bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting Melanoma: Endothelin B Receptor Makes an Encore
Authors: Hansel Donna E.
Published: February 2011

An antibody to the endothelin B receptor coupled to an antimitotic agent can shrink melanoma in vitro and in mouse models.
Genie in a Bottle
Authors: Morozov Alexei
Published: February 2011

Adaptive cell transfer shows efficacy in synovial sarcoma and melanoma.
Innovation in hip arthroscopy: is hip arthritis preventable in the athlete?
Authors: Ellis Henry B , Briggs Karen K , Philippon Marc J
Published: February 2011

Introduction

The hip is the second most common area for injury in collegiate athletes and may account for 2–5% of all sports injuries. Hip and groin pain in the athlete has long been associated with structural abnormalities of the femoral neck, acetabulum and labral pathology.

Review

The relationship between osteoarthritis and femoroacetabular impingement (FAI) is well established now with clinical studies, radiographic studies and computer simulations.

Treatment

The successful treatment of the athlete with FAI and subsequent labral and chondral damage has been well documented. New techniques, such as labral reconstruction, are being developed to address the more complex injuries seen in athletes, while helping to protect the joint surfaces and decrease the risk of early onsite osteoarthritis.

Conclusion

The athlete's painful hip, which is becoming an increasingly more common complaint, is being identified and treated with greater chances of returning to play without compromising long-term hip function and the progression of hip osteoarthritis.
General practitioners' conflicts of interest, the paramountcy principle and safeguarding children: a psychodynamic contribution
Authors: Sutton Adrian
Published: February 2011

Wainwright and Gallagher propose that when child protection concerns emerge significant difficulties arise for General Practitioners because of conflicts between the individual interests of children and parents who are their patients and the Paramountcy Principle. From a psychodynamic perspective their analysis does not give sufficient weight to the nature of personal as opposed to interpersonal conflict of a conscious or unconscious nature. When issues of major import arise, ordinary parenting inevitably involves parents in putting their children's needs first if competing possibilities occur. It is an over-simplification to present this as a conflict between the interests of children and parents. Parents' own best interests are served by securing their children's safety and welfare. An appreciation of this is crucial in order to implement child protection procedures appropriately. Errors may occur because the complex emotions and relationships involved lead professionals to experience themselves as potential agents of harm rather than benefit.
Does the rejection of wrongful life claims rely on a conceptual error?
Authors: Mũrĩithi Paul Mũtuanyingĩ
Published: February 2011

There are four major arguments raised against wrongful life claims: first, that it is impossible to establish harm in wrongful life claims; second, that wrongful life claims are illogical or incoherent; third, that life is inviolable and sacred no matter the quality; and fourth, that there are no rights and duties towards non-existent persons. In this paper, I will examine and evaluate critically the first two arguments. I will reject these objections against wrongful life claims and demonstrate that they rely on a conceptual error/mistake. In doing so, I will reject the logic of comparing existence with non-existence in wrongful life claims. Instead, I will maintain that recognition of the infant's cause of action and recognition of the infant's harmed condition need not imply any preference for non-existence over existence, and it need not to be so severe as to make life not worth living. I will conclude by briefly giving an account of what seems to me to be the right conception of what it is to be harmed.
Control of the Workfunction in Bilayer Metal Gate Stacks by Varying the First Layer Thickness
Authors: Jung Eun-Jae , Lee In-Geun , Cho Mann-Ho , Ko Dae-Hong
Published: February 2011

Ni/TiN and Al/TiN bilayer stacks were investigated to determine the influence of the thin metals on the total effective workfunction. The workfunctions of the bilayer stacks were measured using C-V (capacitance–voltage) curves. The effective workfunctions of both bilayer stacks were controlled by changing the TiN layer thickness. The workfunctions of both bilayer stacks shift toward the workfunction of the upper layer, and the absolute effective workfunction of the Ni/TiN bilayer stack was higher than that of the Al/TiN bilayer stack. The workfunction of the TiN layer itself decreased with the decreasing thickness.
Duodenal-jejunal bypass protects GK rats from β-cell loss and aggravation of hyperglycemia and increases enteroendocrine cells coexpressing GIP and GLP-1
Authors: Speck Madeleine , Cho Young Min , Asadi Ali , Rubino Francesco , Kieffer Timothy J.
Published: February 2011

Dramatic improvement of type 2 diabetes is commonly observed after bariatric surgery. However, the mechanisms behind the alterations in glucose homeostasis are still elusive. We examined the effect of duodenal-jejunal bypass (DJB), which maintains the gastric volume intact while bypassing the entire duodenum and the proximal jejunum, on glycemic control, β-cell mass, islet morphology, and changes in enteroendocrine cell populations in nonobese diabetic Goto-Kakizaki (GK) rats and nondiabetic control Wistar rats. We performed DJB or sham surgery in GK and Wistar rats. Blood glucose levels and glucose tolerance were monitored, and the plasma insulin, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) levels were measured. β-Cell area, islet fibrosis, intestinal morphology, and the density of enteroendocrine cells expressing GLP-1 and/or GIP were quantified. Improved postprandial glycemia was observed from 3 mo after DJB in diabetic GK rats, persisting until 12 mo after surgery. Compared with the sham-GK rats, the DJB-GK rats had an increased β-cell area and a decreased islet fibrosis, increased insulin secretion with increased GLP-1 secretion in response to a mixed meal, and an increased population of cells coexpressing GIP and GLP-1 in the jejunum anastomosed to the stomach. In contrast, DJB impaired glucose tolerance in nondiabetic Wistar rats. In conclusion, although DJB worsens glucose homeostasis in normal nondiabetic Wistar rats, it can prevent long-term aggravation of glucose homeostasis in diabetic GK rats in association with changes in intestinal enteroendocrine cell populations, increased GLP-1 production, and reduced β-cell deterioration.
Effect of diet-induced obesity and metabolic syndrome on skeletal muscles of Ossabaw miniature swine
Authors: Clark Bradley A. , Alloosh Mouhamad , Wenzel James W. , Sturek Michael , Kostrominova Tatiana Y.
Published: February 2011

Ossabaw swine fed excess kilocalorie diet develop metabolic syndrome (MS) characterized by obesity, hypertension, insulin resistance, and glucose intolerance with/without dyslipidemia. The purpose of this study was to test the hypothesis that MS would have a detrimental effect on skeletal muscle structure and cause changes in the expression of myosin heavy chains (MHCs). Adult male Ossabaw swine were fed for 24 wk high-fructose or high-fat/cholesterol/fructose diets to induce normolipidemic MS (MetS) or dyslipidemic MS (DMetS), respectively, and were compared with the lean swine on control diet. MetS swine showed mild MS, lacking increases in total and low density lipoprotein (LDL) cholesterol, both of which were highly upregulated in DMetS swine. There was an ∼1.2-fold increase in the cross-sectional areas of muscle fibers in MetS and DMetS groups compared with control for biceps femoris and plantaris muscles. In plantaris muscles, DMetS diet caused an ∼2-fold decrease in slow MHC mRNA and protein expression and an ∼1.2- to 1.8-fold increase in the number of intramyocellular lipid (IMCL) droplets without large changes in the size of the droplets. There was a trend to the decrease in slow MHC expression in muscles of swine on MetS diet. The number of IMCL droplets in muscle fibers of the MetS group was comparable to controls. These data correlate well with the data on total plasma cholesterol (control = 60, MetS = 70, and DMetS = 298 mg/dl) and LDL (control = 29, MetS = 30, and DMetS = 232 mg/dl). We conclude that structural changes observed in skeletal muscle of obese Ossabaw swine correlate with those previously reported for obese humans.
Fenofibrate, a PPARα agonist, decreases atrogenes and myostatin expression and improves arthritis-induced skeletal muscle atrophy
Authors: Castillero Estíbaliz , Nieto-Bona María Paz , Fernández-Galaz Carmen , Martín Ana Isabel , López-Menduiña María , Granado Miriam , Villanúa María Angeles , López-Calderón Asunción
Published: February 2011

Arthritis is a chronic inflammatory illness that induces cachexia, which has a direct impact on morbidity and mortality. Fenofibrate, a selective PPARα activator prescribed to treat human dyslipidemia, has been reported to decrease inflammation in rheumatoid arthritis patients. The aim of this study was to elucidate whether fenofibrate is able to ameliorate skeletal muscle wasting in adjuvant-induced arthritis, an experimental model of rheumatoid arthritis. On day 4 after adjuvant injection, control and arthritic rats were treated with 300 mg/kg fenofibrate until day 15, when all rats were euthanized. Fenofibrate decreased external signs of arthritis and liver TNFα and blocked arthritis-induced decreased in PPARα expression in the gastrocnemius muscle. Arthritis decreased gastrocnemius weight, which results from a decrease in cross-section area and myofiber size, whereas fenofibrate administration to arthritic rats attenuated the decrease in both gastrocnemius weight and fast myofiber size. Fenofibrate treatment prevented arthritis-induced increase in atrogin-1 and MuRF1 expression in the gastrocnemius. Neither arthritis nor fenofibrate administration modify Akt-FoxO3 signaling. Myostatin expression was not modified by arthritis, but fenofibrate decreased myostatin expression in the gastrocnemius of arthritic rats. Arthritis increased muscle expression of MyoD, PCNA, and myogenin in the rats treated with vehicle but not in those treated with fenofibrate. The results indicate that, in experimental arthritis, fenofibrate decreases skeletal muscle atrophy through inhibition of the ubiquitin-proteasome system and myostatin.
An amino acid mixture improves glucose tolerance and insulin signaling in Sprague-Dawley rats
Authors: Bernard Jeffrey R. , Liao Yi-Hung , Hara Daisuke , Ding Zhenping , Chen Chung-Yu , Nelson Jeffrey L. , Ivy John L.
Published: February 2011

The aims of this investigation were to evaluate the effect of an amino acid supplement on the glucose response to an oral glucose challenge ( experiment 1) and to evaluate whether differences in blood glucose response were associated with increased skeletal muscle glucose uptake ( experimental 2). Experiment 1 rats were gavaged with either glucose (CHO), glucose plus an amino acid mixture (CHO-AA-1), glucose plus an amino acid mixture with increased leucine concentration (CHO-AA-2), or water (PLA). CHO-AA-1 and CHO-AA-2 had reduced blood glucose responses compared with CHO, with no difference in insulin among these treatments. Experiment 2 rats were gavaged with either CHO or CHO-AA-1. Fifteen minutes after gavage, a bolus containing 2-[3H]deoxyglucose and [U-14C]mannitol was infused via a tail vein. Blood glucose was significantly lower in CHO-AA-1 than in CHO, whereas insulin responses were similar. Muscle glucose uptake was higher in CHO-AA-1 compared with CHO in both fast-twitch red (8.36 ± 1.3 vs. 5.27 ± 0.7 μmol·g−1·h−1) and white muscle (1.85 ± 0.3 vs. 1.11 ± 0.2 μmol·g−1·h−1). There was no difference in Akt/PKB phosphorylation between treatment groups; however, the amino acid treatment resulted in increased AS160 phosphorylation in both muscle fiber types. Glycogen synthase phosphorylation was reduced in fast-twitch red muscle of CHO-AA-1 compared with CHO, whereas mTOR phosphorylation was increased. These differences were not noted in fast-twitch white muscle. These findings suggest that amino acid supplementation can improve glucose tolerance by increasing skeletal muscle glucose uptake and intracellular disposal through enhanced intracellular signaling.
Uterine signaling at the emergence of the embryo from obligate diapause
Authors: Lefèvre Pavine L. C. , Palin Marie-France , Beaudry Danièle , Dobias-Goff Mira , Desmarais Joëlle A. , Llerena V. Evelyn M. , Murphy Bruce D.
Published: February 2011

Embryonic diapause is the reversible arrest of embryo development prior to implantation under a regime of uterine control that is not well understood. Our objective was to explore uterine modifications associated with the emergence of embryonic diapause in the mink, a species in which embryonic diapause characterizes every gestation. We investigated the uterine transcriptome at reactivation using the suppressive subtractive hybridization technique. A library of 123 differentially expressed genes between uteri with blastocysts in diapause and reactivated blastocysts was generated. Among those genes, 41.5% encode for potential secreted products that are implicated in regulation of cell proliferation (14%), homeostasis (14%), protein folding (11%), electron transport chain (8%), and innate immune response (8%), therefore suggesting that these biological processes are implicated in blastocyst reactivation. Two genes, the high-mobility group nucleosome binding domain 1 ( HMGN1), a chromatin remodeling factor, and the secreted protein acidic and cystein-rich ( SPARC), which is implicated in extracellular cell-cell interactions, were submitted to more detailed analysis of expression patterns in the mink uterus at blastocyst reactivation. Expression of both HMGN1 and SPARC was increased significantly in the uterus at embryo reactivation compared with diapause, principally in the endometrial epithelium and subepithelial stroma. These results provide new insight into uterine signaling at the emergence of the blastocyst from diapause and highlight the factors HMGN1 and SPARC as potential inductors of uterine environment modifications underlying uterine signaling during emergence of the embryo from embryonic diapause.
Bidirectional control of BK channel open probability by CAMKII and PKC in medial vestibular nucleus neurons
Authors: van Welie Ingrid , du Lac Sascha
Published: February 2011

Large conductance K+ (BK) channels are a key determinant of neuronal excitability. Medial vestibular nucleus (MVN) neurons regulate eye movements to ensure image stabilization during head movement, and changes in their intrinsic excitability may play a critical role in plasticity of the vestibulo-ocular reflex. Plasticity of intrinsic excitability in MVN neurons is mediated by kinases, and BK channels influence excitability, but whether endogenous BK channels are directly modulated by kinases is unknown. Double somatic patch-clamp recordings from MVN neurons revealed large conductance potassium channel openings during spontaneous action potential firing. These channels displayed Ca2+ and voltage dependence in excised patches, identifying them as BK channels. Recording isolated single channel currents at physiological temperature revealed a novel kinase-mediated bidirectional control in the range of voltages over which BK channels are activated. Application of activated Ca2+/calmodulin-dependent kinase II (CAMKII) increased BK channel open probability by shifting the voltage activation range towards more hyperpolarized potentials. An opposite shift in BK channel open probability was revealed by inhibition of phosphatases and was occluded by blockade of protein kinase C (PKC), suggesting that active PKC associated with BK channel complexes in patches was responsible for this effect. Accordingly, direct activation of endogenous PKC by PMA induced a decrease in BK open probability. BK channel activity affects excitability in MVN neurons and bidirectional control of BK channels by CAMKII, and PKC suggests that cellular signaling cascades engaged during plasticity may dynamically control excitability by regulating BK channel open probability.
Contributions of skin and muscle afferent input to movement sense in the human hand
Authors: Cordo Paul J. , Horn Jean-Louis , Künster Daniela , Cherry Anne , Bratt Alex , Gurfinkel Victor
Published: February 2011

In the stationary hand, static joint-position sense originates from multimodal somatosensory input (e.g., joint, skin, and muscle). In the moving hand, however, it is uncertain how movement sense arises from these different submodalities of proprioceptors. In contrast to static-position sense, movement sense includes multiple parameters such as motion detection, direction, joint angle, and velocity. Because movement sense is both multimodal and multiparametric, it is not known how different movement parameters are represented by different afferent submodalities. In theory, each submodality could redundantly represent all movement parameters, or, alternatively, different afferent submodalities could be tuned to distinctly different movement parameters. The study described in this paper investigated how skin input and muscle input each contributes to movement sense of the hand, in particular, to the movement parameters dynamic position and velocity. Healthy adult subjects were instructed to indicate with the left hand when they sensed the unseen fingers of the right hand being passively flexed at the metacarpophalangeal (MCP) joint through a previously learned target angle. The experimental approach was to suppress input from skin and/or muscle: skin input by anesthetizing the hand, and muscle input by unexpectedly extending the wrist to prevent MCP flexion from stretching the finger extensor muscle. Input from joint afferents was assumed not to play a significant role because the task was carried out with the MCP joints near their neutral positions. We found that, during passive finger movement near the neutral position in healthy adult humans, both skin and muscle receptors contribute to movement sense but qualitatively differently. Whereas skin input contributes to both dynamic position and velocity sense, muscle input may contribute only to velocity sense.
Locomotor-activated neurons of the cat. II. Noradrenergic innervation and colocalization with NEα1a or NEα2b receptors in the thoraco-lumbar spinal cord
Authors: Noga Brian R. , Johnson Dawn M. G. , Riesgo Mirta I. , Pinzon Alberto
Published: February 2011

Norepinephrine (NE) is a strong modulator and/or activator of spinal locomotor networks. Thus noradrenergic fibers likely contact neurons involved in generating locomotion. The aim of the present study was to investigate the noradrenergic innervation of functionally related, locomotor-activated neurons within the thoraco-lumbar spinal cord. This was accomplished by immunohistochemical colocalization of noradrenergic fibers using dopamine-β-hydroxylase or NEα1A and NEα2B receptors with cells expressing the c-fos gene activity-dependent marker Fos. Experiments were performed on paralyzed, precollicular-postmamillary decerebrate cats, in which locomotion was induced by electrical stimulation of the mesencephalic locomotor region. The majority of Fos labeled neurons, especially abundant in laminae VII and VIII throughout the thoraco-lumbar (T13-L7) region of locomotor animals, showed close contacts with multiple noradrenergic boutons. A small percentage (10–40%) of Fos neurons in the T7-L7 segments showed colocalization with NEα1A receptors. In contrast, NEα2B receptor immunoreactivity was observed in 70–90% of Fos cells, with no obvious rostrocaudal gradient. In comparison with results obtained from our previous study on the same animals, a significantly smaller proportion of Fos labeled neurons were innervated by noradrenergic than serotonergic fibers, with significant differences observed for laminae VII and VIII in some segments. In lamina VII of the lumbar segments, the degree of monoaminergic receptor subtype/Fos colocalization examined statistically generally fell into the following order: NEα2B = 5-HT2A ≥ 5-HT7 = 5-HT1A > NEα1A. These results suggest that noradrenergic modulation of locomotion involves NEα1A/NEα2B receptors on noradrenergic-innervated locomotor-activated neurons within laminae VII and VIII of thoraco-lumbar segments. Further study of the functional role of these receptors in locomotion is warranted.
The Potency of Hyaluronan of Different Molecular Weights in the Stimulation of Blood Phagocytes
Authors: Safrankova Barbora , Gajdova Silvie , Kubala Lukas
Published: February 2011

The regulatory functions of glycosaminoglycan hyaluronan (HA) are suggested to be dependent on its molecular weight (MW). Proinflammatory and stimulatory effects are proposed mainly for the low MW HA. However, the complex response of blood phagocytes to HA of different MW is unclear. Herein, the effects of highly purified HA of precisely defined MW (52, 250, and 970 kDa) on human blood phagocytes were tested. All MW HA activated blood phagocytes, including the spontaneous production of ROS, degranulation, and the production of tumor necrosis factor alpha, with low MW HA 52 kDa having the highest potency and high MW HA 970 kDa having the lowest potency. Interestingly, HA inhibited ROS production stimulated by opsonized zymosan particles and, in contrast, potentiated starch-activated ROS production, mostly independent of MW. Data showed a significant effect of HA of different MW on blood phagocytes, including high MW HA.
Thin Shell, Segmented X-Ray Mirrors
Authors: Petre R.
Published: February 2011

Thin foil mirrors were introduced as a means of achieving high throughput in an X-ray astronomical imaging system in applications for which high angular resolution was not necessary. Since their introduction, their high filling factor, modest mass, relative ease of construction, and modest cost have led to their use in numerous X-ray observatories, including the Broad Band X-ray Telescope, ASCA, and Suzaku. The introduction of key innovations, including epoxy replicated surfaces, multilayer coatings, and glass mirror substrates, has led to performance improvements and in their becoming widely used for X-ray astronomical imaging at energies above 10 keV. The use of glass substrates has also led to substantial improvement in angular resolution and thus their incorporation into the NASA concept for the International X-ray Observatory with a planned 3 m diameter aperture. This paper traces the development of foil mirrors from their inception in the 1970s through their current and anticipated future applications.
Neural Pathways in Allergic Inflammation
Authors: Mirotti L. , Castro J. , Costa-Pinto F. A. , Russo M.
Published: February 2011

Allergy is on the rise worldwide. Asthma, food allergy, dermatitis, and systemic anaphylaxis are amongst the most common allergic diseases. The association between allergy and altered behavior patterns has long been recognized. The molecular and cellular pathways in the bidirectional interactions of nervous and immune systems are now starting to be elucidated. In this paper, we outline the consequences of allergic diseases, especially food allergy and asthma, on behavior and neural activity and on the neural modulation of allergic responses.
TLRs, Alcohol, HCV, and Tumorigenesis
Authors: Machida Keigo
Published: February 2011

Chronic liver damage caused by viral infection, alcohol, or obesity can result in increased risk for hepatocellular carcinoma (HCC). Ample epidemiological evidence suggests that there is a strong synergism between hepatitis C virus (HCV) and alcoholic liver diseases (ALD). The Toll-like receptor (TLR) signaling pathway is upregulated in chronic liver diseases. Alcoholism is associated with endotoxemia that stimulates expression of proinflammatory cytokine expression and inflammation in the liver and fat tissues. Recent studies of HCC have centered on cancer-initiating stem cell (CSC), including detection of CSC in cancer, identification of CSC markers, and isolation of CSC from human HCC cell lines. Synergism between alcohol and HCV may lead to liver tumorigenesis through TLR signaling.
Engagement of the Mannose Receptor by Tumoral Mucins Activates an Immune Suppressive Phenotype in Human Tumor‐Associated Macrophages
Authors: Allavena P. , Chieppa M. , Bianchi G. , Solinas G. , Fabbri M. , Laskarin G. , Mantovani A.
Published: February 2011

Tumor‐Associated Macrophages (TAMs) are abundantly present in the stroma of solid tumors and modulate several important biological processes, such as neoangiogenesis, cancer cell proliferation and invasion, and suppression of adaptive immune responses. Myeloid C‐type lectin receptors (CLRs) constitute a large family of transmembrane carbohydrate‐binding receptors that recognize pathogens as well as endogenous glycoproteins. Several lines of evidence demonstrate that some CLRs can inhibit the immune response. In this study we investigated TAM‐associated molecules potentially involved in their immune suppressive activity. We found that TAMs isolated from human ovarian carcinoma samples predominantly express the CLRs Dectin‐1, MDL‐1, MGL, DCIR, and most abundantly the Mannose Receptor (MR). Components of carcinomatous ascites and purified tumoral mucins (CA125 and TAG‐72) bound the MR and induced its internalization. MR engagement by tumoral mucins and by an agonist anti‐MR antibody modulated cytokine production by TAM toward an immune‐suppressive profile: increase of IL‐10, absence of IL‐12, and decrease of the Th1‐attracting chemokine CCL3. This study highlights that tumoral mucin‐mediated ligation of the MR on infiltrating TAM may contribute to their immune suppressive phenotype.
Thermal Radiation Effects on Hydromagnetic Mixed Convection Flow along a Magnetized Vertical Porous Plate
Authors: Ashraf Muhammad , Asghar S. , Hossain Md. Anwar
Published: February 2011

Aim of the present work is to investigate the effect of radiation on steady mixed convection boundary layer flow of viscous, incompressible, electrically conducting fluid past a semi‐infinite magnetized vertical porous plate with uniform transpiration and variable transverse magnetic field along the surface. The equations governing the flow magnetic and temperature field
are reduced to dimensionless convenient form using the free variable transformations and solved
numerically by using finite difference method. Effects of physical parameters like Prandtl number,
Pr, the conduction‐radiation parameter Rd, magnetic field parameter S, magnetic Prandtl number
Pm, mixed convection parameter λ, and the surface temperature, θw on the local skin friction coefficient Cfx, local Nusselt number, Nux, and coefficient of magnetic intensity, Mgx against
the local transpiration parameter ξ are shown graphically. Later, the problem is analysed by using
series solution for small and large values of ξ, and the results near and away from the leading
edge are compared with numerical results obtained by finite difference method and found to be in
good agreement.
"Equation missing" -Optimal Solutions in Nonconvex Semi-Infinite Programs with Support Functions
Authors: Kim DoSang , Son TaQuang
Published: February 2011

Approximate optimality conditions for a class of nonconvex semi-infinite programs involving support functions are given. The objective function and the constraint functions are locally Lipschitz functions on "Equation missing". By using a Karush-Kuhn-Tucker (KKT) condition, we deduce a necessary optimality condition for local approximate solutions. Then, generalized KKT conditions for the problems are proposed. Based on properties of "Equation missing"-semiconvexity and semiconvexity applied to locally Lipschitz functions and generalized KKT conditions, we establish sufficient optimality conditions for another kind of local approximate solutions of the problems. Obtained results in case of nonconvex semi-infinite programs and nonconvex infinite programs are discussed.
Quasi‐Exact Solvability of a Hyperbolic Intermolecular Potential Induced by an Effective Mass Step
Authors: Schulze-Halberg Axel
Published: February 2011

It is shown that a nonsolvable third‐order hyperbolic potential becomes quasi‐exactly solvable
after the introduction of a hyperbolic effective mass step. Stationary energies and L2‐solutions of the corresponding Schrödinger equation are obtained in explicit form.
Long‐Term Type 1 Diabetes Enhances In‐Stent Restenosis after Aortic Stenting in Diabetes‐Prone BB Rats
Authors: Onuta Geanina , Groenewegen Hendrik C. , Klatter Flip A. , Walther Boer Mark , Goris Maaike , van Goor Harry , Roks Anton J. M. , Rozing Jan , de Smet Bart J. G. L. , Hillebrands Jan-Luuk
Published: February 2011

Type 1 diabetic patients have increased risk of developing in‐stent restenosis following endovascular stenting. Underlying pathogenetic mechanisms are not fully understood partly due to the lack of a relevant animal model to study the effect(s) of long‐term autoimmune diabetes on development of in‐stent restenosis. We here describe the development of in‐stent restenosis in long‐term (~7 months) spontaneously diabetic and age‐matched, thymectomized, nondiabetic Diabetes Prone BioBreeding (BBDP) rats (n = 6‐7 in each group). Diabetes was suboptimally treated with insulin and was characterized by significant hyperglycaemia, polyuria, proteinuria, and increased HbA1c levels. Stented abdominal aortas were harvested 28 days after stenting. Computerized morphometric analysis revealed significantly increased neointima formation in long‐term diabetic rats compared with nondiabetic controls. In conclusion, long‐term autoimmune diabetes in BBDP rats enhances in‐stent restenosis. This model can be used to study the underlying pathogenetic mechanisms of diabetes‐enhanced in‐stent restenosis as well as to test new therapeutic modalities.
Design of Web-Based Experiments on Acceleration and Speed Transducers
Authors: Mani Ashish , Prasanth R. S. S. , Patvardhan C.
Published: February 2011

Remote laboratories are becoming increasingly popular in academic arena due to availability of web-based technologies and infrastructure. Remote Labs are equipped with real instruments, where experiments are performed by controlling the instruments and observing the real data from a distant location through computer networks. They provide for student centric laboratory experience as students can perform experiments at their own convenience and requirements. Further, Remote Labs reduce management of work involved in running conventional laboratories. This paper describes design and implementation of such an experimental setup for performing characterization experiments on Transducers in general and Acceleration and Speed Transducers in particular from a remote location. The experiment can be made accessible to anyone over a TCP/IP network with a standard Web Browser, relevant plugin, and permission. This paper demonstrates that traditional experiments on sensors and transducers can be successfully made available online to both on-campus and off-campus students at their own schedule and convenience.
Dynamics of an Autoparametric Pendulum‐Like System with a Nonlinear Semiactive Suspension
Authors: Kecik Krzysztof , Warminski Jerzy
Published: February 2011

This paper presents vibration analysis of an autoparametric pendulum‐like mechanism subjected to harmonic excitation. To improve dynamics and control motions, a new suspension composed of a semiactive magnetorheological damper and a nonlinear spring is applied. The influence of essential parameters such as the nonlinear damping or stiffness on vibration, near the main parametric resonance region, are carried out numerically and next verified experimentally in a special experimental rig. Results show that the magnetorheological damper, together with the nonlinear spring can be efficiently used to change the dynamic behaviour of the system. Furthermore, the nonlinear elements applied in the suspension of the autoparametric system allow to reduce the unstable areas and chaotic or rotating motion of the pendulum.
Will Mobile Learning Bring a Paradigm Shift in Higher Education?
Authors: Rajasingham Lalita
Published: February 2011

In the light of technology-driven social change that creates new challenges for universities, this paper considers the potential of mobile learning as a subset of e-learning to effect a paradigm shift in higher education. Universities face exponential growth in demand for higher education, significant decreases in government funding for education, a changing in understanding of the nature of knowledge, changing student demographics and expectations, and global competition. At the same time untethered mobile telephony is connecting large numbers of potential learners to communications networks. A review of some empirical literature on the current status of mobile learning that explores alternatives to help universities fulfil core functions of storage, processing, and disseminating knowledge that can be applied to real life problems, is followed by an examination of the strengths and weaknesses of increased connectivity to mobile communications networks to support constructivist, self-directed quality interactive learning for increasingly mobile learners. This paper also examines whether mobile learning can align the developing technology with changing student expectations and the implications of such an alignment for teaching and institutional strategies. Technologies considered include mobile computing and technology, wireless laptop, hand-held PDAs, and mobile telephony.
Pneumatosis Intestinalis: A Case Report and Approach to Management
Authors: Donovan Sean , Cernigliaro Joseph , Dawson Nancy
Published: February 2011

Pneumatosis intestinalis (PI), defined as gas within the bowel wall, is an uncommon radiographic sign which can represent a wide spectrum of diseases and a variety of underlying diagnoses. Because its etiology can vary greatly, management of PI ranges from surgical intervention to outpatient observation (see, Greenstein et al. (2007), Morris et al. (2008), and Peter et al. (2003)). Since PI is infrequently encountered, clinicians may be unfamiliar with its diagnosis and management; this unfamiliarity, combined with the potential necessity for urgent intervention, may place the clinician confronted with PI in a precarious medical scenario. We present a case of pneumatosis intestinalis in a patient who posed a particularly challenging diagnostic dilemma for the primary team. Furthermore, we explore the differential diagnosis prior to revealing the intervention offered to our patient; our concise yet inclusive differential and thought process for rapid evaluation may be of benefit to clinicians presented with similar clinical scenarios.
Existence of Positive Solutions for Nonlocal Fourth-Order Boundary Value Problem with Variable Parameter
Authors: Han Xiaoling , Gao Hongliang , Xu Jia
Published: February 2011

By using the Krasnoselskii's fixed point theorem and operator spectral theorem, the existence of positive solutions for the nonlocal fourth-order boundary value problem with variable parameter "Equation missing", "Equation missing", "Equation missing", "Equation missing" is considered, where "Equation missing" is a parameter, and "Equation missing", "Equation missing".
A Mitigation Approach to Alleviate Arsenic Accumulation in Rice through Balanced Fertilization
Authors: Imamul Huq S. M. , Sultana Selina , Chakraborty Ganga , Chowdhury M. T. A.
Published: February 2011

Pot experiments with boro and aman season rice on the same soils treated with arsenic contaminated irrigation water and using balanced fertilizer or not revealed that balance fertilization could be a strategy to mitigate arsenic accumulation in rice grain. The study also revealed that there is a carryover effect of As applied through irrigation in the boro season to the subsequent aman season rice. This carryover effect too, could be minimized with balanced fertilization.
Activation of the Androgen Receptor by Intratumoral Bioconversion of Androstanediol to Dihydrotestosterone in Prostate Cancer
Authors: Mohler James L. , Titus Mark A. , Bai Suxia , Kennerley Brian J. , Lih Fred B. , Tomer Kenneth B. , Wilson Elizabeth M.
Published: February 2011

The androgen receptor (AR) mediates the growth of benign and malignant prostate in response to dihydrotestosterone (DHT). In patients undergoing androgen deprivation therapy for prostate cancer, AR drives prostate cancer growth despite low circulating levels of testicular androgen and normal levels of adrenal androgen. In this report, we demonstrate the extent of AR transactivation in the presence of 5α-androstane-3α,17β-diol (androstanediol) in prostate-derived cell lines parallels the bioconversion of androstanediol to DHT. AR transactivation in the presence of androstanediol in prostate cancer cell lines correlated mainly with mRNA and protein levels of 17β-hydroxysteroid dehydrogenase 6 (17β-HSD6), one of several enzymes required for the interconversion of androstanediol to DHT and the inactive metabolite androsterone. Levels of retinol dehydrogenase 5, and dehydrogenase/reductase short-chain dehydrogenase/reductase family member 9, which also convert androstanediol to DHT, were lower than 17β-HSD6 in prostate-derived cell lines and higher in the castration-recurrent human prostate cancer xenograft. Measurements of tissue androstanediol using mass spectrometry demonstrated androstanediol metabolism to DHT and androsterone. Administration of androstanediol dipropionate to castration-recurrent CWR22R tumor-bearing athymic castrated male mice produced a 28-fold increase in intratumoral DHT levels. AR transactivation in prostate cancer cells in the presence of androstanediol resulted from the cell-specific conversion of androstanediol to DHT, and androstanediol increased LAPC-4 cell growth. The ability to convert androstanediol to DHT provides a mechanism for optimal utilization of androgen precursors and catabolites for DHT synthesis. Cancer Res; 71(4); 1486–96. ©2011 AACR.
Noncytotoxic Differentiation Treatment of Renal Cell Cancer
Authors: Negrotto Soledad , Hu Zhenbo , Alcazar Oscar , Ng Kwok Peng , Triozzi Pierre , Lindner Daniel , Rini Brian , Saunthararajah Yogen
Published: February 2011

Current drug therapy for metastatic renal cell cancer (RCC) results in temporary disease control but not cure, necessitating continued investigation into alternative mechanistic approaches. Drugs that inhibit chromatin-modifying enzymes involved in transcription repression (chromatin-relaxing drugs) could have a role, by inducing apoptosis and/or through differentiation pathways. At low doses, the cytosine analogue decitabine (DAC) can be used to deplete DNA methyl-transferase 1 (DNMT1), modify chromatin, and alter differentiation without causing apoptosis (cytotoxicity). Noncytotoxic regimens of DAC were evaluated for in vitro and in vivo efficacy against RCC cell lines, including a p53-mutated RCC cell line developed from a patient with treatment-refractory metastatic RCC. The cell division–permissive mechanism of action—absence of early apoptosis or DNA damage, increase in expression of HNF4α (hepatocyte nuclear factor 4α), a key driver associated with the mesenchymal to epithelial transition, decrease in mesenchymal marker expression, increase in epithelial marker expression, and late increase in cyclin-dependent kinase inhibitor CDKN1B (p27) protein—was consistent with differentiation-mediated cell-cycle exit. In vivo blood counts and animal weights were consistent with minimal toxicity of therapy. The distinctive mechanism of action of a dose and schedule of DAC designed for noncytotoxic depletion of DNMT1 suggests a potential role in treating RCC. Cancer Res; 71(4); 1431–41. ©2011 AACR.
PIPKIγ Regulates β-Catenin Transcriptional Activity Downstream of Growth Factor Receptor Signaling
Authors: Schramp Mark , Thapa Narendra , Heck Jessica , Anderson Richard
Published: February 2011

Increased β-catenin transcriptional activity downstream of the Wnt/Wingless signaling pathway has been observed in many human tumors, most notably colorectal carcinomas. However, β-catenin activation is also observed in many human malignancies with no observable Wnt activity. Wnt-independent pathways that activate β-catenin remain undefined, yet have the potential to play a significant role during tumorigenesis. Here, we report that phosphotidylinositol phosphate kinase Iγ (PIPKIγ), an enzyme that generates phosphoinositide messengers in vivo, directly associates with β-catenin and increases β-catenin activity downstream of growth factor stimulation. PIPKIγ expression and kinase activity enhance β-catenin phosphorylation on residues that promote nuclear importation and transcriptional activity. Lastly, we show that β-catenin is required for PIPKIγ-dependent increased cell proliferation. These results reveal a novel mechanism in which PIPKIγ expression and catalytic activity enhance β-catenin nuclear translocation and expression of its target genes to promote tumorigenic phenotypes. Cancer Res; 71(4); 1282–91. ©2011 AACR.
Genome-Wide Significant Association Between a Sequence Variant at 15q15.2 and Lung Cancer Risk
Authors: Rafnar Thorunn , Sulem Patrick , Besenbacher Soren , Gudbjartsson Daniel F. , Zanon Carlo , Gudmundsson Julius , Stacey Simon N. , Kostic Jelena P. , Thorgeirsson Thorgeir E. , Thorleifsson Gudmar , Bjarnason Hjordis , Skuladottir Halla , Gudbjartsson Tomas , Isaksson Helgi J. , Isla Dolores , Murillo Laura , García-Prats Maria D. , Panadero Angeles , Aben Katja K.H. , Vermeulen Sita H. , van der Heijden Henricus F.M. , Feser William J. , Miller York E. , Bunn Paul A. , Kong Augustine , Wolf Holly J. , Franklin Wilbur A. , Mayordomo Jose I. , Kiemeney Lambertus A. , Jonsson Steinn , Thorsteinsdottir Unnur , Stefansson Kari
Published: February 2011

Genome-wide association studies (GWAS) have identified 3 genomic regions, at 15q24–25.1, 5p15.33, and 6p21.33, which associate with the risk of lung cancer. Large meta-analyses of GWA data have failed to find additional associations of genome-wide significance. In this study, we sought to confirm 7 variants with suggestive association to lung cancer (P < 10−5) in a recently published meta-analysis. In a GWA dataset of 1,447 lung cancer cases and 36,256 controls in Iceland, 3 correlated variants on 15q15.2 (rs504417, rs11853991, and rs748404) showed a significant association with lung cancer, whereas rs4254535 on 2p14, rs1530057 on 3p24.1, rs6438347 on 3q13.31, and rs1926203 on 10q23.31 did not. The most significant variant, rs748404, was genotyped in an additional 1,299 lung cancer cases and 4,102 controls from the Netherlands, Spain, and the United States and the results combined with published GWAS data. In this analysis, the T allele of rs748404 reached genome-wide significance (OR = 1.15, P = 1.1 × 10−9). Another variant at the same locus, rs12050604, showed association with lung cancer (OR = 1.09, 3.6 × 10−6) and remained significant after adjustment for rs748404 and vice versa. rs748404 is located 140 kb centromeric of the TP53BP1 gene that has been implicated in lung cancer risk. Two fully correlated, nonsynonymous coding variants in TP53BP1, rs2602141 (Q1136K) and rs560191 (E353D) showed association with lung cancer in our sample set; however, this association did not remain significant after adjustment for rs748404. Our data show that 1 or more lung cancer risk variants of genome-wide significance and distinct from the coding variants in TP53BP1 are located at 15q15.2. Cancer Res; 71(4); 1356–61. ©2011 AACR.
Clinical Impact of Different Classes of Infiltrating T Cytotoxic and Helper Cells (Th1, Th2, Treg, Th17) in Patients with Colorectal Cancer
Authors: Tosolini Marie , Kirilovsky Amos , Mlecnik Bernhard , Fredriksen Tessa , Mauger Stéphanie , Bindea Gabriela , Berger Anne , Bruneval Patrick , Fridman Wolf-Herman , Pagès Franck , Galon Jérôme
Published: February 2011

The tumor microenvironment includes a complex network of immune T-cell subpopulations. In this study, we systematically analyzed the balance between cytotoxic T cells and different subsets of helper T cells in human colorectal cancers and we correlated their impact on disease-free survival. A panel of immune related genes were analyzed in 125 frozen colorectal tumor specimens. Infiltrating cytotoxic T cells, Treg, Th1, and Th17 cells were also quantified in the center and the invasive margin of the tumors. By hierarchical clustering of a correlation matrix we identified functional clusters of genes associated with Th17 (RORC, IL17A), Th2 (IL4, IL5, IL13), Th1 (Tbet, IRF1, IL12Rb2, STAT4), and cytotoxicity (GNLY, GZMB, PRF1). Patients with high expression of the Th17 cluster had a poor prognosis, whereas patients with high expression of the Th1 cluster had prolonged disease-free survival. In contrast, none of the Th2 clusters were predictive of prognosis. Combined analysis of cytotoxic/Th1 and Th17 clusters improved the ability to discriminate relapse. In situ analysis of the density of IL17+ cells and CD8+ cells in tumor tissues confirmed the results. Our findings argue that functional Th1 and Th17 clusters yield opposite effects on patient survival in colorectal cancer, and they provide complementary information that may improve prognosis. Cancer Res; 71(4); 1263–71. ©2011 AACR.
Polymalic Acid–Based Nanobiopolymer Provides Efficient Systemic Breast Cancer Treatment by Inhibiting both HER2/neu Receptor Synthesis and Activity
Authors: Inoue Satoshi , Ding Hui , Portilla-Arias Jose , Hu Jinwei , Konda Bindu , Fujita Manabu , Espinoza Andres , Suhane Sonal , Riley Marisa , Gates Marcus , Patil Rameshwar , Penichet Manuel L. , Ljubimov Alexander V. , Black Keith L. , Holler Eggehard , Ljubimova Julia Y.
Published: February 2011

Biodegradable nanopolymers are believed to offer great potential in cancer therapy. Here, we report the characterization of a novel, targeted, nanobiopolymeric conjugate based on biodegradable, nontoxic, and nonimmunogenic PMLA [poly(β-l-malic acid)]. The PMLA nanoplatform was synthesized for repetitive systemic treatments of HER2/neu-positive human breast tumors in a xenogeneic mouse model. Various moieties were covalently attached to PMLA, including a combination of morpholino antisense oligonucleotides (AON) directed against HER2/neu mRNA, to block new HER2/neu receptor synthesis; anti-HER2/neu antibody trastuzumab (Herceptin), to target breast cancer cells and inhibit receptor activity simultaneously; and transferrin receptor antibody, to target the tumor vasculature and mediate delivery of the nanobiopolymer through the host endothelial system. The results of the study showed that the lead drug tested significantly inhibited the growth of HER2/neu-positive breast cancer cells in vitro and in vivo by enhanced apoptosis and inhibition of HER2/neu receptor signaling with suppression of Akt phosphorylation. In vivo imaging analysis and confocal microscopy demonstrated selective accumulation of the nanodrug in tumor cells via an active delivery mechanism. Systemic treatment of human breast tumor-bearing nude mice resulted in more than 90% inhibition of tumor growth and tumor regression, as compared with partial (50%) tumor growth inhibition in mice treated with trastuzumab or AON, either free or attached to PMLA. Our findings offer a preclinical proof of concept for use of the PMLA nanoplatform for combination cancer therapy. Cancer Res; 71(4); 1454–64. ©2011 AACR.