bluuebunny/crossref_metadata_2025 huggingface dataset:
Ursolic Acid Inhibits STAT3 Activation Pathway Leading to Suppression of Proliferation and Chemosensitization of Human Multiple Myeloma Cells
Authors: Pathak Ashutosh K. , Bhutani Manisha , Nair Asha S. , Ahn Kwang Seok , Chakraborty Arup , Kadara Humam , Guha Sushovan , Sethi Gautam , Aggarwal Bharat B.
Published: September 2007

The activation of signal transducers and activators of transcription 3 (STAT3) has been linked with the proliferation of a variety of human cancer cells, including multiple myeloma. Agents that can suppress STAT3 activation have potential for prevention and treatment of cancer. In the present report, we tested an agent, ursolic acid, found in basil, apples, prunes, and cranberries, for its ability to suppress STAT3 activation. We found that ursolic acid, a pentacyclic triterpenoid, inhibited both constitutive and interleukin-6–inducible STAT3 activation in a dose- and time-dependent manner in multiple myeloma cells. The suppression was mediated through the inhibition of activation of upstream kinases c-Src, Janus-activated kinase 1, Janus-activated kinase 2, and extracellular signal–regulated kinase 1/2. Vanadate treatment reversed the ursolic acid–induced down-regulation of STAT3, suggesting the involvement of a tyrosine phosphatase. Indeed, we found that ursolic acid induced the expression of tyrosine phosphatase SHP-1 protein and mRNA. Moreover, knockdown of SHP-1 by small interfering RNA suppressed the induction of SHP-1 and reversed the inhibition of STAT3 activation, thereby indicating the critical role of SHP-1 in the action of this triterpene. Ursolic acid down-regulated the expression of STAT3-regulated gene products such as cyclin D1, Bcl-2, Bcl-xL, survivin, Mcl-1, and vascular endothelial growth factor. Finally, ursolic acid inhibited proliferation and induced apoptosis and the accumulation of cells in G1-G0 phase of cell cycle. This triterpenoid also significantly potentiated the apoptotic effects of thalidomide and bortezomib in multiple myeloma cells. Overall, these results suggest that ursolic acid is a novel blocker of STAT3 activation that may have a potential in prevention and treatment of multiple myeloma and other cancers. (Mol Cancer Res 2007;5(9):943–55)
Geldanamycin Anisimycins Activate Rho and Stimulate Rho- and ROCK-Dependent Actin Stress Fiber Formation
Authors: Amiri Anahita , Noei Farahnaz , Feroz Tahir , Lee Jonathan M.
Published: September 2007

Heat shock protein 90 (Hsp90) is a member of the heat shock family of molecular chaperones that regulate protein conformation and activity. Hsp90 regulates multiple cell signaling pathways by controlling the abundance and activity of several important protein kinases and cell cycle–related proteins. In this report, we show that inhibition of Hsp90 by geldanamycin or its derivative, 17-allylamino-17-desmethoxygeldamycin, leads to activation of the Rho GTPase and a dramatic increase in actin stress fiber formation in human tumor cell lines. Inactivation of Rho prevents geldanamycin-induced actin reorganization. Hsp90 inactivation does not alter the appearance of filopodia or lamellipodia and tubulin architecture is not visibly perturbed. Our observations suggest that Hsp90 has an important and specific role in regulating Rho activity and Rho-dependent actin cytoskeleton remodeling. (Mol Cancer Res 2007;5(9):933–42)
Pim-1 Kinase-Dependent Phosphorylation of p21Cip1/WAF1 Regulates Its Stability and Cellular Localization in H1299 Cells
Authors: Zhang Yandong , Wang Zeping , Magnuson Nancy S.
Published: September 2007

Previous studies from our laboratory showed that p21Cip1/WAF1 can be phosphorylated by Pim-1 kinase in vitro, implying that part of the function of Pim-1 might involve influencing the cell cycle. In the present study, site-directed mutagenesis and phosphorylated-specific antibodies were used as tools to identify the sites phosphorylated by Pim-1 and the consequences of this phosphorylation. What we found was that Pim-1 can efficiently phosphorylate p21 on Thr145 in vitro using recombinant protein and in vivo in intact cells. Unexpectedly, we found that Ser146 is a second site that is phosphorylated in vivo, but this phosphorylation event seems to be an indirect result of Pim-1 expression. More importantly, the consequences of phosphorylation of either Thr145 or Ser146 are distinct. When p21 is phosphorylated on Thr145, it localizes to the nucleus and results in the disruption of the association between proliferating cell nuclear antigen and p21. Furthermore, phosphorylation of Thr145 promotes stabilization of p21. On the other hand, when p21 is phosphorylated on Ser146, it localizes primarily in the cytoplasm and the effect of phosphorylation on stability is minimal. Cotransfection of wild-type Pim-1 with p21 increases the rate of proliferation compared with cotransfection of p21 with kinase-dead Pim-1. Knocking down Pim-1 expression greatly decreases the rate of proliferation of H1299 cells and their ability to grow in soft agar. These data suggest that Pim-1 overexpression may contribute to tumorigenesis in part by influencing the cellular localization and stability of p21 and by promoting cell proliferation. (Mol Cancer Res 2007;5(9):909–22)
Mitochondria Are an Essential Mediator of Nitric Oxide/Cyclic Guanosine 3′,5′-Monophosphate Blocking of Glucose Depletion–Induced Cytotoxicity in Human HepG2 Cells
Authors: Hsu Yi-Chiung , Lee Hsin-Chen , Ping Yueh-Hsin , Liu Tsung-Yun , Lui Wing-Yiu , Chi Chin-Wen
Published: September 2007

It is well known that glucose is a major energy source in tumors and that mitochondria are specialized organelles required for energy metabolism. Previous studies have revealed that nitric oxide (NO) protects against glucose depletion–induced cytotoxicity in mouse liver cells and in rat hepatocytes, but the detailed mechanism is not well understood. Therefore, we investigated the involvement of mitochondria in the NO protective effect in human hepatoma HepG2 cells. In this study, we showed that glucose depletion resulted in a time-dependent decrease in intracellular NO and in the protein expression of NO synthases. This glucose depletion–induced decrease in NO was blocked by NO donors. Next, we showed that the cytoprotective effect of NO is via a cyclic guanosine 3′,5′-monophosphate–dependent pathway. Additionally, SNP blocked a glucose depletion–induced decrease in mitochondrial mass, mitochondrial DNA copies, and ATP level in HepG2 cells. Moreover, glucose depletion decreased the expression of various mitochondrial proteins, including cytochrome c, complex I (NADH dehydrogenase), complex III (cytochrome c reductase), and heat shock protein 60; these glucose depletion–induced effects were blocked by SNP. Furthermore, we found that rotenone and antimycin A (mitochondria complex I and III inhibitors, respectively) blocked SNP cytoprotection against glucose depletion–induced cytotoxicity. Taken together, our results indicated that the mitochondria serve as an important cellular mediator of NO during protection against glucose deprivation–induced damage. (Mol Cancer Res 2007;5(9):923–32)
Breast Cancer Molecular Signatures as Determined by SAGE: Correlation with Lymph Node Status
Authors: Abba Martín C. , Sun Hongxia , Hawkins Kathleen A. , Drake Jeffrey A. , Hu Yuhui , Nunez Maria I. , Gaddis Sally , Shi Tao , Horvath Steve , Sahin Aysegul , Aldaz C. Marcelo
Published: September 2007

Global gene expression measured by DNA microarray platforms have been extensively used to classify breast carcinomas correlating with clinical characteristics, including outcome. We generated a breast cancer Serial Analysis of Gene Expression (SAGE) high-resolution database of ∼2.7 million tags to perform unsupervised statistical analyses to obtain the molecular classification of breast-invasive ductal carcinomas in correlation with clinicopathologic features. Unsupervised statistical analysis by means of a random forest approach identified two main clusters of breast carcinomas, which differed in their lymph node status (P = 0.01); this suggested that lymph node status leads to globally distinct expression profiles. A total of 245 (55 up-modulated and 190 down-modulated) transcripts were differentially expressed between lymph node (+) and lymph node (−) primary breast tumors (fold change, ≥2; P < 0.05). Various lymph node (+) up-modulated transcripts were validated in independent sets of human breast tumors by means of real-time reverse transcription-PCR (RT-PCR). We validated significant overexpression of transcripts for HOXC10 (P = 0.001), TPD52L1 (P = 0.007), ZFP36L1 (P = 0.011), PLINP1 (P = 0.013), DCTN3 (P = 0.025), DEK (P = 0.031), and CSNK1D (P = 0.04) in lymph node (+) breast carcinomas. Moreover, the DCTN3 (P = 0.022) and RHBDD2 (P = 0.002) transcripts were confirmed to be overexpressed in tumors that recurred within 6 years of follow-up by real-time RT-PCR. In addition, meta-analysis was used to compare SAGE data associated with lymph node (+) status with publicly available breast cancer DNA microarray data sets. We have generated evidence indicating that the pattern of gene expression in primary breast cancers at the time of surgical removal could discriminate those tumors with lymph node metastatic involvement using SAGE to identify specific transcripts that behave as predictors of recurrence as well. (Mol Cancer Res 2007;5(9):881–90)
Increased Expression and Activity of Nuclear Cathepsin L in Cancer Cells Suggests a Novel Mechanism of Cell Transformation
Authors: Goulet Brigitte , Sansregret Laurent , Leduy Lam , Bogyo Matthew , Weber Ekkehard , Chauhan Shyam S. , Nepveu Alain
Published: September 2007

It is generally accepted that the role of cathepsin L in cancer involves its activities outside the cells once it has been secreted. However, cathepsin L isoforms that are devoid of a signal peptide were recently shown to be present in the nucleus where they proteolytically process the CCAAT-displacement protein/cut homeobox (CDP/Cux) transcription factor. A role for nuclear cathepsin L in cell proliferation could be inferred from the observation that the CDP/Cux processed isoform can accelerate entry into S phase. Here, we report that in many transformed cells the proteolytic processing of CDP/Cux is augmented and correlates with increased cysteine protease expression and activity in the nucleus. Taking advantage of an antibody that recognizes the prodomain of human cathepsin L, we showed that human cells express short cathepsin L species that do not contain a signal peptide, do not transit through the endoplasmic reticulum, are not glycosylated, and localize to the nucleus. We also showed that transformation by the ras oncogene causes rapid increases both in the production of short nuclear cathepsin L isoforms and in the processing of CDP/Cux. Using a cell-based assay, we showed that a cell-permeable inhibitor of cysteine proteases is able to delay the progression into S phase and the proliferation in soft agar of ras-transformed cells, whereas the non–cell-permeable inhibitor had no effect. Taken together, these results suggest that the role of cathepsin L in cancer might not be limited to its extracellular activities but may also involve its processing function in the nucleus. (Mol Cancer Res 2007;5(9):899–907)
Buprenorphine Misuse among Heroin and Amphetamine Users in Malmo, Sweden: Purpose of Misuse and Route of Administration
Authors: Hakansson A. , Medvedeo A. , Andersson M. , Berglund M.
Published: September 2007

Buprenorphine misuse by injecting drug users was assessed in a survey of 350 needle exchangers, either amphetamine (57%) or heroin users (42%). 89% of heroin users and 24% of amphetamine users reported using buprenorphine at some time during the previous year. Most users reported illicit acquisition. Among illicit users, 87% of heroin users reported intake for withdrawal treatment or self-detoxification, and 11% for euphoria. Euphoria seeking was more common among amphetamine users (62%, p < 0.001). Intravenous misuse was reported by 43% of illicit users, and snorting by 29%. Sole sublingual intake was more common among heroin users than among amphetamine users (46 vs. 20%, p < 0.05), and less common among patients reporting euphoria seeking (20 vs. 46%, p < 0.05).
Personality Disorders among Danish Alcoholics Attending Outpatient Treatment
Authors: Nordholm Dorte , Nielsen Bent
Published: September 2007

The aim of the present study was firstly to describe the characteristics of alcoholic outpatients (A) suffering from co-morbid personality disorder (PD) of either the cluster B (A+PDB) or cluster C (A+PDC) type. Secondly, to investigate the effect of various kinds of treatment to be able to single out the most beneficial therapy. Thirdly, to identify the most beneficial treatment. The patients were offered the following outpatient treatments: cognitive behaviour therapy, family therapy and supportive consultations. The material consisted of 363 patients who started psychosocial treatment at the outpatient alcohol clinic at Odense University Hospital, Denmark. It was possible to re-interview 276 (76%) patients 1 year after onset of treatment. Of the 363 patients, 87% were alcohol-dependent (ICD-10) and 34% fulfilled the ICD-10-R criteria for PDs. The basic interviews focused on the seven main areas of the Addiction Severity Index. A+PDC had significantly more serious medical problems than A–PD, while the A+PDB group had significantly more employment, drug use and social problems than the A–PD. As for psychiatric status, A–PD had significantly different scores compared with A+PDB and A+PDC. A+PDB were younger and had a longer history of alcohol abuse than A–PD and A+PDC. After treatment there was no significance between the patients with and without PD concerning alcohol outcome and psychosocial outcome. The significance of co-morbid PD for the prognosis of alcohol abusers may be overestimated. Our results indicate that A+PD can be treated as successfully as other patients in an outpatient alcohol clinic can.
Neurobiological Mechanisms of Aggression and Stress Coping: A Comparative Study in Mouse and Rat Selection Lines
Authors: Veenema Alexa H. , Neumann Inga D.
Published: September 2007

Aggression causes major health and social problems and constitutes a central problem in several psychiatric disorders. There is a close relationship between the display of aggression and stress coping strategies. In order to gain more insight into biochemical pathways associated with aggression and stress coping, we assessed behavioral and neurobiological responses in two genetically selected rodent models, namely wild house mice selectively bred for a short (SAL) and long (LAL) attack latency and Wistar rats bred for high (HAB) or low (LAB) anxiety-related behavior. Compared to their line counterparts, the SAL mice and the LAB rats display a high level of intermale aggression associated with a proactive coping style. Both the SAL mice and the LAB rats show a reduced hypothalamic-pituitary-adrenal (HPA) axis response to non-social stressors. However, when exposed to social stressors (resident-intruder, sensory contact), SAL mice show an attenuated HPA response, whereas LAB rats show an elevated HPA response. In both rodent lines, the display of aggression is associated with high neuronal activation in the central amygdala, but reduced neuronal activation in the lateral septum. Furthermore, in the lateral septum, SAL mice have a reduced vasopressinergic fiber network, and LAB rats show a decreased vasopressin release during the display of aggression. Moreover, the two lines show several indications of an increased serotonergic neurotransmission. The relevance of these findings in relation to high aggression and stress coping is discussed. In conclusion, exploring neurobiological systems in animals sharing relevant behavioral characteristics might be a useful approach to identify general mechanisms of action, which in turn can improve our understanding of specific behavioral symptoms in human psychiatric disorders.
Transhepatic Approach for a Small Paracaval Tumor in Repeat Resection
Authors: Ishizawa Takeaki , Hasegawa Kiyoshi , Ikeda Mami , Aoki Taku , Sano Keiji , Imamura Hiroshi , Kokudo Norihiro , Makuuchi Masatoshi
Published: September 2007

To resect a small liver tumor located in the paracaval portion, we adopted transhepatic enucleation, i.e. enucleation of the tumor from the transected plane along the main portal fissure. In contrast to caudate lobectomy, this procedure can save dissection around the liver and vena cava, which would increase operation time and blood loss especially in repeat surgery after removal of Couinaud’s segment VII or the right lateral sector. It can also minimize the liver parenchymal volume to be resected. The transhepatic enucleation would be a safe and recommendable surgical technique for a small paracaval tumor in repeat resection and/or in patients with poor liver functional reserve.
European Survey on the Application of Vascular Clamping in Liver Surgery
Authors: van der Bilt J.D.W. , Livestro D.P. , Borren A. , van Hillegersberg R. , Borel Rinkes I.H.M.
Published: September 2007

Background: This study evaluated the frequency, the indications and techniques of vascular clamping during liver resection and during thermal destruction therapies, as currently used by hepatic surgeons throughout Europe. Methods: A web-based questionnaire was distributed among 621 physicians, including all members of the European Hepato-Pancreato-Biliary Association and the European Surgical Association. Results: The overall response rate was 50%. During liver resection, vascular clamping is never applied by 10%, on indication by 71%, and routinely by 19%. Routine clamping is particularly performed by high-volume and senior surgeons and appears to be associated with longer ischaemia times. Intermittent inflow occlusion is the clamping method of choice for more than 65% of surgeons and total ischaemia times are usually limited to 15–30 min. During thermal ablation, vascular clamping is never used by 57%, on indication by 37%, and routinely by 7%; it is particularly applied for large tumours and for tumours close to large vessels, and ischaemia times are shorter. Conclusions: Vascular clamping during liver resection is frequently used; during thermal ablation it is preserved for larger tumours or tumours in the vicinity of large vessels. Complete inflow occlusion is the most frequently used technique, with a distinct preference for intermittent clamping.
Treatment of Grade 2 and 3 Hemorrhoids with Doppler-Guided Hemorrhoidal Artery Ligation
Authors: Wallis de Vries B.M. , van der Beek E.S.J. , de Wijkerslooth L.R.H. , van der Zwet W.C. , van der Hoeven J.A.B. , Eeftinck Schattenkerk M. , Eddes E.H.
Published: September 2007

Aim: We evaluated the results of the Doppler-guided hemorrhoidal arterial ligation (DG-HAL) method in the management of symptomatic grade 2 and 3 hemorrhoids. Patients and Methods: Between June 2005 and March 2006, 110 consecutive patients with symptomatic grade 2 and 3 hemorrhoids according to the DG-HAL method were treated. All procedures were performed in daycare under spinal anesthesia. The primary objective was the reduction in hemorrhoidal gradation as determined by proctoscopy; the secondary was patient satisfaction. This was measured by interviewing patients over the telephone. Results: The average age was 47.6 years. 42 patients had grade 2 hemorrhoids, 68 grade 3. An average of 7.3 ligations were placed. Proctoscopy showed that, after 6 weeks, 97 (88%) patients had a significant improvement in their hemorrhoidal gradation. After an average follow-up of 37 weeks, 93 of the 110 (84.5%) patients were satisfied with the postoperative result. Mortality was 0% and morbidity 3%. Conclusion: DG-HAL is a safe and effective treatment in the management of symptomatic grade 2 and 3 hemorrhoids.
The Disregarded West: Diet and Behavioural Ecology of Olive Baboons in the Ivory Coast
Authors: Britta K. Kunz , Linsenmair K. Eduard
Published: September 2007

Despite living under environmental conditions considerably distinct from those of savannah baboons (Papiospp.) in East and southern Africa, very little is known about westernPapiopopulations. We monitored the abundance and group sizes of olive baboons(P. anubis)in the savannah-forest mosaic of the Comoé National Park, northern Ivory Coast, and observed 2 habituated groups of different sizes. Against expectations for the kind of habitat, the individual density was low, yielding only 1.2 baboons/km2. The groups were small, comprising on average 15 individuals, and the proportion of 1-male groups (50–63%) was remarkably high. One-male groups were more female biased than multi-male groups. The baboons were highly frugivorous, spending about 50% of their feeding time on fruits and seeds of at least 79 woody plant species. The 2 habituated groups had comparatively large home ranges and used forests more often than expected by random. We argue that regular subgrouping of the larger focal group and different habitat quality countervailed inter-group variations. Differences from other study sites, however, are not completely explained by current models of baboon (socio)ecology. It appears that the social organization of olive baboons is more flexible than assumed from data on East African populations.
Feasibility of Sequential Therapy with FOLFIRI Followed by Docetaxel/Cisplatin in Patients with Radically Resected Gastric Adenocarcinoma
Authors: Di Bartolomeo Maria , Buzzoni Roberto , Mariani Luigi , Ferrario Erminia , Katia Dotti , Gevorgyan Arpine , Zilembo Nicoletta , Bordonaro Roberto , Bochicchio Anna Maria , Massidda Bruno , Ardizzoia Antonio , Marini Giovanni , Aitini Enrico , Schieppati Giuseppe , Comella Giuseppe , Pinotti Graziella , Palazzo Salvatore , Cicero Giovanni , Bajetta Emilio
Published: September 2007

Objective: Combination therapies of fluorouracil (FU) with irinotecan (CPT-11) and docetaxel plus cisplatin have been proven to be active in metastatic gastric cancer. In this paper, we present the results of a phase III trial in which these two combinations given sequentially were compared to mitomycin C (MMC) monochemotherapy in an adjuvant setting. Methods: 169 patients with radically resected gastric cancer were randomized to receive CPT-11 (180 mg/m2 day 1), leucovorin (100 mg/m2 days 1–2), FU (400–600 mg/m2 days 1–2, q 14; for four cycles; FOLFIRI regimen), followed by docetaxel (85 mg/m2 day 1), cisplatin (75 mg/m2 day 1, q 21; for three cycles; arm A), or MMC (8 mg/m2 days 1–2 as 2-hour infusion, q 42; for four cycles; arm B). All patients had histologically confirmed gastric carcinoma with nodal positivity or pT3/4. A total of 166 patients (85 in arm A and 81 in arm B) were treated. Adjuvant treatment was completed in 76% of the patients in arm A and in 70% of the patients in arm B. The main grade 3/4 side effects recorded were neutropenia in 35%, with only 1 febrile patient, and diarrhea in 11% in arm A, and thrombocytopenia in 10% and neutropenia in 7% in arm B. The FOLFIRI regimen and docetaxel/cisplatin given in sequence was well tolerated and feasible in adjuvant setting. This sequence treatment currently represents the experimental arm of an ongoing multicenter trial.
Hypoxia-Induced Mediators of Stem/Progenitor Cell Trafficking Are Increased in Children With Hemangioma
Authors: Kleinman Mark E. , Greives Matthew R. , Churgin Samara S. , Blechman Keith M. , Chang Eric I. , Ceradini Daniel J. , Tepper Oren M. , Gurtner Geoffrey C.
Published: September 2007

Objective—

The mechanism of neovascularization during the proliferative phase of infantile hemangioma is poorly understood. It is known that circulating bone marrow-derived endothelial progenitor cells (EPCs) form new blood vessels in ischemic tissues using mediators regulated by the transcription factor, HIF-1α. Mobilization of EPCs is enhanced by VEGF-A, matrix metalloproteinase (MMP)-9, and estrogen, whereas homing is secondary to localized expression of stromal cell-derived factor-1α (SDF-1α). We examined whether these mediators of EPC trafficking are upregulated during the proliferation of infantile hemangioma.

Methods and Results—

Surgical specimens and blood samples were obtained from children with proliferating hemangioma and age-matched controls (n=10, each group). VEGF-A and MMP-9 levels were measured in blood, and tissue sections were analyzed for SDF-1α, MMP-9, VEGF-A, and HIF-1α. The role of estrogen as a modulator of hemangioma endothelial cell growth was also investigated. We found that all these mediators of EPC trafficking are elevated in blood and specimens from children with proliferating infantile hemangioma. In vitro, the combination of hypoxia and estrogen demonstrated a synergistic effect on hemangioma endothelial cell proliferation.

Conclusions—

These findings demonstrate that proliferating hemangiomas express known mediators of vasculogenesis and suggest that this process may play a role in the initiation or progression of this disease.
PECAM-1: A Multi-Functional Molecule in Inflammation and Vascular Biology
Authors: Woodfin Abigail , Voisin Mathieu-Benoit , Nourshargh Sussan
Published: September 2007

Platelet endothelial cell adhesion molecule-1 (PECAM-1 or CD31) is a molecule expressed on all cells within the vascular compartment, being expressed to different degrees on most leukocyte sub-types, platelets, and on endothelial cells where its expression is largely concentrated at junctions between adjacent cells. As well as exhibiting adhesive properties, PECAM-1 is an efficient signaling molecule and is now known to have diverse roles in vascular biology including roles in angiogenesis, platelet function, and thrombosis, mechanosensing of endothelial cell response to fluid shear stress, and regulation of multiple stages of leukocyte migration through venular walls. This review will focus on some new developments with respect to the role of PECAM-1 in inflammation and vascular biology, highlighting the emerging complexities associated with the functions of this unique molecule.
Leptin Signaling and Obesity
Authors: Yang Ronghua , Barouch Lili A.
Published: September 2007

Leptin, among the best known hormone markers for obesity, exerts pleiotropic actions on multiple organ systems. In this review, we summarize major leptin signaling pathways, namely Janus-activated kinase/signal transducers and activators of transcription and mitogen-activated protein kinase, including possible mechanisms of leptin resistance in obesity. The effects of leptin on the cardiovascular system are discussed in detail, including its contributions to hypertension, atherosclerosis, depressed myocardial contractile function, fatty acid metabolism, hypertrophic remodeling, and reduction of ischemic/reperfusion injury. The overall goal is to summarize current understanding of how altered leptin signaling in obesity contributes to obesity-related cardiovascular disease.
On Phrase Structure and Brain Responses: A Comment on Bahlmann, Gunter, and Friederici (2006)
Authors: Corballis Michael C.
Published: September 2007

Bahlmann et al. (2006) reported an experiment on event-related brain potentials of sequences of syllables obeying two rules, one defined by AnBn and the other by (AB)n, where the As and Bs are different classes of syllables. They interpreted their findings on the assumption that AnBn are parsed according a center-embedded phrase-structure grammar. In fact, such sequences are much more likely to be parsed in terms of the repetition of element types, without reference to phrase structure. This raises a general issue about attempting to study syntactic processing independently of semantics.
Neural Biases to Covert and Overt Signals of Fear: Dissociation by Trait Anxiety and Depression
Authors: Williams Leanne M. , Kemp Andrew H. , Felmingham Kim , Liddell Belinda J. , Palmer Donna M. , Bryant Richard A.
Published: September 2007

Although biases toward signals of fear may be an evolutionary adaptation necessary for survival, heightened biases may be maladaptive and associated with anxiety or depression. In this study, event-related potentials (ERPs) were used to examine the time course of neural responses to facial fear stimuli (versus neutral) presented overtly (for 500 msec with conscious attention) and covertly (for 10 msec with immediate masking to preclude conscious awareness) in 257 nonclinical subjects. We also examined the impact of trait anxiety and depression, assessed using psychometric ratings, on the time course of ERPs. In the total subject group, controlled biases to overtly processed fear were reflected in an enhancement of ERPs associated with structural encoding (120–220 msec) and sustained evaluation persisting from 250 msec and beyond, following a temporo-occipital to frontal topography. By contrast, covert fear processing elicited automatic biases, reflected in an enhancement of ERPs prior to structural encoding (80–180 msec) and again in the period associated with automatic orienting and emotion encoding (230–330 msec), which followed the reverse frontal to temporo-occipital topography. Higher levels of trait anxiety (in the clinical range) were distinguished by a heightened bias to covert fear (speeding of early ERPs), compared to higher depression which was associated with an opposing bias to overt fear (slowing of later ERPs). Anxiety also heightened early responses to covert fear, and depression to overt fear, with subsequent deficits in emotion encoding in each case. These findings are consistent with neural biases to signals of fear which operate automatically and during controlled processing, feasibly supported by parallel networks. Heightened automatic biases in anxiety may contribute to a cycle of hypervigilance and anxious thoughts, whereas depression may represent a “burnt out” emotional state in which evaluation of fear stimuli is prolonged only when conscious attention is allocated.
Early MEG Activation Dynamics in the Left Temporal and Inferior Frontal Cortex Reflect Semantic Context Integration
Authors: Shtyrov Yury , Pulvermüller Friedemann
Published: September 2007

Traditional views link semantic context integration to neurophysiological activity at 300–500 msec. To study possible early dynamics related to semantic context integration, we recorded, in passive oddball paradigm, magnetic evoked responses to spoken word pairs, the second word being either congruent or incongruent with the first one. The same experimental words were placed in orthogonally varied context, thus providing a strict control for any effects of acoustic, phonological, and psycholinguistic stimulus features. Responses to the same critical words were obtained also outside of semantic context. We found that regardless of their acoustic features, semantically incongruent stimuli elicited a brain response already at ∼115 msec after the critical word onset. The same words did not produce such deflection in semantically legal context. The responses were maximal at left temporal and inferior frontal cortical sites, which was also confirmed by distributed current source analysis. The left temporal activation preceded the frontal one by ∼16 msec. No late response dynamics (>350 msec) were found that would reflect the semantic modulation in this nonattend passive design, indicating the possible role of attention in generating the later responses. Our results suggest that the earliest brain processes of semantic context integration can occur at ∼100 msec after the onset of spoken words in the left inferior frontal and superior temporal cortex.
The Neural Substrates of Visual Perceptual Learning of Words: Implications for the Visual Word Form Area Hypothesis
Authors: Xue Gui , Poldrack Russell A.
Published: September 2007

It remains under debate whether the fusiform visual word form area (VWFA) is specific to visual word form and whether visual expertise increases its sensitivity (Xue et al., 2006; Cohen et al., 2002). The present study examined three related issues: (1) whether the VWFA is also involved in processing foreign writing that significantly differs from the native one, (2) the effect of visual word form training on VWFA activation after controlling the task difficulty, and (3) the transfer of visual word form learning. Eleven native English speakers were trained, during five sessions, to judge whether two subsequently flashed (100-msec duration with 200-msec interval) foreign characters (i.e., Korean Hangul) were identical or not. Visual noise was added to the stimuli to manipulate task difficulty. In functional magnetic resonance imaging scans before and after training, subjects performed the task once with the same noise level (i.e., parameter-matched scan) and once with noise level changed to match performance from pretraining to posttraining (i.e., performance-matched scan). Results indicated that training increased the accuracy in parameter-matched condition but remained constant in performance-matched condition (because of increasing task difficulty). Pretraining scans revealed stronger activation for English words than for Korean characters in the left inferior temporal gyrus and the left inferior frontal cortex, but not in the VWFA. Visual word form training significantly decreased the activation in the bilateral middle and left posterior fusiform when either parameters or performance were matched and for both trained and new items. These results confirm our conjecture that the VWFA is not dedicated to words, and visual expertise acquired with training reduces rather than increases its activity.
Human Attentional Networks: A Connectionist Model
Authors: Wang Hongbin , Fan Jin
Published: September 2007

Recent evidence in cognitive neuroscience has suggested that attention is a complex organ system subserved by at least three attentional networks in the brain, for alerting, orienting, and executive control functions. However, how these different networks work together to give rise to the seemingly unitary mental faculty of attention remains unclear. We describe a connectionist model of human attentional networks to explore the possible interplays among the networks from a computational perspective. This model is developed in the framework of leabra (local, error-driven, and associative, biologically realistic algorithm) and simultaneously involves these attentional networks connected in a biologically inspired way. We evaluate the model by simulating the empirical data collected on normal human subjects using the Attentional Network Test (ANT). The simulation results fit the experimental data well. In addition, we show that the same model, with a single parameter change that affects executive control, is able to simulate the empirical data collected from patients with schizophrenia. This model represents a plausible connectionist explanation for the functional structure and interaction of human attentional networks.
Rapid Onset Relational Memory Effects Are Evident in Eye Movement Behavior, but Not in Hippocampal Amnesia
Authors: Hannula Deborah E. , Ryan Jennifer D. , Tranel Daniel , Cohen Neal J.
Published: September 2007

Little is known about the mechanisms by which memory for relations is accomplished, or about the time course of the critical processes. Here, eye movement measures were used to examine the time course of subjects' access to and use of relational memory. In four experiments, participants studied faces superimposed on scenic backgrounds and were tested with three-face displays superimposed on the scenes viewed earlier. Participants exhibited disproportionate viewing of the face originally studied with the scene, compared to other equally familiar faces in the test display. When a preview of a previously viewed scene was provided, permitting expectancies about the to-be-presented face to emerge, disproportionate viewing was manifested within 500–750 msec after test display onset, more than a full second in advance of explicit behavioral responses, and occurred even when overt responses were not required. In the absence of preview, the viewing effects were delayed by approximately 1 sec. Relational memory effects were absent in the eye movement behavior of amnesic patients with hippocampal damage, suggesting that these effects depend critically on the hippocampal system. The results provide an index of memory for face-scene relations, indicate the time by which retrieval and identification of these relations occur, and suggest that retrieval and use of relational memory depends critically on the hippocampus and occurs obligatorily, regardless of response requirements.
Haptic Feedback in a Telepresence System for Endoscopic Heart Surgery
Authors: Mayer Hermann , Nagy Istvan , Knoll Alois , Braun Eva U , Bauernschmitt Robert , Lange Rüdiger
Published: September 2007

The implementation of telemanipulator systems for cardiac surgery enabled heart surgeons to perform delicate minimally invasive procedures with high precision under stereoscopic view. At present, commercially available systems do not provide force-feedback or Cartesian control for the operating surgeon. The lack of haptic feedback may cause damage to tissue and can cause breaks of suture material. In addition, minimally invasive procedures are very tiring for the surgeon due to the need for visual compensation for the missing force feedback. While a lack of Cartesian control of the end effectors is acceptable for surgeons (because every movement is visually supervised), it prevents research on partial automation. In order to improve this situation, we have built an experimental telemanipulator for endoscopic surgery that provides both force-feedback (in order to improve the feeling of immersion) and Cartesian control as a prerequisite for automation. In this article, we focus on the inclusion of force feedback and its evaluation. We completed our first bimanual system in early 2003 (EndoPAR Endoscopic Partial Autonomous Robot). Each robot arm consists of a standard robot and a surgical instrument, hence providing eight DOF that enable free manipulation via trocar kinematics. Based on the experience with this system, we introduced an improved version in early 2005. The new ARAMIS system (Autonomous Robot Assisted Minimally Invasive Surgery) has four multi-purpose robotic arms mounted on a gantry above the working space. Again, the arms are controlled by two force-feedback devices, and 3D vision is provided. In addition, all surgical instruments have been equipped with strain gauge force sensors that can measure forces along all translational directions of the instrument's shaft. Force-feedback of this system was evaluated in a scenario of robotic heart surgery, which offers an impression very similar to the standard, open procedures with high immersion. It enables the surgeon to palpate arteriosclerosis, to tie surgical knots with real suture material, and to feel the rupture of suture material. Therefore, the hypothesis that haptic feedback in the form of sensory substitution facilitates performance of surgical tasks was evaluated on the experimental platform described in the article (on the EndoPAR version). In addition, a further hypothesis was explored: The high fatigue of surgeons during and after robotic operations may be caused by visual compensation due to the lack of force-feedback (Thompson, J., Ottensmeier, M., & Sheridan, T. 1999. Human Factors in Telesurgery, Telmed Journal, 5 (2) 129–137.).
Binaural Source Localization and Spatial Audio Reproduction for Telepresence Applications
Authors: Keyrouz Fakheredine , Diepold Klaus
Published: September 2007

Telepresence is generally described as the feeling of being immersed in a remote environment, be it virtual or real. A multimodal telepresence environment, equipped with modalities such as vision, audition, and haptic, improves immersion and augments the overall perceptual presence. The present work focuses on acoustic telepresence at both the teleoperator and operator sites. On the teleoperator side, we build a novel binaural sound source localizer using generic Head Related Transfer Functions (HRTFs). This new localizer provides estimates for the direction of a single sound source given in terms of azimuth and elevation angles in free space by using only two microphones. It also uses an algorithm that is efficient compared to the currently known algorithms used in similar localization processes. On the operator side, the paper addresses the problem of spatially interpolating HRTFs for densely sampled high-fidelity 3D sound synthesis. In our telepresence application scenario the synthesized 3D sound is presented to the operator over headphones and shall achieve a high-fidelity acoustic immersion. Using measured HRTF data, we create interpolated HRTFs between the existing functions using a matrix-valued interpolation function. The comparison with existing interpolation methods reveals that our new method offers superior performance and is capable of achieving high-fidelity reconstructions of HRTFs.
Transparent Data Reduction in Networked Telepresence and Teleaction Systems. Part I: Communication without Time Delay
Authors: Hirche Sandra , Hinterseer Peter , Steinbach Eckehard , Buss Martin
Published: September 2007

Limited communication resources represent a major challenge in networked tele-presence and teleaction systems. Video and audio compression schemes are well advanced employing models of human perception. In contrast to that haptic data reduction schemes are rather poorly treated in the known literature. This article introduces a novel approach to reduce network traffic in haptic telepresence systems exploiting limits in human haptic perception. With the proposed deadband control approach, data packets are transmitted only if the signal change exceeds a signal amplitude dependent perception threshold. Experimental user studies show that an average network traffic reduction of up to 85% can be achieved without significantly impairing the perception of the remote environment. The assumption throughout this article is that there is no communication time delay.
THE WCRP CMIP3 Multimodel Dataset: A New Era in Climate Change Research
Authors: Meehl Gerald A. , Covey Curt , Delworth Thomas , Latif Mojib , McAvaney Bryant , Mitchell John F. B. , Stouffer Ronald J. , Taylor Karl E.
Published: September 2007

A coordinated set of global coupled climate model [atmosphere–ocean general circulation model (AOGCM)] experiments for twentieth- and twenty-first-century climate, as well as several climate change commitment and other experiments, was run by 16 modeling groups from 11 countries with 23 models for assessment in the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4). Since the assessment was completed, output from another model has been added to the dataset, so the participation is now 17 groups from 12 countries with 24 models. This effort, as well as the subsequent analysis phase, was organized by the World Climate Research Programme (WCRP) Climate Variability and Predictability (CLIVAR) Working Group on Coupled Models (WGCM) Climate Simulation Panel, and constitutes the third phase of the Coupled Model Intercomparison Project (CMIP3). The dataset is called the WCRP CMIP3 multimodel dataset, and represents the largest and most comprehensive international global coupled climate model experiment and multimodel analysis effort ever attempted. As of March 2007, the Program for Climate Model Diagnostics and Intercomparison (PCMDI) has collected, archived, and served roughly 32 TB of model data. With oversight from the panel, the multimodel data were made openly available from PCMDI for analysis and academic applications. Over 171 TB of data had been downloaded among the more than 1000 registered users to date. Over 200 journal articles, based in part on the dataset, have been published AMERICAN METEOROLOGICAL SOCIETY so far. Though initially aimed at the IPCC AR4, this unique and valuable resource will continue to be maintained for at least the next several years. Never before has such an extensive set of climate model simulations been made available to the international climate science community for study. The ready access to the multimodel dataset opens up these types of model analyses to researchers, including students, who previously could not obtain state-of-the-art climate model output, and thus represents a new era in climate change research. As a direct consequence, these ongoing studies are increasing the body of knowledge regarding our understanding of how the climate system currently works, and how it may change in the future.
Regional Climate Modeling for the Developing World: The ICTP RegCM3 and RegCNET
Authors: Pal Jeremy S. , Giorgi Filippo , Bi Xunqiang , Elguindi Nellie , Solmon Fabien , Gao Xuejie , Rauscher Sara A. , Francisco Raquel , Zakey Ashraf , Winter Jonathan , Ashfaq Moetasim , Syed Faisal S. , Bell Jason L. , Diffenbaugh Noah S. , Karmacharya Jagadish , Konaré Abourahamane , Martinez Daniel , da Rocha Rosmeri P. , Sloan Lisa C. , Steiner Allison L.
Published: September 2007

Regional climate models are important research tools available to scientists around the world, including in economically developing nations (EDNs). The Earth Systems Physics (ESP) group of the Abdus Salam International Centre for Theoretical Physics (ICTP) maintains and distributes a state-of-the-science regional climate model called the ICTP Regional Climate Model version 3 (RegCM3), which is currently being used by a large research community for a diverse range of climate-related studies. The RegCM3 is the central, but not only, tool of the ICTP-maintained Regional Climate Research Network (RegCNET) aimed at creating south–south and north–south scientific interactions on the topic of climate and associated impacts research and modeling. In this paper, RegCNET, RegCM3, and illustrative results from RegCM3 benchmark simulations applied over south Asia, Africa, and South America are presented. It is shown that RegCM3 performs reasonably well over these regions and is therefore useful for climate studies in EDNs.
Estuarine Adjustment
Authors: MacCready Parker
Published: September 2007

Subtidal adjustment of estuarine salinity and circulation to changing river flow or tidal mixing is explored using a simplified numerical model. The model employs tidally averaged, width-averaged physics, following Hansen and Rattray, extended to include 1) time dependence, 2) tidally averaged mixing parameterizations, and 3) arbitrary variation of channel depth and width. By linearizing the volume-integrated salt budget, the time-dependent system may be distilled to a first-order, forced, damped, ordinary differential equation. From this equation, analytical expressions for the adjustment time and sensitivity of the length of the salt intrusion are developed. For estuaries in which the up-estuary salt flux is dominated by vertically segregated gravitational circulation, this adjustment time is predicted to be TADJ = (1/6)L/u, where L is the length of the salt intrusion and u is the section-averaged velocity (i.e., that due to the river flow). The importance of the adjustment time becomes apparent when considering forcing time scales. Seasonal river-flow variation is much slower than typical adjustment times in systems such as the Hudson River estuary, and thus the response may be quasi steady. Spring–neap mixing variation, in contrast, has a period comparable to typical adjustment times, and so unsteady effects are more important. In this case, the stratification may change greatly while the salt intrusion is relatively unperturbed.