bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of induced leg muscle fatigue on exertional dyspnea in healthy subjects
Authors: Sharma Pramod , Morris Norman R. , Adams Lewis
Published: November 2014

The genesis of dyspnea is complex. It appears to be related to central respiratory drive although prevailing leg fatigue could independently potentiate dyspnea. We hypothesized that experimentally induced leg fatigue generates more intense exertional dyspnea for a given level of ventilatory drive. Following familiarization, 19 healthy subjects (32.2 ± 7.6 yr; 11 men) performed a 5-min treadmill test (speed: ∼4 km/h; grade: ∼25%) on two separate days randomized between control (C) and experimentally induced leg fatigue (E) achieved by repeated knee extension against 40% body weight until task failure. Oxygen uptake (V̇o2, l/min), carbon dioxide output (V̇co2, l/min), ventilation (V̇e, l/min), and respiratory rate (fR) were measured breath by breath. Heart rate (HR) and perceived dyspnea intensity (0–10 numerical scale) were recorded continuously. Data were averaged over 30-s intervals. Exertional dyspnea during E was statistically significantly higher (E vs. C: 4.2 ± 0.2 vs. 3.4 ± 0.2, P < 0.001) and accompanied by a significant increase in V̇e (E vs. C: 61.7 ± 3.7 vs. 55.3 ± 2.8, P = 0.005) and fR (E vs. C: 26.7 ± 1.0 vs. 24.2 ± 1.3, P = 0.036). Dyspnea following E remained significantly higher after allowing for the V̇e confound (ANCOVA, P = 0.003). V̇o2, V̇co2, and HR were not significantly different between two conditions. However, the slopes for dyspnea vs. V̇o2 and dyspnea vs. V̇e were similar between E and C, which suggested that gain in dyspnea per unit change in V̇o2 or V̇e was not altered by leg fatigue. These findings support the hypothesis that the intensity of exertional dyspnea is exacerbated by peripheral afferent information from fatigued leg muscles.
Fluence Rate in UV Photoreactor for Disinfection of Water: Isotropically Radiating Cylinder
Authors: Ilinsky Roman , Ulyanov Andrey
Published: November 2014

The calculation of fluence rate in the photochemical reactor using ultraviolet (UV) radiation for disinfection of water for the case, when a cylinder of infinite length is used as a light source, has been considered. Such a cylinder is filled with an isotropically radiating medium. The dependence of the fluent rate on the diameter of the radiating cylinder has been analytically analyzed. The limiting case when the diameter of the radiating cylinder tends to zero has been considered and the notion of “effective interval” has been introduced. Based on this notion, the comparison of fluence rates for the cylinders of finite and infinite lengths has been performed. In the calculations of fluence rate, it is advisable to use the Chebyshev method for the operations of numerical integration.
Paradigm Shift in the Management of the Atrophic Posterior Maxilla
Authors: Nedir Rabah , Nurdin Nathalie , Khoury Paul , El Hage Marc , Abi Najm Semaan , Bischof Mark
Published: November 2014

When the posterior maxilla is atrophic, the reference standard of care would be to perform sinus augmentation with an autologous bone graft through the lateral approach and delayed implant placement. However, placement of short implants with the osteotome sinus floor elevation technique and without graft can be proposed for an efficient treatment of clinical cases with a maxillary residual bone height of 4 to 8 mm. The use of grafting material is recommended only when the residual bone height is ≤4 mm. Indications of the lateral sinus floor elevation are limited to cases with a residual bone height ≤ 2 mm and fused corticals, uncompleted healing of the edentulous site, and absence of flat cortical bone crest or when the patient wishes to wear a removable prosthesis during the healing period. The presented case report illustrates osteotome sinus floor elevation with and without grafting and simultaneous implant placement in extreme conditions: atrophic maxilla, short implant placement, reduced healing time, and single crown rehabilitation. After 6 years, all placed implants were functional with an endosinus bone gain.
Acaricidal Activity of Petroleum Ether Extract of Leaves ofTetrastigma leucostaphylum(Dennst.) Alston againstRhipicephalus (Boophilus) annulatus
Authors: Krishna T. P. Adarsh , Krishna T. P. Ajeesh , Chithra N. D. , Deepa P. E. , Darsana U. , Sreelekha K. P. , Juliet Sanis , Nair Suresh N. , Ravindran Reghu , Ajith Kumar K. G. , Ghosh Srikanta
Published: November 2014

The acaricidal activity of the petroleum ether extract of leaves ofTetrastigma leucostaphylum(Dennst.) Alston (family: Vitaceae) againstRhipicephalus (Boophilus) annulatuswas assessed using adult immersion test (AIT). The per cent of adult mortality, inhibition of fecundity, and blocking of hatching of eggs were studied at different concentrations. The extract at 10% concentration showed 88.96% inhibition of fecundity, 58.32% of adult tick mortality, and 50% inhibition of hatching. Peak mortality rate was observed after day 5 of treatment. Mortality of engorged female ticks, inhibition of fecundity, and hatching of eggs were concentration dependent. The LC50value of the extract againstR. (B.) annulatuswas 10.46%. The HPTLC profiling of the petroleum ether extract revealed the presence of at least seven polyvalent components. In the petroleum ether extract, nicotine was identified as one of the components up to a concentration of 5.4%. However, nicotine did not reveal any acaricidal activity up to 20000 ppm (2%). Coconut oil, used as diluent for dissolving the extract, did not reveal any acaricidal effects. The results are indicative of the involvement of synergistic or additive action of the bioactive components in the tick mortality and inhibition of the oviposition.
Role ofUlva lactucaExtract in Alleviation of Salinity Stress on Wheat Seedlings
Authors: Ibrahim Wael M. , Ali Refaat M. , Hemida Khaulood A. , Sayed Makram A.
Published: November 2014

Seaweeds are potentially excellent sources of highly bioactive materials that could represent useful leads in the alleviation of salinity stress. The effects of presoaking wheat grains in water extract ofUlva lactucaon growth, some enzymatic activities, and protein pattern of salinized plants were investigated in this study. Algal presoaking of grains demonstrated a highly significant enhancement in the percentage of seed germination and growth parameters. The activity of superoxide dismutase (SOD) and catalase (CAT) increased with increasing the algal extract concentration while activity of ascorbate peroxidase (APX) and glutathione reductase (GR) was decreased with increasing concentration of algal extract more than 1% (w/v). The protein pattern of wheat seedling showed 12 newly formed bands as result of algal extract treatments compared with control. The bioactive components inU. lactucaextract such as ascorbic acid, betaine, glutathione, and proline could potentially participate in the alleviation of salinity stress. Therefore, algal presoaking is proved to be an effective technique to improve the growth of wheat seedlings under salt stress conditions.
PELP1 Overexpression in the Mouse Mammary Gland Results in the Development of Hyperplasia and Carcinoma
Authors: Cortez Valerie , Samayoa Cathy , Zamora Andrea , Martinez Lizatte , Tekmal Rajeshwar R. , Vadlamudi Ratna K.
Published: November 2014

Estrogen receptor (ER) coregulator overexpression promotes carcinogenesis and/or progression of endocrine related-cancers in which steroid hormones are powerful mitogenic agents. Recent studies in our laboratory, as well as others, demonstrated that the estrogen receptor coregulator PELP1 is a proto-oncogene. PELP1 interactions with histone demethylase KDM1 play a critical role in its oncogenic functions and PELP1 is a prognostic indicator of decreased survival in patients with breast cancer. However, the in vivo significance of PELP1 deregulation during initiation and progression of breast cancer remains unknown. We generated an inducible, mammary gland-specific PELP1-expressing transgenic (Tg) mouse (MMTVrtTA-TetOPELP1). We found more proliferation, extensive side branching, and precocious differentiation in PELP1-overexpressing mammary glands than in control glands. Aged MMTVrtTA-TetOPELP1 Tg mice had hyperplasia and preneoplastic changes as early as 12 weeks, and ER-positive mammary tumors occurred at a latency of 14 to 16 months. Mechanistic studies revealed that PELP1 deregulation altered expression of a number of known ER target genes involved in cellular proliferation (cyclin D1, CDKs) and morphogenesis (EGFR, MMPs) and such changes facilitated altered mammary gland morphogenesis and tumor progression. Furthermore, PELP1 was hyper-phosphorylated at its CDK phosphorylation site, suggesting an autocrine loop involving the CDK–cyclin D1–PELP1 axis in promoting mammary tumorigenesis. Treatment of PELP1 Tg mice with a KDM1 inhibitor significantly reduced PELP1-driven hyperbranching, reversed alterations in cyclin D1 expression levels, and reduced CDK-driven PELP1 phosphorylation. These results further support the hypothesis that PELP1 deregulation has the potential to promote breast tumorigenesis in vivo and represent a novel model for future investigation into molecular mechanisms of PELP1-mediated tumorigenesis. Cancer Res; 74(24); 7395–405. ©2014 AACR.
Changes in BAI1 and Nestin Expression Are Prognostic Indicators for Survival and Metastases in Breast Cancer and Provide Opportunities for Dual Targeted Therapies
Authors: Meisen Walter Hans , Dubin Samuel , Sizemore Steven T. , Mathsyaraja Haritha , Thies Katie , Lehman Norman L. , Boyer Peter , Jaime-Ramirez Alena Cristina , Elder J. Bradley , Powell Kimerly , Chakravarti Arnab , Ostrowski Michael C. , Kaur Balveen
Published: November 2014

The 2-year survival rate of patients with breast cancer brain metastases is less than 2%. Treatment options for breast cancer brain metastases are limited, and there is an unmet need to identify novel therapies for this disease. Brain angiogenesis inhibitor 1 (BAI1) is a GPCR involved in tumor angiogenesis, invasion, phagocytosis, and synaptogenesis. For the first time, we identify that BAI1 expression is significantly reduced in breast cancer and higher expression is associated with better patient survival. Nestin is an intermediate filament whose expression is upregulated in several cancers. We found that higher Nestin expression significantly correlated with breast cancer lung and brain metastases, suggesting both BAI1 and Nestin can be therapeutic targets for this disease. Here, we demonstrate the ability of an oncolytic virus, 34.5ENVE, to target and kill high Nestin-expressing cells and deliver Vstat120 (extracellular fragment of BAI1). Finally, we created two orthotopic immune-competent murine models of breast cancer brain metastases and demonstrated 34.5ENVE extended the survival of immune-competent mice bearing intracranial breast cancer tumors. Mol Cancer Ther; 14(1); 307–14. ©2014 AACR.
Repurposing the Antihelmintic Mebendazole as a Hedgehog Inhibitor
Authors: Larsen Andrew R. , Bai Ren-Yuan , Chung Jon H. , Borodovsky Alexandra , Rudin Charles M. , Riggins Gregory J. , Bunz Fred
Published: November 2014

The hedgehog (Hh) signaling pathway is activated in many types of cancer and therefore presents an attractive target for new anticancer agents. Here, we show that mebendazole, a benzamidazole with a long history of safe use against nematode infestations and hydatid disease, potently inhibited Hh signaling and slowed the growth of Hh-driven human medulloblastoma cells at clinically attainable concentrations. As an antiparasitic, mebendazole avidly binds nematode tubulin and causes inhibition of intestinal microtubule synthesis. In human cells, mebendazole suppressed the formation of the primary cilium, a microtubule-based organelle that functions as a signaling hub for Hh pathway activation. The inhibition of Hh signaling by mebendazole was unaffected by mutants in the gene that encodes human Smoothened (SMO), which are selectively propagated in cell clones that survive treatment with the Hh inhibitor vismodegib. Combination of vismodegib and mebendazole resulted in additive Hh signaling inhibition. Because mebendazole can be safely administered to adults and children at high doses over extended time periods, we propose that mebendazole could be rapidly repurposed and clinically tested as a prospective therapeutic agent for many tumors that are dependent on Hh signaling. Mol Cancer Ther; 14(1); 3–13. ©2014 AACR.
Prognostic and Predictive Roles of MGMT Protein Expression and Promoter Methylation in Sporadic Pancreatic Neuroendocrine Neoplasms
Authors: Schmitt Anja Maria , Pavel Marianne , Rudolph Thomas , Dawson Heather , Blank Annika , Komminoth Paul , Vassella Erik , Perren Aurel
Published: November 2014

Background/Aims: O6-methylguanine-methyltransferase (MGMT) is an important enzyme of DNA repair. MGMT promoter methylation is detectable in a subset of pancreatic neuroendocrine neoplasms (pNEN). A subset of pNEN responds to the alkylating agent temozolomide (TMZ). We wanted to correlate MGMT promoter methylation with MGMT protein loss in pNEN, correlate the findings with clinico-pathological data and determine the role of MGMT to predict response to TMZ chemotherapy. Methods: We analysed a well-characterized collective of 141 resected pNEN with median follow-up of 83 months for MGMT protein expression and promoter methylation using methylation-specific PCR (MSP). A second collective of 10 metastasized, pretreated and progressive patients receiving TMZ was used to examine the predictive role of MGMT by determining protein expression and promoter methylation using primer extension-based quantitative PCR. Results: In both collectives there was no correlation between MGMT protein expression and promoter methylation. Loss of MGMT protein was associated with an adverse outcome, this prognostic value, however, was not independent from grade and stage in multivariate analysis. Promoter hypermethylation was significantly associated with response to TMZ. Conclusion: Loss of MGMT protein expression is associated with adverse outcome in a surgical series of pNET. MGMT promoter methylation could be a predictive marker for TMZ chemotherapy in pNEN, but further, favourably prospective studies will be needed to confirm this result and before this observation can influence clinical routine.
Development of the Terminal Nerve System in the Shark Scyliorhinus canicula
Authors: Quintana-Urzainqui Idoia , Anadón Ramón , Candal Eva , Rodríguez-Moldes Isabel
Published: November 2014

The nervus terminalis (or terminal nerve) system was discovered in an elasmobranch species more than a century ago. Over the past century, it has also been recognized in other vertebrate groups, from agnathans to mammals. However, its origin, functions or relationship with the olfactory system are still under debate. Despite the abundant literature about the nervus terminalis system in adult elasmobranchs, its development has been overlooked. Studies in other vertebrates have reported newly differentiated neurons of the terminal nerve system migrating from the olfactory epithelium to the telencephalon as part of a ‘migratory mass' of cells associated with the olfactory nerve. Whether the same occurs in developing elasmobranchs (adults showing anatomically separated nervus terminalis and olfactory systems) has not yet been determined. In this work we characterized for the first time the development of the terminal nerve and ganglia in an elasmobranch, the lesser spotted dogfish (Scyliorhinus canicula), by means of tract-tracing techniques combined with immunohistochemical markers for the terminal nerve (such as FMRF-amide peptide), for the developing components of the olfactory system (Gα0 protein, GFAP, Pax6), and markers for early postmitotic neurons (HuC/D) and migrating immature neurons (DCX). We discriminated between embryonic olfactory and terminal nerve systems and determined that both components may share a common origin in the migratory mass. We also localized the exact point where they split off near the olfactory nerve-olfactory bulb junction. The study of the development of the terminal nerve system in a basal gnathostome contributes to the knowledge of the ancestral features of this system in vertebrates, shedding light on its evolution and highlighting the importance of elasmobranchs for developmental and evolutionary studies.
Antithrombotic Therapy in Carotid Artery Stenosis: An Update
Authors: Paciaroni Maurizio , Bogousslavsky Julien
Published: November 2014

Carotid stenosis is generally associated with high risks of stroke and vascular events. In asymptomatic and symptomatic patients, with or without revascularization, optimal managements of carotid artery stenosis require the use of medications or lifestyle modifications (stopping smoking and monitoring hypertension, hyperlipidemia, and diabetes) to control the processes associated with atheroma to reduce the risk of embolic events. Moreover, antiplatelet therapy should be considered. There is little evidence that antiplatelet therapy is beneficial in preventing stroke or the progression of stenosis in asymptomatic patients, whereas, evidence of a benefit from antiplatelet therapy for secondary prevention of recurrent stroke in symptomatic patients with carotid atherosclerosis is more robust. Also, in patients undergoing carotid endarterectomy, perioperative antithrombotic therapy should include aspirin, while the addition of clopidogrel should be decided case-by-case. Furthermore, perioperative antithrombotic therapy in patients undergoing carotid stenting should consist a combination of aspirin plus clopidogrel. i 2014 S. Karger AG, Basel
Onset and Phoneme Awareness and Its Relationship to Letter Knowledge in German-Speaking Preschool Children
Authors: Schaefer Blanca , Bremer Maike , Herrmann Frank
Published: November 2014

Objectives: The aim was to explore whether word-initial onset awareness is acquired before phoneme awareness and whether onset complexity influences performance on identification tasks. In addition, the relationship between onset and phoneme awareness and letter knowledge was investigated. Method: In this study, 22 monolingual German-speaking preschool children aged 5;00-5;11 were tested. Onset, phoneme identification, and letter knowledge tasks were administered. The children were presented with pictures of word pairs. Both words in each pair shared a single-consonant onset, a two-consonant onset cluster or the first consonant of a consonant cluster. The children were asked to pronounce the shared sound(s). Additionally, they were asked to name all 26 upper-case letters. Results: Onset awareness tasks were significantly easier to complete than phoneme awareness tasks. However, no influence of onset complexity on onset awareness performance was found. Moreover, letter knowledge correlated with all phonological awareness tasks. Conclusions: The results corroborate that phoneme awareness develops already at preschool age irrespective of explicit literacy tuition. Nevertheless, letter knowledge is closely related and should be linked to onset/phoneme awareness tasks. © 2014 S. Karger AG, Basel
A Patient-Invented Maneuver to Alleviate Freezing of Gait Using a Foot Loop Band
Authors: Okuma Yasuyuki
Published: November 2014

Freezing of gait (FOG) is a disabling gait disorder in parkinsonian patients characterized by the inability to initiate or continue locomotion. I herein present a 65-year-old man with Parkinson's disease who invented a unique method (foot loop band) to alleviate FOG, which has not been previously described in the literature. The mechanisms to alleviate FOG include not only facilitating mechanical weight shift, but also restoring internal cueing and driving motor commands for gait initiation. This patient-invented maneuver may be recommended for patients having intractable FOG, because it is portable, cheap and safe.
Agouti-Related Protein Neuron Circuits That Regulate Appetite
Authors: Sternson Scott M. , Atasoy Deniz
Published: November 2014

New tools for mapping and manipulating molecularly defined neural circuits have improved the understanding of how the central nervous system regulates appetite. Studies that focused on Agouti-related protein neurons, a starvation-sensitive hypothalamic population, have identified multiple circuit elements that can elicit or suppress feeding behavior. Distinct axon projections of this neuron population point to different circuits that regulate long-term appetite, short-term feeding, or visceral malaise-mediated anorexia. Here, we review recent studies examining these neural circuits that control food intake.
Inflammasome Activation by Mitochondrial Oxidative Stress in Macrophages Leads to the Development of Angiotensin II–Induced Aortic Aneurysm
Authors: Usui Fumitake , Shirasuna Koumei , Kimura Hiroaki , Tatsumi Kazuki , Kawashima Akira , Karasawa Tadayoshi , Yoshimura Koichi , Aoki Hiroki , Tsutsui Hiroko , Noda Tetsuo , Sagara Junji , Taniguchi Shun’ichiro , Takahashi Masafumi
Published: November 2014

Objective—

Abdominal aortic aneurysm (AAA) is considered a chronic inflammatory disease; however, the molecular basis underlying the sterile inflammatory response involved in the process of AAA remains unclear. We previously showed that the inflammasome, which regulates the caspase-1–dependent interleukin-1β production, mediates the sterile cardiovascular inflammatory responses. Therefore, we hypothesized that the inflammasome is a key mediator of initial inflammation in AAA formation.

Approach and Results—

Apoptosis-associated speck-like protein containing a caspase recruitment domain is highly expressed in adventitial macrophages in human and murine AAA tissues. Using an established mouse model of AAA induced by continuous infusion of angiotensin II in
Apoe
–/–
mice, NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain, and caspase-1 deficiency in
Apoe
–/–
mice were shown to decrease the incidence, maximal diameter, and severity of AAA along with adventitial fibrosis and inflammatory responses significantly, such as inflammatory cell infiltration and cytokine expression in the vessel wall. NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain, and caspase-1 deficiency in
Apoe
–/–
mice also reduced elastic lamina degradation and metalloproteinase activation in the early phase of AAA formation. Furthermore, angiotensin II stimulated generation of mitochondria-derived reactive oxygen species in the adventitial macrophages, and this mitochondria-derived reactive oxygen species generation was inhibited by NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain, and caspase-1 deficiency. In vitro experiments revealed that angiotensin II stimulated the NLRP3 inflammasome activation and subsequent interleukin-1β release in macrophages, and this activation was mediated through an angiotensin type I receptor/mitochondria-derived reactive oxygen species–dependent pathway.

Conclusions—

Our results demonstrate the importance of the NLRP3 inflammasome in the initial inflammatory responses in AAA formation, indicating its potential as a novel therapeutic target for preventing AAA progression.
Iron, Inflammation, and Early Death in Adults With Sickle Cell Disease
Authors: van Beers Eduard J. , Yang Yanqin , Raghavachari Nalini , Tian Xin , Allen Darlene T. , Nichols James S. , Mendelsohn Laurel , Nekhai Sergei , Gordeuk Victor R. , Taylor James G. , Kato Gregory J.
Published: November 2014

Rationale:

Patients with sickle cell disease (SCD) have markers of chronic inflammation, but the mechanism of inflammation and its relevance to patient survival are unknown.

Objective:

To assess the relationship between iron, inflammation, and early death in SCD.

Methods and Results:

Using peripheral blood mononuclear cell transcriptome profile hierarchical clustering, we classified 24 patients and 10 controls in clusters with significantly different expression of genes known to be regulated by iron. Subsequent gene set enrichment analysis showed that many genes associated with the high iron cluster were involved in the toll-like receptor system (TLR4, TLR7, and TLR8) and inflammasome complex pathway (NLRP3, NLRC4, and CASP1). Quantitative PCR confirmed this classification and showed that ferritin light chain, TLR4, and interleukin-6 expression were >100-fold higher in patients than in controls (
P
<0.001). Further linking intracellular iron and inflammation, 14 SCD patients with a ferroportin Q248H variant that causes intracellular iron accumulation had significantly higher levels of interleukin-6 and C-reactive protein compared with 14 matched SCD patients with the wild-type allele (
P
<0.05). Finally, in a cohort of 412 patients followed for a median period of 47 months (interquartile range, 24–82), C-reactive protein was strongly and independently associated with early death (hazard ratio, 3.0; 95% confidence interval, 1.7–5.2;
P
<0.001).

Conclusions:

Gene expression markers of high intracellular iron in patients with SCD are associated with markers of inflammation and mortality. The results support a model in which intracellular iron promotes inflammatory pathways, such as the TLR system and the inflammasome, identifying important new pathways for additional investigation.
Canonical Wnt Signaling Regulates Atrioventricular Junction Programming and Electrophysiological Properties
Authors: Gillers Benjamin S. , Chiplunkar Aditi , Aly Haytham , Valenta Tomas , Basler Konrad , Christoffels Vincent M. , Efimov Igor R. , Boukens Bastiaan J. , Rentschler Stacey
Published: November 2014

Rationale:

Proper patterning of the atrioventricular canal (AVC) is essential for delay of electrical impulses between atria and ventricles, and defects in AVC maturation can result in congenital heart disease.

Objective:

To determine the role of canonical Wnt signaling in the myocardium during AVC development.

Methods and Results:

We used a novel allele of β-catenin that preserves β-catenin’s cell adhesive functions but disrupts canonical Wnt signaling, allowing us to probe the effects of Wnt loss of function independently. We show that the loss of canonical Wnt signaling in the myocardium results in tricuspid atresia with hypoplastic right ventricle associated with the loss of AVC myocardium. In contrast, ectopic activation of Wnt signaling was sufficient to induce formation of ectopic AV junction-like tissue as assessed by morphology, gene expression, and electrophysiological criteria. Aberrant AVC development can lead to ventricular pre-excitation, a characteristic feature of Wolff–Parkinson–White syndrome. We demonstrate that postnatal activation of Notch signaling downregulates canonical Wnt targets within the AV junction. Stabilization of β-catenin protein levels can rescue Notch-mediated ventricular pre-excitation and dysregulated ion channel gene expression.

Conclusions:

Our data demonstrate that myocardial canonical Wnt signaling is an important regulator of AVC maturation and electric programming upstream of Tbx3. Our data further suggest that ventricular pre-excitation may require both morphological patterning defects, as well as myocardial lineage reprogramming, to allow robust conduction across accessory pathway tissue.
Intravenous Autologous Bone Marrow Mononuclear Stem Cell Therapy for Ischemic Stroke
Authors: Prasad Kameshwar , Sharma Alka , Garg Ajay , Mohanty Sujata , Bhatnagar Shinjini , Johri Sharat , Singh Kunwar Karni , Nair Velu , Sarkar Ravi Shankar , Gorthi Sankar Prasad , Hassan Kaukab Maqbool , Prabhakar Sudesh , Marwaha Neelam , Khandelwal Niranjan , Misra Usha Kant , Kalita Jayantee , Nityanand Soniya
Published: November 2014

Background and Purpose—

Pilot studies have suggested benefit from intravenous administration of bone marrow mononuclear stem cells (BMSCs) in stroke. We explored the efficacy and safety of autologous BMSCs in subacute ischemic stroke.

Methods—

This was a phase II, multicenter, parallel group, randomized trial with blinded outcome assessment that included 120 patients. Patients with subacute ischemic stroke were randomly assigned to the arm that received intravenous infusion of autologous BMSCs or to control arm. Coprimary clinical efficacy outcomes were Barthel Index score and modified Rankin scale at day 180. Secondary outcomes were change in infarct volume, National Institute of Health Stroke Scale (NIHSS) at day 90 and 180. Main safety outcomes were adverse events, any new area of
18
fluorodeoxyglucose positron emission tomography uptake in any body part over 365 days.

Results—

Fifty-eight patients received a mean of 280.75 million BMSCs at median of 18.5 days after stroke onset. There was no significant difference between BMSCs arm and control arm in the Barthel Index score (63.1 versus 63.6;
P
=0.92), modified Rankin scale shift analysis (
P
=0.53) or score >3 (47.5% versus 49.2%;
P
=0.85), NIHSS score (6.3 versus 7.0;
P
=0.53), change in infarct volume (−11.1 versus −7.36;
P
=0.63) at day 180. Adverse events were also similar in the 2 arms, and no patient showed any new area of
18
fluorodeoxyglucose uptake.

Conclusions—

With the methods used, results of this hitherto first randomized controlled trial indicate that intravenous infusion of BMSCs is safe, but there is no beneficial effect of treatment on stroke outcome.

Clinical Trial Registration—

URLs:
http://ctri.nic.in/Clinicaltrials
and
http://www.clinicaltrials.gov
. Unique identifiers: CTRI-ROVCTRI/2008/091/0004 and NCT0150177.
Spatiotemporal Conditional Inference and Hypothesis Tests for Neural Ensemble Spiking Precision
Authors: Harrison Matthew T. , Amarasingham Asohan , Truccolo Wilson
Published: November 2014

The collective dynamics of neural ensembles create complex spike patterns with many spatial and temporal scales. Understanding the statistical structure of these patterns can help resolve fundamental questions about neural computation and neural dynamics. Spatiotemporal conditional inference (STCI) is introduced here as a semiparametric statistical framework for investigating the nature of precise spiking patterns from collections of neurons that is robust to arbitrarily complex and nonstationary coarse spiking dynamics. The main idea is to focus statistical modeling and inference not on the full distribution of the data, but rather on families of conditional distributions of precise spiking given different types of coarse spiking. The framework is then used to develop families of hypothesis tests for probing the spatiotemporal precision of spiking patterns. Relationships among different conditional distributions are used to improve multiple hypothesis-testing adjustments and design novel Monte Carlo spike resampling algorithms. Of special note are algorithms that can locally jitter spike times while still preserving the instantaneous peristimulus time histogram or the instantaneous total spike count from a group of recorded neurons. The framework can also be used to test whether first-order maximum entropy models with possibly random and time-varying parameters can account for observed patterns of spiking. STCI provides a detailed example of the generic principle of conditional inference, which may be applicable to other areas of neurostatistical analysis.
Foundations of Support Constraint Machines
Authors: Gnecco Giorgio , Gori Marco , Melacci Stefano , Sanguineti Marcello
Published: November 2014

The mathematical foundations of a new theory for the design of intelligent agents are presented. The proposed learning paradigm is centered around the concept of constraint, representing the interactions with the environment, and the parsimony principle. The classical regularization framework of kernel machines is naturally extended to the case in which the agents interact with a richer environment, where abstract granules of knowledge, compactly described by different linguistic formalisms, can be translated into the unified notion of constraint for defining the hypothesis set. Constrained variational calculus is exploited to derive general representation theorems that provide a description of the optimal body of the agent (i.e., the functional structure of the optimal solution to the learning problem), which is the basis for devising new learning algorithms. We show that regardless of the kind of constraints, the optimal body of the agent is a support constraint machine (SCM) based on representer theorems that extend classical results for kernel machines and provide new representations. In a sense, the expressiveness of constraints yields a semantic-based regularization theory, which strongly restricts the hypothesis set of classical regularization. Some guidelines to unify continuous and discrete computational mechanisms are given so as to accommodate in the same framework various kinds of stimuli, for example, supervised examples and logic predicates. The proposed view of learning from constraints incorporates classical learning from examples and extends naturally to the case in which the examples are subsets of the input space, which is related to learning propositional logic clauses.
Optimizing the Representation of Orientation Preference Maps in Visual Cortex
Authors: Hughes Nicholas J. , Goodhill Geoffrey J.
Published: November 2014

The colorful representation of orientation preference maps in primary visual cortex has become iconic. However, the standard representation is misleading because it uses a color mapping to indicate orientations based on the HSV (hue, saturation, value) color space, for which important perceptual features such as brightness, and not just hue, vary among orientations. This means that some orientations stand out more than others, conveying a distorted visual impression. This is particularly problematic for visualizing subtle biases caused by slight overrepresentation of some orientations due to, for example, stripe rearing. We show that displaying orientation maps with a color mapping based on a slightly modified version of the HCL (hue, chroma, lightness) color space, so that primarily only hue varies between orientations, leads to a more balanced visual impression. This makes it easier to perceive the true structure of this seminal example of functional brain architecture.
Toward a Multisubject Analysis of Neural Connectivity
Authors: Oates C. J. , Costa L. , Nichols T. E.
Published: November 2014

Directed acyclic graphs (DAGs) and associated probability models are widely used to model neural connectivity and communication channels. In many experiments, data are collected from multiple subjects whose connectivities may differ but are likely to share many features. In such circumstances, it is natural to leverage similarity among subjects to improve statistical efficiency. The first exact algorithm for estimation of multiple related DAGs was recently proposed by Oates, Smith, Mukherjee, and Cussens ( 2014 ). In this letter we present examples and discuss implications of the methodology as applied to the analysis of fMRI data from a multisubject experiment. Elicitation of tuning parameters requires care, and we illustrate how this may proceed retrospectively based on technical replicate data. In addition to joint learning of subject-specific connectivity, we allow for heterogeneous collections of subjects and simultaneously estimate relationships between the subjects themselves. This letter aims to highlight the potential for exact estimation in the multisubject setting.
Headedness in Word Formation and Lexical Semantics: Evidence from Italiot and Cypriot (University of Patras, 2014)
Authors: Andreou Marios
Published: November 2014

In this contribution, I offer a summary of my 2014 Ph.D. dissertation from the University of Patras on headedness in word formation and lexical semantics.
Dal greco antico al greco moderno: alcuni aspetti dell’evoluzione morfosintattica (Università degli Studi di Firenze, 2012)
Authors: Zinzi Mariarosaria
Published: November 2014

In this contribution, I offer a summary of my 2012 Ph.D. dissertation from the University of Florence (Firenze) on given morphosyntactic changes between Ancient Greek and Modern Greek.
A Constructionist View of Complex Interactions between Inflection and Derivation: The Case of SMG and Griko (University of Patras, 2013)
Authors: Koutsoukos Nikos
Published: November 2014

In this contribution, I offer a summary of my 2013 Ph.D. dissertation from the University of Patras on inflection and derivation from a Construction Morphology standpoint.
Additions to Cuban Selaginella (Selaginellaceae)
Authors: Valdespino Ivan Alberto , Lopez Christian , Araujo Goes Luiz
Published: November 2014

Three new Selaginella species from Cuba, S. myriostachya, S. nanophylla and S. phiara, are described, illustrated with Scanning Electron Micrographs, and compared to similar species. Selaginella myriostachya and S. phiara are from Pinar del Río province, the latter one is also found in Isla de la Juventud special municipality, both in the western part of Cuba. In contrast, S. nanophylla is from Guantánamo, Holguín, and Santiago de Cuba provinces in the eastern part of the island. Information about their habitat, distribution, and conservation status is provided. Selaginella myriostachya lives in cave openings on limestone rocks in Mogotes formations; S. nanophylla is one of the smallest plants reported for the genus and seems adapted to serpentine soils. Selaginella phiara has idioblasts with several bright, papillae on the upper surface of median leaves and lower surface of lateral leaves, and short hairs on the upper surface of the apices of median leaves.
Heterodera guangdongensis n. sp. (Nematoda: Heteroderinae) from bamboo in Guangdong Province, China—a new cyst nematode in the Cyperi group
Authors: ZHUO KAN , WANG HONGHONG , ZHANG HONGLING , LIAO JINLING
Published: November 2014

Heterodera guangdongensis n. sp. is described from bamboo (Phyllostachys pubescens Mazel) based on morphology and molecular analyses of rRNA D2D3 expansion domains of large subunit (LSU D2D3) and internal transcribed spacer (ITS) sequences. This new species can be classified in the Cyperi group. Cysts are characterized by a prominent, ambifenestrate vulval cone with weak underbridge, a vulva-anus distance of 28.9–35.9 μm and a vulval slit of 31.1–41.0 μm, but without bullae. Females are characterized by a 25.1–27.6 μm stylet with rounded knobs sloping slightly posteriorly. Males are characterized by a 21.5–23.0 μm stylet with knobs slightly projecting or flat anteriorly, lateral field with four lines, and a 22.0–26.0 μm spicule with bifurcate tip. Second-stage juveniles are characterized by a 19.3–21.3 stylet with slightly projecting or anteriorly flattened knobs, lateral field with three lines, a 41.7–61.3 μm tail with finely rounded terminus and hyaline portion forming 43.0–57.1% of the tail length. Molecular analyses show that the species has unique D2D3 and ITS rRNA sequences and RFLP-ITS-rRNA profiles.
Cool-Season Precipitation Patterns Associated with Teleconnection Interactions in the United States
Authors: Wise Erika K. , Wrzesien Melissa L. , Dannenberg Matthew P. , McGinnis David L.
Published: November 2014

Seasonal climate forecasts are regularly published to provide decision makers with insights on upcoming climate conditions. Precipitation forecasts, in particular, are useful for fields such as agriculture and water resources. Projections frequently cite a single climate oscillation such as El Niño–Southern Oscillation (ENSO) or the North Atlantic Oscillation (NAO) when suggesting whether a region will be wetter or drier than normal. The complex climate system is composed of a multitude of simultaneous oceanic and atmospheric oscillations, however. Through the study of five atmospheric-pressure-based oscillations, their interactions, and associated precipitation values, this research demonstrates the wide variety of precipitation patterns that can arise when different phases of prominent climate modes occur. Results show that incorporating other Northern Hemisphere teleconnections can dampen or shift expected ENSO and NAO impact patterns. These results indicate that seasonal precipitation projections may be improved by incorporating multiple, regionally important teleconnection indices into the forecast.
Video methodologies in research: Unlocking the complexities of occupation
Authors: Bailliard Antoine L.
Published: November 2014

Background.

Video methods are used by numerous academic disciplines researching human action. Occupational therapists and scientists have primarily employed video data to enumerate subcomponents of occupational behaviour, to conduct reliability tests, and to study clinical reasoning. There is a gap in the literature using video data to explore complex dimensions of typical occupational behaviour.

Purpose.

This paper aims to encourage the use of video methodology beyond its current state in research on occupation.

Key Issues.

Drawing on recent theoretical developments in the literature and empirical illustrations from a video-based project with migrants, this paper demonstrates the potential contributions of video data to understandings of identity, the physical environment, the stream of occupations, and collective occupations. The paper also discusses the unique advantages and richness of collecting video data in comparison to interviews and traditional observations. The challenges in employing video methodologies are discussed.

Implications.

Video research offers unprecedented opportunities to study human occupation in incommensurable detail as it unfolds through sociocultural and physical environments.
Using the mouse grimace scale to assess pain associated with routine ear notching and the effect of analgesia in laboratory mice
Authors: Miller AL , Leach MC
Published: November 2014

Social housing is recommended where possible for laboratory mice. In order to achieve this, mice must be individually identifiable. Although, various methods are available, permanent identification is often required, such as ear notching. This method is likely to be painful and to date there is limited literature on pain assessment and alleviation for this routine husbandry practice. Here we aimed to determine if the mouse grimace scale (MGS) could be used to assess pain in C57BL/6 mice following routine ear notching. Langford et al. found that very acute noxious stimuli (i.e. < 10 min in duration) did not produce a change in MGS score in comparison to baseline. Here, no significant difference was found between MGS scores at baseline and immediately post ear notching, potentially indicating that the pain associated with ear notching is either too acute to assess using the MGS tool or the practice is not painful. Studies in other species indicate that ear notching is painful, therefore, unless we can confidently conclude that the process of ear notching is not painful, we should err on the side of caution and assume it is painful due to the large number of mice ear-notched and potential welfare consequences. Alternative methods of assessing pain following this routine practice should be used in order to assess both the potential pain in mice, and the effectiveness of analgesics or local anaesthetics to relieve any associated pain.
Are Leftists More Emotion-Driven Than Rightists? The Interactive Influence of Ideology and Emotions on Support for Policies
Authors: Pliskin Ruthie , Bar-Tal Daniel , Sheppes Gal , Halperin Eran
Published: November 2014

Although emotions and ideology are important factors guiding policy support in conflict, their interactive influence remains unclear. Based on prior findings that ideological leftists’ beliefs are more susceptible to change than rightists’ beliefs, we tested a somewhat counterintuitive extension that leftists would be more susceptible to influence by their emotional reactions than rightists. In three laboratory studies, inducing positive and negative emotions affected Jewish–Israeli leftists’, but not rightists’, support for conciliatory policies toward an adversarial (Studies 1 and 3) and a non-adversarial (Study 2) outgroup. Three additional field studies showed that positive and negative emotions were related to leftists’, but not rightists’, policy support in positive as well as highly negative conflict-related contexts, among both Jewish (Studies 4 and 5) and Palestinian (Study 6) citizens of Israel. Across different conflicts, emotions, conflict-related contexts, and even populations, leftists’ policy support changed in accordance with emotional reactions more than rightists’ policy support.
‘Movement’ justice and the capabilities approach
Authors: Threadcraft Shatema
Published: November 2014

The capability approach described by Amartya Sen illustrates the multiple aspects of injustice in such fields as racially motivated sexual harassment or segregation in urban space. In response to Sen’s pointing out that we should focus not simply on institutions but also on the social realizations they engender, the article illustrates the function of the natural and social environments for racial groups in affecting the distribution of resources necessary to secure justice.
Interlaminar properties of carbon fiber composite laminates with resin transfer molding/prepreg co-curing process
Authors: Ma Xuqiang , Gu Yizhuo , Li Yanxia , Li Min , Zhang Zuoguang
Published: November 2014

Co-cured resin transfer molding (co-RTM) process, which combined resin transfer molding (RTM) process with prepreg process, was adopted to fabricate carbon fiber/epoxy resin laminates. The compatibility between prepreg resin and injection resin was investigated by nano-indention test and glass transition temperature with different resin mixture ratios. Processing quality of co-RTM laminates was evaluated by optical micrographs and thickness dimension. Mode I ( GIC) and mode II ( GIIC) interlaminar fracture toughness tests were measured to characterize the mechanical properties of co-cured interface. Moreover, prepreg resin impregnation into fiber fabric was studied by fluorescent micrographs and its influences on processing quality and interlaminar property were analyzed. The results show that good resin compatibility can be obtained between two resin systems. There are no obvious defects except for some resin rich region at co-cured interface for co-RTM laminates. The GIC and GIIC test values of co-RTM laminates locate between those of prepreg laminates and RTM laminates, which exhibit no weak effect occurs at co-cured interface. In addition, increasing holding temperature and prolonging holding time promote prepreg resin impregnation effect, improving the fiber compaction and interlaminar performances at co-cured interface. Therefore, co-RTM process is a hopeful technique for manufacturing composite structure with effective cost saving.
CEC’s Standards for Classifying the Evidence Base of Practices in Special Education
Authors: Cook Bryan G. , Buysse Virginia , Klingner Janette , Landrum Timothy J. , McWilliam R. A. , Tankersley Melody , Test David W.
Published: November 2014

As an initial step toward improving the outcomes of learners with disabilities, special educators have formulated guidelines for identifying evidence-based practices. We describe the Council of Exceptional Children’s new set of standards for identifying evidence-based practices in special education and how they (a) were systematically vetted by expert special education researchers through a Delphi study, (b) demonstrated adequate inter-rater reliability in a pilot study, (c) delineate specific criteria in many areas and provide flexibility to tailor other criteria, (d) provide an integrated set of standards for classifying the evidence base of practices based on findings from both group comparison and single-subject studies, and (e) can be applied by independent special education researchers. We conclude by noting limitations to the standards, briefly comparing these new standards with other evidence-based practice standards, and providing recommendations for future research and for refining the standards.