bluuebunny/crossref_metadata_2025 huggingface dataset:
Vulnerability of continence structures to injury by simulated childbirth
Authors: Phull Hardeep S. , Pan Hui Q. , Butler Robert S. , Hansel Donna E. , Damaser Margot S.
Published: May 2011

The goal of this study was to examine acute morphological changes, edema, muscle damage, inflammation, and hypoxia in urethral and vaginal tissues with increasing duration of vaginal distension (VD) in a rat model. Twenty-nine virgin Sprague-Dawley rats underwent VD under anesthesia with the use of a modified Foley catheter inserted into the vagina and filled with saline for 0, 1, 4, or 6 h. Control animals were anesthetized for 4 h without catheter placement. Urogenital organs were harvested after intracardiac perfusion of fixative. Tissues were embedded, sectioned, and stained with Masson's trichrome or hematoxylin and eosin stains. Regions of hypoxia were measured by hypoxyprobe-1 immunohistochemistry. Within 1 h of VD, the urethra became vertically elongated and displaced anteriorly. Edema was most prominent in the external urethral sphincter (EUS) and urethral/vaginal septum within 4 h of VD, while muscle disruption and fragmentation of the EUS occurred after 6 h. Inflammatory damage was characterized by the presence of polymorphonuclear leukocytes in vessels and tissues after 4 h of VD, with the greatest degree of infiltration occurring in the EUS. Hypoxia localized mostly to the vaginal lamina propria, urethral smooth muscle, and EUS within 4 h of VD. Increasing duration of VD caused progressively greater tissue edema, muscle damage, and morphological changes in the urethra and vagina. The EUS underwent the greatest insult, demonstrating its vulnerability to childbirth injury.
WNK4 kinase inhibits Maxi K channel activity by a kinase-dependent mechanism
Authors: Zhuang Jieqiu , Zhang Xuemei , Wang Dexuan , Li Juan , Zhou Bo , Shi Zhen , Gu Dingying , Denson Donald D. , Eaton Douglas C. , Cai Hui
Published: May 2011

WNK [with no lysine (k)] kinase is a serine/threonine kinase subfamily. Mutations in two of the WNK kinases result in pseudohypoaldosteronism type II (PHA II) characterized by hypertension, hyperkalemia, and metabolic acidosis. Recent studies showed that both WNK1 and WNK4 inhibit ROMK activity. However, little is known about the effect of WNK kinases on Maxi K, a large-conductance Ca2+and voltage-activated potassium (K) channel. Here, we report that WNK4 wild-type (WT) significantly inhibits Maxi K channel activity in HEK αBK stable cell lines compared with the control group. However, a WNK4 dead-kinase mutant, D321A, has no inhibitory effect on Maxi K activity. We further found that WNK4 inhibits total and cell surface protein expression of Maxi K equally compared with control groups. A dominant-negative dynamin mutant, K44A, did not alter the WNK4-mediated inhibitory effect on Maxi K surface expression. Treatment with bafilomycin A1 (a proton pump inhibitor) and leupeptin (a lysosomal inhibitor) reversed WNK4 WT-mediated inhibition of Maxi K total protein expression. These findings suggest that WNK4 WT inhibits Maxi K activity by reducing Maxi K protein at the membrane, but that the inhibition is not due to an increase in clathrin-mediated endocytosis of Maxi K, but likely due to enhancing its lysosomal degradation. Also, WNK4's inhibitory effect on Maxi K activity is dependent on its kinase activity.
Ischemic preconditioning of the muscle improves maximal exercise performance but not maximal oxygen uptake in humans
Authors: Crisafulli Antonio , Tangianu Flavio , Tocco Filippo , Concu Alberto , Mameli Ombretta , Mulliri Gabriele , Caria Marcello A.
Published: May 2011

Brief episodes of nonlethal ischemia, commonly known as “ischemic preconditioning” (IP), are protective against cell injury induced by infarction. Moreover, muscle IP has been found capable of improving exercise performance. The aim of the study was the comparison of standard exercise performances carried out in normal conditions with those carried out following IP, achieved by brief muscle ischemia at rest (RIP) and after exercise (EIP). Seventeen physically active, healthy male subjects performed three incremental, randomly assigned maximal exercise tests on a cycle ergometer up to exhaustion. One was the reference (REF) test, whereas the others were performed after the RIP and EIP sessions. Total exercise time (TET), total work (TW), and maximal power output (Wmax), oxygen uptake (VO2max), and pulmonary ventilation (VEmax) were assessed. Furthermore, impedance cardiography was used to measure maximal heart rate (HRmax), stroke volume (SVmax), and cardiac output (COmax). A subgroup of volunteers ( n = 10) performed all-out tests to assess their anaerobic capacity. We found that both RIP and EIP protocols increased in a similar fashion TET, TW, Wmax, VEmax, and HRmax with respect to the REF test. In particular, Wmax increased by ∼4% in both preconditioning procedures. However, preconditioning sessions failed to increase traditionally measured variables such as VO2max, SVmax, COmax, and anaerobic capacity. It was concluded that muscle IP improves performance without any difference between RIP and EIP procedures. The mechanism of this effect could be related to changes in fatigue perception.
The locomotor central pattern generator of the rat spinal cord in vitro is optimally activated by noisy dorsal root waveforms
Authors: Taccola Giuliano
Published: May 2011

The spinal cord contains an intrinsic locomotor program driven by a central pattern generator that rhythmically activates flexor and extensor limb motor pools. Although long-lasting locomotor activity can be generated pharmacologically, trains of afferent stimuli trigger only few locomotor cycles. The present study investigated whether a new electrical stimulation protocol (termed FL istim) could elicit long-lasting fictive locomotion (FL) in the rat spinal cord in vitro. Thus, after first inducing FL by bath application of N-methyl-d-aspartate and serotonin, the recorded waveform obtained from a lumbar ventral root was digitized and then applied to either a lumbar dorsal root or the cauda equina following washout of pharmacological agents. Two FL istim cycles were the threshold input to evoke an episode of FL from ventral roots. Longer cycles (up to 1 min) induced sustained FL (up to 1 min) with stereotyped periodicity (2.2 ± 0.5 s), despite changing frequency (2–4 s) or cycle amplitude of FL istim. Gradual filtering out of the noise from FL istim trace concomitantly decreased the efficiency of FL so that stimulation with equivalent pure sinusoids produced asynchronous, irregular discharges only that could not be converted to FL by adding spontaneous basal activity. This study is the first demonstration that epochs of rhythmic locomotor-like oscillations applied to a dorsal root represent an efficient stimulus to evoke FL as long as they contain the electrophysiological noise produced within FL cycles. These observations suggest novel strategies to improve the efficiency of electrical stimulation delivered by clinical devices for neurorehabilitation after spinal injury.
An inexpensive drivable cannulated microelectrode array for simultaneous unit recording and drug infusion in the same brain nucleus of behaving rats
Authors: du Hoffmann Johann , Kim James J. , Nicola Saleem M.
Published: May 2011

Neurons are functionally segregated into discrete populations that perform specific computations. These computations, mediated by neuron-neuron electrochemical signaling, form the neural basis of behavior. Thus fundamental to a brain-based understanding of behavior is the precise determination of the contribution made by specific neurotransmitters to behaviorally relevant neural activity. To facilitate this understanding, we have developed a cannulated microelectrode array for use in behaving rats that enables simultaneous neural ensemble recordings and local infusion of drugs in the same brain nucleus. The system is inexpensive, easy to use, and produces robust and quantitatively reproducible drug effects on recorded neurons.
Fine frequency tuning in monkey auditory cortex and thalamus
Authors: Bartlett Edward L. , Sadagopan Srivatsun , Wang Xiaoqin
Published: May 2011

The frequency resolution of neurons throughout the ascending auditory pathway is important for understanding how sounds are processed. In many animal studies, the frequency tuning widths are about 1/5th octave wide in auditory nerve fibers and much wider in auditory cortex neurons. Psychophysical studies show that humans are capable of discriminating far finer frequency differences. A recent study suggested that this is perhaps attributable to fine frequency tuning of neurons in human auditory cortex (Bitterman Y, Mukamel R, Malach R, Fried I, Nelken I. Nature 451: 197–201, 2008). We investigated whether such fine frequency tuning was restricted to human auditory cortex by examining the frequency tuning width in the awake common marmoset monkey. We show that 27% of neurons in the primary auditory cortex exhibit frequency tuning that is finer than the typical frequency tuning of the auditory nerve and substantially finer than previously reported cortical data obtained from anesthetized animals. Fine frequency tuning is also present in 76% of neurons of the auditory thalamus in awake marmosets. Frequency tuning was narrower during the sustained response compared to the onset response in auditory cortex neurons but not in thalamic neurons, suggesting that thalamocortical or intracortical dynamics shape time-dependent frequency tuning in cortex. These findings challenge the notion that the fine frequency tuning of auditory cortex is unique to human auditory cortex and that it is a de novo cortical property, suggesting that the broader tuning observed in previous animal studies may arise from the use of anesthesia during physiological recordings or from species differences.
Optogenetic analysis of GABABreceptor signaling inCaenorhabditis elegansmotor neurons
Authors: Schultheis Christian , Brauner Martin , Liewald Jana F. , Gottschalk Alexander
Published: May 2011

In the nervous system, a perfect balance of excitation and inhibition is required, for example, to enable coordinated locomotion. In Caenorhabditis elegans, cholinergic and GABAergic motor neurons (MNs) effect waves of contralateral muscle contraction and relaxation. Cholinergic MNs innervate muscle as well as GABAergic MNs, projecting to the opposite side of the body, at dyadic synapses. Only a few connections exist from GABAergic to cholinergic MNs, emphasizing that GABA signaling is mainly directed toward muscle. Yet, a GABABreceptor comprising GBB-1 and GBB-2 subunits, expressed in cholinergic MNs, was shown to affect locomotion, likely by feedback inhibition of cholinergic MNs in response to spillover GABA. In the present study, we examined whether the GBB-1/2 receptor could also affect short-term plasticity in cholinergic MNs with the use of channelrhodopsin-2-mediated photostimulation of GABAergic and cholinergic neurons. The GBB-1/2 receptor contributes to acute body relaxation, evoked by photoactivation of GABAergic MNs, and to effects of GABA on locomotion behavior. Loss of the plasma membrane GABA transporter SNF-11, as well as acute photoevoked GABA release, affected cholinergic MN function in opposite directions. Prolonged stimulation of GABA MNs had subtle effects on cholinergic MNs, depending on stimulus duration and gbb-2. Thus GBB-1/2 receptors serve mainly for linear feedback inhibition of cholinergic MNs but also evoke minor plastic changes.
Active and passive movement are encoded equally by head direction cells in the anterodorsal thalamus
Authors: Shinder Michael E. , Taube Jeffrey S.
Published: May 2011

The head direction (HD) system is composed of cells that represent the direction in which the animal's head is facing. Each HD cell responds optimally when the head is pointing in a particular, or preferred, direction. Although vestibular system input is necessary to generate the directional signal, motor/proprioceptive inputs can also influence HD cell responses. Previous studies comparing active and passive movement have reported significant suppression of the HD signal during passive restraint. However, in each of these studies there was considerable variability across cells, and the animal's head was never completely fixed. To address these issues, we developed a passive restraint system that more fully prevented head and body movement. HD cell responses in the anterodorsal thalamus (ADN) were evaluated during active and passive movement with this new system. Contrary to previous reports, HD cell responses were not affected by passive restraint. Both head-fixed and hand-held restraint failed to produce significant inhibition of the active HD cell response. Furthermore, direction-specific firing was maintained regardless of 1) the animal's previous experience with restraint, 2) whether it was tested in the light or dark, or 3) the position of the animal relative to the axis of rotation. The maintenance of a stable directional signal without appropriate motor, proprioceptive, or visual input indicates that vestibular input is necessary and sufficient for the generation of the HD signal. Motor and proprioceptive influences may therefore be important for the control of the preferred firing direction of HD cells, but not the generation of the signal itself.
Higher‐Order Generalized Invexity in Control Problems
Authors: Padhan S. K. , Nahak C.
Published: May 2011

We introduce a
higher‐order duality (Mangasarian type and
Mond‐Weir type) for the control problem. Under
the higher‐order generalized invexity
assumptions on the functions that compose the
primal problems, higher‐order duality results
(weak duality, strong duality, and converse
duality) are derived for these pair of problems.
Also, we establish few examples in support of our
investigation.
Developing the US Wildland Fire Decision Support System
Authors: Noonan-Wright Erin K. , Opperman Tonja S. , Finney Mark A. , Zimmerman G. Thomas , Seli Robert C. , Elenz Lisa M. , Calkin David E. , Fiedler John R.
Published: May 2011

A new decision support tool, the Wildland Fire Decision Support System (WFDSS) has been developed to support risk‐informed decision‐making for individual fires in the United States. WFDSS accesses national weather data and forecasts, fire behavior prediction, economic assessment, smoke management assessment, and landscape databases to efficiently formulate and apply information to the decision making process. Risk‐informed decision‐making is becoming increasingly important as a means of improving fire management and offers substantial opportunities to benefit natural and community resource protection, management response effectiveness, firefighter resource use and exposure, and, possibly, suppression costs. This paper reviews the development, structure, and function of WFDSS, and how it contributes to increased flexibility and agility in decision making, leading to improved fire management program effectiveness.
Advancement in Nanoscale CMOS Device Design En Route to Ultra-Low-Power Applications
Authors: Dhar Subhra , Pattanaik Manisha , Rajaram Poolla
Published: May 2011

In recent years, the demand for power sensitive designs has grown significantly due to the fast growth of battery-operated portable applications. As the technology scaling continues unabated, subthreshold device design has gained a lot of attention due to the low-power and ultra-low-power consumption in various applications. Design of low-power high-performance submicron and deep submicron CMOS devices and circuits is a big challenge. Short-channel effect is a major challenge for scaling the gate length down and below 0.1 μm. Detailed review and potential solutions for prolonging CMOS as the leading information technology proposed by various researchers in the past two decades are presented in this paper. This paper attempts to categorize the challenges and solutions for low-power and low-voltage application and thus provides a roadmap for device designers working in the submicron and deep submicron region of CMOS devices separately.
Magnetic Properties of Co0.5Zn0.5Fe2O4Nanoparticles Synthesized by a Template-Assisted Hydrothermal Method
Authors: He H. Y.
Published: May 2011

In the present paper, nickel cobalt ferrite (Co0.5Zn0.5Fe2O4) nanoparticles were synthesized using a template-assisted hydrothermal method. Carboxymethyl cellulose was used as the templating agent for controlling the morphology of the Co0.5Zn0.5Fe2O4nanoparticles. The synthesized nanoparticles were characterized using X-ray diffraction, scanning electron microscopy, and a vibrating sample magnetometer. The results indicated that the morphology of the nanoparticles changed from granular and superparamagnetic to platelike and ferromagnetic with the addition of the template. The Co0.5Zn0.5Fe2O4nanoparticles synthesized without the template exhibited a saturation magnetization and coercivity 2.81 T and 0.2 kA⋅m−1, while when the template was used, the saturation magnetization and coercivity increased to 3.13 T and 76.6 kA⋅m−1as the template proportion increased to 0.3.
Solar Energy Modelling over a Residential Community in the City of Calgary, Alberta, Canada
Authors: Hassan Quazi K. , Rahman K. Mahmud , Haque Anis S. , Ali Ahad
Published: May 2011

Solar energy is an abundant source of renewable/sustainable energy, which has an enormous potential in reducing the foot print of the greenhouse gases. In this paper, we presented a modelling framework of estimating solar energy over a portion of a residential community of Sandstone in the northwest of Calgary, Canada. We calculated the actual daily incident solar radiation as a function of latitude, day of year, and possible day light hours; and also employed high-resolution remote sensing images to calculate the effective roof area for installing photovoltaic cells. Strong relationships (r2:0.91–0.98) were observed between the ground-based measurements and the modelled actual incident solar radiation at three test locations in Alberta. Over the portion of Sandstone, ~1706.49 m2roof surface area was suitable for potential installation of the photovoltaic cells. With 15% efficient photovoltaic cells, our analysis revealed that we might be able to produce significant amount (i.e., in the range of ~67–100%) of electrical energy needs of the residents of Sandstone community during the period between April and September.
NK Cells and Psoriasis
Authors: Dunphy Sinéad , Gardiner Clair M.
Published: May 2011

Psoriasis is a chronic condition of the skin characterised by distinctive scaly plaques. The immune system is now thought to play a major role in the development and pathogenesis of psoriasis with immune cells and cytokines influencing keratinocyte function. Keratinocytes in turn, can activate and recruit immune cells leading to a positive feedback loop in disease. Natural Killer (NK) cells are lymphocytes that are best known for killing virally infected and cancer cells. However, evidence is emerging to support a role for NK cells in psoriasis. NK cells are found in the inflammatory infiltrate in psoriatic skin lesions. They can produce a range of inflammatory cytokines, many of which are important in the pathogenesis of psoriasis. Recent genetic studies have identified a range of potential molecules relating to NK cell biology that are known to be important in psoriasis. This paper will discuss the evidence, both cellular and genetic, for NK cell involvement in psoriasis.
Toxicity and Neuropharmacological Effects of Elenine
Authors: Navarro Eduardo , Alonso S. J. , Navarro R.
Published: May 2011

Elenine is the aglycone of elenoside, a cytotoxic arylnaphthalene lignan (NSC
644013‐W/1) derived from Justicia hyssopifolia. (Family: Acanthaceae). Elenoside
is a β‐D‐glucoside, with a similar chemical structure to etoposide, exhibiting
central depressant activity. In the present study, elenine was given to mice and
rats at doses of 10, 20, and 40 mg/kg. Acute toxicity (24 h) and general
behaviour in mice was studied as well as its effects on muscular relaxant
activity, locomotor activity (Varimex test), and the open‐field test and were compared
with 10 mg/kg of chlorpromazine. Elenine produced a reduction in the
permanence time in muscular relaxant activity (traction test). Spontaneous
activity was lower in the Varimex test. The ambulation and rearing were lower
compared with the control group, and an increase in boluses was observed in the
open‐field test. Thus, it can be concluded that elenine has central sedative
effects at lower doses than those used with elenoside and has a possible
application in conditions of anxiety.
Dynamically Focused Gaussian Beams for Seismic Imaging
Authors: Nowack Robert L.
Published: May 2011

An initial study is performed in which dynamically focused Gaussian beams are investigated for seismic imaging. Focused Gaussian beams away from the source and receiver plane allow the narrowest and planar portions of the beams to occur at the depth of a specific target structure. To match the seismic data, quadratic phase corrections are required for the local slant stacks of the surface data. To provide additional control of the imaging process, dynamic focusing is investigated where all subsurface points are specified to have the same planar beam fronts. This gives the effect of using nondiffracting beams, but actually results from the use of multiple focusing depths for each Gaussian beam. However, now different local slant stacks must be performed depending on the position of the subsurface scattering point. To speed up the process, slant stacking of the local data windows is varied to match the focusing depths along individual beams when tracked back into the medium. The approach is tested with a simple model of 5-point scatterers which are then imaged with the data, and then to the imaging of a single dynamically focused beam for one shot gather computed from the Sigsbee2A model.
Bilateral Burkitt Lymphoma of the Ovaries: A Report of a Case in a Child with Williams Syndrome
Authors: Onimoe Grace Ifeyinwa , Kahwash Samir , Termuhlen Amanda , Gross Thomas G. , Varga Elizabeth , Rose Melissa J.
Published: May 2011

A 10-year-old female with Williams Syndrome (WS) presented with a two-month history of fatigue, weight loss, and bilateral ovarian masses. Histologic, immunophenotypic, and cytogenetic studies confirmed the diagnosis of Burkitt lymphoma (BL). While there is no established association between the two disorders, this is the third case in the literature of Burkitt lymphoma in a patient with Williams Syndrome.
A Sextuple Product Identity with Applications
Authors: Zhu Jun-Ming
Published: May 2011

We get a new proof of a sextuple product identity depending on the Laurent expansion of an analytic function in an annulus. Many identities, including an identity for , are obtained from this sextuple product identity.
The Refined Positive Definite and Unimodal Regions for the Gram-Charlier and Edgeworth Series Expansion
Authors: Spiring Fred
Published: May 2011

Gram-Charlier and Edgeworth Series Expansions are used in the field of statistics to approximate probability density functions. The expansions have proven useful but have experienced limitations due to the values of the moments that admit a proper probability density function. An alternative approach in developing the boundary conditions for the boundary of the positive region for both series expansions is investigated using Sturm's theorem. The result provides a more accurate representation of the positive region developed by others.
The End of Leisure: Are Preferred Leisure Activities Contraindicated for Education-Related Stress/Anxiety Reduction?
Authors: Daly Beth , Morton L. L.
Published: May 2011

Teacher stress is an increasing problem not only for practicing teachers but for student teachers as well. It leads to professional teachers leaving the profession, and future teachers enduring much stress and anxiety throughout teacher education programs. To further explore effects of stress, teacher candidates were surveyed with respect to (1) the role of their leisure preferences and (2) their stress levels related to Pedagogy, Evaluation, Class Management, and Interpersonal Relations. In Study One (n=216), a profile of leisure preferences was comprised, and findings from the relationship between leisure preferences and teaching anxieties contributed to a profile to explore reduced anxiety over time. A follow-up investigation (Study Two,n=136) tested the discriminatory potential of these leisure profile variables to separate those who showed less anxiety over time from those who regressed. Surprisingly, increased anxiety was associated with higher leisure in Sports, Adventure, Travel, and Exotica and with non-Science majors, Human Kinesiology majors, and Males. Some leisure preferences appear to be counterintuitive, given commonsense notions of the value of leisure. A Leisure Preferences Profile serves to facilitate discrimination between groups (improvement in anxiety levels versus no improvement) with respect to Pedagogical and Evaluation anxiety. A Composite Profile suggests that Leisure preferences related to Sports, Adventure, and Exotica are counterproductive in reducing stress related to Pedagogy. Implications are discussed.
A Note on the Inversion of Sylvester Matrices in Control Systems
Authors: Li Hongkui , Li Ranran
Published: May 2011

We give a sufficient condition (the solvability of two standard equations) of Sylvester matrix by using the displacement structure of the Sylvester matrix, and, according to the sufficient condition, we derive a new fast algorithm for the inversion of a Sylvester matrix, which can be denoted as a sum of products of two triangular Toeplitz matrices. The stability of the inversion formula for a Sylvester matrix is also considered. The Sylvester matrix is numerically forward stable if it is nonsingular and well conditioned.
The Roles of Interleukin-6 in the Pathogenesis of Rheumatoid Arthritis
Authors: Hashizume Misato , Mihara Masahiko
Published: May 2011

Several clinical studies have demonstrated that the humanized anti-interleukin-6 (IL-6) receptor antibody tocilizumab (TCZ) improves clinical symptoms and prevents progression of joint destruction in rheumatoid arthritis (RA). However, the precise mechanism by which IL-6 blockade leads to the improvement of RA is not well understood. IL-6 promotes synovitis by inducing neovascularization, infiltration of inflammatory cells, and synovial hyperplasia. IL-6 causes bone resorption by inducing osteoclast formation via the induction of RANKL in synovial cells, and cartilage degeneration by producing matrix metalloproteinases (MMPs) in synovial cells and chondrocytes. Moreover, IL-6 is involved in autoimmunity by altering the balance between Th17 cells and Treg. IL-6 also acts on changing lipid concentrations in blood and on inducing the production of hepcidin which causes iron-deficient anemia. In conclusion, IL-6 is a major player in the pathogenesis of RA, and current evidence indicates that the blockade of IL-6 is a beneficial therapy for RA patients.
Migraine and Vertigo
Authors: Karatas Mehmet
Published: May 2011

Migraine and vertigo are common disorders in medicine, affecting about 14–16% and 7–10%, respectively, of the general population. Recent epidemiologic studies indicate that 3.2% of the population have both migraine and vertigo. Vertigo may occur in up to 25% of patients with migraine. Migraine is the most frequent vascular disorder causing vertigo in all age groups. Migraine leads to various central or peripheral vestibular syndromes with vertigo such as migrainous vertigo, basilar-type migraine, benign paroxysmal vertigo of childhood, and other vertigo syndromes related to migraine. Migrainous vertigo is the most common cause of spontaneous recurrent vertigo. Diagnostic criteria for migrainous vertigo have been proposed but are not included in the most recent International Headache Society classification of migraine. On the other hand, there are statistical associations between migraine and vertigo syndromes including benign paroxysmal positional vertigo, Meniere's disease, persistent cerebellar symptoms, anxiety-related dizziness, and motion sickness. Vertigo can also act as a migraine trigger. Although some mutations in the CACNA1A gene have been identified in some familial cases, the mechanism of migraine-associated vertigo is still obscure. Treatment includes vestibular suppressants for acute attacks and migraine prophylaxis for patients with frequent attacks.
Target and PADC Track Detectors for Rare Isotope Studies
Authors: Bermudez J. , Sajo-Bohus L. , Tecchio L. , Palfalvi J. K. , Palacios D.
Published: May 2011

A higher yield of rare isotope production methods, for example, isotope separation on-line (ISOL), is expected to be developed for the EURISOL facility. In this paper as a part of the ongoing project, high power-target assembly and passive detector inclusion are given. Theoretical calculations of several configurations were done using Monte Carlo code FLUKA aimed to produce 1015 fiss/s on LEU-Cx target. The proposed radioactive ion beam (RIB) production relies on a high-power (4 MW) multibody target; a complete target design is given. Additionally we explore the possibility to employ PADC passive detector as a complementary system for RIB characterization, since these already demonstrated their importance in nuclear interactions phenomenology. In fact, information and recording rare and complex reaction product or short-lived isotope detection is obtained in an integral form through latent track formation. Some technical details on track formation and PADC detector etching conditions complete this study.
Systematic Review of Primary Hyperparathyroidism in India: The Past, Present, and the Future Trends
Authors: Pradeep P. V. , Jayashree B. , Mishra Anjali , Mishra S. K.
Published: May 2011

Primary hyperparathyroidism (PHPT) has become an asymptomatic disease in the Western world with the introduction of routine calcium screening. However, the same phenomenon is not observed in India. We have now systematically reviewed the status of PHPT in India. While there is a paucity of literature on PHPT from India when compared to Western countries, some information can be gleaned upon. Most patients present with symptomatic disease whereas very few are screen-detected cases (bone disease 77%, renal disease 36%, and 5.6% asymptomatic). Mean calcium, parathyroid hormone (PTH), and alkaline phosphate levels are high while Vitamin D levels are low. The average parathyroid gland weight is large and the majority being parathyroid adenomas (89.1%). Hungry bone syndrome (HBS) is common in the postoperative period. The disease-related mortality rate is 7.4%, recurrence 4.16%, and persistent disease 2.17%. We suggest that dedicated efforts are needed to pick up asymptomatic disease in India by methods like incorporating calcium estimation in the routine health check-up programs.
Joint Symptoms, Aromatase Inhibitor-Related Adverse Reactions, Are Indirectly Associated with Decreased Serum Estradiol
Authors: Honda Junko , Kanematsu Miyuki , Nakagawa Misako , Takahashi Masako , Nagao Taeko , Tangoku Akira , Sasa Mitsunori
Published: May 2011

Background. Joint symptoms (JSs) are problematic adverse drug reactions (ADRs) of aromatase inhibitors (AIs). Involvement of decreased serum estradiol (SE) has been suggested.Patients and Methods. 104 postmenopausal breast cancer patients administered an AI were prospectively investigated regarding various clinical parameters, JS and hot flashes as ADRs, and the SE level.Results. JS manifested in 31.7% of patients and hot flashes in 18.3%. Chi-square testing showed a significantly higher incidence of JS in several patient strata: <55 years old, decreased SE, and elevated total cholesterol (TC). In univariate analysis, JS correlated significantly with a pre-AI % YAM of ≥80%, decreased SE, and elevated TC. Eight (7.7%) patients maintained SE at ≥5 pg/mL for >6 consecutive months, with no JS. In chi-square testing, hot flashes showed a significantly higher incidence in patients <55 years old.Conclusion. AI-ADRs occurred more readily in younger patients. Decreased SE may be indirectly involved in JS.
Software-Defined Radio Technologies for
GNSS Receivers: A Tutorial Approach to a Simple
Design and Implementation
Authors: Principe Fabio , Bacci Giacomo , Giannetti Filippo , Luise Marco
Published: May 2011

The field of satellite navigation has witnessed the
advent of a number of new systems and technologies: after
the landmark design and development of the Global Positioning
System (GPS), a number of new independent Global Navigation
Satellite Systems (GNSSs) were or are being
developed all over the world: Russia's GLONASS, Europe's
GALILEO, and China's BEIDOU-2, to mention a few. In this ever-changing context, the availability of reliable and flexible receivers is becoming a priority for a host of
applications, including research, commercial, civil, and military.
Flexible means here both easily upgradeable for future needs
and/or on-the-fly reprogrammable to adapt to different signal
formats. An effective approach to meet these design goals is the
software-defined radio (SDR) paradigm. In the last few years, the
availability of new processors with high computational power
enabled the development of (fully) software receivers whose
performance is comparable to or better than that of conventional
hardware devices, while providing all the advantages of a flexible
and fully configurable architecture. The aim of this tutorial paper
is surveying the issue of the general architecture and design
rules of a GNSS software receiver, through a comprehensive
discussion of some techniques and algorithms, typically applied
in simple PC-based receiver implementations.
Current Insights into Surgery for Intramedullary Spinal Cord Metastases: A Literature Review
Authors: Kalita Ondrej
Published: May 2011

Intramedullary spinal cord metastasis (ISCM) is the rarest type of CNS involvement by systemic malignant tumours. Optimal management of patients with ISCMs remains ambiguous. Based on two cases reported from our department, we focused on the strategy for intramedullary spinal cord metastases surgery.
VEGF and c-Met Blockade Amplify Angiogenesis Inhibition in Pancreatic Islet Cancer
Authors: You Weon-Kyoo , Sennino Barbara , Williamson Casey W. , Falcón Beverly , Hashizume Hiroya , Yao Li-Chin , Aftab Dana T. , McDonald Donald M.
Published: May 2011

Angiogenesis inhibitors that block VEGF receptor (VEGFR) signaling slow the growth of many types of tumors, but eventually the disease progresses. Multiple strategies are being explored to improve efficacy by concurrent inhibition of other functionally relevant receptor tyrosine kinases (RTK). XL880 (foretinib, GSK1363089) and XL184 (cabozantinib) are small-molecule inhibitors that potently block multiple RTKs, including VEGFR and the receptor of hepatocyte growth factor c-Met, which can drive tumor invasion and metastasis. This study compared the cellular effects of XL880 and XL184 with those of an RTK inhibitor (XL999) that blocks VEGFR but not c-Met. Treatment of RIP-Tag2 mice with XL999 resulted in 43% reduction in vascularity of spontaneous pancreatic islet tumors over 7 days, but treatment with XL880 or XL184 eliminated approximately 80% of the tumor vasculature, reduced pericytes and empty basement membrane sleeves, caused widespread intratumoral hypoxia and tumor cell apoptosis, and slowed regrowth of the tumor vasculature after drug withdrawal. Importantly, XL880 and XL184 also decreased invasiveness of primary tumors and reduced metastasis. Overall, these findings indicate that inhibition of c-Met and functionally related kinases amplifies the effects of VEGFR blockade and leads to rapid, robust, and progressive regression of tumor vasculature, increased intratumoral hypoxia and apoptosis, and reduced tumor invasiveness and metastasis. Cancer Res; 71(14); 4758–68. ©2011 AACR.
Insights into ALK-Driven Cancers Revealed through Development of Novel ALK Tyrosine Kinase Inhibitors
Authors: Lovly Christine M. , Heuckmann Johannes M. , de Stanchina Elisa , Chen Heidi , Thomas Roman K. , Liang Chris , Pao William
Published: May 2011

Aberrant forms of the anaplastic lymphoma kinase (ALK) have been implicated in the pathogenesis of multiple human cancers, where ALK represents a rational therapeutic target in these settings. In this study, we report the identification and biological characterization of X-376 and X-396, two potent and highly specific ALK small molecule tyrosine kinase inhibitors (TKIs). In Ambit kinome screens, cell growth inhibition studies, and surrogate kinase assays, X-376 and X-396 were more potent inhibitors of ALK but less potent inhibitors of MET compared to PF-02341066 (PF-1066), an ALK/MET dual TKI currently in clinical trials. Both X-376 and X-396 displayed potent antitumor activity in vivo with favorable pharmacokinetic and toxicity profiles. Similar levels of drug sensitivity were displayed by the three most common ALK fusion proteins in lung cancer (EML4-ALK variants E13;A20, E20;A20, and E6b;A20) as well as a KIF5B–ALK fusion protein. Moreover, X-396 could potently inhibit ALK kinases engineered with two point mutations associated with acquired resistance to PF-1066, L1196M, and C1156Y, when engineered into an E13;A20 fusion variant. Finally, X-396 displayed synergistic growth inhibitory activity when combined with the mTOR inhibitor rapamycin. Our findings offer preclinical proof-of-concept for use of these novel agents to improve therapeutic outcomes of patients with mutant ALK-driven malignancies. Cancer Res; 71(14); 4920–31. ©2011 AACR.
High-Risk Endometrial Carcinoma Profiling Identifies TGF-β1 as a Key Factor in the Initiation of Tumor Invasion
Authors: Muinelo-Romay Laura , Colas Eva , Barbazan Jorge , Alonso-Alconada Lorena , Alonso-Nocelo Marta , Bouso Marta , Curiel Teresa , Cueva Juan , Anido Urbano , Forteza Jeronimo , Gil-Moreno Antonio , Reventos Jaume , Lopez-Lopez Rafael , Abal Miguel
Published: May 2011

Endometrial cancer is among the three most common cancers in females in industrialized countries. In the majority of cases, the tumor is confined to the uterus at the time of diagnosis and presents a good prognosis. However, after primary surgery, 15% to 20% of these tumors recur and have limited response to systemic therapy. We carried out gene expression profiling of high-risk recurrence endometrial cancers to identify new therapeutic approaches targeting the molecular pathways involved in the acquisition of an aggressive tumor phenotype. A microarray gene-expression analysis on a total of 51 human endometrial carcinomas revealed 77 genes specifically altered in high-risk recurrence tumors (P < 0.001). The bioinformatics analysis of gene–gene interactions and molecular relationships among these genes pointed to a prominent role for TGF-β1 signaling in the acquisition of an aggressive phenotype. We further showed that TGF-β1 has a principal role at the initiation of endometrial carcinoma invasion through the promotion of the epithelial to mesenchymal transition that leads to the acquisition of an invasive phenotype in HEC-1A and RL95-2 cells. Impairment of this initial step with SB-431542, a specific TGF-β1 inhibitor, precluded further persistent endometrial carcinoma invasion. In conclusion, we showed that the characterization of the molecular changes associated with the acquisition of an aggressive phenotype represents a realistic strategy for the rational identification and characterization of new potential therapeutic targets in an effort to improve the clinical management and the outcome of high-risk endometrial cancer patients. Mol Cancer Ther; 10(8); 1357–66. ©2011 AACR.
Heterozygosity Loss at 22q and Lack of INI1 Gene Mutation in Gastrointestinal Stromal Tumor
Authors: Yamamoto Hidetaka , Kohashi Kenichi , Tsuneyoshi Masazumi , Oda Yoshinao
Published: May 2011

Objectives: Gastrointestinal stromal tumor (GIST) is characterized by KIT or PDGFRA gene mutation. Although chromosomal losses of 22q are frequent in GIST, it is unclear which tumor suppressor genes might be inactivated in association with such losses. The INI1 gene, located at 22q11.23, is a tumor suppressor gene that is frequently altered in malignant rhabdoid tumor. Methods: To elucidate the hypothesis that the INI1 gene might be altered along with 22q loss in GIST, we examined the loss of heterozygosity (LOH) at 22q11.23, homozygous deletion and mutation of the INI1 gene, and its gene product expression as well as mutations of KIT and PDGFRA in 27 cases of GIST. Results: Among the 27 informative cases, 19 (70.4%) showed LOH of at least one of the microsatellite markers on 22q11.23. None of the cases (0%) showed homozygous deletion or mutation of the INI1 gene. Immunohistochemically, the INI1 expression was focally reduced in 17/27 (63%) cases, and the INI1 protein level and INI1 mRNA level were each correlated with the presence of 22q11.23 LOH. Although the 22q11.23 LOH was more frequently present in high- than in low-grade tumors, INI1 expression level was not correlated with tumor grade, tumor size, proliferative activity and the expression levels of cyclin D1 and p16INK4a. KIT mutations were found in 18/27 (66.7%) GISTs; however, the KIT genotype was not correlated with the status of LOH at 22q11.23. Conclusions: The results suggest that 22q11.23 LOH is frequently present in GIST irrespective of KIT genotype and it might play a role in part of the development of GIST. However, the hemiallelic loss of INI1 gene causing reduced expression of INI1 protein probably does not have a major impact in the progression of GIST.
Aberrant Expression of Disintegrin-Metalloprotease Proteins in the Formation and Progression of Uterine Cervical Cancer
Authors: Shaker Mohammed , Yokoyama Yuhki , Mori Seiji , Tsujimoto Masahiko , Kawaguchi Naomasa , Kiyono Tohru , Nakano Toru , Matsuura Nariaki
Published: May 2011

Objective: Dysregulated expression of disintegrin-metalloprotease proteins [a disintegrin and metalloproteases (ADAMs) and ADAMs with thrombospondin motif (ADAMTSs)] has been reported in many types of cancers and is believed to play an important role in cancer formation and metastasis. However, little is known about the expression of ADAMs and ADAMTSs in the development of human cervical cancer. Methods: Reverse transcriptase polymerase chain reaction and immunoblotting were performed to assess the expression of several disintegrin-metalloproteases and tissue inhibitors of metalloproteinases (TIMPs) in squamous-type cervical cancer cells and oncogenically modified keratinocytes (immortalized human cervical keratinocytes transduced with human papilloma virus-16 E6/E7 proteins with or without oncogenes). Immunohistochemistry of ADAM-9, ADAM-10 and TIMP-3 was performed on 31 primary human cervical tissue specimens of preinvasive and invasive cervical carcinoma. Results: mRNA levels of ADAM-9, ADAM-10, ADAM-12, TIMP-2 and TIMP-3 were upregulated as cervical cells progressed from dysplastic to malignant lesions compared to normal cervical cells. These results were corroborated at the protein level by Western blot analysis and immunohistochemistry. Conclusion: The expression of disintegrin-metalloproteases and their endogenous regulators was dysregulated during cervical carcinogenesis. The aberrant expression of ADAMs might contribute to the pathogenesis of cervical cancer formation and progression.
Lipoprotein Abnormalities in Patients with Atherosclerotic Renovascular Disease
Authors: Nowakowska Fortuna Elzbieta , Herlitz Hans , Saeed Aso , Attman Per-Ola , Jensen Gert , Alaupovic Petar , Guron Gregor
Published: May 2011

Background: Patients with atherosclerotic renovascular disease (ARVD) have a high risk of cardiovascular death. The primary aim was to characterize abnormalities in apolipoprotein (Apo)-defined lipoprotein (Lp) subclasses in patients with ARVD. Methods: Baseline measurements were performed on 42 patients with ARVD 4 weeks after renal angioplasty (PTRA). All patients were on statin treatment. Twenty age-matched healthy subjects without medications served as controls. Subsequently, patients were randomized to treatment with either candesartan (n = 21), or antihypertensive treatment without inhibitors of the renin-angiotensin-aldosterone system (n = 21) and followed for 11 months. Results: At baseline, ApoC-III (12.7 ± 4.6 vs. 8.8 ± 2.6 (SD) mg/dl, p < 0.05), LpB:C:E (13.3 ± 5.4 vs. 8.4 ± 4.3 mg/dl, p < 0.05), and the sum of ApoC-III-containing lipoproteins, i.e. LpB:C + LpB:C:E + LpA-II:B:C:D:E (46 ± 15 vs. 37 ± 8 mg/dl, p < 0.05), were significantly elevated in ARVD patients versus healthy controls. Multiple regression analyses showed that only plasma renin activity was independently associated with ApoC-III levels at baseline (p < 0.05, r = 0.74). Treatment with candesartan did not correct abnormalities. Conclusions: Patients with ARVD treated with statins have an atherogenic lipoprotein profile characterized by elevated levels of ApoC-III-containing, triglyceride-rich lipoproteins that could accelerate atherosclerotic disease.
Fetuin-A Pretransplant Serum Levels, Kidney Allograft Function and Rejection Episodes: A 3-Year Posttransplantation Follow-Up
Authors: Roos Marcel , Heinemann Falko M. , Lindemann Monika , Horn Peter A. , Lutz Jens , Stock Konrad , Thürmel Klaus , Baumann Marcus , Witzke Oliver , Heemann Uwe
Published: May 2011

Background: Fetuin-A is a negative acute-phase protein, which acts as a potent calcification inhibitor and an antagonist of transforming growth factor-β. Thus, fetuin-A levels are influenced by chronic inflammation and actively affect fibrosis and calcification processes, respectively. Graft rejection, interstitial fibrosis and tubular atrophy, chronic inflammation and calcification are common causes for kidney allograft loss. This study evaluated whether pretransplant fetuin-A levels predict long-term graft survival and rejection episodes in patients after kidney transplantation. Methods: In 206 renal transplant recipients pretransplant fetuin-A levels were measured in serum by ELISA. During the 36 months’ active follow-up (median 1,249 days) 13 patients died (94% patient survival) and renal allograft failure was reported in 18 patients (91% graft survival). Results: Pretransplant fetuin-A levels did not differ among patients with incident graft failures as compared to patients with functional graft after long-term follow-up or rejection episodes (fetuin-A: 393.6 ± 46 vs. 384.4 ± 69 vs. 405 ± 27.4 µg/ml). In logistic regression analysis, pretransplant fetuin-A levels did not correlate with graft failure after 3 years’ follow-up (p = 0.895). In COX regression analysis, fetuin-A levels were not associated with the time to graft loss. Moreover, fetuin-A levels correlated neither with renal and metabolic parameters nor with cellular or humoral rejection episodes. Conclusion: Pretransplant levels of fetuin-A are not a predictor for renal allograft loss or rejection episodes after 36 months’ follow-up in transplant recipients.