of 1 embryonic lethal, 1 larval lethal, and 1 adult recessive mutant exhibiting cardiac hypertrophy at 1 year of age. Further characterization of these mutants uncovered an essential function of
methionine adenosyltransferase II, α a (mat2aa)
in cardiogenesis, an essential function of
mitochondrial ribosomal protein S18B (mrps18b)
in cardiac mitochondrial homeostasis, as well as a function of
DnaJ (Hsp40) homolog, subfamily B, member 6b (dnajb6b)
in adult cardiac hypertrophy.

Conclusions:

We demonstrate that transposon-based gene trapping is an efficient approach for identifying both embryonic and adult recessive mutants with cardiac expression. The generation of a zebrafish insertional cardiac mutant collection shall facilitate the annotation of a vertebrate cardiac genome, as well as enable heart-based adult screens.
Aortic Pathology Determines Midterm Outcome After Endovascular Repair of the Thoracic Aorta
Authors: Patterson Benjamin , Holt Peter , Nienaber Chrisoph , Cambria Richard , Fairman Ronald , Thompson Matt
Published: January 2013

Background—

Endovascular repair of the thoracic aorta has become an increasingly utilized therapy. Although the short-term mortality advantage over open surgery is well documented, late mortality and the impact of presenting pathology on long-term outcomes remain poorly reported.

Methods and Results—

A database was built from 5 prospective studies and a single institutional series. Rates of perioperative adverse events were calculated, as were midterm death and reintervention rates. Multivariate analysis was performed with the use of logistic regression modeling. Kaplan-Meier survival curves were drawn for midterm outcomes. The database contained 1010 patients: 670 patients with thoracic aortic aneurysm, 195 with chronic type B aortic dissection, and 114 with acute type B aortic dissection. Lower elective mortality was observed in patients with chronic dissections (3%) compared with patients with aneurysms (5%). Multivariate analysis identified age, mode of admission, American Society of Anesthesiologists grade, and pathology as independent predictors of 30-day death (
P
< 0.05). In the midterm, the all-cause mortality rate was 8, 4.9, and 3.2 deaths per 100 patient-years for thoracic aortic aneurysm, acute type B aortic dissection, and chronic type B aortic dissection, respectively. The rates of aortic-related death were 0.6, 1.2, and 0.4 deaths per 100 patient-years for thoracic aortic aneurysm, acute type B aortic dissection, and chronic type B aortic dissection, respectively.

Conclusions—

This study indicated that the midterm outcomes of endovascular repair of the thoracic aorta are defined by presenting pathology, associated comorbidities, and mode of admission. Nonaortic mortality is high in the midterm for patients with thoracic aortic aneurysm, and managing modifiable risk factors appears vital. Endovascular repair of the thoracic aorta results in excellent midterm protection from aortic-related mortality, regardless of presenting pathology.
Angiotensin Receptor Agonistic Autoantibody-Mediated Soluble Fms-Like Tyrosine Kinase-1 Induction Contributes to Impaired Adrenal Vasculature and Decreased Aldosterone Production in Preeclampsia
Authors: Siddiqui Athar H. , Irani Roxanna A. , Zhang Weiru , Wang Wei , Blackwell Sean C. , Kellems Rodney E. , Xia Yang
Published: January 2013

Preeclampsia (PE) is a life-threatening hypertensive disorder during pregnancy associated with decreased circulating aldosterone levels. However, the molecular mechanisms underlying aldosterone reduction in PE remain unidentified. Here we demonstrate that reduced circulating aldosterone levels in preeclamptic women are associated with the presence of angiotensin II type 1 receptor agonistic autoantibody and elevated soluble Fms-like tyrosine kinase-1, 2 prominent pathogenic factors in PE. Using an adoptive transfer animal model of PE, we provide in vivo evidence that the injection of IgG from women with PE, but not IgG from normotensive individuals, resulted in hypertension, proteinuria, and a reduction in aldosterone production from 1377±272 pg/mL to 544±92 pg/mL (
P
<0.05) in pregnant mice. These features were prevented by coinjection with an epitope peptide that blocks antibody-mediated angiotensin type 1 receptor activation. In contrast, injection of IgG from preeclamptic women into nonpregnant mice induced aldosterone levels from 213±24 pg/mL to 615±48 pg/mL (
P
<0.05). These results indicate that maternal circulating autoantibody in preeclamptic women is a detrimental factor causing decreased aldosterone production via angiotensin type 1 receptor activation in a pregnancy-dependent manner. Next, we found that circulating soluble Fms-like tyrosine kinase-1 was only induced in autoantibody-injected pregnant mice but not nonpregnant mice. As such, we further observed vascular impairment in adrenal glands of pregnant mice. Finally, we demonstrated that infusion of vascular endothelial growth factor
121
attenuated autoantibody-induced adrenal gland vascular impairment resulting in a recovery in circulating aldosterone (from 544±92 to 1110±269 pg/mL;
P
<0.05). Overall, we revealed that angiotensin II type 1 receptor agonistic autoantibody-induced soluble Fms-like tyrosine kinase-1 elevation is a novel pathogenic mechanism underlying decreased aldosterone production in PE.
Central Rho Kinase Inhibition Restores Baroreflex Sensitivity and Angiotensin II Type 1 Receptor Protein Imbalance in Conscious Rabbits With Chronic Heart Failure
Authors: Haack Karla K.V. , Gao Lie , Schiller Alicia M. , Curry Pamela L. , Pellegrino Peter R. , Zucker Irving H.
Published: January 2013

The small GTPase RhoA and its associated kinase ROCKII are involved in vascular smooth muscle cell contraction and endothelial NO synthase mRNA destabilization. Overactivation of the RhoA/ROCKII pathway is implicated in several pathologies, including chronic heart failure (CHF), and may contribute to the enhanced sympathetic outflow seen in CHF as a result of decreased NO availability. Thus, we hypothesized that central ROCKII blockade would improve the sympathovagal imbalance in a pacing rabbit model of CHF in an NO-dependent manner. CHF was induced by rapid ventricular pacing and characterized by an ejection fraction of ≤45%. Animals were implanted with an intracerbroventricular cannula and osmotic minipump (rate, 1 μL/h) containing sterile saline, 1.5 µg/kg per day fasudil (Fas, a ROCKII inhibitor) for 4 days or Fas+100 µg/kg per day Nω-Nitro-
l
-arginine methyl ester hydrochloride, a NO synthase inhibitor. Arterial baroreflex control was assessed by intravenous infusion of sodium nitroprusside and phenylephrine. Fas infusion significantly lowered resting heart rate by decreasing sympathetic and increasing vagal tone. Furthermore, Fas improved baroreflex gain in CHF in an NO-dependent manner. In CHF Fas animals, the decrease in heart rate in response to intravenous metoprolol was similar to Sham and was reversed by Nω-Nitro-
l
-arginine methyl ester hydrochloride. Fas decreased angiotensin II type 1 receptor and phospho-ERM protein expression and increased endothelial NO synthase expression in the brain stem of CHF animals. These data strongly suggest that central ROCKII activation contributes to cardiac sympathoexcitation in the setting of CHF and that central Fas restores vagal and sympathetic tone in an NO-dependent manner. ROCKII may be a new central therapeutic target in the setting of CHF.
Differential Predictors of Insulin Resistance in Nondiabetic Salt-Resistant and Salt-Sensitive Subjects
Authors: Laffer Cheryl L. , Elijovich Fernando
Published: January 2013

We studied the characteristics of insulin resistance in 19 normotensive and 25 hypertensive subjects who underwent an acute protocol for determination of salt-sensitivity of blood pressure. Hypertensive subjects were older and more obese, with higher creatinine, lipids, and aldosterone than normotensive volunteers. They also had higher glucose and insulin levels with a marked decrease in insulin sensitivity (HOMA2-S index). Once all participants were classified into salt-sensitive (SS) and salt-resistant (SR) groups, most of these differences were no longer present. In contrast, SS had classical characteristics of this phenotype (higher percentage of blacks, suppressed plasma renin, increased aldosterone-to-renin ratio, and blunted renin and aldosterone responses to changes in salt balance). Despite similar insulin levels, HOMA2-S was significantly lower in SS than SR. Salt-loading did not change HOMA2-S in SS or SR. In contrast, salt-depletion, by significantly increasing glucose and insulin of SR, decreased their HOMA2-S to the levels observed in SS. Correlates of insulin resistance in SR included age, triglycerides, body mass index, mean arterial pressure, aldosterone, and epinephrine. However, only body mass index and aldosterone remained as significant predictors in multivariate analyses. Correlates of insulin resistance in SS were mean arterial pressure, epinephrine, and norepinephrine, all remaining as significant predictors in multivariate modeling. Our data confirm that salt-sensitivity of blood pressure is associated with insulin resistance, suggest that salt restriction may be beneficial in SS but perhaps detrimental in SR subjects, and uncover possible differences in mechanisms of insulin resistance between SS and SR, with implications for pharmacological therapy.
Sense of Community and Its Association With the Neighborhood Built Environment
Authors: French Sarah , Wood Lisa , Foster Sarah Alexandra , Giles-Corti Billie , Frank Lawrence , Learnihan Vincent
Published: January 2013

We investigated the influence of neighborhood built form on sense of community in Perth, Western Australia. It was hypothesized that sense of community would be stronger in individuals living in pedestrian-friendly neighborhoods. Multivariate linear regression models explored associations between walking and sense of community, with progressive adjustment for objective and perceived neighborhood characteristics. Sense of community was positively associated with walking for transport and positive perceptions of neighborhood quality, and negatively associated with residential density. The findings highlight the influence of local area perceptions on sense of community that appeared to be more important than objective environment characteristics. However, the latter may influence perceptions, and this requires investigation.
Do Humans Have Souls? Perspectives from Philosophy, Science, and Religion
Authors: Murphy Nancey
Published: January 2013

This essay seeks to promote a concept of human nature that is usually called nonreductive physicalism, which is at least not ruled out by Scripture, and may in fact be closer to biblical thinking than dualism. The essay then looks to neuroscience to show that it provides useful insights into how and why we behave as we do.
Novel approach for mold filling simulation of the processing of natural fiber reinforced composites by resin transfer molding
Authors: Francucci Gastón , Rodríguez Exequiel S , Morán Juan
Published: January 2013

Modeling the infiltration of reinforcements during the processing of composite materials by liquid composite molding techniques is an important instrument for the prediction of flow front patterns, filling times and pressure gradients. Darcy’s law is widely used to model most of these processes. However, when polar fluids are used together with natural fibers, fiber swelling may occur and introduce further complexity to the simulation. In this work, a model that includes the aforementioned phenomena is proposed, leading to a more accurate prediction of the flow front position than the classic models that use a constant permeability value.