bluuebunny/crossref_metadata_2025 huggingface dataset:
Muscle-tendon unit stiffness does not independently affect voluntary explosive force production or muscle intrinsic contractile properties
Authors: Hannah Ricci , Folland Jonathan P.
Published: October 2014

This study examined the relationship of muscle-tendon unit (MTU) stiffness and explosive force production during voluntary and evoked contractions of the knee extensors. Thirty-four untrained participants performed a series of explosive voluntary and electrically evoked (octets (8 pulses, 300 Hz) via femoral nerve stimulation) isometric contractions. Maximum voluntary force (MVF) was assessed during maximum voluntary contractions. Explosive force production was assessed as the time taken, from force onset (0 N), to achieve specific levels of absolute (25–300 N) and relative force (5%–75% MVF) during the explosive contractions. Ultrasonic images of the vastus lateralis were recorded during 10-s ramp contractions to assess MTU stiffness, which was expressed in absolute (N·mm−1) and relative (to MVF and resting tendon-aponeurosis length) terms. Bivariate correlations suggested that absolute MTU stiffness was associated with voluntary explosive force (time to achieve 150–300 N: r = –0.35 to –0.54, P < 0.05). However, no relationships between stiffness and voluntary explosive force were observed when the influence of MVF was removed, either via partial correlations of absolute values (P ≥ 0.49) or considering relative values (P ≥ 0.14). Similarly, absolute MTU stiffness was related to explosive force during evoked octet contractions (r = –0.41 to –0.64, P < 0.05), but these correlations were no longer present when accounting for the influence of MVF (P ≥ 0.15). Therefore, once maximum strength was considered, MTU stiffness had no independent relationship with voluntary explosive force production or the evoked capacity for explosive force.
Adapting a rapid seismic screening method for the evaluation of school buildings
Authors: Tischer Helene , Mitchell Denis , McClure Ghyslaine
Published: October 2014

The poor seismic performance of schools has made their assessment and retrofit a priority in moderate and high seismic zones. Given the large building inventory to evaluate, rapid seismic screening methods are often implemented to prioritize detailed interventions. This paper describes schools’ specific characteristics to be considered when applying these procedures, and shows how the FEMA154 approach can be modified to consider them. The adapted method is a score assignment procedure based on the following six essential characteristics: seismicity, lateral load resisting system, construction year, potential structural weaknesses (or irregularities), potential for pounding of adjacent buildings, and local soil conditions. The method is illustrated with case studies, applied to 101 school buildings in Quebec. Results show that most of the parameters considered influence the final scores. In particular, the treatment of structural weaknesses and potential for pounding proved effective in differentiating the likely seismic performance of the buildings.
MHD mixed convection stagnation-point flow of a viscoelastic fluid towards a stretching sheet in a porous medium with heat generation and radiation
Authors: Abdou M. Modather M. , EL-Zahar E. Roshdy , Chamkha Ali J.
Published: October 2014

An analysis was carried out to study the effect of thermal radiation on magnetohydrodynamic boundary layer flow and heat transfer characteristics of a non-Newtonian viscoelastic fluid near the stagnation point of a vertical stretching sheet in a porous medium with internal heat generation–absorption. The flow is generated because of linear stretching of the sheet and influenced by the uniform magnetic field that is applied horizontally in the flow region. Using a similarity variable, the governing nonlinear partial differential equations have been transformed into a set of coupled nonlinear ordinary differential equations, which are solved numerically using an accurate implicit finite difference scheme. A comparison of the obtained results with previously published numerical results is done and the results are found to be in good agreement. The effects of the viscoelastic fluid parameter, magnetic field parameter, nonuniform heat source–sink, and the thermal radiation parameter on the heat transfer characteristics are presented graphically and discussed. The values of the skin friction coefficient and the local Nusselt number are tabulated for both cases of assisting and opposing flows.
Tree level relations in a composite electroweak theory
Authors: Fariborz Amir H. , Jora Renata , Schechter Joseph
Published: October 2014

We work out simple tree level relations in a top condensate model with dynamical electroweak symmetry breaking. We find that in this picture the mass of the composite Higgs boson at tree level is given by [Formula: see text] where mt is the mass of the top quark.
The effect ofCodoping on structural, magnetic and magnetocaloric properties ofLa0.8Ca0.2Mn1-xCoxO3perovskites (0 ≤ x ≤ 0.3)
Authors: Turki D. , Cherif R. , Hlil E. K. , Ellouze M. , Elhalouani F.
Published: October 2014

Studies of the structural, magnetic and magnetocaloric properties of polycrystalline La0.8Ca0.2Mn1-xCoxO3compounds (0 ≤ x ≤0.3) perovskite manganites were carried out. Samples were synthesized by sol–gel process and then heated at 1000°C for 3 h. X-ray powder diffraction and magnetic measurements were used to investigate the structural and magnetic properties. Rietveld analysis shows that the samples crystallize in the orthorhombic structure with Pnma space group. Crystallographic analysis shows a variation in lattice parameters as cobalt substitution increases, accompanied by a variation in the interatomic distances and a small increase in MT–O–MT angles (MT = cobalt and manganese). Magnetocaloric studies on La0.8Ca0.2Mn1-xCoxO3compounds with x = 0 and x = 0.2 have been investigated by measuring the magnetization as a function of temperature. At 2 T, the maximum magnetic entropy [Formula: see text] is about 3.09 J⋅Kg-1⋅K-1and 1.123 J⋅Kg-1⋅K-1for x = 0 and 0.2, respectively. Besides, the RCP value decreases with increasing Co content from 55.845 J⋅Kg-1to 49.971 J⋅Kg-1. Also, the existence of Griffiths Phase and its influence in the phase transition is discussed.
Desynchronization in an ensemble of globally coupled chaotic bursting neuronal oscillators by dynamic delayed feedback control
Authors: Che Yanqiu , Yang Tingting , Li Ruixue , Li Huiyan , Han Chunxiao , Wang Jiang , Wei Xile
Published: October 2014

In this paper, we propose a dynamic delayed feedback control approach or desynchronization of chaotic-bursting synchronous activities in an ensemble of globally coupled neuronal oscillators. We demonstrate that the difference signal between an ensemble's mean field and its time delayed state, filtered and fed back to the ensemble, can suppress the self-synchronization in the ensemble. These individual units are decoupled and stabilized at the desired desynchronized states while the stimulation signal reduces to the noise level. The effectiveness of the method is illustrated by examples of two different populations of globally coupled chaotic-bursting neurons. The proposed method has potential for mild, effective and demand-controlled therapy of neurological diseases characterized by pathological synchronization.
Towards a solution of the puzzle posed by superconductingSrTiO3
Authors: Malik G. P.
Published: October 2014

Suitably doped SrTiO3was found in 1964 to undergo a superconducting transition below 1 K with a dome-like Tcversus n (electron concentration) plot. The apex of the dome — a point of inflection — corresponds to the point (n≈9 ×1019cm-3, Tc≈0.30 K ). On either side of it, Tcgoes down to ≈0.1 K for the extreme values between which n was varied. A single value of Tcis thus observed for two different values of n. The puzzle for the theory has been to explain this result. Treating the problem in all its generality, we present here three equations: the μ1-incorporated BCS equation for Tc, the μ0-incorporated equation for the T = 0 gap Δ0, where μ1and μ0are the chemical potentials at T = Tcand T = 0 respectively, and an equation that relates the interaction parameters λ1and λ0at these temperatures. Because there are five unknowns in the problem, we tackle these equations via an approximation scheme that includes setting μ1= μ0and λ1= λ0. The latter of these is factually a basic tenet of the BCS theory. Salient features of our findings are: (i) the solutions for Tcand Δ0on the RHS (LHS) of the dome correspond to μ> kBθD(μ < kBθD); kB= Boltzmann constant, θD= Debye temperature, (ii) for solutions on the LHS the limits of the integrals in the equations need to be curtailed to obtain real solutions and (iii) the point μ = kBθDis a point of inflection in the Tcversus μ plot. Since the puzzle has remained unsolved for a long time, we also offer here a purely mathematical model for λ(μ) — sans physical justification — which leads to a Tcversus μ plot qualitatively in agreement with experiment.
Phase Field Modeling of Nonequilibrium Patterns on the Surface of a Liquid Film Under Lateral Oscillations at the Substrate
Authors: Borcia Rodica , Bestehorn Michael
Published: October 2014

We use a phase field model which couples the generalized Navier–Stokes equation (including the Korteweg stress tensor) with the continuity equation for studying nonlinear pattern formation on the surface of a liquid film under (linear and circular) lateral harmonic vibrations at the solid substrate. First, we prove the thermodynamic consistency of our phase field model. Next, we present computer simulations in three spatial dimensions. We illustrate nonequilibrium patterns at the instability onset, confirming in this way the results recently reported in Phys. Rev. E 88, 023025 (2013). The lateral profiles of the deflected surface are compared with those reported in J. Fluid Mech. 686, 409 (2011) for Faraday instability excited by vertical harmonic vibrations at the bottom plate.
Discrete Switching Host-Parasitoid Models with Integrated Pest Control
Authors: Xiang Changcheng , Xiang Zhongyi , Tang Sanyi , Wu Jianhong
Published: October 2014

The switched discrete host-parasitoid model concerning integrated pest management (IPM) has been proposed in the present work, and the economic threshold (ET) is chosen to guide the switches. That is, if the density of host (pest) population increases and exceeds the ET, then the biological and chemical tactics are applied together. Those multiple control measures are suspended once the density of host falls below the ET. Firstly, the existence and stability of several types of equilibria of switched system have been discussed briefly, and two- or three-parameter bifurcation diagrams reveal the regions of different types of equilibria including regular and virtual equilibria. Secondly, numerical bifurcation analyses show that the switched discrete system may have very complex dynamics including the co-existence of multiple attractors and switched-like behavior among attractors. Finally, we address how the key parameters and initial values of both host and parasitoid populations affect the host outbreaks, switching frequencies or mean switching frequency, and consequently the relative biological implications with respect to pest control are discussed.
Phase Transition in Elementary Cellular Automata with Memory
Authors: Ninagawa Shigeru , Adamatzky Andrew , Alonso-Sanz Ramón
Published: October 2014

We study elementary cellular automata with memory. The memory is a weighted function averaged over cell states in a time interval, with a varying factor which determines how strongly a cell's previous states contribute to the cell's present state. We classify selected cell-state transition functions based on Lempel–Ziv compressibility of space-time automaton configurations generated by these functions and the spectral analysis of their transitory behavior. We focus on rules 18, 22, and 54 because they exhibit the most intriguing behavior, including computational universality. We show that a complex behavior is observed near the nonmonotonous transition to null behavior (rules 18 and 54) or during the monotonic transition from chaotic to periodic behavior (rule 22).
Scaling Laws for Large Numbers of Coexisting Attracting Periodic Solutions in the Border-Collision Normal Form
Authors: Simpson David J. W.
Published: October 2014

A wide variety of intricate dynamics may be created at border-collision bifurcations of piecewise-smooth maps, where a fixed point collides with a surface at which the map is nonsmooth. For the border-collision normal form in two dimensions, a codimension-three scenario was described in previous work at which the map has a saddle-type periodic solution and an infinite sequence of stable periodic solutions that limit to a homoclinic orbit of the saddle-type solution. This paper introduces an alternate scenario of the same map at which there is an infinite sequence of stable periodic solutions due to the presence of a repeated unit eigenvalue in the linearization of some iterate of the map. It is shown that this scenario is codimension-four and that the sequence of periodic solutions is unbounded, aligning with eigenvectors corresponding to the unit eigenvalue. Arbitrarily many attracting periodic solutions coexist near either scenario. It is shown that if K denotes the number of attracting periodic solutions, and ε denotes the distance in parameter space from one of the two scenarios, then in the codimension-three case ε scales with λ-K, where λ > 1 denotes the unstable stability multiplier associated with the saddle-type periodic solution, and in the codimension-four case ε scales with K-2. Since K-2 decays significantly slower than λ-K, large numbers of attracting periodic solutions coexist in open regions of parameter space extending substantially further from the codimension-four scenarios than the codimension-three scenarios.
CASE REPORT: SPLENIC FIBROSARCOMA IN A CAMPBELL'S HAMSTER
Authors: Yang Chung-Chun , Liao Jiunn-Wang , Yu Yun-Chen , Kao Ju-Po
Published: October 2014

A 2.5-year-old intact female hamster (Phodopus campbelli) was referred to the VMTH of NCHU on May 7th, 2013 for a swelling of left abdomen and significant decrease in appetite. Physical examination revealed the enlarged abdomen slightly affected the patient's mobility. A firm mass was palpated in the left abdominal cavity. Tentative diagnosis was an abdominal mass. An exploratory laparotomy and splenectomy was performed together with the removal of a mass of 1 × 1 × 0.8 cm in size and 3.6 g in weight. Grossly, the mass was well capsulated and covered by a sac which filled with blood-like discharge. Histologically, diagnoses were made according to the results of hematoxylin and eosin, Masson's trichrome and vimentin immunohistochemistry stained sections. Based on the histological characteristics, the final diagnosis was a splenic fibrosarcoma in a Campbell's hamster. The patient is fully recovered after surgery but the hamster died of natural causes four months later.
Phase I, Dose-Escalation Study of the Targeted Cytotoxic LHRH Analog AEZS-108 in Patients with Castration- and Taxane-Resistant Prostate Cancer
Authors: Liu Stephen V. , Tsao-Wei Denice D. , Xiong Shigang , Groshen Susan , Dorff Tanya B. , Quinn David I. , Tai Yu-Chong , Engel Juergen , Hawes Debra , Schally Andrew V. , Pinski Jacek K.
Published: October 2014

Purpose: AEZS-108, formerly AN-152, is a cytotoxic hybrid molecule consisting of a luteinizing hormone-releasing hormone (LHRH) agonist moiety covalently coupled to doxorubicin, allowing it to deliver doxorubicin selectively to cells expressing LHRH receptors. LHRH receptors are expressed on the cell membrane of many tumors, including prostate cancer. This phase I study determined the maximum tolerated dose (MTD) of AEZS-108 in men with taxane- and castration-resistant prostate cancer (CRPC) while providing additional information on the safety profile and efficacy of this agent.

Experimental Design: AEZS-108 was administered as an intravenous infusion every 21 days until progression or unacceptable toxicity in cohorts of 3 or 6 patients until the MTD was reached. Blood was collected for capture of circulating tumor cells (CTC) to visualize internalization of AEZS-108, an autofluorescent molecule.

Results: The MTD of AEZS-108 in this cohort was 210 mg/m2, which was lower than that seen in a phase I study conducted in women with endometrial or ovarian cancers. The dose-limiting toxicity was persistent neutropenia. Three patients had a PSA response with an additional 10 patients maintaining PSA stable disease. Of the 10 patients evaluable by RECIST criteria, 9 achieved stable disease. AEZS-108 internalization in CTCs was routinely visualized using its autofluorescence.

Conclusion: These findings show that AEZS-108 has an acceptable safety profile and a signal of efficacy, lowering PSA in heavily pretreated patients with prostate cancer, and that internalization of AEZS-108 in prostate cancer CTCs may be a viable pharmacodynamic marker. A phase II study in men with prostate cancer is ongoing. Clin Cancer Res; 20(24); 6277–83. ©2014 AACR.
Pilot Clinical Trial of Hedgehog Pathway Inhibitor GDC-0449 (Vismodegib) in Combination with Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma
Authors: Kim Edward J. , Sahai Vaibhav , Abel Ethan V. , Griffith Kent A. , Greenson Joel K. , Takebe Naoko , Khan Gazala N. , Blau John L. , Craig Ronald , Balis Ulysses G. , Zalupski Mark M. , Simeone Diane M.
Published: October 2014

Purpose: The hedgehog (HH) signaling pathway is a key regulator in tumorigenesis of pancreatic adenocarcinoma and is upregulated in pancreatic adenocarcinoma cancer stem cells (CSCs). GDC-0449 is an oral small-molecule inhibitor of the HH pathway. This study assessed the effect of GDC-0449–mediated HH inhibition in paired biopsies, followed by combined treatment with gemcitabine, in patients with metastatic pancreatic adenocarcinoma.

Experimental Design: Twenty-five patients were enrolled of which 23 underwent core biopsies at baseline and following 3 weeks of GDC-0449. On day 29, 23 patients started weekly gemcitabine while continuing GDC-0449. We evaluated GLI1 and PTCH1 inhibition, change in CSCs, Ki-67, fibrosis, and assessed tumor response, survival and toxicity.

Results: On pretreatment biopsy, 75% of patients had elevated sonic hedgehog (SHH) expression. On posttreatment biopsy, GLI1 and PTCH1 decreased in 95.6% and 82.6% of 23 patients, fibrosis decreased in 45.4% of 22, and Ki-67 in 52.9% of 17 evaluable patients. No significant changes were detected in CSCs pre- and postbiopsy. The median progression-free and overall survival for all treated patients were 2.8 and 5.3 months. The response and disease control rate was 21.7% and 65.2%. No significant correlation was noted between CSCs, fibrosis, SHH, Ki-67, GLI1, PTCH1 (baseline values or relative change on posttreatment biopsy), and survival. Grade ≥3 adverse events were noted in 56% of patients.

Conclusion: We show that GDC-0449 for 3 weeks leads to downmodulation of GLI1 and PTCH1, without significant changes in CSCs compared with baseline. GDC-0449 and gemcitabine were not superior to gemcitabine alone in the treatment of metastatic pancreatic cancer. Clin Cancer Res; 20(23); 5937–45. ©2014 AACR.
Promising Cell-Based Immunotherapy Using Gamma Delta T Cells: Together Is Better
Authors: Déchanet-Merville Julie
Published: October 2014

Gamma delta T-cell response to cellular stress signals expressed by tumor cells makes them promising candidates for cancer immunotherapy. The proof of concept for clinical scale propagation of polyclonal γδ T-cell lines with efficient in vitro and in vivo response against cancer is an important step in this direction. Clin Cancer Res; 20(22); 5573–5. ©2014 AACR.
PET Imaging of β-Glucuronidase Activity by an Activity-Based 124I-Trapping Probe for the Personalized Glucuronide Prodrug Targeted Therapy
Authors: Su Yu-Cheng , Cheng Ta-Chun , Leu Yu-Ling , Roffler Steve R. , Wang Jaw-Yuan , Chuang Chih-Hung , Kao Chien-Han , Chen Kai-Chuan , Wang Hsin-Ell , Cheng Tian-Lu
Published: October 2014

Beta-glucuronidase (βG) is a potential biomarker for cancer diagnosis and prodrug therapy. The ability to image βG activity in patients would assist in personalized glucuronide prodrug cancer therapy. However, whole-body imaging of βG activity for medical usage is not yet available. Here, we developed a radioactive βG activity–based trapping probe for positron emission tomography (PET). We generated a 124I-tyramine–conjugated difluoromethylphenol beta-glucuronide probe (TrapG) to form 124I-TrapG that could be selectively activated by βG for subsequent attachment of 124I-tyramine to nucleophilic moieties near βG-expressing sites. We estimated the specificity of a fluorescent FITC-TrapG, the cytotoxicity of tyramine-TrapG, and the serum half-life of 124I-TrapG. βG targeting of 124I-TrapG in vivo was examined by micro-PET. The biodistribution of 131I-TrapG was investigated in different organs. Finally, we imaged the endogenous βG activity and assessed its correlation with therapeutic efficacy of 9-aminocamptothecin glucuronide (9ACG) prodrug in native tumors. FITC-TrapG showed specific trapping at βG-expressing CT26 (CT26/mβG) cells but not in CT26 cells. The native TrapG probe possessed low cytotoxicity. 124I-TrapG preferentially accumulated in CT26/mβG but not CT26 cells. Meanwhile, micro-PET and whole-body autoradiography results demonstrated that 124I-TrapG signals in CT26/mβG tumors were 141.4-fold greater than in CT26 tumors. Importantly, Colo205 xenografts in nude mice that express elevated endogenous βG can be monitored by using infrared glucuronide trapping probes (NIR-TrapG) and suppressed by 9ACG prodrug treatment. 124I-TrapG exhibited low cytotoxicity allowing long-term monitoring of βG activity in vivo to aid in the optimization of prodrug targeted therapy. Mol Cancer Ther; 13(12); 2852–63. ©2014 AACR.
Small Molecule BMH-Compounds That Inhibit RNA Polymerase I and Cause Nucleolar Stress
Authors: Peltonen Karita , Colis Laureen , Liu Hester , Jäämaa Sari , Zhang Zhewei , af Hällström Taija , Moore Henna M. , Sirajuddin Paul , Laiho Marikki
Published: October 2014

Activation of the p53 pathway has been considered a therapeutic strategy to target cancers. We have previously identified several p53-activating small molecules in a cell-based screen. Two of the compounds activated p53 by causing DNA damage, but this modality was absent in the other four. We recently showed that one of these, BMH-21, inhibits RNA polymerase I (Pol I) transcription, causes the degradation of Pol I catalytic subunit RPA194, and has potent anticancer activity. We show here that three remaining compounds in this screen, BMH-9, BMH-22, and BMH-23, cause reorganization of nucleolar marker proteins consistent with segregation of the nucleolus, a hallmark of Pol I transcription stress. Further, the compounds destabilize RPA194 in a proteasome-dependent manner and inhibit nascent rRNA synthesis and expression of the 45S rRNA precursor. BMH-9– and BMH-22–mediated nucleolar stress was detected in ex vivo–cultured human prostate tissues indicating good tissue bioactivity. Testing of closely related analogues showed that their activities were chemically constrained. Viability screen for BMH-9, BMH-22, and BMH-23 in the NCI60 cancer cell lines showed potent anticancer activity across many tumor types. Finally, we show that the Pol I transcription stress by BMH-9, BMH-22, and BMH-23 is independent of p53 function. These results highlight the dominant impact of Pol I transcription stress on p53 pathway activation and bring forward chemically novel lead molecules for Pol I inhibition, and, potentially, cancer targeting. Mol Cancer Ther; 13(11); 2537–46. ©2014 AACR.
Pulmonary Sarcoid–like Granulomatosis after Multiple Vaccinations of a Long-term Surviving Patient with Metastatic Melanoma
Authors: Bordry Natacha , Costa-Nunes Carla-Marisa , Cagnon Laurène , Gannon Philippe O. , Abed-Maillard Samia , Baumgaertner Petra , Murray Timothy , Letovanec Igor , Lazor Romain , Bouchaab Hasna , Rufer Nathalie , Romano Emanuela , Michielin Olivier , Speiser Daniel E.
Published: October 2014

Autoimmune side effects are frequent in patients with cancer treated with immune checkpoint–targeting antibodies, but are rare with cancer vaccines. Here, we present a case report on a patient with metastatic melanoma who developed pulmonary sarcoid–like granulomatosis following repetitive vaccinations with peptides and CpG. Despite multiple metastases, including one lesion in the brain, the patient is alive and well more than 13 years after the diagnosis of metastatic disease. The strongly activated tumor-specific CD8+ T cells showed robust long-term memory and effector functions. It is possible that long-term survival and adverse autoimmune events may become more common for vaccines inducing robust anticancer immune responses as were present in this patient. Cancer Immunol Res; 2(12); 1148–53. ©2014 AACR.
Death of an Alcohol-Dependent Patient following Intentional Drug Intoxication: Implication of Baclofen?
Authors: Pape Elise , Roman Emilie , Scala-Bertola Julien , Thivilier Carine , Javot Lucie , Saint-Marcoux Franck , Jouzeau Jean Yves , Gambier Nicolas
Published: October 2014

Used in the treatment of spasticity at low doses, baclofen is also prescribed off-label at high doses for the treatment of alcohol dependence. Several cases of baclofen intoxication have been reported, but only 1 case deals with the treatment of alcohol dependence. Thus, we report the first death in the context of baclofen off-label use of an alcohol-dependent patient with a high blood baclofen concentration after intentional drug intoxication. The safety profile of baclofen in the treatment of alcohol dependence is reviewed and discussed, underlining the obligatory caution that may support any prescription of high doses of baclofen in this off-label indication and especially in patients with concomitant psychiatric disorders.
The Neurobiological Bases of Memory Formation: From Physiological Conditions to Psychopathology
Authors: Bisaz Reto , Travaglia Alessio , Alberini Cristina M.
Published: October 2014

The formation of long-term memories is a function necessary for an adaptive survival. In the last two decades, great progress has been made in the understanding of the biological bases of memory formation. The identification of mechanisms necessary for memory consolidation and reconsolidation, the processes by which the posttraining and postretrieval fragile memory traces become stronger and insensitive to disruption, has indicated new approaches for investigating and treating psychopathologies. In this review, we will discuss some key biological mechanisms found to be critical for memory consolidation and strengthening, the role/s and mechanisms of memory reconsolidation, and how the interference with consolidation and/or reconsolidation can modulate the retention and/or storage of memories that are linked to psychopathologies.
Prenatal Diagnosis and Patient Preferences in Patients with Neural Tube Defects around the Advent of Fetal Surgery in Belgium and Holland
Authors: Ovaere Céline , Eggink Alex , Richter Jute , Cohen-Overbeek Titia E. , Van Calenbergh Frank , Jansen Katrien , Oepkes Dick , Devlieger Roland , De Catte Luc , Deprest Jan A.
Published: October 2014

Introduction: We review the characteristics and prenatal choices of patients recently evaluated for neural tube defects (NTD) at two tertiary units. The prenatal diagnosis of NTD allows parents to consider all prenatal options. In selected cases of spina bifida aperta this also includes fetal surgery, which we started offering after combined ‘in-house' and ‘exported' training. Material and Methods: This is a retrospective review of prospectively collected data on NTD diagnosed over the last 8 years and recent fetal surgery referrals. Results: A total of 167 patients were referred for assessment at a median of 19 weeks. Cranial lesions were diagnosed significantly earlier than spinal lesions. Of the open spinal lesions, 77% were isolated. Of these, 22% were managed expectantly and 1 (1%) had fetal surgery. There was no correlation between parental decisions on prenatal management with disease-specific severity markers. We had 14 fetal surgery referrals, all but 1 from beyond our typical referral area; 6 of the assessed patients were operated on, 4 were expectantly managed and 4 requested termination of pregnancy (TOP). These pregnancy outcomes were in the expected range. Discussion: Open spina bifida is mainly diagnosed in the second trimester and 76% of subjects request TOP, irrespective of the severity indicators. The number of local patients considering fetal surgery is low.
Longitudinal Declines in Instrumental Activities of Daily Living in Stable and Progressive Mild Cognitive Impairment
Authors: Hsiao Julia J. , Lu Po H. , Grill Joshua D. , Teng Edmond
Published: October 2014

Background: Previous cross-sectional studies suggest that assessments of instrumental activities of daily living (IADLs) may be useful for operationalizing the differences in functional deficits seen in mild cognitive impairment (MCI) and dementia. However, their utility for longitudinal changes in IADLs in the transition between MCI and dementia remains unclear. Methods: We analyzed longitudinal IADL data with the Functional Activities Questionnaire (FAQ) in stable (MCI-S; n = 1,318) or progressive (MCI-P; n = 1,108) MCI patients. Results: Larger increases in FAQ scores were seen in the MCI-P group across a 14.5-month interval, but overlapping distributions in the two groups yielded poorer discriminatory power than prior cross-sectional reports. Conclusion: Our findings emphasize the difficulties in operationalizing the criterion of ‘essentially intact' IADLs in MCI, which may complicate the interpretation of disease progression in MCI treatment trials. © 2014 S. Karger AG, Basel
Is It Barrett's Esophagus or Gastric Heterotopia
Authors: Mungan Zeynel
Published: October 2014

Columnar epithelium in the distal part of the esophagus is generally related to Barrett's esophagus. Barrett's esophagus is a well-known premalignant lesion for adenocarcinoma of the esophagus. Therefore, its diagnosis and surveillance are important. Columnar epithelium in the esophagus other than Barrett's esophagus can be gastric heterotopia, which generally takes place in the upper part of the esophagus and is named inlet patch. The presence of gastric metaplasia in the distal part of the esophagus is rare and can cause misdiagnosis. Therefore, its differentiation from Barrett's esophagus is important. Here we present a case of gastric heterotopia located in the distal part of the esophagus that caused reflux-like symptoms and needed differentiation from Barrett's esophagus.
Neuroendocrine Tumor Biomarkers: Current Status and Perspectives
Authors: Modlin Irvin M. , Oberg Kjell , Taylor Andrew , Drozdov Ignat , Bodei Lisa , Kidd Mark
Published: October 2014

The identification of accurate harbingers of disease status and therapeutic efficacy are critical requirements in precise diagnosis and effective management. Initially, tissue analysis was regarded as ideal but invasive strategies represent risk compared with peripheral blood sampling. Thus far, most biomarkers, whether in tissue or blood/urine, have been single analytes with varying degrees of sensitivity and specificity. Some analytes have not exhibited robust metrics or have lacked methodological rigor. Neuroendocrine disease represents an area of dire biomarker paucity since the individual biomarkers (gastrin, insulin, etc.) are not widely applicable to the diverse types of neuroendocrine neoplasia. Broad-spectrum markers such as chromogranin A have limitations in sensitivity, specificity and reproducibility. Monoanalytes cannot define the multiple variables (proliferation, metabolic activity, invasive potential, metastatic propensity) that constitute tumor growth. The restricted status of the neuroendocrine neoplasia field has resulted in a lack of comprehensive knowledge of the molecular and cellular biology of the disease, with tardy application of innovative technology. This overview examines limitations in current practice and describes contemporary viable strategies under evaluation, including the identification of novel analytes (gene transcripts, microRNA), circulating tumor cells and metabolic imaging agents that identify disease. Novel requirements are necessary to develop biomathematical algorithms for synchronous calibration of multiple molecular markers and predictive nomograms that interface biological variables to delineate disease progress or treatment efficacy. Optimally, the application of novel techniques and amalgamations of multianalyte assessment will provide a personalized molecular disease signature extrapolative of neuroendocrine neoplasia status and likelihood of progression and predictive of therapeutic opportunity.
Effects of the Estrous Cycle and Ovarian Hormones on Central Expression of Interleukin-1 Evoked by Stress in Female Rats
Authors: Arakawa Keiko , Arakawa Hiroyuki , Hueston Cara M. , Deak Terrence
Published: October 2014

Exposure to stressors such as foot shock (FS) leads to increased expression of multiple inflammatory factors, including the proinflammatory cytokine interleukin-1 (IL-1) in the brain. Studies have indicated that there are sex differences in stress reactivity, suggesting that the fluctuations in gonadal steroid levels across the estrous cycle may play a regulatory role in the stress-induced cytokine expression. The present studies were designed to investigate the role of 17-β-estradiol (E2) and progesterone (Pg) in regulating the cytokine response within the paraventricular nucleus (PVN) of the hypothalamus through analysis of gene expression with real-time RT-PCR. Regularly cycling female rats showed a stress-induced increase in PVN IL-1 levels during the diestrous, proestrous, and estrous stages. During the metestrous stage, no change in IL-1 levels was seen following FS; however, estrogen receptor (ER)-β levels did increase. Ovariectomy resulted in an increase in PVN IL-1 levels, which was attenuated by treatment with estradiol benzoate (10 or 50 µg), indicating an E2-mediated anti-inflammatory effect. Ovariectomized rats treated with Pg (500 or 1,250 µg) showed no alteration in IL-1 levels, but Pg did up-regulate ER-β gene expression. The results from the current study implicate a potential mechanism through which high availability of endogenous Pg during the metestrous stage increases ER-β sensitivity, which in turn attenuates the PVN IL-1 response to stress. Thus, the interaction between gonadal steroid hormones and their central receptors may exert a powerful inhibitory effect on neuroimmune consequences of stress throughout the estrous cycle.
Redundancy and Interaction of Thrombin- and Collagen-Mediated Platelet Activation in Tail Bleeding and Carotid Thrombosis in Mice
Authors: Bynagari-Settipalli Yamini S. , Cornelissen Ivo , Palmer Daniel , Duong Daniel , Concengco Cherry , Ware Jerry , Coughlin Shaun R.
Published: October 2014

Objective—

Current antiplatelet strategies to prevent myocardial infarction and stroke are limited by bleeding risk. A better understanding of the roles of distinct platelet-activating pathways is needed. We determined whether platelet activation by 2 key primary activators, thrombin and collagen, plays distinct, redundant, or interacting roles in tail bleeding and carotid thrombosis in mice.

Approach and Results—

Platelets from mice deficient for the thrombin receptor protease-activated receptor-4 (Par4) and the collagen receptor glycoprotein VI protein (GPVI) lack responses to thrombin and collagen, respectively. We examined tail bleeding and FeCl
3
-induced carotid artery occlusion in mice lacking Par4, GPVI, or both. We also examined a series of Par mutants with increasing impairment of thrombin signaling in platelets. Ablation of thrombin signaling alone by Par4 deficiency increased blood loss in the tail bleeding assay and impaired occlusive thrombus formation in the carotid occlusion assay. GPVI deficiency alone had no effect. Superimposing GPVI deficiency on Par4 deficiency markedly increased effect size in both assays. In contrast to complete ablation of thrombin signaling, 9- and 19-fold increases in EC
50
for thrombin-induced platelet activation had only modest effects.

Conclusions—

The observation that loss of Par4 uncovered large effects of GPVI deficiency implies that Par4 and GPVI made independent, partially redundant contributions to occlusive thrombus formation in the carotid and to hemostatic clot formation in the tail under the experimental conditions examined. At face value, these results suggest that thrombin- and collagen-induced platelet activation can play partially redundant roles, despite important differences in how these agonists are made available to platelets.
Age-Related Differences in Phosphodiesterase Activity and Effects of Chronic Phosphodiesterase Inhibition in Idiopathic Dilated Cardiomyopathy
Authors: Nakano Stephanie J. , Miyamoto Shelley D. , Movsesian Matthew , Nelson Penny , Stauffer Brian L. , Sucharov Carmen C.
Published: October 2014

Background—

Despite the application of proven adult heart failure therapies to children with idiopathic dilated cardiomyopathy (IDC), prognosis remains poor. Clinical experience with phosphodiesterase 3 inhibitors (PDE3i) in pediatric patients with IDC, however, demonstrates improved heart failure symptoms without the increased incidence of sudden death seen in adults treated with PDE3i. We sought to determine age-related differences in PDE activity and associated intracellular signaling responsible for the efficacy and relative safety of chronic PDE3i in pediatric heart failure.

Methods and Results—

cAMP levels, PDE activity, and phospholamban phosphorylation (pPLB) were determined in explanted human left ventricular myocardium (pediatric n=41; adult n=88). Adults and children with IDC (not treated with PDE3i) had lower cAMP and pPLB compared with nonfailing controls. In contrast to their adult counterparts, pediatric IDC patients chronically treated with PDE3i had elevated cAMP (
P
=0.0403) and pPLB (
P
=0.0119). In addition, total PDE- and PDE3-specific activities were not altered in pediatric IDC patients on PDE3i, whereas adult IDC patients on PDE3i demonstrated higher total PDE-specific (74.6±13.8 pmol/mg per minute) and PDE3-specific (48.2±15.9 pmol/mg per minute) activities in comparison with those of nonfailing controls (59.5±14.4 and 35.5±12.8 pmol/mg per minute, respectively).

Conclusions—

Elevated cAMP and higher pPLB may contribute to sustained hemodynamic benefits in pediatric IDC patients treated with PDE3i. In contrast, higher total PDE and PDE3 activities in adult IDC patients treated with PDE3i may perpetuate lower myocardial cAMP and pPLB levels, limiting the potential benefits of PDE3i therapy.
Les juristes malikites en Occident musulman entre soumission et révolte (IIe-IXe/VIIIe-XVe siècle)
Authors: Hentati Nejmeddine
Published: October 2014

Dans cette étude, nous montrons que l’attitude des juristes malikites vis-à-vis du prince n’était pas unifiée, ce qui nous permet de classer ces juristes en trois catégories : les révoltés, les soumis et les réservés. Si les révoltés participèrent à des révoltes et se permirent même dans certains cas de tirer l’épée contre le prince, les soumis, que les sources qualifient de ʿulamā’ al-salāṭīn, cherchèrent à rendre divers services au prince et mirent l’accent sur l’obligation des sujets de lui être soumis. La troisième catégorie de juristes porta son attention sur les devoirs du prince et tenta de se faire les porte – parole du petit peuple et de la religion. Nous rattachons cette diversité d’attitudes à plusieurs données historiques, dont la position ambiguë de Mālik b. Anas vis-à-vis du prince. 

In this study, I show that the attitudes of Mālikī jurists towards the ruler fall into three categories: rebellious, submissive, and reserved: Rebelious jurists participated in revolts and, in some cases, drew their swords against the ruler; submissive jurists – identified in the sources as ʿulamāʾ al-salāṭīn – performed favors for the ruler and emphasized the obligation of his subjects to submit to him; reserved jurists focused on the duties of the ruler and attempted to give voice to the common people and religion. I link these three positions to historical data, including the ambiguous position of Mālik b. Anas vis-à-vis the ruler.
Light-dependent green gall formation induced by Meloidogyne incognita
Authors: Nishiyama Hidetaka , Nakagami Satoru , Todaka Akihiko , Arita Tetsuya , Ishida Takashi , Sawa Shinichiro
Published: October 2014

Meloidogyne incognita is one of the most detrimental root-knot nematode pests in the world because of its wide range of hosts, infecting almost all plant species. Following infection, this nematode induces gall formation in the root. We have found that these induced galls turn green in tomato roots exposed to light. This gall greening was light-dependent and inhibited by auxin treatment. Chlorophyll was detected in these green galls, and chloroplasts were also observed in the root-knot region. Expression of the chlorophyll a/b-binding protein-4 gene was upregulated in the galls. These results indicate that light treatment induces chloroplast development in tomato plants infected with M. incognita during gall development.
Behavioural features of Bursaphelenchus xylophilus in the mating process
Authors: Liu Bao-Jun , Hu Jia-Fu , Liu Zhen-Yu , Xu Liang , Lu Quan , Li Yong-Xia , Zhang Xing-Yao
Published: October 2014

The pine wood nematode (PWN), Bursaphelenchus xylophilus, is able to produce hundreds of thousands of offspring in a short time. Its mating behaviour might play a basic role in this marked fecundity. We investigated the features of the mating behaviour of B. xylophilus using long-time microscope video and repeated observations. The mating behaviour of B. xylophilus could be separated into a series of sequential sub-behaviours, including cruising, approaching, encountering, touching, hooping, locating, attaching, ejaculating, separating, quiescence and roaming. Overall, the process of mating behaviour could be divided into four different phases, searching, contacting, copulating and lingering; the mean times for these different phases varied significantly with 21.8 ± 2.0 min, 28.0 ± 1.9 min, 23.6 ± 0.7 min and 7.2 ± 0.5 min for each of the four phases, respectively. Attraction between the sexes was observed, indicating that sex pheromone(s) might be involved in mating behaviour of B. xylophilus. In addition, when one female was placed with three males, male-male competition was observed, which might be caused by mating-choice pressure from the female. Intra-sexual competition of females was also occasionally observed.
Description of two Pseudaphelenchus species (Tylenchomorpha: Aphelenchoididae) associated with Asian termites and proposal of Tylaphelenchinae n. subfam.
Authors: Kanzaki Natsumi , Li Hou-Feng , Lan Yen-Chiu , Giblin-Davis Robin M.
Published: October 2014

Two newPseudaphelenchusspecies were discovered from subterranean and arboreal termites from the East Asian subtropics.Pseudaphelenchus suin. sp. isolated fromCoptotermes formosanuswas collected from Miyako Isl., Okinawa, Japan, andP. scheffrahnin. sp. was isolated fromNasutitermes takasagoensiscollected from the Kenting National Park in Taiwan. The two new species andP. vindai, previously described from Panamanian termites, are close to each other, and are not easily distinguished morphologically,i.e., these three are almost ‘cryptic species’. However, they can be distinguished based on minor morphological differences, including shape of male bursa (clearest inP. vindai, vague inP. suin. sp. and intermediate inP. scheffrahnin. sp.), male tail tip (P. suin. sp. often have a small mucron but the others do not), and in the character of the female tail (the two new species have stronger ventral curvature thanP. vindai, and further,P. suin. sp. has clear annulation at distal part, while the other species do not). Molecular phylogenetic analysis based upon near-full-length sequences of the small subunit of the ribosomal RNA gene suggested thatPseudaphelenchusandTylaphelenchusform a strongly-supported clade at the base of the family Aphelenchoididae, and thatTylaphelenchusis included inPseudaphelenchusas an inner clade. Therefore, based on their phylogenetic status and common morphological characters,e.g., small body and spherical median bulb, a subfamily, Tylaphelenchinae n. subfam. is proposed to embrace these two genera. In addition,Ruehmaphelenchus ipidicolan. comb. (= Tylaphelenchusipidicola) is proposed.
The Trouble with Opium. Taste, Reason and Experience in Late Galenic Pharmacology with Special Regard to the University of Leiden (1575–1625)
Authors: Klerk Saskia
Published: October 2014

In the seventeenth century, the discrepancy between the taste of some drugs and their effects on the body was used to criticize Galenic medicine. In this paper, I argue that such contradictions were brought to light by the sixteenth-century study of drug properties within the Galenic tradition itself. Investigating how the taste of a drug corresponded to the effects it had on the body became a core problem for maintaining a medical practice that was both rational and effective. I discuss four physicians, connected to the University of Leiden, who attempted to understand drug properties, including taste, within a Galenic framework. The sixteenth-century discussions about the relationship between the senses, reason and experience, will help us understand the seventeenth-century criticism of Galenic medicine and the importance of discussions about materia medica for ideas regarding the properties of matter proposed in this period.
Problems with Rhubarb: Accommodating Experience in Aristotelian Theories of Science
Authors: Heßbrüggen-Walter Stefan
Published: October 2014

The paper examines controversies over the role of experience in the constitution of scientific knowledge in early modern Aristotelianism. While for Jacopo Zabarella, experience helps to confirm the results of demonstrative science, the Bologna Dominican Chrysostomo Javelli assumes that it also contributes to the discovery of new truths in what he calls ‘beginning science’. Both thinkers use medical plants as a philosophical example. Javelli analyses the proposition ‘rhubarb purges bile’ as the conclusion of a yet unknown scientific proof. Zabarella uses instead hellebore, a plant that is found all over Europe, and defends the view that propositions about purgative powers of plants are based on their ‘identity of substance’, an identity that had become questionable with regard to rhubarb due to new empirical findings in the sixteenth century.
On the systematic position of the genus Timmiella (Dicranidae, Bryopsida) and its allied genera, with the description of a new family Timmiellaceae
Authors: Inoue Yuya , Tsubota Hiromi
Published: October 2014

Based on our molecular phylogenetic analysis of haplolepideous mosses with concatenated sequences of chloroplast rps4 and rbcL genes, a new family Timmiellaceae is erected to accommodate the genera Timmiella and Luisierella, both of which have been formerly included in the family Pottiaceae.  The family Timmiellaceae is resolved as a second-branching clade together with Distichium (Distichiaceae) within the Dicranidae (haplolepideous moss) lineages and phylogenetically distinct from the Pottiaceae.  Reassessment of morphological characters suggests that a combination of the characters: 1) adaxially bulging and abaxially flat leaf surfaces, 2) sinistrorse or straight peristomes, when present, and 3) sinistrorsely arranged operculum cells is unique to Timmiellaceae and discriminates it from other haplolepideous moss families.
A new angiocarpous Lactarius species from Thailand
Authors: VERBEKEN ANNEMIEKE , Hampe Felix , WISSITRASSAMEEWONG KOMSIT , HYDE KEVIN , EBERHARDT URSULA , NUYTINCK JORINDE
Published: October 2014

Lactarius bisporus sp. nov. is described from primary tropical forest in Thailand. Morphological characters and DNA sequence data are given. Comparisons with the closely related angiocarpous taxon Lactarius pomiolens are provided.