bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase I study on combined therapy with proton-beam radiotherapy and in situ tumor vaccination for locally advanced recurrent hepatocellular carcinoma
Authors: Abei Masato , Okumura Toshiyuki , Fukuda Kuniaki , Hashimoto Takayuki , Araki Masahiro , Ishige Kazunori , Hyodo Ichinosuke , Kanemoto Ayae , Numajiri Haruko , Mizumoto Masashi , Sakae Takeji , Sakurai Hideyuki , Zenkoh Junko , Ariungerel Gerelchuluun , Sogo Yu , Ito Atsuo , Ohno Tadao , Tsuboi Koji
Published: October 2013

Background

Proton-beam radiotherapy (PBT) has been shown to be effective to hepatocellular carcinoma (HCC) as a nonsurgical local treatment option. However, HCC still remains as one of the most difficult cancers to be cured because of frequent recurrences. Thus, methods to inhibit the recurrence need to be explored. To prevent the HCC recurrence, we here report on a prospective phase I study of‘in situ’tumor vaccination using CalTUMP, a newly developed immunoadjuvant consisting of BCG extract bound to hydroxyapatite and microparticulated tuberculin, following local PBT for HCC.

Methods

Patients with locally advanced recurrent HCC, which had been heavily pretreated with various treatments, were enrolled. PBT was performed with the conventional method to the target HCC. Subsequently, CalTUMP was injected into the same irradiated-tumor three times at one-week intervals. Three dose-levels of CalTUMP (1/10, 1/3, and 1/1) were administered to 3 patients each. Vital signs, blood samples, ultrasound, and computed tomographic scans were monitored to evaluate the safety.

Results

Three intratumoral injections of CalTUMP following PBT (median dose: 72.6 GyE) were accomplished in 9 patients. Transient low-grade fever and minor laboratory changes were observed in 7 patients after CalTUMP injections. No other treatment-related adverse events were observed. Median progression-free survival was 6.0 months (range: 2.1-14.2) and 4 patients were progression-free for more than 1 year.

Conclusions

Intratumoral injection of CalTUMP following PBT was feasible and safe in patients with heavily pre-treated HCC. Further clinical studies to evaluate the efficacy of thisin situtumor vaccination are warranted.
Secretome diversity and quantitative analysis of cellulolytic Aspergillus fumigatusZ5 in the presence of different carbon sources
Authors: Liu Dongyang , Li Juan , Zhao Shuang , Zhang Ruifu , Wang Mengmeng , Miao Youzhi , Shen Yifei , Shen Qirong
Published: October 2013

Background

Aspergillus fumigatus Z5 has a strong ability to decompose lignocellulose biomass, and its extracellular protein secretion has been reported in earlier studies employing traditional techniques. However, a comprehensive analysis of its secretion in the presence of different carbon sources is still lacking. The goal of this work was to identify, quantify and compare the secretome of A. fumigatus Z5 in the presence of different carbon sources to understand in more details the mechanisms of lignocellulose decomposition by Aspergillus fumigatus Z5.

Results

Cellulolytic A. fumigatus Z5 was grown in the presence of glucose (Gl), Avicel (Av) and rice straw (RS), and the activities of several lignocellulosic enzymes were determined with chromatometry method. The maximum activities of endoglucanase, exoglucanase, β-glucosidase, laminarinase, lichenase, xylanase and pectin lyase were 12.52, 0.59, 2.30, 2.37, 1.68, 15.02 and 11.40 U·ml-1, respectively. A total of 152, 125 and 61 different proteins were identified in the presence of RS, Av and Gl, respectively, and the proteins were functionally divided into glycoside hydrolases, lipases, peptidases, peroxidases, esterases, protein translocating transporters and hypothetical proteins. A total of 49 proteins were iTRAQ-quantified in all the treatments, and the quantification results indicated that most of the cellulases, hemicellulases and glycoside hydrolases were highly upregulated when rice straw and Avicel were used as carbon sources (compared with glucose).

Conclusions

The proteins secreted from A. fumigatus Z5 in the present of different carbon source conditions were identified by LC-MS/MS and quantified by iTRAQ-based quantitative proteomics. The results indicated that A. fumigatus Z5 could produce considerable cellulose-, hemicellulose-, pectin- and lignin-degrading enzymes that are valuable for the lignocellulosic bioenergy industry.
Gene dysregulation by histone variant H2A.Z in bladder cancer
Authors: Kim Kyunghwan , Punj Vasu , Choi Jongkyu , Heo Kyu , Kim Jin-Man , Laird Peter W , An Woojin
Published: October 2013

Background

The incorporation of histone variants into nucleosomes is one of the main strategies that the cell uses to regulate the structure and function of chromatin. Histone H2A.Z is an evolutionarily conserved histone H2A variant that is preferentially localized within nucleosomes at the transcriptional start site (TSS). H2A.Z reorganizes the local chromatin structure and recruits the transcriptional machinery for gene activation. High expression of H2A.Z has been reported in several types of cancers and is causally linked to genomic instability and tumorigenesis. However, it is not entirely clear how H2A.Z overexpression in cancer cells establishes aberrant chromatin states and promotes gene expression.

Results

Through integration of genome-wide H2A.Z ChIP-seq data with microarray data, we demonstrate that H2A.Z is enriched around the TSS of cell cycle regulatory genes in bladder cancer cells, and this enrichment is correlated with the elevated expression of cancer-promoting genes. RNAi-mediated knockdown of H2A.Z in the cancer cells causes transcriptional suppression of multiple cell cycle regulatory genes with a distinct decrease in cell proliferation. H2A.Z nucleosomes around the TSS have higher levels of H3K4me2/me3, which coincides with the recruitment of two chromatin factors, WDR5 and BPTF. The observed recruitment is functional, as the active states of H2A.Z target genes are largely erased by suppressing the expression of WDR5 or BPTF, effects resembling H2A.Z knockdown.

Conclusions

We conclude that H2A.Z is overexpressed in bladder cancer cells and contributes to cancer-related transcription pathways. We also provide evidence in support of the engagement of H3K4me2/me3 and WDR5/BPTF in H2A.Z-induced cancer pathogenesis. Further studies are warranted to understand how H2A.Z overexpression contributes to the recruitment of the full repertoire of transcription machinery to target genes in bladder cancer cells.
Lipopolysaccharide infusion enhances dynamic cerebral autoregulation without affecting cerebral oxygen vasoreactivity in healthy volunteers
Authors: Berg Ronan MG , Plovsing Ronni R , Evans Kevin A , Christiansen Claus B , Bailey Damian M , Holstein-Rathlou Niels-Henrik , Møller Kirsten
Published: October 2013

Introduction

Sepsis may be associated with disturbances in cerebral oxygen transport and cerebral haemodynamic function, thus rendering the brain particularly susceptible to hypoxia. The purpose of this study was to assess the impact of isocapnic hypoxia and hyperoxia on dynamic cerebral autoregulation in a human-experimental model of the systemic inflammatory response during the early stages of sepsis.

Methods

A total of ten healthy volunteers were exposed to acute isocapnic inspiratory hyperoxia (FIO2 = 40%) and hypoxia (FIO2 = 12%) before and after a 4-hour lipopolysaccharide (LPS) infusion (2 ng kg-1). Middle cerebral artery blood follow velocity was assessed using transcranial Doppler ultrasound, and dynamic autoregulation was evaluated by transfer function analysis.

Results

Transfer function analysis revealed an increase in the phase difference between mean arterial blood pressure and middle cerebral artery blood flow velocity in the low frequency range (0.07–0.20 Hz) after LPS (P<0.01). In contrast, there were no effects of either isocapnic hyperoxia or hypoxia on dynamic autoregulation, and the cerebral oxygen vasoreactivity to both hyperoxia and hypoxia was unaffected by LPS.

Conclusions

The observed increase in phase suggests that dynamic cerebral autoregulation is enhanced after LPS infusion and resistant to any effects of acute hypoxia; this may protect the brain from ischaemia and/or blood–brain barrier damage during the early stages of sepsis.
Comparison of cold crystalloid and colloid infusions for induction of therapeutic hypothermia in a porcine model of cardiac arrest
Authors: Skulec Roman , Truhlar Anatolij , Turek Zdenek , Parizkova Renata , Dostal Pavel , Hicks Shawn , Lehmann Christian , Cerny Vladimir
Published: October 2013

Introduction

Large-volume cold intravenous infusion of crystalloids has been used for induction of therapeutic hypothermia after cardiac arrest. However, the effectiveness of cold colloids has not been evaluated. Therefore, we performed an experimental study to investigate the cooling effect of cold normal saline compared to colloid solution in a porcine model of ventricular fibrillation.

Methods

Ventricular fibrillation was induced for 15 minutes in 22 anesthetized domestic pigs. After spontaneous circulation was restored, the animals were randomized to receive either 45 ml/kg of 1°C cold normal saline (Group A, 9 animals); or 45 ml/kg of 1°C cold colloid solution (Voluven®, 6% hydroxyethyl starch 130/0.4 in 0.9% NaCl) during 20 minutes (Group B, 9 animals); or to undergo no cooling intervention (Group C, 4 animals). Then, the animals were observed for 90 minutes. Cerebral, rectal, intramuscular, pulmonary artery, and subcutaneous fat body temperatures (BT) were recorded. In the mechanical ex-vivo sub study we added a same amount of cold normal saline or colloid into the bath of normal saline and calculated the area under the curve (AUC) for induced temperature changes.

Results

Animals treated with cold fluids achieved a significant decrease of BT at all measurement sites, whereas there was a consistent significant spontaneous increase in group C. At the time of completion of infusion, greater decrease in pulmonary artery BT and cerebral BT in group A compared to group B was detected (−2.1 ± 0.3 vs. -1.6 ± 0.2°C, and −1.7 ± 0.4 vs. -1.1 ± 0.3°C, p < 0.05, respectively). AUC analysis of the decrease of cerebral BT revealed a more vigorous cooling effect in group A compared to group B (−91 ± 22 vs. -68 ± 23°C/min, p = 0.046). In the mechanical sub study, AUC analysis of the induced temperature decrease of cooled solution revealed that addition of normal saline led to more intense cooling than colloid solution (−7155 ± 647 vs. -5733 ± 636°C/min, p = 0.008).

Conclusions

Intravenous infusion of cold normal saline resulted in more intense decrease of cerebral and pulmonary artery BT than colloid infusion in this porcine model of cardiac arrest. This difference is at least partially related to the various specific heat capacities of the coolants.
The tyrosine kinase inhibitor GNF-2 suppresses osteoclast formation and activity
Authors: Kim Hyun-Ju , Yoon Hye-Jin , Choi Je-Yong , Lee In-Kyu , Kim Shin-Yoon
Published: October 2013

GNF-2, a tyrosine kinase inhibitor, was developed to overcome imatinib-resistant mutations found in CML patients. Osteoclasts are the principal bone-resorbing cells that are responsible for bone diseases, such as osteoporosis, tumor-induced osteolysis, and metastatic cancers. In this study, we investigated the effect of GNF-2 on osteoclast development induced by RANKL and M-CSF. We found that GNF-2 inhibited osteoclast differentiation from BMMs. GNF-2 suppressed RANKL-induced NF-κB transcriptional activity and the induction of c-Fos and NFATc1, which are two key transcription factors in osteoclastogenesis. We also observed that GNF-2 dose-dependently inhibited the proliferation of osteoclast precursors through the suppression of the M-CSFR c-Fms. In addition, GNF-2 accelerated osteoclast apoptosis by inducing caspase-3 and Bim expression. Furthermore, GNF-2 interfered with actin cytoskeletal organization and subsequently blocked the bone-resorbing activity of mature osteoclasts. In agreement with its in vitro effects, GNF-2 reduced osteoclast number and bone loss in a mouse model of LPS-induced bone destruction. Taken together, our data reveal that GNF-2 possesses anti-bone-resorptive properties, suggesting that GNF-2 may have therapeutic value for the treatment of bone-destructive disorders that can occur as a result of excessive osteoclastic bone resorption.
Strength Degradation Model for Low-Rise Reinforced Concrete Walls Derived from Dynamic and Quasi-Static Tests
Authors: Carrillo Julian , Alcocer Sergio M.
Published: October 2013

Results from a previous experimental program demonstrated that loading rate, strength mechanisms associated with the failure mode, low-cycle fatigue, and cumulative values of displacement, and dissipated energy strongly affect the degradation properties of reinforced concrete (RC) walls for low-rise housing. Thus, data obtained from quasi-static (QS) cyclic tests should not immediately be assumed to represent a conservative lower bound on a specimen's capacity. Aimed at numerically correlating results measured during dynamic and QS-cyclic testing, this paper proposes a strength degradation model. The model is readily applicable to seismic design or assessment of performance of existing and new structures. A seismic demand model is also proposed for correlating the intensity and duration of a given earthquake-induced movement to parameters that define the degradation model. Correlations are deemed useful for interpreting the results of QS-cyclic tests and for calibrating hysteretic and behavioral analytical models obtained from QS testing.
A Consistent Cross-Border Seismic Hazard Methodology for Loss Estimation and Risk Management along the Border Regions of Canada and the United States
Authors: Thenhaus Paul C. , Campbell Kenneth W. , Gupta Nitin , Smith David F. , Khater Mahmoud M.
Published: October 2013

We provide a methodology that seamlessly integrates national seismic hazard models across the Canada-U.S. border to provide earthquake risk managers with updated and consistent seismic hazard science and technology in the two countries. Consistent with our U.S. hazard model, we developed a new Canadian model that incorporates (1) spatially varying seismicity for the major metropolitan areas of southeastern and southwestern Canada and the United States, (2) a comprehensive probabilistic model for the Cascadia subduction zone that includes M 8.0–9.2 interface earthquakes, (3) a consistent set of ground motion prediction equations across eastern and western North America, and (4) a soil-based attenuation (SBA) methodology that mitigates uncertainty in the conversion of earthquake motions from rock to soil, on which the majority of exposure is located. NEHRP site conditions are mapped for all of Canada from existing geological data, and NEHRP site factors are used to account for local site conditions.
Seismic Response of a Concrete Frame with Weak Beam-Column Joints
Authors: Bayhan B. , Moehle J. P. , Yavari S. , Elwood K. J. , Lin S. H. , Wu C. L. , Hwang S. J.
Published: October 2013

A reduced-scale, planar, two-story by two-bay reinforced concrete frame with weak beam-column joints was subjected to earthquake simulations on a shaking table. The beam-column joints did not contain transverse reinforcement, as is typical in older construction designed without attention to detail for ductile response. A series of linear and nonlinear analytical models of the frame were developed in accordance with American Society of Civil Engineers standards and subjected to the input base motions. The goodness of fit between analytical and measured results depended on the details of the analytical model. Reasonably accurate reproduction of the measured response was obtained only by modeling the inelastic responses of both columns and beam-column joints. The results confirm the importance of modeling nonlinear joint behavior in older concrete buildings with deficient beam-column joints.
Experimental Seismic Performance Evaluation of Unreinforced Brick Masonry Shear Walls
Authors: Javed Mohammed , Magenes Guido , Alam Bashir , Khan Akhtar Naeem , Ali Qaisar , Syed Ali M.
Published: October 2013

Unreinforced masonry buildings, constructed with stones or bricks, are common in the northern areas of Pakistan. In the October 2005 Kashmir earthquake, the seismic performance of stone masonry buildings was found to be poor, which was the primary source of fatalities. Unreinforced brick masonry (URBM) buildings, however, performed well even in severely jolted areas. The performance of URBM could have been much better if the affected buildings were constructed by using proper guidelines. Taking lessons from the disaster, an experimental investigation, based on typical geometry and precompression levels of the URBM shear walls in the affected region, was conducted to evaluate their seismic performance. Twelve walls were tested in the in-plane direction using quasi-static cyclic loading. First-story drift ratios for various performance levels in URBM buildings are proposed. The influences of relative precompression level and aspect ratio on the damage pattern, ultimate drift ratio, and equivalent viscous damping of the walls are examined.
Crystal Structure and Solid-state Ionic Conductivity of Cyclic Sulfonylamide Salts with Cyano-substituted Quaternary Ammonium Cations
Authors: Moriya Makoto , Watanabe Takaaki , Nabeno Shohei , Sakamoto Wataru , Yogo Toshinobu
Published: October 2013

Novel organic ionic plastic crystals containing cyclic perfluorosulfonylamide anions were synthesized by anion metathesis between a cyano-functionalized quaternary ammonium halide and Li[N(SO2CF2)2CF2] (LiCPFSA). The structure of [N(CH3)2(CH2CN)2][CPFSA] was disclosed by single-crystal X-ray diffraction study. This is the first report on the crystal structure of cyclic perfluorosulfonylamide anion.
Identification of the binding site of Rlp7 on assembling 60S ribosomal subunits in Saccharomyces cerevisiae
Authors: Dembowski Jill A. , Ramesh Madhumitha , McManus C. Joel , Woolford John L.
Published: October 2013

Eukaryotic ribosome assembly requires over 200 assembly factors that facilitate rRNA folding, ribosomal protein binding, and pre-rRNA processing. One such factor is Rlp7, an essential RNA binding protein required for consecutive pre-rRNA processing steps for assembly of yeast 60S ribosomal subunits: exonucleolytic processing of 27SA3 pre-rRNA to generate the 5′ end of 5.8S rRNA and endonucleolytic cleavage of the 27SB pre-rRNA to initiate removal of internal transcribed spacer 2 (ITS2). To better understand the functions of Rlp7 in 27S pre-rRNA processing steps, we identified where it crosslinks to pre-rRNA. We found that Rlp7 binds at the junction of ITS2 and the ITS2-proximal stem, between the 3′ end of 5.8S rRNA and the 5′ end of 25S rRNA. Consistent with Rlp7 binding to this neighborhood during assembly, two-hybrid and affinity copurification assays showed that Rlp7 interacts with other assembly factors that bind to or near ITS2 and the proximal stem. We used in vivo RNA structure probing to demonstrate that the proximal stem forms prior to Rlp7 binding and that Rlp7 binding induces RNA conformational changes in ITS2 that may chaperone rRNA folding and regulate 27S pre-rRNA processing. Our findings contradict the hypothesis that Rlp7 functions as a placeholder for ribosomal protein L7, from which Rlp7 is thought to have evolved in yeast. The binding site of Rlp7 is within eukaryotic-specific RNA elements, which are not found in bacteria. Thus, we propose that Rlp7 coevolved with these RNA elements to facilitate eukaryotic-specific functions in ribosome assembly and pre-rRNA processing.
Flexible Micro Spring Array Device for High-Throughput Enrichment of Viable Circulating Tumor Cells
Authors: Harouaka Ramdane A , Zhou Ming-Da , Yeh Yin-Ting , Khan Waleed J , Das Avisnata , Liu Xin , Christ Christine C , Dicker David T , Baney Tara S , Kaifi Jussuf T , Belani Chandra P , Truica Cristina I , El-Deiry Wafik S , Allerton Jeffrey P , Zheng Si-Yang
Published: October 2013

BACKGROUND

The dissemination of circulating tumor cells (CTCs) that cause metastases in distant organs accounts for the majority of cancer-related deaths. CTCs have been established as a cancer biomarker of known prognostic value. The enrichment of viable CTCs for ex vivo analysis could further improve cancer diagnosis and guide treatment selection. We designed a new flexible micro spring array (FMSA) device for the enrichment of viable CTCs independent of antigen expression.

METHODS

Unlike previous microfiltration devices, flexible structures at the micro scale minimize cell damage to preserve viability, while maximizing throughput to allow rapid enrichment directly from whole blood with no need for sample preprocessing. Device performance with respect to capture efficiency, enrichment against leukocytes, viability, and proliferability was characterized. CTCs and CTC microclusters were enriched from clinical samples obtained from breast, lung, and colorectal cancer patients.

RESULTS

The FMSA device enriched tumor cells with 90% capture efficiency, higher than 104 enrichment, and better than 80% viability from 7.5-mL whole blood samples in <10 min on a 0.5-cm2 device. The FMSA detected at least 1 CTC in 16 out of 21 clinical samples (approximately 76%) compared to 4 out of 18 (approximately 22%) detected with the commercial CellSearch® system. There was no incidence of clogging in over 100 tested fresh whole blood samples.

CONCLUSIONS

The FMSA device provides a versatile platform capable of viable enrichment and analysis of CTCs from clinically relevant volumes of whole blood.
Modeling of Basil Leaves Drying by GA–ANN
Authors: Taheri-Garavand Amin , Rafiee Shahin , Keyhani Alireza , Javadikia Payam
Published: October 2013

In this research, the experiment is done by a dryer. It could provide any desired drying air temperature between 20 and 120°C and air relative humidity between 5 and 95% and air velocity between 0.1 and 5.0 m/s with high accuracy, and the drying experiment was conducted at five air temperatures of 40, 50, 60, 70 and 80°C and at three relative humidity 20, 40 and 60% and air velocity of 1.5, 2 and 2.5 m/s to dry Basil leaves. Then with developed Program in MATLAB software and by Genetic Algorithm could find the best Feed-Forward Neural Network (FFNN) structure to model the moisture content of dried Basil in each condition; anyway the result of best network by GA had only one hidden layer with 11 neurons. This network could predict moisture content of dried basil leaves with correlation coefficient of 0.99.
A Mechanism Design of Dispute Resolution Systems in a Regional-Free Trade Agreement
Authors: Miljkovic Dragan , Gomez Miguel
Published: October 2013

We examine the problem of mechanism design of how individual produce firms within NAFTA make their decisions to belong to the Dispute Resolution Corporation (DRC) when facing a set of criteria to which they previously agreed upon. We design a dominant strategy (the truth-telling) mechanism where both Pareto optimality and optimization of DRC’s welfare are achieved. If there are pivotal firms within the DRC, necessary assumptions made for such a mechanism to work cannot be all satisfied. Next, we compare the assumptions necessary for the mechanism to function and the current system for dispute resolution of the DRC. Casual empiricism and to-date existence of the DRC suggest the existence of pivotal firms.
Extraction of Text Lines from Handwritten Documents Using Piecewise Water Flow Technique
Authors: Sarkar Ram , Das Nibaran , Basu Subhadip , Kundu Mahantapas , Nasipuri Mita
Published: October 2013

A novel piecewise water flow technique for text line extraction from multi-skewed document images of handwritten text of different scripts is presented here. The basic water flow technique assumes that the hypothetical water flows from both left and right sides of the image frame. This flow of water fills up the gaps between consecutive objects (texts) but faces obstruction if any object lies in the path of the flow. All unwetted regions in the document image are then labeled distinctly to extract the text lines. However, the technique fails when two neighboring text lines touch each other, as water gets obstructed by the touching segment(s). To get rid of this difficulty, we have modified the basic water flow technique by iteratively applying the same over the vertically segmented document images. The main purpose of this vertical segmentation is to localize the text line segment(s) where two text lines get joined. These segments are then horizontally fragmented, and each fragment is placed suitably to the text line in which it actually belongs to. This way, the probable data loss during isolation of the touching text line segment is minimized. Both the techniques (current and basic ones) have been tested on three different databases, viz., CMATERdb 1.1.1, CMATERdb 1.1.2, and ICDAR2009 handwritten segmentation contest pages, respectively. The test results show that the present technique outperforms the basic one for all three databases.
Asymptotic Theory for Regressions with Smoothly Changing Parameters
Authors: Hillebrand Eric , Medeiros Marcelo C. , Xu Junyue
Published: October 2013

Abstract: We derive asymptotic properties of the quasi-maximum likelihood estimator of smooth transition regressions when time is the transition variable. The consistency of the estimator and its asymptotic distribution are examined. It is shown that the estimator converges at the usual -rate and has an asymptotically normal distribution. Finite sample properties of the estimator are explored in simulations. We illustrate with an application to US inflation and output data.
Optionality and locality: Evidence from Navajo sibilant harmony
Authors: Berkson Kelly Harper
Published: October 2013

While many phonological processes are local, consonant harmony is of interest phonologically because it can occur non-locally. Sibilant harmony in Navajo requires that sibilants within a word have matching anteriority specifications. The process is described as being sometimes mandatory and sometimes optional, but neither the statistical nature of the occurrence in optional settings nor the factors contributing to the optionality are fully understood. This paper provides preliminary investigation into these issues using the first person possessive morpheme, which is underlyingly /ʃi-/ but may harmonize to [si-]. Experiment 1, an online grammaticality judgment survey, reveals that the harmonized prefix is dispreferred in all environments. Experiment 2 presents acoustic data from three Navajo speakers: though none harmonize overtly, the spectral mean and lower bound of frication energy of the prefixal fricative are affected by the presence of [+anterior] sibilants in noun stems. The overall implication of these findings is that harmony is not only optional but is dispreferred or wholly absent for some speakers. While multiple factors are investigated, the only one that consistently affects harmony is adjacency of the trigger and target, indicating that, although consonant harmony may indeed be a non-local process, its occurrence is heavily mediated by distance.
Gradient clash, faithfulness, and sonority sequencing effects in Russian compound stress
Authors: Gouskova Maria , Roon Kevin
Published: October 2013

Russian normally does not have secondary stress, but it is variably realized in compounds. We examined the factors that contribute to secondary stress realization in a rating study, where listeners were asked to rate compounds pronounced without secondary stress and with secondary stress in various locations. We refine some generalizations from impressionistic descriptions: in compounds whose left-hand stems have mobile lexical stress, acceptability of secondary stress decreases with token frequency of the compound, and acceptability of pronunciations without stress increases with frequency. Ratings improve as distance between stresses increases, and this effect is gradient rather than categorical. We also identify new generalizations about secondary stress that relates to the properties of the left-hand stem. First, we identify a faithfulness effect: stress realization is optional on lexically stressed stems, but stress movement is strongly penalized. Second, we identify a sonority sequencing effect: secondary stress is not tolerated well on linker vowels in compounds, but acceptability improves significantly when the linker is the only vowel in a stem with a falling sonority cluster. Thus, the stress system distinguishes clusters with falling sonority from other types.
First language suprasegmentally-conditioned syllable length distinctions influence perception and production of second language vowel contrasts
Authors: Krebs-Lazendic Lidija , Best Catherine T.
Published: October 2013

Adult second language (L2) learners often have difficulty perceiving and producing L2 speech segments with native-like accuracy. The Speech Learning Model (SLM; Flege 1995) attributes this to perceptual distance between native (L1) and L2 segments, the Perceptual Assimilation Model (PAM; Best 1995; Best and Tyler 2007) to L1 assimilation of L2 segmental contrasts. In a novel extension of these models, we examined whether experience with an L1 suprasegmental duration contrast can affect performance on L2 segmental vowel distinctions that are non-contrastive in the L1. Serbian employs an unusual type of relevant suprasegmental duration distinction, specifically morphological alternations in pitch-accented syllable duration. We assessed L1-Serbian participants' perception and production of L2-English /i-ɪ/ versus /æ-ɛ/, which involve both spectral and temporal distinctions but differ in magnitude of their temporal difference. The results indicate that experience with L1 syllable durations conditioned by pitch-accent systematically influences perception and production of L2 vowel contrasts.
Functional Subdomains within Human FFA
Authors: Çukur Tolga , Huth Alexander G. , Nishimoto Shinji , Gallant Jack L.
Published: October 2013

The fusiform face area (FFA) is a well-studied human brain region that shows strong activation for faces. In functional MRI studies, FFA is often assumed to be a homogeneous collection of voxels with similar visual tuning. To test this assumption, we used natural movies and a quantitative voxelwise modeling and decoding framework to estimate category tuning profiles for individual voxels within FFA. We find that the responses in most FFA voxels are strongly enhanced by faces, as reported in previous studies. However, we also find that responses of individual voxels are selectively enhanced or suppressed by a wide variety of other categories and that these broader tuning profiles differ across FFA voxels. Cluster analysis of category tuning profiles across voxels reveals three spatially segregated functional subdomains within FFA. These subdomains differ primarily in their responses for nonface categories, such as animals, vehicles, and communication verbs. Furthermore, this segregation does not depend on the statistical threshold used to define FFA from responses to functional localizers. These results suggest that voxels within FFA represent more diverse information about object and action categories than generally assumed.
Relationship between the Local Structure of Orientation Map and the Strength of Orientation Tuning of Neurons in Monkey V1: A 2-Photon Calcium Imaging Study
Authors: Ikezoe Koji , Mori Yoshiya , Kitamura Kazuo , Tamura Hiroshi , Fujita Ichiro
Published: October 2013

A majority of neurons in the monkey primary visual cortex (V1) are tuned to stimulus orientations. Preferred orientations and tuning strengths vary among V1 neurons. The preferred orientation of neurons gradually changes across the cortex with occasional failures of this organization. How V1 neurons are arranged by the strength of orientation tuning and whether neuronal arrangement for tuning strength relates to orientation preference maps remains controversial. In this study, we performedin vivotwo-photon calcium imaging in macaque V1 to examine the local spatial organization of orientation tuning at the level of single cells. We recorded fluorescence signals from individual neurons loaded with a calcium-sensitive dye in layer 2 and the uppermost tier of layer 3. The strength of orientation tuning was shared by nearby neurons, and changed across the cortex. The neurons with similar tuning strength were distributed across at least the entire thickness of layer 2. The tuning strength was weaker in regions where neurons exhibited heterogeneous preferred orientations, as compared with regions where neurons shared similar orientation preferences. Nearby direction-selective neurons often shared their preferred directions, although only a few neurons were direction selective in the layers examined. Thus, the orientation tuning strength of V1 neurons is partially predictable from the local structure of orientation map. The weaker orientation tuning we found in regions with heterogeneous orientation preferences suggests that orientation-independent interactions among local populations of V1 neurons play a critical role in determining their orientation tuning.
Distinct Parietal and Temporal Connectivity Profiles of Ventrolateral Frontal Areas Involved in Language Production
Authors: Margulies Daniel S. , Petrides Michael
Published: October 2013

Broca's region, which in the language-dominant hemisphere of the human brain plays a major role in language production, includes two distinct cytoarchitectonic areas: 44 and 45. The unique connectivity patterns of these two areas have not been well established. In a resting-state functional connectivity study, we tested predictions about these areas from invasive tract-tracing studies of the connectivity of their homologs in the macaque monkey. We demonstrated their distinct connectivity profiles as well as their differences from the caudally adjacent ventral parts of the premotor cortex and the primary motor cortical region that represent the orofacial musculature. Area 45 is strongly connected with the superior temporal sulcus and the cortex on the adjacent superior and middle temporal gyri. In the parietal region, area 45 is connected with the angular gyrus, whereas area 44 is connected with the supramarginal gyrus. The primary motor cortical region in the caudal precentral gyrus is not connected with the posterior parietal region, which lies outside the confines of the postcentral gyrus, whereas the ventrorostral premotor cortical area 6VR, in the most anterior part of the precentral gyrus, has strong connections with the rostral supramarginal gyrus. Thus, area 44, which has stronger connections to the posterior supramarginal gyrus, can be distinguished from both the adjacent area 6VR and area 45. These findings provide a major improvement in understanding the connectivity of the areas in the ventrolateral frontal region that are involved in language production.
Modeling Fall Propensity in Parkinson's Disease: Deficits in the Attentional Control of Complex Movements in Rats with Cortical-Cholinergic and Striatal–Dopaminergic Deafferentation
Authors: Kucinski Aaron , Paolone Giovanna , Bradshaw Marc , Albin Roger L. , Sarter Martin
Published: October 2013

Cognitive symptoms, complex movement deficits, and increased propensity for falls are interrelated and levodopa-unresponsive symptoms in patients with Parkinson's disease (PD). We developed a test system for the assessment of fall propensity in rats and tested the hypothesis that interactions between loss of cortical cholinergic and striatal dopaminergic afferents increase fall propensity. Rats were trained to traverse stationary and rotating rods, placed horizontally or at inclines, and while exposed to distractors. Rats also performed an operant Sustained Attention Task (SAT). Partial cortical cholinergic and/or caudate dopaminergic deafferentation were produced by bilateral infusions of 192 IgG-saporin (SAP) into the basal forebrain and/or 6-hydroxydopamine (6-OHDA) into the caudate nucleus, respectively, modeling the lesions seen in early PD. Rats with dual cholinergic–dopaminergic lesions (DL) fell more frequently than SAP or 6-OHDA rats. Falls in DL rats were associated with incomplete rebalancing after slips and low traversal speed. Ladder rung walking and pasta handling performance did not indicate sensorimotor deficits. SAT performance was impaired in DL and SAP rats; however, SAT performance and falls were correlated only in DL rats. Furthermore, in DL rats, but not in rats with only dopaminergic lesions, the placement and size of dopaminergic lesion correlated significantly with fall rates. The results support the hypothesis that after dual cholinergic–dopaminergic lesions, attentional resources can no longer be recruited to compensate for diminished striatal control of complex movement, thereby “unmasking” impaired striatal control of complex movements and yielding falls.
The Prion Protein Ligand, Stress-Inducible Phosphoprotein 1, Regulates Amyloid-β Oligomer Toxicity
Authors: Ostapchenko Valeriy G. , Beraldo Flavio H. , Mohammad Amro H. , Xie Yu-Feng , Hirata Pedro H. F. , Magalhaes Ana C. , Lamour Guillaume , Li Hongbin , Maciejewski Andrzej , Belrose Jillian C. , Teixeira Bianca L. , Fahnestock Margaret , Ferreira Sergio T. , Cashman Neil R. , Hajj Glaucia N. M. , Jackson Michael F. , Choy Wing-Yiu , MacDonald John F. , Martins Vilma R. , Prado Vania F. , Prado Marco A. M.
Published: October 2013

In Alzheimer's disease (AD), soluble amyloid-β oligomers (AβOs) trigger neurotoxic signaling, at least partially, via the cellular prion protein (PrPC). However, it is unknown whether other ligands of PrPCcan regulate this potentially toxic interaction. Stress-inducible phosphoprotein 1 (STI1), an Hsp90 cochaperone secreted by astrocytes, binds to PrPCin the vicinity of the AβO binding site to protect neurons against toxic stimuli. Here, we investigated a potential role of STI1 in AβO toxicity. We confirmed the specific binding of AβOs and STI1 to the PrP and showed that STI1 efficiently inhibited AβO binding to PrPin vitro(IC50of ∼70 nm) and also decreased AβO binding to cultured mouse primary hippocampal neurons. Treatment with STI1 prevented AβO-induced synaptic loss and neuronal death in mouse cultured neurons and long-term potentiation inhibition in mouse hippocampal slices. Interestingly, STI1-haploinsufficient neurons were more sensitive to AβO-induced cell death and could be rescued by treatment with recombinant STI1. Noteworthy, both AβO binding to PrPCand PrPC-dependent AβO toxicity were inhibited by TPR2A, the PrPC-interacting domain of STI1. Additionally, PrPC–STI1 engagement activated α7 nicotinic acetylcholine receptors, which participated in neuroprotection against AβO-induced toxicity. We found an age-dependent upregulation of cortical STI1 in the APPswe/PS1dE9 mouse model of AD and in the brains of AD-affected individuals, suggesting a compensatory response. Our findings reveal a previously unrecognized role of the PrPCligand STI1 in protecting neurons in AD and suggest a novel pathway that may help to offset AβO-induced toxicity.
Object Representation in Inferior Temporal Cortex Is Organized Hierarchically in a Mosaic-Like Structure
Authors: Sato Takayuki , Uchida Go , Lescroart Mark D. , Kitazono Jun , Okada Masato , Tanifuji Manabu
Published: October 2013

There are two dominant models for the functional organization of brain regions underlying object recognition. One model postulates category-specific modules while the other proposes a distributed representation of objects with generic visual features. Functional imaging techniques relying on metabolic signals, such as fMRI and optical intrinsic signal imaging (OISI), have been used to support both models, but due to the indirect nature of the measurements in these techniques, the existing data for one model cannot be used to support the other model. Here, we used large-scale multielectrode recordings over a large surface of anterior inferior temporal (IT) cortex, and densely mapped stimulus-evoked neuronal responses. We found that IT cortex is subdivided into distinct domains characterized by similar patterns of responses to the objects in our stimulus set. Each domain spanned several millimeters on the cortex. Some of these domains represented faces (“face” domains) or monkey bodies (“monkey-body” domains). We also identified domains with low responsiveness to faces (“anti-face” domains). Meanwhile, the recording sites within domains that displayed category selectivity showed heterogeneous tuning profiles to different exemplars within each category. This local heterogeneity was consistent with the stimulus-evoked feature columns revealed by OISI. Taken together, our study revealed that regions with common functional properties (domains) consist of a finer functional structure (columns) in anterior IT cortex. The “domains” and previously proposed “patches” are rather like “mosaics” where a whole mosaic is characterized by overall similarity in stimulus responses and pieces of the mosaic correspond to feature columns.
Studies on DNA Binding of a Double-chain Surfactant
Cobalt(III) Complex Containing 2,2′-Bipyridine
Ligand
Authors: Nagaraj Karuppiah , Arunachalam Sankaralingam
Published: October 2013

The critical micelle concentration (CMC) value of the double
chain surfactant-cobalt(III) complex,
cis-[Co(bpy)2(DA)2](ClO4)3
(bpy = 2,2′-bipyridine, DA = dodecyl amine) in aqueous
β-cyclodextrin medium was obtained from
conductance measurements at 303, 308 and 313 K. The CMC value was
found to be higher in β-cyclodextrin medium
compared to that in aqueous medium containing no
β-cyclodextrin. These results indicate that the
surfactant complex has been incorporated into the cavity of
β-cyclodextrin through its two aliphatic chains
thereby reduce the capacity of our complex to form micelles. This
strong interaction between β-cyclodextrin and our
complex has been confirmed by the changes occurred in the
UV-Visible absorption spectrum of the complex in
β-cyclodextrin. The surfactant complex has been
found to bind strongly to CT DNA with apparent binding constants
at below and above CMC are 1.69 × 105,
2.1 × 106 M−1 respectively. Binding of this
surfactant-cobalt(III) complex with CT DNA was through
intercalative mode via the long aliphatic chains present in the
ligands. The binding was investigated by various techniques,
UV-Visible absorption, fluorescence spectroscopy, circular
dichroism, and viscosity measurements. This binding of the
surfactant cobalt(III) complex with CT DNA has been reduced in
presence of β-cyclodextrin medium due to the
combined effect of incorporation of the aliphatic chains into the
cavity of β-cyclodextrin and trapping of a base
from within the DNA by β-cyclodextrin. The
cytotoxic activity of the surfactant cobalt(III) complex was
tested in vitro on human tumor cell lines (HepG2 liver carcinoma)
using different cell death indicator stains and MTT assay and
found to be active. The experiments suggest that the complex
suffered loss of viability and death mostly through apoptosis.
The relationship between circulating estradiol and thyroid autoimmunity in males
Authors: Chailurkit La-or , Aekplakorn Wichai , Ongphiphadhanakul Boonsong
Published: October 2013

Introduction

Although autoimmune thyroid disease is less common in males, it is unclear whether estrogen contributes to the difference in susceptibility among males.

Objective

To examine whether circulating estradiol (E2) is related to thyroid autoimmunity in males.

Patients and methods

One-thousand two-hundred and sixty-three males aged 15–94 years were studied. Serum levels of E2, TSH receptor antibody (TRAb), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), free thyroxine (FT4), and TSH were measured by ELISA.

Results

Circulating E2varied widely in males, ranging 18.4–403.7 pmol/l with a mean value of 136.2±51.7 pmol/l. E2increased with age (r=0.18,P<0.001). No relationship between E2and BMI was found. When comparing the difference in E2according to the test results of TRAb, TPOAb, and TgAb, it was found that E2was significantly higher in subjects with positive TRAb (TRAb positive, E2=170.3±59.8 pmol/l; TRAb negative, E2=134.0±50.6 pmol/l;P<0.001). No difference in E2was demonstrated according to the results of TPOAb or TgAb. Logistic regression analysis showed that E2was a determinant of positive TRAb, independent of age and BMI. There was no relationship between serum E2and TSH or FT4. However, E2was negatively related to TSH (r=−0.45,P<0.01) in subjects whose TSH levels fell below the reference range (0.3–4.2 mIU/l).

Conclusion

Higher circulating E2is related to thyroid autoimmunity in males as reflected by positive TRAb.
Interferência da redução no volume de aplicação sobre o controle da mancha preta (Guignardia citricarpa Kiely) em frutos de laranja 'Valência'
Authors: Araújo Demétrius de , Raetano Carlos Gilberto , Ramos Hamilton Humberto , Spósito Marcel Belatto , Prado Evandro Pereira
Published: October 2013

O controle químico do agente causal da mancha-preta-dos-citros (MPC) tem merecido destaque pelo excessivo número de pulverizações, elevando sobremaneira os custos de produção na citricultura. A busca por melhorias na eficiência das pulverizações e reduções na quantidade dos produtos fitossanitários já tem sido realizada, mas os resultados dessa prática ainda não são consistentes para que possa ser aplicado em escala comercial. Sendo assim, essa pesquisa objetivou avaliar a interferência da redução no volume de aplicação, sobre o controle químico da mancha preta em frutos cítricos. O experimento foi conduzido em pomar comercial com plantas de 16 anos de idade, da variedade Valência durante o ano agrícola 2007. Os tratamentos consistiram de três volumes de calda, 3,5; 4,5 e 8,5 L planta-1, aplicados por pulverizador de jato transportado Arbus 2000/Export, com ramal especial de bicos, utilizando-se fungicidas e períodos recomendados para o controle da doença em um total de quatro pulverizações e mais um tratamento testemunha (sem pulverização). As avaliações de incidência e severidade da doença ocorreram através de escala visual diagramática de notas em duas épocas (pré-colheita e colheita), em três alturas (baixo, médio e alto) da planta e mais três setores horizontais (entrada, frontal e saída) em dois lados da planta. Os frutos caídos foram contados quinzenalmente, em plantas previamente selecionadas, do início da maturação até a colheita com a quantificação da produção (kg planta-1). A incidência e severidade da doença foram menores quando as pulverizações foram realizadas com 8,5 L planta-1 na primeira época de avaliação (pré-colheita), porém na colheita, não houve diferenças entre os mesmos parâmetros, quando pulverizados 4,5 ou 8,5 L planta-1. Nenhum tratamento reduziu a doença no setor alto da planta, em comparação a testemunha. Os setores da planta com os frutos mais expostos aos raios solares, lado direito e alto da planta, apresentaram maior incidência e severidade da doença. A redução no volume de 8,5 para 4,5 L planta-1 pode ser praticada na citricultura sem prejuízo do nível de controle da MPC.
Reação de genótipos de algodoeiro à mancha de Ramularia em diferentes épocas e ambientes
Authors: Cia Edivaldo , Fuzatto Milton Geraldo , Kondo Júlio Isao , Ohl Guilherme de Almeida , Galbieri Rafael
Published: October 2013

Genótipos de algodoeiro, compreendendo cultivares e linhagens avançadas, foram avaliados quanto à reação à mancha de Ramularia (Ramularia areola), em experimentos de campo e sob infestação natural, aos 60; 90 e 110 dias após a emergência das plantas em Ituverava-SP, e aos 75; 100 e 120 dias em Primavera do Leste-MT. Nos dois locais a avaliação mais tardia foi fundamental para discriminar adequadamente os genótipos e determinar seu grau efetivo de resistência ao patógeno. As avaliações realizadas mais cedo ou foram ineficazes para isso ou subestimaram a suscetibilidade de alguns genótipos. Interação genótipo x ambiente altamente significativa e correlação muito baixa, não significativa, entre as notas médias dos genótipos nos dois experimentos, expressaram desempenho contraditório de alguns genótipos, conforme o local, indicando possível existência de variabilidade genética desse patógeno no Brasil.