bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient treatment of breast cancer xenografts with multifunctionalized iron oxide nanoparticles combining magnetic hyperthermia and anti-cancer drug delivery
Authors: Kossatz Susanne , Grandke Julia , Couleaud Pierre , Latorre Alfonso , Aires Antonio , Crosbie-Staunton Kieran , Ludwig Robert , Dähring Heidi , Ettelt Volker , Lazaro-Carrillo Ana , Calero Macarena , Sader Maha , Courty José , Volkov Yuri , Prina-Mello Adriele , Villanueva Angeles , Somoza Álvaro , Cortajarena Aitziber L , Miranda Rodolfo , Hilger Ingrid 
Published: May 2015

Abstract
Introduction
Tumor cells can effectively be killed by heat, e.g. by using magnetic hyperthermia. The main challenge in the field, however, is the generation of therapeutic temperatures selectively in the whole tumor region. We aimed to improve magnetic hyperthermia of breast cancer by using innovative nanoparticles which display a high heating potential and are functionalized with a cell internalization and a chemotherapeutic agent to increase cell death.

Methods
The superparamagnetic iron oxide nanoparticles (MF66) were electrostatically functionalized with either Nucant multivalent pseudopeptide (N6L; MF66-N6L), doxorubicin (DOX; MF66-DOX) or both (MF66-N6LDOX). Their cytotoxic potential was assessed in a breast adenocarcinoma cell line MDA-MB-231. Therapeutic efficacy was analyzed on subcutaneous MDA-MB-231 tumor bearing female athymic nude mice.

Results
All nanoparticle variants showed an excellent heating potential around 500 W/g Fe in the alternating magnetic field (AMF, conditions: H = 15.4 kA/m, f = 435 kHz). We could show a gradual inter- and intracellular release of the ligands, and nanoparticle uptake in cells was increased by the N6L functionalization. MF66-DOX and MF66-N6LDOX in combination with hyperthermia were more cytotoxic to breast cancer cells than the respective free ligands. We observed a substantial tumor growth inhibition (to 40% of the initial tumor volume, complete tumor regression in many cases) after intratumoral injection of the nanoparticles in vivo. The proliferative activity of the remaining tumor tissue was distinctly reduced.

Conclusion
The therapeutic effects of breast cancer magnetic hyperthermia could be strongly enhanced by the combination of MF66 functionalized with N6L and DOX and magnetic hyperthermia. Our approach combines two ways of tumor cell killing (magnetic hyperthermia and chemotherapy) and represents a straightforward strategy for translation into the clinical practice when injecting nanoparticles intratumorally.
Alzheimer’s disease progression by geographical region in a clinical trial setting
Authors: Henley David B , Dowsett Sherie A , Chen Yun-Fei , Liu-Seifert Hong , Grill Joshua D , Doody Rachelle S , Aisen Paul , Raman Rema , Miller David S , Hake Ann M , Cummings Jeffrey 
Published: May 2015

Abstract
Introduction
To facilitate enrollment and meet local registration requirements, sponsors have increasingly implemented multi-national Alzheimer’s disease (AD) studies. Geographic regions vary on many dimensions that may affect disease progression or its measurement. To aid researchers designing and implementing Phase 3 AD trials, we assessed disease progression across geographic regions using placebo data from four large, multi-national clinical trials of investigational compounds developed to target AD pathophysiology.

Methods
Four similarly-designed 76 to 80 week, randomized, double-blind placebo-controlled trials with nearly identical entry criteria enrolled patients aged ≥55 years with mild or moderate NINCDS/ADRDA probable AD. Descriptive analyses were performed for observed mean score and observed mean change in score from baseline at each scheduled visit. Data included in the analyses were pooled from the intent-to-treat placebo-assigned overall (mild and moderate) AD dementia populations from all four studies. Disease progression was assessed as change from baseline for each of 5 scales - the AD Assessment Scale-cognitive subscale (ADAS-cog11), the AD Cooperative Study- Activities of Daily Living Scale (ADCS-ADL), Mini-Mental State Examination (MMSE), the Clinical Dementia Rating scored by the sum of boxes method (CDR-SB), and the Neuropsychiatric Inventory (NPI).

Results
Regions were heterogeneous at baseline. At baseline, disease severity as measured by ADAS-cog11, ADCS-ADL, and CDR-SB was numerically worse for Eastern Europe/Russia compared with other regions. Of all regional populations, Eastern Europe/Russia showed the greatest cognitive and functional decline from baseline; Japan, Asia and/or S. America/Mexico showed the least cognitive and functional decline.

Conclusions
These data suggest that in multi-national clinical trials, AD progression or its measurement may differ across geographic regions; this may be in part due to heterogeneity across populations at baseline. The observed differences in AD progression between outcome measures across geographic regions may generalize to 'real-world' clinic populations, where heterogeneity is the norm.

Trial registrations
ClinicalTrials.gov NCT00594568 – IDENTITY. Registered 11 January 2008.
ClinicalTrials.gov NCT00762411 – IDENTITY2. Registered 26 September 2008
ClinicalTrials.gov NCT00905372 – EXPEDITION. Registered 18 May 2009
ClinicalTrials.gov NCT00904683 – EXPEDITION2. Registered 18 May 2009
Once an entrepreneur, always an entrepreneur? The impacts of skills developed before, during and after college on firm start-ups
Authors: Orazem Peter F , Jolly Robert , Yu Li 
Published: May 2015

Abstract
By allowing agents to switch from entrepreneurship to wage work and vice versa over the life cycle, this study proposes a dynamic Jacks-of-All-Trades (JAT) model where entrepreneurs invest in highly varied skills to manage their business. We simultaneously endogenize human capital investment and occupational decisions. Using the survey data of Iowa State alumni graduating between 1982 and 2006, we find that the probability of selecting a broad curriculum, having a more varied career, and becoming an entrepreneur are jointly positively correlated. Academic diversity is found to be initially important in starting a business shortly after completing schooling, but its importance declines over time.
Wage returns to mid-career investments in job training through employer supported course enrollment: evidence for Canada
Authors: Ci Wen , Galdo Jose , Voia Marcel , Worswick Christopher 
Published: May 2015

AbstractUsing longitudinal data for Canada, we analyze the incidence and wage returns to employer supported course enrollment for men and women. Availability of confidential data, along with a relatively rich set of observable covariates, lead us to the estimation of difference-in-differences matching models of the effect of employer supported course enrolment on wages. The estimated average treatment effects on the treated range from 5.5 to 7.2 percent for men and 7.1 to 9.0 for women. While high-skilled workers show disproportionately higher rates of participation in employer-supported training, we observe no wage premiums for these types of workers. Statistically significant positive wage returns are found, on the other hand, for low-skilled workers.JEL codes:C14, I20, J24, J31, M53
Extraction methods for uncertain inference rules by ant colony optimization
Authors: Chen Ling , Sun Yun , Zhu Yuanguo 
Published: May 2015

Abstract
In recent years, the research on data mining methods has received increasing attention. In this paper, we design an uncertain system with the extracted uncertain inference rules to solve the classification problems in data mining. And then, two extraction methods integrated with ant colony optimization are proposed for the generation of the uncertain inference rules. Finally, two applications are given to verify the effectiveness and superiority of the proposed methods.
α-synuclein and synapsin III cooperatively regulate synaptic function in dopamine neurons
Authors: Zaltieri Michela , Grigoletto Jessica , Longhena Francesca , Navarria Laura , Favero Gaia , Castrezzati Stefania , Colivicchi Maria Alessandra , Della Corte Laura , Rezzani Rita , Pizzi Marina , Benfenati Fabio , Spillantini Maria Grazia , Missale Cristina , Spano PierFranco , Bellucci Arianna 
Published: May 2015

ABSTRACT
The main neuropathological features of Parkinson's disease are dopaminergic nigrostriatal neuron degeneration, and intraneuronal and intraneuritic proteinaceous inclusions named Lewy bodies and Lewy neurites, respectively, which mainly contain α-synuclein (α-syn, also known as SNCA). The neuronal phosphoprotein synapsin III (also known as SYN3), is a pivotal regulator of dopamine neuron synaptic function. Here, we show that α-syn interacts with and modulates synapsin III. The absence of α-syn causes a selective increase and redistribution of synapsin III, and changes the organization of synaptic vesicle pools in dopamine neurons. In α-syn-null mice, the alterations of synapsin III induce an increased locomotor response to the stimulation of synapsin-dependent dopamine overflow, despite this, these mice show decreased basal and depolarization-dependent striatal dopamine release. Of note, synapsin III seems to be involved in α-syn aggregation, which also coaxes its increase and redistribution. Furthermore, synapsin III accumulates in the caudate and putamen of individuals with Parkinson's disease. These findings support a reciprocal modulatory interaction of α-syn and synapsin III in the regulation of dopamine neuron synaptic function.
The MAL protein is crucial for proper membrane condensation at the ciliary base, which is required for primary cilium elongation
Authors: Reales Elena , Bernabé-Rubio Miguel , Casares-Arias Javier , Rentero Carles , Fernández-Barrera Jaime , Rangel Laura , Correas Isabel , Enrich Carlos , Andrés Germán , Alonso Miguel A. 
Published: May 2015

ABSTRACT
The base of the primary cilium contains a zone of condensed membranes whose importance is not known. Here, we have studied the involvement of MAL, a tetraspanning protein that exclusively partitions into condensed membrane fractions, in the condensation of membranes at the ciliary base and investigated the importance of these membranes in primary cilium formation. We show that MAL accumulates at the ciliary base of epithelial MDCK cells. Knockdown of MAL expression resulted in a drastic reduction in the condensation of membranes at the ciliary base, the percentage of ciliated cells and the length of the cilia, but did not affect the docking of the centrosome to the plasma membrane or produce missorting of proteins to the pericentriolar zone or to the membrane of the remaining cilia. Rab8 (for which there are two isoforms, Rab8A and Rab8b), IFT88 and IFT20, which are important components of the machinery of ciliary growth, were recruited normally to the ciliary base of MAL-knockdown cells but were unable to elongate the primary cilium correctly. MAL, therefore, is crucial for the proper condensation of membranes at the ciliary base, which is required for efficient primary cilium extension.
Two New Sesquiterpenoids from the Root of Strophanthus divaricatus
Authors: Chen Neng-Hua , Zhang Yu-Bo , Li Zhen-Hua , Jiang Jian-Wei , Li Guo-Qiang , Wang Guo-Cai , Li Yao-Lan 
Published: May 2015

Abstract
Two new sesquiterpenoids, strophanthoids A and B (1 and 2), along with seven known cardiac glycosides were isolated from the roots of Strophanthus divaricatus. Their structures were elucidated on the basis of extensive analyses by IR, HR-ESI-MS, NMR, and single-crystal X-ray diffraction. And the new compounds were tested cytotoxic activities on the tumor cells SK-MEL-110 and SK-MEL-28.
Clinical use of cold atmospheric pressure argon plasma in chronic leg ulcers: A pilot study
Authors: Ulrich C. , Kluschke F. , Patzelt A. , Vandersee S. , Czaika V.A. , Richter H. , Bob A. , Hutten J. von , Painsi C. , Hüge R. , Kramer A. , Assadian O. , Lademann J. , Lange-Asschenfeldt B. 
Published: May 2015

Objective: In the age of multiresistant microbes and the increasing lack of efficient antibiotics, conventional antiseptics play a critical role in the prevention and therapy of wound infections. Recent studies have demonstrated the antiseptic effects of cold atmospheric pressure plasma (APP). In this pilot, study we investigate the overall suitability of one of the first APP sources for wound treatment focusing on its potential antimicrobial effects. Method: The wound closure rate and the bacterial colonisation of the wounds were investigated. Patients suffering from chronic leg ulcers were treated in a clinical controlled monocentric trial with either APP or octenidine (OCT). In patients who presented with more than one ulceration in different locations, one was treated with APP and the other one with OCT. Each group was treated three times a week over a period of two weeks. The antimicrobial efficacy was evaluated immediately after and following two weeks of treatment. Results: Wounds treated with OCT showed a significantly higher microbial reduction (64%) compared to wounds treated with APP (47%) immediately after the treatment. Over two weeks of antiseptic treatment the bacterial density was reduced within the OCT group (-35%) compared to a slight increase in bacterial density in the APP-treated group (+12%). Clinically, there were no signs of delayed wound healing observed in either group and both treatments were well tolerated. Conclusion: The immediate antimicrobial effects of the APP prototype source were almost comparable to OCT without any signs of cytotoxicity. This pilot study is limited by current configurations of the plasma source, where the narrow plasma beam made it difficult to cover larger wound surface areas and in order to avoid untreated areas of the wound bed, smaller wounds were assigned to the APP-treatment group. This limits the significance of AAP-related effects on the wound healing dynamics, as smaller wounds tend to heal faster than larger wounds. However, clinical wound healing studies on a larger scale now seem justifiable. A more advanced plasma source prototype allowing the treatment of larger wounds will address APP's influence on healing dynamics, synergetic treatment with current antiseptics and effects on multiresistant bacteria.
Variáveis que influenciam no uso da bicicleta e as crenças da teoria do comportamento planejado
Authors: Da Silveira Mariana Oliveira , Maia Maria Leonor Alves 
Published: May 2015

<p>Pesquisas sobre bicicleta que trabalham o componente ‘comportamento’ vêm ganhando destaque no intuito de entender as barreiras e os motivadores ao uso deste modo de transporte e ajudam a planejar melhores formas de estimular seu uso. O objetivo deste artigo é apresentar um panorama das variáveis que influenciam no uso da bicicleta e classificá-las junto às crenças e constructos da Teoria do Comportamento Planejado (TCP). Este panorama foi baseado em pesquisa da base SCOPUS e em artigos de anais e periódicos, teses e dissertações nacionais, o qual, além de enumerar fatores que influenciam no uso da bicicleta, servirá de apoio às pesquisas que pretendem aplicar a Teoria do Comportamento Planejado na avaliação de comportamentos de uso deste modo de transporte. As variáveis ‘tempo de deslocamento com o uso da bicicleta’, ‘condições meteorológicas’, ‘segurança do trânsito’, ‘infraestrutura cicloviária’ e ‘comportamento no trânsito entre motoristas e ciclistas’ foram as que mais se destacaram, de acordo com o levantamento bibliográfico, na interferência de intenção e de comportamento de uso da bicicleta.</p><p> </p>
Physical Demands of Multimodal Training Competitions and Their Relationship to Measures of Performance
Authors: Jagim Andrew R. , Rader Owen , Jones Margaret T. , Oliver Jonathan M. 
Published: May 2015

Abstract
Jagim, AR, Rader, O, Jones, MT, and Oliver, JM. Physical demands of multimodal training competitions and their relationship to measures of performance. J Strength Cond Res 31(5): 1212–1220, 2017—The purpose of this study was to identify the physical demands of multimodal training (MMT) competitions and to determine the extent of their relationship to select measures of performance. Eighteen (>1.5 years of strength training experience) men (n = 10) and women (n = 8) (mean ± SD; age: 37.8 ± 10.6 years, height: 172.8 ± 8 cm, weight: 77.4 ± 13.2 kg, 16.6 ± 6% body fat) with experience performing MMT participated in a simulated MMT competition. All participants were assessed for body composition, countermovement vertical jump, and aerobic capacity during baseline testing. All participants then participated in a simulated MMT-style competition on a separate day within 10 days of baseline testing. The simulated MMT-style competition consisted of 3 events with 90 minutes of recovery allowed in between events. During the events, changes in blood lactate (La), heart rate (HR), and estimated V̇o
2 were recorded. Bivariate (Pearson) correlations were computed to determine if a relationship existed between traditional measures of performance and those of the MMT-style competition. Significance was set at p ≤ 0.05. Mean change in La ranged between 9 and 12 mmol·L−1 during the events. Mean HR and estimated V̇o
2 values ranged from 145 to 172 b·min−1 and 24 to 35 ml·kg−1·min−1, respectively, during the events. A strong correlation was observed (r = −0.722; p < 0.001) between aerobic capacity and time to completion for event 1. There was a strong correlation between lean body mass and lower-body strength performance (r = 0.882; p < 0.001) and time to completion for event 3 (r = −0.792; p < 0.001). A strong correlation was observed between lower-body power and time to completion for event 1 (r = −0.755; p < 0.001) and event 3 (r = −0.818; p < 0.001). Based on the results of this study, MMT-style competitions appear to be physically demanding activities performed at a high intensity with a great involvement of the anaerobic energy system and that some measures of aerobic capacity and power correlate with performance. When training for MMT-style competitions, it may be beneficial to focus on improving lower-body power and/or aerobic capacity.
MSH3 Promotes Dynamic Behavior of Trinucleotide Repeat Tracts In Vivo
Authors: Williams Gregory M , Surtees Jennifer A 
Published: May 2015

Abstract
Trinucleotide repeat (TNR) expansions are the underlying cause of more than 40 neurodegenerative and neuromuscular diseases, including myotonic dystrophy and Huntington’s disease, yet the pathway to expansion remains poorly understood. An important step in expansion is the shift from a stable TNR sequence to an unstable, expanding tract, which is thought to occur once a TNR attains a threshold length. Modeling of human data has indicated that TNR tracts are increasingly likely to expand as they increase in size and to do so in increments that are smaller than the repeat itself, but this has not been tested experimentally. Genetic work has implicated the mismatch repair factor MSH3 in promoting expansions. Using Saccharomyces cerevisiae as a model for CAG and CTG tract dynamics, we examined individual threshold-length TNR tracts in vivo over time in MSH3 and msh3Δ backgrounds. We demonstrate, for the first time, that these TNR tracts are highly dynamic. Furthermore, we establish that once such a tract has expanded by even a few repeat units, it is significantly more likely to expand again. Finally, we show that threshold- length TNR sequences readily accumulate net incremental expansions over time through a series of small expansion and contraction events. Importantly, the tracts were substantially stabilized in the msh3Δ background, with a bias toward contractions, indicating that Msh2-Msh3 plays an important role in shifting the expansion-contraction equilibrium toward expansion in the early stages of TNR tract expansion.
Exploring the Length Scale Limits of Porous Silicon Combustion
Authors: Piekiel Nicholas W. , Morris Christopher J. , Churaman Wayne A. , Lunking David M. 
Published: May 2015

ABSTRACTThe present study explores the burning of microscale porous silicon channels with sodium perchlorate. These on-chip porous silicon energetics were embedded in crystalline silicon, and therefore surrounded on three sides by an efficient thermal conductor. For slow burning systems, this presents complications as heat loss to the crystalline silicon substrate can result in inconsistent burning or flame extinction. We investigated <100 μm wide porous silicon strips, sparsely filled with sodium perchlorate (NaClO4), to probe the limits of on-chip combustion. Four different etch times were attempted to decrease the dimensions of the porous silicon strips. The smallest size achieved was 12 x 64 µm, and despite the small dimensions, demonstrated the same flame speed as the larger porous silicon strips of 6-7 m/s. We predict that unreacted porous silicon acts as a thermal insulator to aid combustion for slow burning porous silicon channels, and SEM images provide evidence to support this. We also investigated the small scale combustion of a rapidly burning sample (∼1200 m/s). Despite the rapid flame speed, the propagation followed a designed, winding flame path. The use of these small scale porous silicon samples could significantly reduce the energetic material footprint for future microscale applications.
Can a National Network of Undergraduate Research Program Directors Validate a Set of Professional Skills-Building Science Communication Workshops?
Authors: Alpert Carol Lynn , Thate Karine 
Published: May 2015

ABSTRACTThis paper reports on the progress of an ongoing strategy for dissemination of a set of science communication workshops targeted to students participating in undergraduate research experiences on university campuses. Previous MRS Proceedings papers by the first author and collaborators focused on (1) the development and validation of the REU Science Communication Workshop (REU SCW) model through iterative practice, research and evaluation between 2005 and 2009, and (2) the 2012 testing of a scaffolded and piggybacked "beyond train-the-trainer” mode of dissemination of the REU SCW model to multiple university campuses, as compared to a highly-validated but less efficient one-to-one transfer process deployed between Boston and Madison between 2010 and 2012. This new paper reports on the follow-up effort to confirm and validate the success of the REU SCW workshop model as implemented at the second-wave of dissemination sites by the new cohort of participating undergraduate research program directors. We analyze data gathered in 2013 and 2014 from the participating students, faculty, and providers. The results indicate that the second-wave providers were able to reproduce the successful results achieved at the origination and first dissemination sites, and that providers and stakeholders at these additional sites value the model enough to continue providing it and in some cases to laterally expand it to other programs on campus. These findings suggest that it is possible to greatly expand the number of undergraduate research experience students receiving quality coaching in professional science communication skills by providing their program directors with a comprehensive professional development experience, employing the scaffolded, piggybacked, “beyond train-the-trainer” professional development model.
SET and RESET Kinetics of SrTiO3-based Resistive Memory Devices
Authors: Fleck Karsten , Böttger Ulrich , Waser Rainer , Menzel Stephan 
Published: May 2015

ABSTRACTIn this paper we present a study of the switching kinetics of SrTiO3 based resistive switching memory devices. A pulse scheme is used to cycle the cells between the high resistive state (HRS) and the low resistive state (LRS) thereby monitoring the transient currents for a precise analysis of the SET and RESET transitions. By variation of the width and amplitude of the applied pulses the switching kinetics are studied between 10-8 and 104 s. Taking the pre-switching currents into account, a power dependency of the SET is found that emphasizes the importance of local Joule heating for the nonlinearity of the switching kinetics.