bluuebunny/crossref_metadata_2025 huggingface dataset:
Matrix Remodeling Maintains Embryonic Stem Cell Self-Renewal by Activating Stat3
Authors: Przybyla Laralynne M. , Theunissen Thorold W. , Jaenisch Rudolf , Voldman Joel
Published: February 2013

While a variety of natural and synthetic matrices have been used to influence embryonic stem cell (ESC) self-renewal or differentiation, and ESCs also deposit a rich matrix of their own, the mechanisms behind how extracellular matrix affects cell fate are largely unexplored. The ESC matrix is continuously remodeled by matrix metalloproteinases (MMPs), a process that we find is enhanced by the presence of mouse embryonic fibroblast feeders in a paracrine manner. Matrix remodeling by MMPs aids in the self-renewal of ESCs, as inhibition of MMPs inhibits the ability of ESCs to self-renew. We also find that addition of the interstitial collagenase MMP1 is sufficient to maintain long-term leukemia inhibitory factor (LIF)-independent mouse ESC (mESC) self-renewal in a dose-dependent manner. This remarkable ability is due to the presence of endogenously produced self-renewal-inducing signals, including the LIF-family ligand ciliary neurotrophic factor, that are normally trapped within the ECM and become exposed upon MMP-induced matrix remodeling to signal through JAK and Stat3. These results uncover a new role for feeder cells in maintaining self-renewal and show that mESCs normally produce sufficient levels of autocrine-acting pro-self-renewal ligands.
Impact of India's watershed development programs on biomass productivity
Authors: Bhalla R. S. , Devi Prasad K. V. , Pelkey Neil W.
Published: February 2013

Key Points

Watershed guidelines in India fail to increase biomass productivities

Guidelines depart from restoration by overemphasising poverty alleviation

Guidelines need to adopt a scientific watershed restoration centric approach
Developing melanoma therapeutics: overview and update
Authors: Korman John B. , Fisher David E.
Published: February 2013

Melanoma is a common, often deadly malignancy, historically associated with limited treatment options for advanced disease. In recent years, systems‐based research has resulted in significant clinical advancements. Strategic inhibition of mutated oncoproteins and targeting of immune checkpoints have emerged as very promising approaches. Vemurafenib, which received US Food and Drug Administration (FDA) approval in 2011, selectively inhibits BRAFV600E, a hyperactivated mutant signaling kinase in the mitogen‐activated protein kinase (MAPK) pathway. Another recently FDA‐approved drug, ipilimumab, blocks the cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) pathway from inhibiting T cell activation. Despite this apparent progress, compelling challenges remain for both researchers and clinicians. Responses to therapy remain unacceptably incomplete and, in most cases, resistance mechanisms quickly develop that lead to relapse and subsequent patient mortality. Combining therapeutic modalities may increase the percentage of responding patients as well as the magnitude and durability of response. Notably, combined therapies involving selective BRAF inhibitors (SBIs) and other inhibitors of MAPK‐dependent or MAPK‐independent resistance pathways appear particularly promising. Preclinical and clinical studies are needed to comprehensively evaluate the optimal combinations of therapies, to identify melanoma subtypes that will be most responsive, and to determine optimal dosing, timing, and route of delivery. WIREs Syst Biol Med 2013, 5:257–271. doi: 10.1002/wsbm.1210

This article is categorized under:

Translational, Genomic, and Systems Medicine > Therapeutic Methods
Lower urinary tract development and disease
Authors: Rasouly Hila Milo , Lu Weining
Published: February 2013

Congenital anomalies of the lower urinary tract (CALUT) are a family of birth defects of the ureter, the bladder, and the urethra. CALUT includes ureteral anomaliesc such as congenital abnormalities of the ureteropelvic junction (UPJ) and ureterovesical junction (UVJ), and birth defects of the bladder and the urethra such as bladder‐exstrophy‐epispadias complex (BEEC), prune belly syndrome (PBS), and posterior urethral valves (PUVs). CALUT is one of the most common birth defects and is often associated with antenatal hydronephrosis, vesicoureteral reflux (VUR), urinary tract obstruction, urinary tract infections (UTI), chronic kidney disease, and renal failure in children. Here, we discuss the current genetic and molecular knowledge about lower urinary tract development and genetic basis of CALUT in both human and mouse models. We provide an overview of the developmental processes leading to the formation of the ureter, the bladder, and the urethra, and different genes and signaling pathways controlling these developmental processes. Human genetic disorders that affect the ureter, the bladder and the urethra and associated gene mutations are also presented. As we are entering the postgenomic era of personalized medicine, information in this article may provide useful interpretation for the genetic and genomic test results collected from patients with lower urinary tract birth defects. With evidence‐based interpretations, clinicians may provide more effective personalized therapies to patients and genetic counseling for their families. WIREs Syst Biol Med 2013, 5:307–342. doi: 10.1002/wsbm.1212

This article is categorized under:

Developmental Biology > Developmental Processes in Health and Disease

Translational, Genomic, and Systems Medicine > Translational Medicine
Prompt photon in association with a heavy-quark jet in Pb-Pb collisions at the LHC
Authors: Stavreva Tzvetalina , Arleo François , Schienbein Ingo
Published: February 2013

Abstract

We present a phenomenological study of the associated production of a prompt photon and a heavy quark jet (charm or bottom) in Pb-Pb collisions at the LHC. This channel allows for estimating the amount of energy loss experienced by the charm and bottom quarks propagating in the dense QCD medium produced in those collisions. Calculations are carried out at next-to-leading order (NLO) accuracy using the BDMPS-Z heavy-quark quenching weights. The quenching of the single heavy-quark jet spectrum reflects fairly the hierarchy in the heavy quark energy loss assumed in the perturbative calculation. On the contrary, the single photon spectrum in heavy-ion collisions is only modified at low momenta, for which less heavy-quark jets pass the kinematic cuts. On top of single particle spectra, the two-particle final state provides a range of observables (photon-jet pair momentum, jet asymmetry, among others) which are studied in detail. The comparison of the photon-jet pair momentum, from p-p to Pb-Pb collisions, is sensitive to the amount of energy lost by the heavy-quarks and could therefore be used in order to better understand parton energy loss processes in the heavy quark sector.
Cloning of a novel feruloyl esterase gene from rumen microbial metagenome and enzyme characterization in synergism with endoxylanases
Authors: Wong Dominic W S , Chan Victor J , Liao Hans , Zidwick Mary J
Published: February 2013

A feruloyl esterase (FAE) gene was isolated from a rumen microbial metagenome, cloned into E. coli, and expressed in active form. The enzyme (RuFae2) was identified as a type C feruloyl esterase. The RuFae2 alone released ferulic acid from rice bran, wheat bran, wheat-insoluble arabinoxylan, corn fiber, switchgrass, and corn bran in the order of decreasing activity. Using a saturating amount of RuFae2 for 100 mg substrate, a maximum of 18.7 and 80.0 μg FA was released from 100 mg corn fiber and wheat-insoluble arabinoxylan, respectively. Addition of GH10 endoxylanase (EX) synergistically increased the release of FA with the highest level of 6.7-fold for wheat bran. The synergistic effect of adding GH11 EX was significantly smaller with all the substrates tested. The difference in the effect of the two EXs was further analyzed by comparing the rate in the release of FA with increasing EX concentration using wheat-insoluble arabinoxylan as the substrate.
Craniocervical decompression in patients with mucopolysaccharidosis VI: development of a scoring system to determine indication and outcome of surgery
Authors: Lampe Christina , Lampe Christian , Schwarz Manfred , Müller‐Forell Wibke , Harmatz Paul , Mengel Eugen
Published: February 2013

Objective

To analyse diagnostic value of somato‐sensory evoked potentials (SEP), magnetic resonance imaging (MRI), and clinical neurological examination in the decision for decompression surgery in mucopolysaccharidosis (MPS) VI patients with craniocervical cord compression (CCJ).

Methods

We retrospectively analysed neurological examination, SEP of the median nerve and MRI outcomes from 31 MPS VI patients. Individual scores for each test (based on severity of findings) and a sum of scores of all three procedures (CCJ score) were evaluated for their potential to measure the need for and improvement after surgery. Differences between rapidly and slowly progressive patients were also evaluated.

Results

Fourteen patients (45 %) aged 4–34 years underwent decompression surgery. Median age at first operation was lower in rapidly than in slowly progressive patients (12 vs. 24 years; P = 0.008). Neurological and SEP findings but not MRI results differed significantly between non‐operated and operated patients (P < 0.001, P = 0.003 and P = 0.08, respectively). A significant relationship was found between MRI and clinical neurological examination (P < 0.001) and between SEP and clinical neurological examination (P = 0.01) but not between MRI and SEP (P = 0.06). The CCJ score discriminated between operated and non‐operated patients (4–9 points vs. 0–3 points; P < 0.001) and decreased in 61.5 % of patients after surgery.

Conclusions

CCJ is common in rapidly and slowly progressive MPS VI patients. The CCJ score is an objective and transparent tool for assessing pathology of the CCJ, the need for surgery, and improvement after surgery.
Hypertrichosis in presymptomatic mitochondrial disease
Authors: Baertling Fabian , Mayatepek Ertan , Distelmaier Felix
Published: February 2013

Leigh syndrome is a neurometabolic disorder commonly associated with disturbed oxidative phosphorylation, which leads to bilateral symmetric necrotizing lesions in the central nervous system. Neurological symptoms may be accompanied by cutaneous abnormalities. Here, we present images of distinct hypertrichosis in an otherwise asymptomatic one‐year‐old patient with pathogenic SURF1 gene mutations. We conclude that, if Leigh syndrome is suspected, the presence of characteristic hypertrichosis should prompt SURF1 mutation analysis.
Disclosure of amyloid imaging results to research participants: Has the time come?
Authors: Lingler Jennifer H. , Klunk William E.
Published: February 2013

Amyloid imaging is becoming an increasingly popular tool in clinical research on Alzheimer's disease. In early studies, questions of whether to disclose amyloid imaging results were largely mooted by the immature state of the science. Lack of clarity as to what constituted a positive scan and what a positive scan meant from a prognostic or diagnostic perspective required investigators to advise research participants that, because their scans could not be meaningfully interpreted in a clinical sense, individual research scan results would not be disclosed. With a focus on the most widely used research tracer, Pittsburgh Compound B (PiB), we consider how advances in amyloid imaging are raising new questions about the appropriateness of withholding research results from study participants. We conclude that, although it remains advisable to withhold amyloid scan results from cognitively normal participants, it is no longer reasonable to uphold policies that unilaterally advise research participants with documented cognitive impairment that their PiB scans are uninterpretable. We outline circumstances that we believe compel investigators to provide research participants with the option of receiving their PiB scan results in a carefully managed fashion. Our findings can potentially be generalized to research involving all validated amyloid tracers.
Residual Limb Claudication in a Traumatic Transtibial Amputee
Authors: Murray Andrew L. , Morgenroth David C. , Czerniecki Joseph M.
Published: February 2013

Residual limb pain is a common symptom in the lower extremity amputee population with a fairly broad differential diagnosis. One etiology of residual limb pain that has previously received limited discussion in the literature is that of vascular claudication. Increased awareness of this etiology is important given the prevalence of vascular disease in both the general population and in lower extremity amputees. This article discusses a presentation of residual limb vascular claudication, describes a clinical approach to the problem, and discusses a potential pathophysiologic mechanism for vascular claudication in the amputee that differs from the nonamputee.
“Functional Pain,” Functional Outcomes, and Quality of Life After Hyaluronic Acid Intra‐articular Injection for Knee Osteoarthritis
Authors: Vincent Heather K. , Montero Cindy , Conrad Bryan P. , Horodyski MaryBeth , Connelly Jacob , Martenson Matthew , Seay Amanda N. , Vincent Kevin R.
Published: February 2013

Objective

To compare the effect of hyaluronic acid (HA) intra‐articular knee injections on pain and functional outcomes in persons with knee osteoarthritis (OA) over 6 months, and to determine whether or not changes in functional pain are related to improvements in quality of life.

Design

A prospective cohort study.

Setting

A research laboratory in an academic medical center.

Participants

Patients with knee OA (N = 53) who were receiving medical care for OA.

Interventions

Intra‐articular knee injections of HA (3 injections, each separated by 1 week) and a comparative noninjection group.

Main Outcome Measurements

Functional pain and outcomes assessments during chair rise, stair climbing, and a 6‐minute walking test (by using 0‐10 point numerical pain ratings during each test); gait parameters; Medical Outcomes Short Form‐36 (SF‐36) scores and subscores; the Western Ontario McMaster University Osteoarthritis Index (WOMAC).

Results

Six months after HA, the completion times for the chair rise and stair climb tasks, and the distance covered during the 6‐minute walk were not different between the groups. However, functional pain ratings during stair climbing decreased in the HA‐treated group (P = .05). Six‐month changes in gait velocity, cadence, stride length, step length, and the percentage of the gait cycle spent in single support were all higher after HA injection at month 6 (all P < .05). Significant group‐by‐time interactions existed for total WOMAC scores. SF‐36 Vitality subscores improved by 13%, and Role Physical scores were higher in patients treated with HA injection compared with participants in the noninjection group (P < .05). Regression analyses revealed that changes in the functional pain measures did not correspond with SF‐36 scores.

Conclusions

HA is associated with lower functional pain severity, with minimal impact on functional test scores. We interpreted this finding to represent an increase in the quality of the movement and functional activity. The change in functional pain did not correspond to changes in SF‐36 quality‐of‐life scores.
Sinusoidal input-based visual control for nonholonomic vehicles
Authors: Aranda M. , López-Nicolás G. , Sagüés C.
Published: February 2013

This paper proposes a new visual control approach based on sinusoidal inputs to be used on a nonholonomic robot. We present several contributions: In our method, developed considering a unicycle kinematic model, sinusoids are used in such a way that the generated vehicle trajectories are feasible, smooth and versatile. Our technique improves previous sinusoidal-based control works in terms of efficiency and flexibility. As further contributions, we present analytical expressions for the evolution of the robot's state, and propose a new state-feedback control law based on these expressions. All the information used in the control scheme is obtained from omnidirectional vision by means of the one-dimensional trifocal tensor. Stability analysis of the proposed approach is presented, and its performance is illustrated through experiments.
Tip-contact force control of a single-link flexible arm using feedback and parallel compensation approach
Authors: Liu Liang-Yih , Lin Hsiung-Cheng
Published: February 2013

In this paper, the force control of a constrained one-link flexible arm is investigated using a feedback parallel compensation algorithm based on a linear distributed parameter model with internal damping of Kelvin–Voigt type. Generally, the non-collocation of the joint torque input and the tip contact force output comes along with the non-minimum phase in nature. To overcome this inherent limitation, a new input induced by the measurement of root-bending moment and its derivative, and a virtual contact force output generated by a parallel compensator are defined. Therefore, the transfer function from the new input to the virtual contact force output is proved not only strictly minimum phase but also in a stable condition. A PD controller then improves the performance of the overall closed-loop system. Furthermore, the perfect asymptotic tracking of a desired contact force trajectory with internal stability can be achieved accurately. The exact solutions of the infinite-dimensional system are obtained using the infinite product formulation. The proposed system promises stability robustness to parameter uncertainties, also free of spillover problems. Numerical simulations are provided to verify the effectiveness of the proposed approach.
Pertussis resurgence: waning immunity and pathogen adaptation – two sides of the same coin
Authors: MOOI F. R. , VAN DER MAAS N. A. T. , De MELKER H. E.
Published: February 2013

Pertussis or whooping cough has persisted and resurged in the face of vaccination and has become one of the most prevalent vaccine-preventable diseases in Western countries. The high circulation rate ofBordetella pertussisposes a threat to infants that have not been (completely) vaccinated and for whom pertussis is a severe, life-threatening, disease. The increase in pertussis is mainly found in age groups in which immunity has waned and this has resulted in the perception that waning immunity is the main or exclusive cause for the resurgence of pertussis. However, significant changes inB. pertussispopulations have been observed after the introduction of vaccinations, suggesting a role for pathogen adaptation in the persistence and resurgence of pertussis. These changes include antigenic divergence with vaccine strains and increased production of pertussis toxin. Antigenic divergence will affect both memory recall and the efficacy of antibodies, while higher levels of pertussis toxin may increase suppression of the innate and acquired immune system. We propose these adaptations ofB. pertussishave decreased the period in which pertussis vaccines are effective and thus enhanced the waning of immunity. We plead for a more integrated approach to the pertussis problem which includes the characteristics of the vaccines, theB. pertussispopulations and the interaction between the two.
Filling in the gaps: Linking theory and practice through telecollaboration in teacher education
Authors: Dooly Melinda , Sadler Randall
Published: February 2013

This article discusses a two-year telecollaborative project in teacher education that took an integrated approach to teaching about and through technological resources in order to introduce student-teachers to innovative methods for communicative-based language learning through computer-mediated communication (CMC). Via ‘technological immersion’, student-teachers in two groups in Spain and the US were required to work together online to give peer feedback and evaluation of several activities, including teaching sequences. They also co-created podcasts, along with accompanying educational activities. Some of the tools used were Moodle, Skype, emails, wikis, Second Life and podcasting. The article analyzes and discusses multimodal data collected during the collaboration. Results indicate that the online collaboration enhanced teacher development through opportunities unavailable in more traditional teacher education classrooms and enabled student-teachers to better make connections between theory and practice.
Evaluating a web-based video corpus through an analysis of user interactions
Authors: Caws Catherine G.
Published: February 2013

As shown by several studies, successful integration of technology in language learning requires a holistic approach in order to scientifically understand what learners do when working with web-based technology (cf. Raby, 2007). Additionally, a growing body of research in computer assisted language learning (CALL) evaluation, design and development, has indicated that analysis of learners’ behaviours is an essential element to implementing high-quality technology (e.g., Chapelle, 2001; Levy & Stockwell, 2006). Hence, carefully evaluating the effectiveness of CALL by collecting empirical data on user interactions while focusing on the process of learning is integral to a holistic understanding of students’ behaviours (e.g. Felix, 2005; Hémard, 2006).

This article examines a design-based research that seeks to analyse and understand the dynamics of user interactions with a specific web-based CALL tool in the context of a French as a second language (FSL) course. To this end, we present a sample of results based on an analysis of specific tasks carried out with this CALL tool that is designed in part to encourage students’ integration of critical and electronic literacies. By way of conclusion, we identify the steps that are necessary to enhance this particular CALL system and help users better achieve their learning goals. In particular, we explain the process of recycling our results in the next design phase of the CALL tool in a continuous improvement effort.
Integrating cross-cultural interaction through video-communication and virtual worlds in foreign language teaching programs: is there an added value?
Authors: Canto Silvia , Jauregi Kristi , van den Bergh Huub
Published: February 2013

Organizing and implementing telecollaboration projects in foreign language curricula is not an easy endeavour (Belz & Thorne, 2006; Guth & Helm, 2010), as pedagogical, organizational and technical issues have to be addressed before cross-cultural interaction sessions can be carried out (O'Dowd & Ritter, 2006; O'Dowd, 2011). These issues make many teaching practitioners reluctant to try to integrate telecollaboration in their teaching, as they are more aware of the burden such initiatives might impose than of the benefits they might have for language learners.

Within the European project NIFLAR1we have tried to study the added value that integrating synchronous collaboration projects through video-web communication orSecond Lifemight have in language learning. The study presented in this paper measures the oral communicative growth of language students, who were allocated at random to one of three research conditions: (1) the VC experimental group carried out interactions with native peers through video-web communication; (2) the SL experimental group carried out the same tasks with native peers inSecond Lifeand (3) the control group performed the tasks face to face with classroom peers and had no opportunity to interact with native experts. Communicative growth was measured by comparing oral pre- and post-tests across conditions. Results show significant differences, the experimental groups outperforming the control group.
Enhancement of automatization through vocabulary learning using CALL: Can prompt language processing lead to better comprehension in L2 reading?
Authors: Sato Takeshi , Matsunuma Mitsuyasu , Suzuki Akio
Published: February 2013

Our study aims to optimize a multimedia application for vocabulary learning for English as a Foreign Language (EFL). Our study is based on the concept that difficulty in reading a text in a second language is due to the need for more working memory for word decoding skills, although the working memory must also be used for text comprehension skills. This implies that the automatization of word decoding to free the working memory is indispensable. Therefore, developing a multimedia application for vocabulary learning with a time-control function, our study hypothesizes that vocabulary learning with this function brings about the automatization of word decoding or faster recall of the meanings, and, as a result of freeing more working memory, better comprehension of text. According to our research, multimedia application users not only retained more words and recalled their meanings more quickly but also obtained higher scores on reading comprehension tests that contained the words learned through the application. From this result, we conclude that multimedia vocabulary learning with a time-control function can automatize word decoding skills and therefore free more working memory, thereby leading to better comprehension of the text.
Metamemory in Temporal Lobe Epilepsy: A Study of Sensitivity to Repetition at Encoding
Authors: Howard Charlotte E. , Andrés Pilar , Mazzoni Giuliana
Published: February 2013

The purpose of the current study was to determine whether the level of metacognitive sensitivity previously observed in global Judgments-of-Learning (JOLs) in temporal lobe epilepsy (TLE) patients could also be established when making item-by-item JOLs. Fourteen TLE patients and 14 control participants were compared on a memory task where 39 semantically unrelated word pairs were presented at three different levels of repetition. Thirteen word pairs were assigned to each level. A combined JOL and Feeling-of-Knowing (FOK) task was used to examine metamemory monitoring and control processes. The results showed that control participants outperformed TLE patients on recall and recognition. However, both groups were sensitive to repetition of the word pairs throughout the list, revealing intact online monitoring and control processes at encoding. These results are consistent with the findings of Howard et al. (2010) of intact metamemory in TLE patients and extend the findings of Andrés et al. (2010) of metamemory sensitivity from the global level to the item-by-item level. Finally, the current findings provide additional evidence of a dissociation between memory and metamemory in TLE patients. (JINS, 2013,19, 1–10)
Transmission Electron Microscopy Specimen Preparation Method for Multiphase Porous Functional Ceramics
Authors: Zhang W. , Kuhn L. Theil , Jørgensen P.S. , Thydén K. , Bentzen J.J. , Abdellahi E. , Sudireddy B.R. , Chen M. , Bowen J.R.
Published: February 2013

An optimum method is proposed to prepare thin foil transmission electron microscopy (TEM) lamellae of multiphase porous functional ceramics: prefilling the pore space of these materials with an epoxy resin prior to focused ion beam milling. Several advantages of epoxy impregnation are demonstrated by successful preparation of TEM specimens that maintain the structural integrity of the entire lamella. Feasibility of the TEM alignment procedure is demonstrated, and ideal TEM analyses are illustrated on solid oxide fuel cell and solid oxide electrolysis cell materials. Some potential drawbacks of the TEM specimen preparation method are listed for other samples.
Acute NK1 receptor antagonist administration affects reward incentive anticipation processing in healthy volunteers
Authors: Saji Kanako , Ikeda Yumiko , Kim Woochan , Shingai Yoshitoshi , Tateno Amane , Takahashi Hidehiko , Okubo Yoshiro , Fukayama Haruhisa , Suzuki Hidenori
Published: February 2013

The primary brain structures of reward processing are mainly situated in the mid-brain dopamine system. The nucleus accumbens (NAc) receives dopaminergic projections from the ventral tegmental area and works as a key brain region for the positive incentive value of rewards. Because neurokinin-1 (NK1) receptor, the cognate receptor for substance P (SP), is highly expressed in the NAc, we hypothesized that the SP/NK1 receptor system might play a role in positive reward processing in the NAc in humans. Therefore, we conducted a functional MRI (fMRI) study to assess the effects of an NK1 receptor antagonist on human reward processing through a monetary incentive delay task that is known to elicit robust activation in the NAc especially during gain anticipation. Eighteen healthy adults participated in two series of an fMRI study, taking either a placebo or the NK1 receptor antagonist aprepitant. Behavioural measurements revealed that there was no significant difference in reaction time, hit rate, or self-reported effort for incentive cues between the placebo and aprepitant treatments. fMRI showed significant decrease in blood oxygenation-level-dependent signals in the NAc during gain anticipation with the aprepitant treatment compared to the placebo treatment. These results suggest that SP/NK1 receptor system is involved in processing of positive incentive anticipation and plays a role in accentuating positive valence in association with the primary dopaminergic pathways in the reward circuit.
An MRI-Histological Study of White Matter in Stroke-Free SHRSP
Authors: Brittain John F , McCabe Christopher , Khatun Halima , Kaushal Nitika , Bridges Leslie R , Holmes William M , Barrick Thomas R , Graham Delyth , Dominiczak Anna F , Macrae I Mhairi , Hainsworth Atticus H
Published: February 2013

Hypertension is associated with cerebral small vessel disease (SVD) and with diffuse white matter hyperintensities (WMH) on T2-weighted magnetic resonance imaging (MRI). We tested whether stroke-prone spontaneously hypertensive rats (SHRSP), a model of chronic hypertension, exhibit WMH. Male SHRSP (age 10 months) without stroke symptoms were compared with age-matched male WKY rats. Stroke-prone spontaneously hypertensive rats exhibited no WMH on MRI scans (T2, T2∗, diffusion tensor imaging) and no neuropathological lesions. While leptomeningeal arteries exhibited fibrohyaline wall thickening, with decreased smooth muscle actin relative to WKY, deep penetrating arterioles within the caudate nuclei had no vasculopathy. We conclude that WMH are not an obligate feature of stroke-free SHRSP aged up to 10 months.
Quantitative Imaging of Cerebral Blood Flow Velocity and Intracellular Motility using Dynamic Light Scattering–Optical Coherence Tomography
Authors: Lee Jonghwan , Radhakrishnan Harsha , Wu Weicheng , Daneshmand Ali , Climov Mihail , Ayata Cenk , Boas David A
Published: February 2013

This paper describes a novel optical method for label-free quantitative imaging of cerebral blood flow (CBF) and intracellular motility (IM) in the rodent cerebral cortex. This method is based on a technique that integrates dynamic light scattering (DLS) and optical coherence tomography (OCT), named DLS–OCT. The technique measures both the axial and transverse velocities of CBF, whereas conventional Doppler OCT measures only the axial one. In addition, the technique produces a three-dimensional map of the diffusion coefficient quantifying nontranslational motions. In the DLS–OCT diffusion map, we observed high-diffusion spots, whose locations highly correspond to neuronal cell bodies and whose diffusion coefficient agreed with that of the motion of intracellular organelles reported in vitro in the literature. Therefore, the present method has enabled, for the first time to our knowledge, label-free imaging of the diffusion-like motion of intracellular organelles in vivo. As an example application, we used the method to monitor CBF and IM during a brief ischemic stroke, where we observed an induced persistent reduction in IM despite the recovery of CBF after stroke. This result supports that the IM measured in this study represent the cellular energy metabolism-related active motion of intracellular organelles rather than free diffusion of intracellular macromolecules.
A Mathematical Model for the Rational Design of Chimeric Ligands in Selective Drug Therapies
Authors: Doldán‐Martelli V , Guantes R , Míguez DG
Published: February 2013

Chimeric drugs with selective potential toward specific cell types constitute one of the most promising forefronts of modern Pharmacology. We present a mathematical model to test and optimize these synthetic constructs, as an alternative to conventional empirical design. We take as a case study a chimeric construct composed of epidermal growth factor (EGF) linked to different mutants of interferon (IFN). Our model quantitatively reproduces all the experimental results, illustrating how chimeras using mutants of IFN with reduced affinity exhibit enhanced selectivity against cell overexpressing EGF receptor. We also investigate how chimeric selectivity can be improved based on the balance between affinity rates, receptor abundance, activity of ligand subunits, and linker length between subunits. The simplicity and generality of the model facilitate a straightforward application to other chimeric constructs, providing a quantitative systematic design and optimization of these selective drugs against certain cell‐based diseases, such as Alzheimer's and cancer.

CPT: Pharmacometrics & Systems Pharmacology(2013) 2, e26; doi:10.1038/psp.2013.2; advance online publication 13 February 2013
DBC1 (Deleted in Breast Cancer 1) modulates the stability and function of the nuclear receptor Rev-erbα
Authors: Chini Claudia C. S. , Escande Carlos , Nin Veronica , Chini Eduardo N.
Published: February 2013

The nuclear receptor Rev-erbα has been implicated as a major regulator of the circadian clock and integrates circadian rhythm and metabolism. Rev-erbα controls circadian oscillations of several clock genes and Rev-erbα protein degradation is important for maintenance of the circadian oscillations and also for adipocyte differentiation. Elucidating the mechanisms that regulate Rev-erbα stability is essential for our understanding of these processes. In the present paper, we report that the protein DBC1 (Deleted in Breast Cancer 1) is a novel regulator of Rev-erbα. Rev-erbα and DBC1 interact in cells and in vivo, and DBC1 modulates the Rev-erbα repressor function. Depletion of DBC1 by siRNA (small interfering RNA) in cells or in DBC1-KO (knockout) mice produced a marked decrease in Rev-erbα protein levels, but not in mRNA levels. In contrast, DBC1 overexpression significantly enhanced Rev-erbα protein stability by preventing its ubiquitination and degradation. The regulation of Rev-erbα protein levels and function by DBC1 depends on both the N-terminal and C-terminal domains of DBC1. More importantly, in cells depleted of DBC1, there was a dramatic decrease in circadian oscillations of both Rev-erbα and BMAL1. In summary, our data identify DBC1 as an important regulator of the circadian receptor Rev-erbα and proposes that Rev-erbα could be involved in mediating some of the physiological effects of DBC1.
Spectral action for a one-parameter family of Dirac operators on $\bm{ SU}\textbf {(2)}$SU(2) and $\bm{SU}\textbf {(3)}$SU(3)
Authors: Lai Alan , Teh Kevin
Published: February 2013

The one-parameter family of Dirac operators containing the Levi-Civita, cubic, and the trivial Dirac operators on a compact Lie group is analyzed. The spectra for the one-parameter family of Dirac Laplacians on SU(2) and SU(3) are computed by considering a diagonally embedded Casimir operator. Then the asymptotic expansions of the spectral actions for SU(2) and SU(3) are computed, using the Poisson summation formula and the two-dimensional Euler-Maclaurin formula, respectively. The inflation potential and slow-roll parameters for the corresponding pure gravity inflationary theory are generated, using the full asymptotic expansion of the spectral action on SU(2).
Enhanced depth of field laser processing using an ultra-high-speed axial scanner
Authors: Duocastella M. , Arnold C. B.
Published: February 2013

Lasers are ubiquitous in materials processing, but the requirement of precise control of the focal plane in order to ensure optimal performance constitutes a time limiting step for high-throughput laser manufacturing. Here, we overcome this limitation by axially scanning the focus at high speeds using an acoustically driven liquid lens. We demonstrate this approach by processing silicon surfaces, and we find it is possible to enhance the depth-of-field by an order of magnitude without loss in lateral resolution. These results open the door to a fundamental change in the paradigm for laser processing by eliminating the need in z-focus control.
Enrichment of live unlabelled cardiomyocytes from heterogeneous cell populations using manipulation of cell settling velocity by magnetic field
Authors: Sofla Aarash , Cirkovic Bojana , Hsieh Anne , Miklas Jason W. , Filipovic Nenad , Radisic Milica
Published: February 2013

The majority of available cardiomyocyte markers are intercellular proteins, limiting our ability to enrich live cardiomyocytes from heterogeneous cell preparations in the absence of genetic labeling. Here, we describe enrichment of live cardiomyocytes from the hearts of adult mice in a label-free microfluidic approach. The separation device consisted of a vertical column (15 mm long, 700 μm diameter), placed between permanent magnets resulting in a field strength of 1.23 T. To concentrate the field at the column wall, the column was wrapped with 69 μm diameter nickel wire. Before passing the cells through the column, the cardiomyocytes in the cell suspension had been rendered paramagnetic by treatment of the adult mouse heart cell preparation with sodium nitrite (2.5 mM) for 20 min on ice. The cell suspension was loaded into the vertical column from the top and upon settling, the non-myocytes were removed by the upward flow from the column. The cardiomyocytes were then collected from the column by applying a higher flow rate (144 μl/min). We found that by applying a separation flow rate of 4.2 μl/min in the first step, we can enrich live adult cardiomyocytes to 93% ± 2% in a label-free manner. The cardiomyocytes maintained viability immediately after separation and upon 24 h in culture.
On Lyapunov boundary control of unstable magnetohydrodynamic plasmas
Authors: Tasso H. , Throumoulopoulos G. N.
Published: February 2013

Starting from a simple, marginally stable model considered for Lyapunov based boundary control of flexible mechanical systems, we add a term driving an instability and prove that for an appropriate control condition the system can become Lyapunov stable. A similar approximate extension is found for the general energy principle of linearized magnetohydrodynamics. The implementation of such external instantaneous actions may, however, impose challenging constraints for fusion plasmas.
The Hamiltonian structure and Euler-Poincaré formulation of the Vlasov-Maxwell and gyrokinetic systems
Authors: Squire J. , Qin H. , Tang W. M. , Chandre C.
Published: February 2013

We present a new variational principle for the gyrokinetic system, similar to the Maxwell-Vlasov action presented in H. Cendra et al., [J. Math. Phys. 39, 3138 (1998)]. The variational principle is in the Eulerian frame and based on constrained variations of the phase space fluid velocity and particle distribution function. Using a Legendre transform, we explicitly derive the field theoretic Hamiltonian structure of the system. This is carried out with a modified Dirac theory of constraints, which is used to construct meaningful brackets from those obtained directly from Euler-Poincaré theory. Possible applications of these formulations include continuum geometric integration techniques, large-eddy simulation models, and Casimir type stability methods.
On the toroidal plasma rotations induced by lower hybrid waves
Authors: Guan Xiaoyin , Qin Hong , Liu Jian , Fisch Nathaniel J.
Published: February 2013

A theoretical model is developed to explain the plasma rotations induced by lower hybrid waves in Alcator C-Mod. In this model, torodial rotations are driven by the Lorentz force on the bulk-electron flow across flux surfaces, which is a response of the plasma to the resonant-electron flow across flux surfaces induced by the lower hybrid waves. The flow across flux surfaces of the resonant electrons and the bulk electrons are coupled through the radial electric field initiated by the resonant electrons, and the friction between ions and electrons transfers the toroidal momentum to ions from electrons. An improved quasilinear theory with gyrophase dependent distribution function is developed to calculate the perpendicular resonant-electron flow. Toroidal rotations are determined using a set of fluid equations for bulk electrons and ions, which are solved numerically by a finite-difference method. Numerical results agree well with the experimental observations in terms of flow profile and amplitude. The model explains the strong correlation between torodial flow and internal inductance observed experimentally, and predicts both counter-current and co-current flows, depending on the perpendicular wave vectors of the lower hybrid waves.
Ignition criterion for heterogeneous energetic materials based on hotspot size-temperature threshold
Authors: Barua A. , Kim S. , Horie Y. , Zhou M.
Published: February 2013

A criterion for the ignition of granular explosives (GXs) and polymer-bonded explosives (PBXs) under shock and non-shock loading is developed. The formulation is based on integration of a quantification of the distributions of the sizes and locations of hotspots in loading events using a cohesive finite element method (CFEM) developed recently and the characterization by Tarver et al. [C. M. Tarver et al., "Critical conditions for impact- and shock-induced hot spots in solid explosives," J. Phys. Chem. 100, 5794–5799 (1996)] of the critical size-temperature threshold of hotspots required for chemical ignition of solid explosives. The criterion, along with the CFEM capability to quantify the thermal-mechanical behavior of GXs and PBXs, allows the critical impact velocity for ignition, time to ignition, and critical input energy at ignition to be determined as functions of material composition, microstructure, and loading conditions. The applicability of the relation between the critical input energy (E) and impact velocity of James [H. R. James, "An extension to the critical energy criterion used to predict shock initiation thresholds," Propellants, Explos., Pyrotech. 21, 8–13 (1996)] for shock loading is examined, leading to a modified interpretation, which is sensitive to microstructure and loading condition. As an application, numerical studies are undertaken to evaluate the ignition threshold of granular high melting point eXplosive, octahydro-1,3,5,7-tetranitro-1,2,3,5-tetrazocine (HMX) and HMX/Estane PBX under loading with impact velocities up to 350 ms−1 and strain rates up to 105 s−1. Results show that, for the GX, the time to criticality (tc) is strongly influenced by initial porosity, but is insensitive to grain size. Analyses also lead to a quantification of the differences between the responses of the GXs and PBXs in terms of critical impact velocity for ignition, time to ignition, and critical input energy at ignition. Since the framework permits explicit tracking of the influences of microstructure, loading, and mechanical constraints, the calculations also show the effects of stress wave reflection and confinement condition on the ignition behaviors of GXs and PBXs.
Communication: X-ray excited optical luminescence from TbCl3 at the giant resonance of terbium
Authors: Heigl F. , Jürgensen A. , Zhou X.-T. , Hu Y.-F. , Zuin L. , Sham T. K.
Published: February 2013

We have studied the optical recombination channels of TbCl3 using x-ray excited optical luminescence at the N4,5 absorption edge of Tb (giant resonance) in both the energy and time domain. The luminescence exhibits a relatively fast 5D3, and a slow 5D4 decay channel in the blue and green, respectively. The rather short lifetime of the 5D3 state indicates that the decay is mainly driven by Tb-Tb ion interaction via non-radiative energy transfer (cross-relaxation). At the giant resonance the X-ray Absorption Near Edge Structure (XANES) recorded using partial photoluminescence yield is inverted. In the pre-edge region the contrast of the spectral feature is significantly better in optical XANES than in total electron yield. Changes in the intensity of 5D3–7F5 (544 nm) and 5D4–7F6 (382 nm) optical transitions as the excitation energy is tuned across the giant resonance are also noted. The results provide detailed insight into the dynamics of the optical recombination channels and an alternative method to obtain high sensitivity, high energy resolution XANES at the giant resonance of light emitting rare-earth materials.
Ultra-thin filaments revealed by the dielectric response across the metal-insulator transition in VO2
Authors: Ramírez J.-G. , Schmidt Rainer , Sharoni A. , Gómez M. E. , Schuller Ivan K. , Patiño Edgar J.
Published: February 2013

Temperature dependent dielectric spectroscopy measurements on vanadium dioxide thin films allow us to distinguish between the resistive, capacitive, and inductive contributions to the impedance across the metal-insulator transition (MIT). We developed a single, universal, equivalent circuit model to describe the dielectric behavior above and below the MIT. Our model takes account of phase-coexistence of metallic and insulating regions. We find evidence for the existence at low temperature of ultra-thin threads as described by a resistor-inductor element. A conventional resistor-capacitor element connected in parallel accounts for the insulating phase and the dielectric relaxation.
Nanoscale imaging of photoelectrons using an atomic force microscope
Authors: Yu Ping , Kirschner Jürgen
Published: February 2013

Photoemission current imaging at the nanoscale is demonstrated by combining an atomic force microscope with laser excitation. Photoelectrons emitted from the sample are collected by the tip while the tip-sample distance is precisely controlled by their van der Waals force interaction. We observe pronounced photoemission current contrast with spatial resolution of 5 nm on a cesium covered Au(111) surface. This high spatial resolution can be attributed to the strong dependence of the local potential barrier on the tip-sample distance. Our experiments provide a method for photoelectron imaging with high spatial resolution and extend the functionality of state-of-the-art scanning probe techniques.
Thermally driven asymmetric responses of grains versus spin-glass related distributions of blocking temperature in exchange biased Co/IrMn bilayers
Authors: Baltz V.
Published: February 2013

Controlling ferromagnetic/antiferromagnetic blocking temperatures in exchange biased based devices appears crucial for applications. The blocking temperature is ascribed to the ability of both antiferromagnetic grains and interfacial spin-glass-like phases to withstand ferromagnetic magnetization reversal. To better understand the respective contributions of grains versus spin-glass, blocking temperature distributions were measured after various thermal treatments for cobalt/iridium-manganese bilayers. The high-temperature contribution linked to antiferromagnetic grains shifts towards lower temperatures above a threshold thermal annealing. In contrast, the occurrence and evolution of training effects for the low-temperature contribution only agree with its inferred interfacial spin-glass-like origin.
Large photoresponse of Cu:7,7,8,8-tetracyanoquinodimethane nanowire arrays formed as aligned nanobridges
Authors: Basori Rabaya , Das K. , Kumar Prashant , Narayan K. S. , Raychaudhuri A. K.
Published: February 2013

We report large photoresponse in an array of Cu:TCNQ (TCNQ-7,7,8,8-tetracyanoquinodimethane) nanowires fabricated as nanobridge device. The device shows highest photoresponse for excitation wavelength = 405 nm. The current gain at zero bias can reach ∼104 with an illumination power density of 2 × 106 W/m2. The zero bias responsivity is ∼0.3 mA/W, which increases upto 1 A/W for an applied bias of 2.0 V. Dark and illuminated I-V data are analyzed by a model of two Schottky diodes connected back-to-back, which shows that the predominant photocurrent in the device arises from the photoconductive response of the nanowires.