bluuebunny/crossref_metadata_2025 huggingface dataset:
Toll-like receptor 9 plays a key role in the autonomic cardiac and baroreflex control of arterial pressure
Authors: Rodrigues Fernanda Luciano , Silva Luiz Eduardo V. , Hott Sara Cristina , Bomfim Gisele F. , da Silva Carlos Alberto Aguiar , Fazan Rubens , Resstel Leonardo B. M. , Tostes Rita C. , Carneiro Fernando S.
Published: February 2015

The crosstalk between the immune and the autonomic nervous system may impact the cardiovascular function. Toll-like receptors are components of the innate immune system and play developmental and physiological roles. Toll-like receptor 9 (TLR9) is involved in the pathogenesis of cardiovascular diseases, such as hypertension and heart failure. Since such diseases are commonly accompanied by autonomic imbalance and lower baroreflex sensitivity, we hypothesized that TLR9 modulates cardiac autonomic and baroreflex control of arterial pressure (AP). Toll-like receptor 9 knockout (TLR9 KO) and wild-type (WT) mice were implanted with catheters into carotid artery and jugular vein and allowed to recover for 3 days. After basal recording of AP, mice received methyl-atropine or propranolol. AP and pulse interval (PI) variability were evaluated in the time and frequency domain (spectral analysis), as well as by multiscale entropy. Spontaneous baroreflex was studied by sequence technique. Behavioral and cardiovascular responses to fear-conditioning stress were also evaluated. AP was similar between groups, but TLR9 KO mice exhibited lower basal heart rate (HR). AP variability was not different, but PI variability was increased in TLR9 KO mice. The total entropy was higher in TLR9 KO mice. Moreover, baroreflex function was found higher in TLR9 KO mice. Atropine-induced tachycardia was increased in TLR9 KO mice, whereas the propranolol-induced bradycardia was similar to WT mice. TLR9 KO mice exhibit increased behavioral and decreased tachycardia responses to fear-conditioning stress. In conclusion, our findings suggest that TLR9 may negatively modulate cardiac vagal tone and baroreflex in mice.
Intermittent reductions in respiratory neural activity elicit spinal TNF-α-independent, atypical PKC-dependent inactivity-induced phrenic motor facilitation
Authors: Baertsch Nathan A. , Baker-Herman Tracy L.
Published: February 2015

In many neural networks, mechanisms of compensatory plasticity respond to prolonged reductions in neural activity by increasing cellular excitability or synaptic strength. In the respiratory control system, a prolonged reduction in synaptic inputs to the phrenic motor pool elicits a TNF-α- and atypical PKC-dependent form of spinal plasticity known as inactivity-induced phrenic motor facilitation (iPMF). Although iPMF may be elicited by a prolonged reduction in respiratory neural activity, iPMF is more efficiently induced when reduced respiratory neural activity (neural apnea) occurs intermittently. Mechanisms giving rise to iPMF following intermittent neural apnea are unknown. The purpose of this study was to test the hypothesis that iPMF following intermittent reductions in respiratory neural activity requires spinal TNF-α and aPKC. Phrenic motor output was recorded in anesthetized and ventilated rats exposed to brief intermittent (5, ∼1.25 min), brief sustained (∼6.25 min), or prolonged sustained (30 min) neural apnea. iPMF was elicited following brief intermittent and prolonged sustained neural apnea, but not following brief sustained neural apnea. Unlike iPMF following prolonged neural apnea, spinal TNF-α was not required to initiate iPMF during intermittent neural apnea; however, aPKC was still required for its stabilization. These results suggest that different patterns of respiratory neural activity induce iPMF through distinct cellular mechanisms but ultimately converge on a similar downstream pathway. Understanding the diverse cellular mechanisms that give rise to inactivity-induced respiratory plasticity may lead to development of novel therapeutic strategies to treat devastating respiratory control disorders when endogenous compensatory mechanisms fail.
Unilateral ureteral obstruction attenuates intrarenal angiotensin II generation induced by podocyte injury
Authors: Okabe Masahiro , Miyazaki Yoichi , Niimura Fumio , Pastan Ira , Nishiyama Akira , Yokoo Takashi , Ichikawa Iekuni , Matsusaka Taiji
Published: February 2015

The renal tissue renin-angiotensin system is activated in chronic kidney diseases. We previously demonstrated that intrarenal ANG II is synthesized primarily from liver-derived angiotensinogen filtered through the glomerulus and that podocyte injury increases the passage of angiotensinogen into the tubular lumen and generation of ANG II. In the present study, we tested the effect of cessation of glomerular filtration by ureteral obstruction on renal ANG II generation in kidneys with podocyte injury under two experimental conditions. Ureteral obstruction is known to activate the renin-angiotensin system in nonproteinuric kidneys. Transgenic mice expressing hCD25 in podocyte (NEP25) were injected with 1.25 or 10 ng/g body wt of LMB2, a hCD25-targeted immunotoxin, subjected to unilateral ureteral ligation on the following day, and euthanized 7 and 4 days later, respectively. In both experiments, compared with the kidney in untreated wild-type mice, renal angiotensinogen protein, as assessed by immunostaining and Western blot analysis, was increased in the contralateral unobstructed kidney. However, it was markedly decreased in the obstructed kidney. Whereas intrarenal ANG II content was increased in the contralateral kidney compared with the untreated kidney (248 ± 83 vs. 106 ± 21 and 298 ± 185 vs. 64.8 ± 20 fmol/g kidney, respectively), this increase was suppressed in the obstructed kidney (161 ± 75 and 113 ± 34 fmol/g kidney, respectively), a pattern opposite to what we expected in obstructed kidneys without podocyte injury. Thus, our study indicates that the major source of increased renal ANG II in podocyte injury is filtered angiotensinogen.
Temporal evolution of both premotor and motor cortical tuning properties reflect changes in limb biomechanics
Authors: Suminski Aaron J. , Mardoum Philip , Lillicrap Timothy P. , Hatsopoulos Nicholas G.
Published: February 2015

A prevailing theory in the cortical control of limb movement posits that premotor cortex initiates a high-level motor plan that is transformed by the primary motor cortex (MI) into a low-level motor command to be executed. This theory implies that the premotor cortex is shielded from the motor periphery, and therefore, its activity should not represent the low-level features of movement. Contrary to this theory, we show that both dorsal (PMd) and ventral premotor (PMv) cortexes exhibit population-level tuning properties that reflect the biomechanical properties of the periphery similar to those observed in M1. We recorded single-unit activity from M1, PMd, and PMv and characterized their tuning properties while six rhesus macaques performed a reaching task in the horizontal plane. Each area exhibited a bimodal distribution of preferred directions during execution consistent with the known biomechanical anisotropies of the muscles and limb segments. Moreover, these distributions varied in orientation or shape from planning to execution. A network model shows that such population dynamics are linked to a change in biomechanics of the limb as the monkey begins to move, specifically to the state-dependent properties of muscles. We suggest that, like M1, neural populations in PMd and PMv are more directly linked with the motor periphery than previously thought.
Computational study of synchrony in fields and microclusters of ephaptically coupled neurons
Authors: Stacey R. Greg , Hilbert Lennart , Quail Thomas
Published: February 2015

Neuronal hypersynchrony is implicated in epilepsy and other diseases. The low-frequency, spatially averaged electric fields from many thousands of neurons have been shown to promote synchrony. It remains unclear whether highly transient, spatially localized electric fields from single action potentials (ephaptic coupling) significantly affect spike timing of neighboring cells and in consequence, population synchrony. In this study, we simulated the extracellular potentials and the resulting coupling between neurons in the NEURON environment and generalized their connection rules to create an oscillator network model of a sheet of ephaptically coupled neurons. With the use of both models, we explained several aspects of epileptiform behavior not previously modeled by synaptically coupled networks. Importantly, reduction of neuron spacing induced synchronization via single-spike ephaptic coupling, agreeing with seizure suppression seen clinically and in vitro via extracellular volume adjustment. Further reduction of neuron spacing yielded locally synchronized clusters, providing a mechanism for recent in vitro observations of localized neuronal synchrony in the absence of synaptic and gap-junction coupling.
Formation of model-free motor memories during motor adaptation depends on perturbation schedule
Authors: Orban de Xivry Jean-Jacques , Lefèvre Philippe
Published: February 2015

Motor adaptation to an external perturbation relies on several mechanisms such as model-based, model-free, strategic, or repetition-dependent learning. Depending on the experimental conditions, each of these mechanisms has more or less weight in the final adaptation state. Here we focused on the conditions that lead to the formation of a model-free motor memory (Huang VS, Haith AM, Mazzoni P, Krakauer JW. Neuron 70: 787–801, 2011), i.e., a memory that does not depend on an internal model or on the size or direction of the errors experienced during the learning. The formation of such model-free motor memory was hypothesized to depend on the schedule of the perturbation (Orban de Xivry JJ, Ahmadi-Pajouh MA, Harran MD, Salimpour Y, Shadmehr R. J Neurophysiol 109: 124–136, 2013). Here we built on this observation by directly testing the nature of the motor memory after abrupt or gradual introduction of a visuomotor rotation, in an experimental paradigm where the presence of model-free motor memory can be identified (Huang VS, Haith AM, Mazzoni P, Krakauer JW. Neuron 70: 787–801, 2011). We found that relearning was faster after abrupt than gradual perturbation, which suggests that model-free learning is reduced during gradual adaptation to a visuomotor rotation. In addition, the presence of savings after abrupt introduction of the perturbation but gradual extinction of the motor memory suggests that unexpected errors are necessary to induce a model-free motor memory. Overall, these data support the hypothesis that different perturbation schedules do not lead to a more or less stabilized motor memory but to distinct motor memories with different attributes and neural representations.
Transspinal direct current stimulation immediately modifies motor cortex sensorimotor maps
Authors: Song Weiguo , Truong Dennis Q. , Bikson Marom , Martin John H.
Published: February 2015

Motor cortex (MCX) motor representation reorganization occurs after injury, learning, and different long-term stimulation paradigms. The neuromodulatory approach of transspinal direct current stimulation (tsDCS) has been used to promote evoked cortical motor responses. In the present study, we used cathodal tsDCS (c-tsDCS) of the rat cervical cord to determine if spinal cord activation can modify the MCX forelimb motor map. We used a finite-element method model based on coregistered high-resolution rat MRI and microcomputed tomography imaging data to predict spinal current density to target stimulation to the caudal cervical enlargement. We examined the effects of cathodal and anodal tsDCS on the H-reflex and c-tsDCS on responses evoked by intracortical microstimulation (ICMS). To determine if cervical c-tsDCS also modified MCX somatic sensory processing, we examined sensory evoked potentials (SEPs) produced by wrist electrical stimulation and induced changes in ongoing activity. Cervical c-tsDCS enhanced the H-reflex, and anodal depressed the H-reflex. Using cathodal stimulation to examine cortical effects, we found that cervical c-tsDCS immediately modified the forelimb MCX motor map, with decreased thresholds and an expanded area. c-tsDCS also increased SEP amplitude in the MCX. The magnitude of changes produced by c-tsDCS were greater on the motor than sensory response. Cervical c-tsDCS more strongly enhanced forelimb than hindlimb motor representation and had no effect on vibrissal representation. The finite-element model indicated current density localized to caudal cervical segments, informing forelimb motor selectivity. Our results suggest that c-tsDCS augments spinal excitability in a spatially selective manner and may improve voluntary motor function through MCX representational plasticity.
Sensory-evoked perturbations of locomotor activity by sparse sensory input: a computational study
Authors: Bui Tuan V. , Brownstone Robert M.
Published: February 2015

Sensory inputs from muscle, cutaneous, and joint afferents project to the spinal cord, where they are able to affect ongoing locomotor activity. Activation of sensory input can initiate or prolong bouts of locomotor activity depending on the identity of the sensory afferent activated and the timing of the activation within the locomotor cycle. However, the mechanisms by which afferent activity modifies locomotor rhythm and the distribution of sensory afferents to the spinal locomotor networks have not been determined. Considering the many sources of sensory inputs to the spinal cord, determining this distribution would provide insights into how sensory inputs are integrated to adjust ongoing locomotor activity. We asked whether a sparsely distributed set of sensory inputs could modify ongoing locomotor activity. To address this question, several computational models of locomotor central pattern generators (CPGs) that were mechanistically diverse and generated locomotor-like rhythmic activity were developed. We show that sensory inputs restricted to a small subset of the network neurons can perturb locomotor activity in the same manner as seen experimentally. Furthermore, we show that an architecture with sparse sensory input improves the capacity to gate sensory information by selectively modulating sensory channels. These data demonstrate that sensory input to rhythm-generating networks need not be extensively distributed.
Speech networks at rest and in action: interactions between functional brain networks controlling speech production
Authors: Simonyan Kristina , Fuertinger Stefan
Published: February 2015

Speech production is one of the most complex human behaviors. Although brain activation during speaking has been well investigated, our understanding of interactions between the brain regions and neural networks remains scarce. We combined seed-based interregional correlation analysis with graph theoretical analysis of functional MRI data during the resting state and sentence production in healthy subjects to investigate the interface and topology of functional networks originating from the key brain regions controlling speech, i.e., the laryngeal/orofacial motor cortex, inferior frontal and superior temporal gyri, supplementary motor area, cingulate cortex, putamen, and thalamus. During both resting and speaking, the interactions between these networks were bilaterally distributed and centered on the sensorimotor brain regions. However, speech production preferentially recruited the inferior parietal lobule (IPL) and cerebellum into the large-scale network, suggesting the importance of these regions in facilitation of the transition from the resting state to speaking. Furthermore, the cerebellum (lobule VI) was the most prominent region showing functional influences on speech-network integration and segregation. Although networks were bilaterally distributed, interregional connectivity during speaking was stronger in the left vs. right hemisphere, which may have underlined a more homogeneous overlap between the examined networks in the left hemisphere. Among these, the laryngeal motor cortex (LMC) established a core network that fully overlapped with all other speech-related networks, determining the extent of network interactions. Our data demonstrate complex interactions of large-scale brain networks controlling speech production and point to the critical role of the LMC, IPL, and cerebellum in the formation of speech production network.
The periaqueductal gray and descending pain modulation: why should we study them and what role do they play in chronic pain?
Authors: Hemington Kasey S. , Coulombe Marie-Andrée
Published: February 2015

In this Neuro Forum we discuss the significance of a recent study by Yu et al. ( Neuroimage Clin 6: 100–108, 2014). The authors examined functional connectivity of a key node of the descending pain modulation pathway, the periaqueductal gray (PAG), in chronic back pain patients. Altered PAG connectivity to pain-related regions was found; we place results within the context of recent literature and emphasize the importance of understanding the descending component of pain in pain research.
Altered excitatory and inhibitory inputs to striatal medium-sized spiny neurons and cortical pyramidal neurons in the Q175 mouse model of Huntington's disease
Authors: Indersmitten Tim , Tran Conny H. , Cepeda Carlos , Levine Michael S.
Published: February 2015

The Q175 knockin mouse model of Huntington's disease (HD) carries a CAG trinucleotide expansion of the human mutant huntingtin allele in its native mouse genomic context and recapitulates the genotype more closely than transgenic models. In this study we examined the progression of changes in intrinsic membrane properties and excitatory and inhibitory synaptic transmission, using whole cell patch-clamp recordings of medium-sized spiny neurons (MSNs) in the dorsolateral striatum and cortical pyramidal neurons (CPNs) in layers 2/3 of the primary motor cortex in brain slices from heterozygous (Q175+/−) and homozygous (Q175+/+) mice. Input resistance in MSNs from Q175+/+ and Q175+/− mice was significantly increased compared with wild-type (WT) littermates beginning at 2 mo. Furthermore, the frequency of spontaneous and miniature excitatory postsynaptic currents (EPSCs) was significantly reduced in MSNs from Q175+/+ and Q175+/− mice compared with WTs beginning at 7 mo. In contrast, the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) and IPSC-to-EPSC ratios were increased in MSNs from Q175+/+ mice beginning at 2 mo. Morphologically, significant decreases in spine density of MSNs from Q175+/− and Q175+/+ mice occurred at 7 and 12 mo. In CPNs, sIPSC frequencies and IPSC-to-EPSC ratios were significantly increased in Q175+/− mice compared with WTs at 12 mo. There were no changes in intrinsic membrane properties or morphology. In summary, we show a number of alterations in electrophysiological and morphological properties of MSNs in Q175 mice that are similar to other HD mouse models. However, unlike other models, CPN inhibitory activity is increased in Q175+/− mice, indicating reduced cortical excitability.
Method for 3D Airway Topology Extraction
Authors: Grothausmann Roman , Kellner Manuela , Heidrich Marko , Lorbeer Raoul-Amadeus , Ripken Tammo , Meyer Heiko , Kuehnel Mark P. , Ochs Matthias , Rosenhahn Bodo
Published: February 2015

In lungs the number of conducting airway generations as well as bifurcation patterns varies across species and shows specific characteristics relating to illnesses or gene variations. A method to characterize the topology of the mouse airway tree using scanning laser optical tomography (SLOT) tomograms is presented in this paper. It is used to test discrimination between two types of mice based on detected differences in their conducting airway pattern. Based on segmentations of the airways in these tomograms, the main spanning tree of the volume skeleton is computed. The resulting graph structure is used to distinguish between wild type and surfactant protein (SP-D) deficient knock-out mice.
Subspace Learning via Local Probability Distribution for Hyperspectral Image Classification
Authors: Luo Huiwu , Tang Yuan Yan , Yang Lina
Published: February 2015

The computational procedure of hyperspectral image (HSI) is extremely complex, not only due to the high dimensional information, but also due to the highly correlated data structure. The need of effective processing and analyzing of HSI has met many difficulties. It has been evidenced that dimensionality reduction has been found to be a powerful tool for high dimensional data analysis. Local Fisher’s liner discriminant analysis (LFDA) is an effective method to treat HSI processing. In this paper, a novel approach, called PD-LFDA, is proposed to overcome the weakness of LFDA. PD-LFDA emphasizes the probability distribution (PD) in LFDA, where the maximum distance is replaced with local variance for the construction of weight matrix and the class prior probability is applied to compute the affinity matrix. The proposed approach increases the discriminant ability of the transformed features in low dimensional space. Experimental results on Indian Pines 1992 data indicate that the proposed approach significantly outperforms the traditional alternatives.
Acute Retinal Pigment Epitheliitis: Spectral Domain Optical Coherence Tomography, Fluorescein Angiography, and Autofluorescence Findings
Authors: Aydoğan Tuğba , Güney Esra , Akçay Betül İlkay Sezgin , Bozkurt Tahir Kansu , Ünlü Cihan , Ergin Ahmet
Published: February 2015

A 17-year-old presented with central and paracentral scotomas in his right eye for one week. There was no remarkable medical or ocular history. Blood analyses were within normal range. At presentation both eyes’ best-corrected visual acuities were 20/20. Slit-lamp examination result was normal. Fundus examination revealed yellow-white hypopigmented areas in the macula. Fluorescein angiography (FA) showed hypofluorescence surrounded by ring of hyperfluorescence. Fundus autofluorescence (FAF) was slightly increased. Spectral domain optical coherence tomography (SD-OCT) showed disruption of IS/OS junction with expansion of abnormal hyperreflectivity from retinal pigment epithelium to the outer nuclear layer (ONL). One month later fundus examination showed disappearance of the lesions. FA revealed transmission hyperfluorescence. FAF showed increased autofluorescence and pigment clumping. Hyperreflective band in SD-OCT disappeared. Loss of photoreceptor segment layers was observed in some of the macular lesions. The diagnosis of acute retinal pigment epitheliitis can be challenging after disappearance of fundus findings. FA, FAF, and SD-OCT are important tests for diagnosis after resolution of the disease.
Cellular Responses Evoked by Different Surface Characteristics of Intraosseous Titanium Implants
Authors: Feller Liviu , Jadwat Yusuf , Khammissa Razia A. G. , Meyerov Robin , Schechter Israel , Lemmer Johan
Published: February 2015

The properties of biomaterials, including their surface microstructural topography and their surface chemistry or surface energy/wettability, affect cellular responses such as cell adhesion, proliferation, and migration. The nanotopography of moderately rough implant surfaces enhances the production of biological mediators in the peri-implant microenvironment with consequent recruitment of differentiating osteogenic cells to the implant surface and stimulates osteogenic maturation. Implant surfaces with moderately rough topography and with high surface energy promote osteogenesis, increase the ratio of bone-to-implant contact, and increase the bonding strength of the bone to the implant at the interface. Certain features of implant surface chemistry are also important in enhancing peri-implant bone wound healing. It is the purpose of this paper to review some of the more important features of titanium implant surfaces which have an impact on osseointegration.
Synergistic Activations ofREG IαandREG IβPromoters by IL-6 and Glucocorticoids through JAK/STAT Pathway in Human PancreaticβCells
Authors: Yamauchi Akiyo , Itaya-Hironaka Asako , Sakuramoto-Tsuchida Sumiyo , Takeda Maiko , Yoshimoto Kiyomi , Miyaoka Tomoko , Fujimura Takanori , Tsujinaka Hiroki , Tsuchida Chikatsugu , Ota Hiroyo , Takasawa Shin
Published: February 2015

Reg(Regenerating gene) gene was originally isolated from rat regenerating islets and its encoding protein was revealed as an autocrine/paracrine growth factor forβcells. RatReggene is activated in inflammatory conditions forβcell regeneration. In human, although five functionalREGfamily genes (REG Iα, REG Iβ, REG III, HIP/PAP, andREG IV) were isolated, their expressions inβcells under inflammatory conditions remained unclear. In this study, we found that combined addition of IL-6 and dexamethasone (Dx) inducedREG IαandREG Iβexpression in human 1.1B4βcells. Promoter assay revealed that a signal transducer and activator of transcription- (STAT-) binding site in each promoter ofREG Iα(TGCCGGGAA) andREG Iβ(TGCCAGGAA) was essential for the IL-6+Dx-induced promoter activation. A Janus kinase 2 (JAK2) inhibitor significantly inhibited the IL-6+Dx-inducedREG IαandREG Iβtranscription. Electrophoretic mobility shift assay and chromatin immunoprecipitation revealed that IL-6+Dx stimulation increased STAT3 binding to theREG Iαpromoter. Furthermore, small interfering RNA-mediated targeting of STAT3 blocked the IL-6+Dx-induced expression ofREG IαandREG Iβ. These results indicate that the expression ofREG IαandREG Iβshould be upregulated in humanβcells under inflammatory conditions through the JAK/STAT pathway.
Procoagulatory State in Inflammatory Bowel Diseases Is Promoted by Impaired Intestinal Barrier Function
Authors: Pastorelli Luca , Dozio Elena , Pisani Laura Francesca , Boscolo-Anzoletti Massimo , Vianello Elena , Munizio Nadia , Spina Luisa , Tontini Gian Eugenio , Peyvandi Flora , Corsi Romanelli Massimiliano Marco , Vecchi Maurizio
Published: February 2015

Inflammatory and immune mediated disorders are risk factors for arterial and venous thromboembolism. Inflammatory bowel diseases (IBD) confer an even greater risk of thromboembolic events than other inflammatory conditions. It has been shown that IBD patients display defective intestinal barrier functions. Thus, pathogen-associated molecular patterns (PAMPs) coming from the intestinal bacterial burden might reach systemic circulation and activate innate immunity receptors on endothelial cells and platelets, promoting a procoagulative state. Aim of the study was to test this hypothesis, correlating the presence of circulating PAMPs with the activation of innate immune system and the activation of the coagulatory cascade in IBD patients. Specifically, we studied lipopolysaccharide (LPS), Toll-like receptor (TLR) 2, TLR4, and markers of activated coagulation (i.e., D-Dimer and prothrombin fragmentF1+2) in the serum and plasma of IBD patients. We found that LPS levels are increased in IBD and correlate with TLR4 concentrations; although a mild correlation between LPS and CRP levels was detected, clinical disease activity does not appear to influence circulating LPS. Instead, serum LPS correlates with both D-Dimer andF1+2measurements. Taken together, our data support the role of an impairment of intestinal barrier in triggering the activation of the coagulatory cascade in IBD.
The Impact of a Pure Protein Load on the Glucose Levels in Type 1 Diabetes Patients Treated with Insulin Pumps
Authors: Klupa Tomasz , Benbenek-Klupa Teresa , Matejko Bartlomiej , Mrozinska Sandra , Malecki Maciej T.
Published: February 2015

We aimed to estimate the impact of ingestion of a pure protein load on the glucose levels in T1DM patients treated with insulin pumps. We examined 10 T1DM patients (6 females, mean age—32.3 years, mean HbA1c—6.8%) treated with insulin pumps equipped with a continuous glucose monitoring system (CGMS). In Phase I, baseline insulin infusion was optimized to minimize the differences in fasting glucose levels to less than 30 mg/dL between any two time points between 9 a.m. and 3 p.m. In Phase II, the patients were exposed to single pure protein load. CGMS record was performed and the glucose pattern was defined for 6 hours of each phase. The maximal glucose level increment was similar for the entire duration of the fasting and the protein load test (26.6 versus 27.6 mg/dL, resp.,P<0.78). There was only a borderline difference in change between baseline versus 6th hour glucose (12.5 and 19.0 mg/dL,P=0.04). Glucose variability, assessed by standard deviation of mean glucose levels, was 36.4 and 37.9 mg/dL, respectively (P=0.01). The administration of a pure protein load does not seem to have a clinically significant impact on glucose levels in T1DM patients treated with insulin pumps.
Chemotaxis Away from 4-Chloro-2-nitrophenol, 4-Nitrophenol, and 2,6-Dichloro-4-nitrophenol byBacillus subtilisPA-2
Authors: Arora Pankaj Kumar , Jeong Mi-Jeong , Bae Hanhong
Published: February 2015

Bacterial strain PA-2 exhibits chemotaxis away from 4-chloro-2-nitrophenol, 4-nitrophenol, and 2,6-dichloro-4-nitrophenol. This strain was identified asBacillus subtilison the basis of the 16S rRNA gene sequencing. The drop plate assay and the chemical-in-plug method were used to demonstrate negative chemotactic behavior of strain PA-2. The growth studies showed that strain PA-2 did not utilize 4-chloro-2-nitrophenol, 4-nitrophenol, and 2,6-dichloro-4-nitrophenol as its sole sources of carbon and energy. This is the first report of negative chemotaxis of 4-chloro-2-nitrophenol, 4-nitrophenol, and 2,6-dichloro-4-nitrophenol by any bacterium.
Enhanced Fatigue Strength of Commercially Pure Ti Processed by Rotary Swaging
Authors: ALkhazraji Hasan , El-Danaf Ehab , Wollmann Manfred , Wagner Lothar
Published: February 2015

Fully reversed bending fatigue tests were performed on polished hour-glass specimens of commercially pure titanium grade 1 with three different grain sizes, that were produced by severe plastic deformation (rotary swaging) and subheat treatments, in order to examine the effect of grain size on fatigue. An improvement in fatigue strength was observed, as the polycrystal grain size was refined. The endurance limit stress was shown to depend on the inverse square root of the grain size as described empirically by a type of Hall-Petch relation. The effect of refining grain size on fatigue crack growth is to increase the number of microstructural barriers to the advancing crack and to reduce the slip length ahead of the crack tip, and thereby lower the crack growth rate. It was found that postdeformation annealing above recrystallization temperature could additionally enhance the work-hardening capability and the ductility of the swaged material, which led to a marked reduction in the fatigue notch sensitivity. At the same time, this reduction was accompanied with a pronounced loss in strength. The high cycle fatigue performance was discussed in detail based on microstructure and mechanical properties.
Characterizing Facial Skin Ageing in Humans: Disentangling Extrinsic from Intrinsic Biological Phenomena
Authors: Trojahn Carina , Dobos Gabor , Lichterfeld Andrea , Blume-Peytavi Ulrike , Kottner Jan
Published: February 2015

Facial skin ageing is caused by intrinsic and extrinsic mechanisms. Intrinsic ageing is highly related to chronological age. Age related skin changes can be measured using clinical and biophysical methods. The aim of this study was to evaluate whether and how clinical characteristics and biophysical parameters are associated with each other with and without adjustment for chronological age. Twenty-four female subjects of three age groups were enrolled. Clinical assessments (global facial skin ageing, wrinkling, and sagging), and biophysical measurements (roughness, colour, skin elasticity, and barrier function) were conducted at both upper cheeks. Pearson’s correlations and linear regression models adjusted for age were calculated. Most of the measured parameters were correlated with chronological age (e.g., association with wrinkle score,r=0.901) and with each other (e.g., residual skin deformation and wrinkle score,r=0.606). After statistical adjustment for age, only few associations remained (e.g., mean roughness (Rz) and luminance (L*),  β=-0.507,R2=0.377). Chronological age as surrogate marker for intrinsic ageing has the most important influence on most facial skin ageing signs. Changes in skin elasticity, wrinkling, sagging, and yellowness seem to be caused by additional extrinsic ageing.
Optimal Harvesting Effort for Nonlinear Predictive Control Model for a Single Species Fishery
Authors: Bounkhel Messaoud , Tadj Lotfi
Published: February 2015

We use nonlinear model predictive control to find the optimal harvesting effort of a renewable resource system with a nonlinear state equation that maximizes a nonlinear profit function. A solution approach is proposed and discussed and satisfactory numerical illustrations are provided.
Patient Related Factors Affecting Adherence to Antimalarial Medication in an Urban Estate in Ghana
Authors: Amponsah Alexandria O. , Vosper Helen , Marfo Afia F. A.
Published: February 2015

Our aim was to measure the adherence to Artemisinin based Combination Therapy and to determine patient related factors that affect adherence. Three hundred (300) patients receiving ACT treatment dispensed from the community pharmacy were randomly selected and followed up on the fourth day after the start of their three-day therapy to assess adherence. Adherence was measured by pill count. Quantitative interviews using a semistructured questionnaire were used to assess patients’ knowledge and beliefs on malaria and its treatment. Adherence levels to the ACTs were 57.3%. Patient related factors that affected adherence to ACTs were patients’ knowledge on the dosage (P=0.007; v=0.457), efficacy (P=0.009; v=0.377), and side effects (P=0.000; v=0.403) of the ACTs used for the management of malaria, patients’ awareness of the consequences of not completing the doses of antimalarial dispensed (P=0.001; v=0.309), and patients’ belief that “natural remedies are safer than medicines” and “prescribers place too much trust in medicines.” There was no significant relationship between adherence and patients’ knowledge on the causes, signs, and symptoms of malaria. There is the need for pharmacy staff to stress on these variables when counseling patients on antimalarials as these affect adherence levels.
Aquaporin 5 Expression in Mouse Mammary Gland Cells Is Not Driven by Promoter Methylation
Authors: Arbeithuber Barbara , Thuenauer Roland , Gravogl Yasmin , Balogi Zsolt , Römer Winfried , Sonnleitner Alois , Tiemann-Boege Irene
Published: February 2015

Several studies have revealed that aquaporins play a role in tumor progression and invasion. In breast carcinomas, high levels of aquaporin 5 (AQP5), a membrane protein involved in water transport, have been linked to increased cell proliferation and migration, thus facilitating tumor progression. Despite the potential role of AQP5 in mammary oncogenesis, the mechanisms controlling mammary AQP5 expression are poorly understood. In other tissues, AQP5 expression has been correlated with its promoter methylation, yet, very little is known about AQP5 promoter methylation in the mammary gland. In this work, we used the mouse mammary gland cell line EpH4, in which we controlled AQP5 expression via the steroid hormone dexamethasone (Dex) to further investigate mechanisms regulating AQP5 expression. In this system, we observed a rapid drop of AQP5 mRNA levels with a delay of several hours in AQP5 protein, suggesting transcriptional control of AQP5 levels. Yet, AQP5 expression was independent of its promoter methylation, or to the presence of negative glucocorticoid receptor elements (nGREs) in its imminent promoter region, but was rather influenced by the cell proliferative state or cell density. We conclude that AQP5 promoter methylation is not a universal mechanism for AQP5 regulation and varies on cell and tissue type.
First Reported Case of Isolated Persistent Genital Arousal Disorder in a Male
Authors: Stevenson Bradford J. , Köhler Tobias S.
Published: February 2015

Introduction. Persistent genital arousal disorder (PGAD) is a newly recognized disorder in women. It is described as unwanted, persistent feelings of genital arousal unrelated to sexual desire and not relieved by orgasm. Its prevalence is estimated to approach 1% of young women. Until now, this has not been described in men.Aim. Here we present a case of a 27-year-old male with symptoms consistent with PGAD and describe successful treatment.Methods. A 27-year-old male presented to urology clinic with the chief complain of persistent feelings of impending orgasm. He reported a sensation similar, but not identical, to sexual arousal that did not occur in the setting of sexual thoughts or desire. Orgasm alleviated the arousal for only a short time after which the symptoms would return. This had become quite bothersome to him.Results. After assessing for a neurological cause and finding none, the patient was started on paroxetine daily with complete resolution of symptoms.Conclusions. PGAD is a disorder previously described only in females. Although symptoms of PGAD have been described in a male as part of another disorder complex, this report describes the first reported isolated case in a male and the successful treatment.
Volterra Type Integral Operators and Composition Operators on Model Spaces
Authors: Mengestie Tesfa
Published: February 2015

We study some mapping properties of Volterra type integral operators and composition operators on model spaces. We also discuss and give out a couple of interesting open problems in model spaces where any possible solution of the problems can be used to study a number of other operator theoretic related problems in the spaces.
Valproate Prescribing in Women of Childbearing Age: An Audit of Clinical Practice
Authors: Atturu Harini , Odelola Adedeji
Published: February 2015

Background. Evidence is accruing regarding the risks of valproate exposure in women of childbearing age. Recommendations have recently been made for a higher standard of prenatal counselling and prescribing practice in respect of valproate use in this patient group. Aim and Method. A reaudit was carried out to review the standard of clinical discussion around teratogenic
risk and pregnancy planning offered to women of child-bearing age prescribed valproate.
Case notes and prescription charts of women 45 years old or less were examined and compared with the results of a previous audit in 2005. Results. The use of valproate was increased overall by 64% and there was an 18% increase in off-label
valproate use. The rate of clinical discussion carried out during commencement
declined from 70% to 35% and at annual review from 50% to 22%. There was less clinical discussion in outpatients and in older patients. More than 40% of doctors surveyed were not confident about giving information to women. Clinical Implication. There is a need for a multidisciplinary approach and action at Healthcare Trust level, to
increase awareness and reduce risks associated with valproate prescribing in childbearing
women.
Design and Implementation of Three‐Level DC‐DC Converter with Golden Section Search Based MPPT for the Photovoltaic Applications
Authors: Balakishan Chouki , Sandeep N. , Aware M. V.
Published: February 2015

In many photovoltaic (PV) energy conversion systems,
nonisolated DC‐DC converters with high voltage gain are
desired. The PV exhibits a nonlinear power characteristic which
greatly depends on the environmental conditions. Hence in order to
draw maximum available power various algorithms are used with
PV voltage/current or both as an input for the maximum power
point tracking (MPPT) controller. In this paper, golden section
search (GSS) based MPPT control and its application with three‐level
DC‐DC boost converter for MPPT are demonstrated. The
three‐level boost converter provides the high voltage transfer
which enables the high power PV system to work with low size
inductors with high efficiency. The balancing of the voltage across
the two capacitors of the converter and MPPT is achieved using
a simple duty cycle based voltage controller. Detailed simulation
of three‐level DC‐DC converter topology with GSS algorithm is
carried out in MATLAB/SIMULINK platform. The validation of
the proposed system is done by the experiments carried out on
hardware prototype of 100 W converter with low cost AT’mega328
controller as a core controller. From the results, the proposed
system suits as one of the solutions for PV based generation system
and the experimental results show high performance, such as a
conversion efficiency of 94%.
Inhibitory Properties of Aqueous Ethanol Extracts of Propolis on Alpha-Glucosidase
Authors: Zhang Hongcheng , Wang Guangxin , Beta Trust , Dong Jie
Published: February 2015

The objective of the present study was to evaluate the inhibitory properties of various extracts of propolis on alpha-glucosidase from baker’s yeast and mammalian intestine. Inhibitory activities of aqueous ethanol extracts of propolis were determined by using 4-nitrophenyl-D-glucopyranoside, sucrose and maltose as substrates, and acarbose as a positive reference. All extracts were significantly effective in inhibitingα-glucosidase from baker’s yeast and rat intestinal sucrase in comparison with acarbose (P<0.05). The 75% ethanol extracts of propolis (75% EEP) showed the highest inhibitory effect onα-glucosidase and sucrase and were a noncompetitive inhibition mode. 50% EEP, 95%, EEP and 100% EEP exhibited a mixed inhibition mode, while water extracts of propolis (WEP) and 25% EEP demonstrated a competitive inhibition mode. Furthermore, WEP presented the highest inhibitory activity against maltase. These results suggest that aqueous ethanol extracts of propolis may be used as nutraceuticals for the regulation of postprandial hyperglycemia.
The Effect ofHydrocotyle sibthorpioidesLam. Extracts onIn VitroDengue Replication
Authors: Husin Fitrien , Chan Yean Yean , Gan Siew Hua , Sulaiman Siti Amrah , Shueb Rafidah Hanim
Published: February 2015

Objective. To investigate the potential effect ofHydrocotyle sibthorpioidesLam. (H. sibthorpioides) extracts againstin vitrodengue viral replication.Methods. The cytotoxicity ofH. sibthorpioideswas evaluated using a cell viability assay. Cells were pre- and posttreated with water and methanol extracts ofH. sibthorpioides, and the viral inhibitory effect was investigated by observing the morphological changes, which were further confirmed by plaque assay.Results. The methanolic extract cytotoxicity was higher in Vero and C6/36 cells than the cytotoxicity of the water extract. Preincubation of the cells withH. sibthorpioidesextract showed nonexistent to mild prophylactic effects. The posttreatment of Vero cells withH. sibthorpioidesmethanolic extract presented higher antidengue activities when compared with the water extract. Surprisingly, posttreatment of C6/36 cells resulted in an enhancement of viral replication.Conclusion.H. sibthorpioideshad variable effects on dengue viral replication, depending on the treatment, cell lines, and solvent types. This study provides important novel insights on the phytomedicinal properties ofH. sibthorpioidesextracts on dengue virus.
Synthesis and Structural Studies of a New Complex of Di[hexabromobismuthate (III)] 2,5-Propylaminepyrazinium [C10H28N4]Bi2Br10
Authors: Touati Mohamed El Mehdi , Boughzala Habib
Published: February 2015

A new organic-inorganic hybrid material, [C10H28N4]Bi2Br10, has been synthesized and characterized. The compound crystallizes in monoclinic P21/c space group with a = 11.410(4) Å, b = 11.284(4) Å, c = 12.599(3) Å, β = 115.93(2)°, and V = 1458.8(8) Å3. The structure consists of discrete dinuclear [Bi2Br10]4− anions and [C10H28N4]4+ cations. It consists of a 0-D anion built up of edge-sharing bioctahedron. The crystal net contains N–H⋯Br hydrogen bonds. The differential scanning calorimetry (DSC) reveals an irreversible phase transition at −17°C. The frontier molecular orbital and the energy gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) calculation allow the classification of the material as an insulator.
HPLC-Fluorescent Analysis of Memantine: An Investigation on Fluorescent Derivative Formation
Authors: Prapatpong Pornpan , Techa-In Thanayu , Padungpuak Wantaporn , Buranaphalin Sawanya , Suntornsuk Leena
Published: February 2015

Memantine is an N-methyl-D-aspartate receptor antagonist recommended for treatment of Alzheimer’s disease. Due to the lack of chromophores/fluorophores in memantine molecule, this work focuses on a novel procedure for memantine-fluorescent derivative formation enabling it to be monitored by a fluorescence detector. 4-(N-Chloroformylmethyl-N-methyl)amino-7-N,N-dimethylaminosulphonyl 2,1,3-benzoxadiazole (DBD-COCl) was chosen as a fluorescent probe since the carbonyl chloride of DBD-COCl could easily react with the amine on memantine to form the fluorescent derivative. The derivatization was achieved at 5 : 1 of DBD-COCl and memantine, at 60°C for 50 min. Structure elucidation from mass spectrometry and infrared spectroscopy spectra confirmed the amide bond of memantine-DBD-COCl. The derivative was stable up to 24 h and could be monitored by high performance liquid chromatography (HPLC) coupled with a fluorescence detector using a VertiSep GES C18 column, acetonitrile and water (80 : 20) as the mobile phase with a flow rate of 1 mL/min using the excitation and emission wavelengths at 430 and 520 nm, respectively. The derivative was eluted at 4.50 min and was separated from the DBD-COCl. Preliminary validation data reveals good linearity (r2≥0.99), repeatability (%RSD < 0.54) and accuracy (%Rbetween 94 and 119%) with a limit of detection of 0.79 μg/mL.
A Hybrid Finite Difference Method for Pricing Two-Asset Double Barrier Options
Authors: Hsiao Y. L. , Shen S. Y. , Wang Andrew M. L.
Published: February 2015

The pricing of the two-asset double barrier option is modeled as an initial-boundary value problem of the two-dimensional Black-Scholes partial differential equation. We use the hybrid finite different method to solve the problem. The hybrid method is a combination of the Laplace transform and a finite difference method. It is more efficient than a traditional finite difference method to obtain a solution without a step-by-step process. The method is implemented on a computer. Two numerical examples are calculated to verify the performance of the hybrid method. In our numerical examples, the convergence rate of the method is approximately two. We conclude that the method is efficient for pricing two-asset barrier options.
Correlation between Clinical Characteristics and Chest Computed Tomography Findings of Pulmonary Cryptococcosis
Authors: Yamakawa Hideaki , Yoshida Masahiro , Yabe Masami , Baba Emiri , Okuda Keitaro , Fujimoto Shota , Katagi Hiroaki , Ishikawa Takeo , Takagi Masamichi , Kuwano Kazuyoshi
Published: February 2015

Objective. The aim of this study was to review HIV-negative patients with pulmonary cryptococcosis to analyze the correlations between clinical characteristics and chest computed tomography (CT) findings.Methods. We retrospectively analyzed medical records of 16 HIV-negative patients with pulmonary cryptococcosis diagnosed at our institution, and clinical characteristics of the patients with nodules or masses without ground-glass attenuation (GGA)/consolidation type were compared with those of patients with inclusive GGA or consolidation type.Results. Host status was immunocompromised (81.2%) in most of the patients, and 6 (37.5%) were asymptomatic. The most frequent radiologic abnormalities on chest CT scans were one or more nodules (87.5%), GGA (37.5%), and consolidations (18.8%). Most lesions were located in the lower lung. Levels of hemoglobin and platelets were significantly lower in patients with inclusive GGA or consolidation type. Although the differences were not significant, patients with inclusive GGA or consolidation type tended to have a C-reactive protein level of ≥1.0 mg/dL.Conclusion. If a patient with anemia and thrombocytopenia shows GGA or consolidation in the lung, pulmonary cryptococcosis should be given careful consideration.