bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Significance and Therapeutic Potential of the Programmed Death-1 Ligand/Programmed Death-1 Pathway in Human Pancreatic Cancer
Authors: Nomi Takeo , Sho Masayuki , Akahori Takahiro , Hamada Kaoru , Kubo Atsushi , Kanehiro Hiromichi , Nakamura Shinji , Enomoto Koji , Yagita Hideo , Azuma Miyuki , Nakajima Yoshiyuki
Published: April 2007

Purpose: The programmed death-1 ligand/programmed death-1 (PD-L/PD-1) pathway has been recently suggested to play a pivotal role in the immune evasion of tumors from host immune system. In this study, we tried to reveal the clinical importance and therapeutic potential of the PD-L/PD-1 pathway in pancreatic cancer, which is one of the most aggressive and intractable malignant tumors.

Experimental Design: We used immunohistochemistry to investigate PD-L expression in 51 patients with pancreatic cancer who underwent surgery and explored the therapeutic efficacy of blocking the PD-L1/PD-1 pathway in murine pancreatic cancer in vivo.

Results: PD-L1–positive patients had a significantly poorer prognosis than the PD-L1–negative patients, whereas there was no significant correlation of tumor PD-L2 expression with patient survival. PD-L1 expression was inversely correlated with tumor-infiltrating T lymphocytes, particularly CD8+ T cells. These clinical data have suggested that the PD-L1/PD-1 pathway may be a critical regulator in human pancreatic cancer. Monoclonal antibodies against PD-L1 or PD-1 induced a substantial antitumor effect on murine pancreatic cancer in vivo. PD-L1 blockade promoted CD8+ T-cell infiltration into the tumor and induced local immune activation. Furthermore, the combination of anti–PD-L1 monoclonal antibody and gemcitabine exhibited a significant synergistic effect on murine pancreatic cancer and resulted in complete response without overt toxicity.

Conclusion: Our data suggest for the first time that PD-L1 status may be a new predictor of prognosis for patients with pancreatic cancer and provide the rationale for developing a novel therapy of targeting the PD-L/PD-1 pathway against this fatal disease.
Phase I Evaluation of a Fully Human Anti–αv Integrin Monoclonal Antibody (CNTO 95) in Patients with Advanced Solid Tumors
Authors: Mullamitha Saifee A. , Ton Nhuan C. , Parker Geoff J.M. , Jackson Alan , Julyan Peter J. , Roberts Caleb , Buonaccorsi Gio A. , Watson Yvonne , Davies Karen , Cheung Sue , Hope Lynn , Valle Juan W. , Radford John A. , Lawrance Jeremy , Saunders Mark P. , Munteanu Mihaela C. , Nakada Marian T. , Nemeth Jeffrey A. , Davis Hugh M. , Jiao Qun , Prabhakar Uma , Lang Zhihui , Corringham Robert E. , Beckman Robert A. , Jayson Gordon C. ,   in association with the Biotherapy Development Association
Published: April 2007

Purpose: A fully human monoclonal antibody to anti–αv integrins (CNTO 95) has been shown to inhibit angiogenesis and tumor growth in preclinical studies. We assessed the safety and pharmacokinetics of CNTO 95 in patients with advanced refractory solid tumors.

Experimental Design: In this phase I trial, CNTO 95 (0.1, 0.3, 1.0, 3.0, and 10.0 mg/kg) was infused on days 0, 28, 35, and 42, and clinical assessments, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and [18F]-2-fluorodeoxyglucose positron emission tomography (FDG-PET) were done. Patients achieving stable disease or better were eligible for extended dosing every 3 weeks for up to 12 months.

Results: Among the 24 enrolled patients, CNTO 95 was associated with one episode of grade III and four episodes of grade II infusion-related fever (all responded to acetaminophen). Of the six patients who received extended dosing, one patient (10.0 mg/kg), with cutaneous angiosarcoma, had a 9-month partial response. Pre- and post-treatment lesion biopsies confirmed tumor cell αv integrin expression, as well as CNTO 95 penetration of the tumor and localization to tumor cells in association with reduced bcl-2 expression. A lesion in one patient (10.0 mg/kg) with stable ovarian carcinosarcoma was no longer detectable by FDG-PET by day 49. Exposure to CNTO 95 seemed to increase in a greater-than-dose-proportional manner; dose-dependent mean half-life ranged from 0.26 to 6.7 days.

Conclusions: CNTO 95 was generally well tolerated. Six patients received extended therapy, including one patient with a prolonged response. Biopsy data confirmed tumor localization and pharmacodynamic activity.
Targeting Checkpoint Kinase 1 in Cancer Therapeutics
Authors: Tse Archie N. , Carvajal Richard , Schwartz Gary K.
Published: April 2007

Progression through the cell cycle is monitored by surveillance mechanisms known as cell cycle checkpoints. Our knowledge of the biochemical nature of checkpoint regulation during an unperturbed cell cycle and following DNA damage has expanded tremendously over the past decade. We now know that dysfunction in cell cycle checkpoints leads to genomic instability and contributes to tumor progression, and most agents used for cancer therapy, such as cytotoxic chemotherapy and ionizing radiation, also activate cell cycle checkpoints. Understanding how checkpoints are regulated is therefore important from the points of view of both tumorigenesis and cancer treatment. In this review, we present an overview of the molecular hierarchy of the checkpoint signaling network and the emerging role of checkpoint targets, especially checkpoint kinase 1, in cancer therapy. Further, we discuss the results of recent clinical trials involving the nonspecific checkpoint kinase 1 inhibitor, UCN-01, and the challenges we face with this new therapeutic approach.
Sixteen Years of Experience with Stone Management in Horseshoe Kidneys
Authors: Viola Domenico , Anagnostou Theodore , Thompson Trevor J. , Smith Gordon , Moussa Sami A. , Tolley David A.
Published: March 2007

Introduction: Horseshoe kidney is the commonest congenital renal fusion anomaly, and is often complicated by urolithiasis. We focus on our 16 years of experience with stone management in horseshoe kidneys. Materials and Methods: We reviewed the progress of 44 patients treated between 1987 and 2002. Shock wave lithotripsy (SWL) was used in 25 patients; the average stone surface area was 91 (range 10–1,600) mm2 and average follow-up was 36.5 (range 1–91) months. 19 patients underwent percutaneous nephrolithotomy (PCNL); the average stone surface area was 197 (range 6–2,400) mm2. Follow-up data are available for 8 patients and the average follow-up was 42.3 (range 3–144) months. Results: In the SWL group the 3-month stone-free rate (SFR) was only 31%. In the PCNL group the SFR was 75% on the postoperative day-1 KUB. Complications occurred in 9 patients. Conclusions: Stone management in horseshoe kidneys is challenging: PCNL produces a higher SFR with minimal major complications and failed access. PCNL thus appears to be the preferred management option in patients with urolithiasis in horseshoe kidneys.
Is Second-Line Enuretic Alarm Therapy after Unsuccessful Pharmacotherapy Superior to First-Line Therapy in the Treatment of Monosymptomatic Nocturnal Enuresis?
Authors: Tuygun Can , Eroglu Muzaffer , Bakirtas Hasan , Gucuk Adnan , Zengin Kursad , Imamoglu Abdurrahim
Published: March 2007

Introduction: We aimed at comparing the success rates of primary enuretic alarm therapy with those of secondary alarm therapy after failed pharmacotherapy in the treatment of monosymptomatic nocturnal enuresis (MNE). Patients and Methods: We randomly applied enuretic alarm therapy in 35 MNE patients (group 1) and desmopressin therapy in 49 MNE patients (group 2). The success and rebound rates after 3 and 6 months were determined. We also applied enuretic alarm therapy as a secondary treatment in 19 group 2 patients with complete rebound after 6 months (group 3). The success rates of patients who have received primary and secondary enuretic alarm therapy were compared. Results: The success rates for groups 1 and 2 were 82.65 and 81.63%, respectively (p = 0.885), at 3 months and 54.28 and 26.53%, respectively (p = 0.007), at 6 months. The success rates in group 3 were 84.21 and 52.63%, respectively, at 3 and 6 months. When these success rates were compared between groups 1 and 3, no statistically significant difference was found (p = 1.000). Conclusion: Prior pharmacotherapy did not increase success rates of alarm therapy in our MNE patients.
Maturational Effects of Single and Multiple Early-Life Seizures on AMPA Receptors in Prepubescent Hippocampus
Authors: Friedman L.K. , Avallone J.M. , Magrys B.
Published: April 2007

The effects of single versus multiple episodes of status epilepticus on the expression of AMPA receptors during a critical growth spurt are unknown. To determine whether the pattern of hippocampal AMPA receptor subunit expression depends upon the age of the animal, timing and number of perinatal seizures, we characterized maturational changes in AMPA receptor protein levels of the hippocampus with immunohistochemistry and Western blotting in rats of juvenile ages with and without a history of neonatal seizures. Kainic acid (KA) was used to induce a single episode of status epilepticus (1 × KA) in rats on P20 or P30. Animals with a history of multiple seizures (3 × KA) were given KA on P6, P9, and then on P20 or P30. After 1 × KA, in P20 and P30 rats that are preferentially sensitive to CA1 damage, GluR1 immunoreactivity was depleted remarkably in CA1 stratum pyramidale and stratum lucidum and only morphologically healthy cells were faintly labeled. At P30, GluR2 subunit expression was nearly absent in the healthy cells and increased within the injured CA1 neuronal population. Western blot analysis confirmed that the GluR1/GluR2 ratio was decreased at P20 and further decreased at P30. A history of perinatal seizures (3 × KA) prevented the age-dependent alterations in the CA1. Except for areas of cell loss, NR1 and NR2A/B antibody labeling was relatively stable throughout the hippocampus at both ages and conditions examined. Data suggest that (i) Ca2+ permeable AMPA receptors may not be responsible for neuronal injury or irreversible cell loss and that (ii) the expression of AMPA receptors after status epilepticus depends upon the age of the animal, the timing of the first insult and subsequent formation of AMPA receptor subunit compositions within specific populations of hippocampal neurons.
Comparative Aspects of GH and Metabolic Regulation in Lower Vertebrates
Authors: Rousseau Karine , Dufour Sylvie
Published: April 2007

In all vertebrates, the regulations of growth and energy balance are complex phenomena which involve elaborate interactions between the brain and peripheral signals. Most vertebrates adopt and maintain a life style after birth, but lower vertebrates may have complex life histories involving metamorphoses, migrations and long periods of fasting. In order to achieve the complex developmental programs associated with these changes, coordinated regulation of all aspects of energy metabolism is required. Somatotropic axis (somatostatin (SRIH) growth hormone (GH) and insulin-like growth factor 1 (IGF1), is known to be involved in the regulation of growth and energy balance. Interestingly, recent studies showed that additional factors such as pituitary adenylate cyclase-activated polypeptide (PACAP), corticotropin-releasing hormone (CRH), ghrelin and leptin could also have major roles in the control of growth and metabolism in lower vertebrates (fish, amphibians and reptiles). This mini-review will survey the function of GH and metabolic regulation in lower vertebrates.
The Differentiation between ‘Lack of Insight’ and ‘Dysfunctional Health Beliefs’ in Schizophrenia
Authors: Linden Michael , Godemann Frank
Published: March 2007

Background: ‘Lack of insight’ into one’s own illness is a frequent symptom in schizophrenic disorders. ‘Health beliefs’ are psychological explanations of one’s own health status and are held by all individuals. The question is how they relate to each other. Methods: Lack of insight (according to the definition of the AMDP System) and health beliefs (measured with the Illness Concept Scale) were assessed in 364 schizophrenic outpatients who participated in a study on neuroleptic long-term treatment. Results: ‘Insight into illness’ and ‘health beliefs’ are independent of each other. Insight is related to the current psychopathological status as measured by the Brief Psychiatric Rating Scale, whereas health beliefs are related to personal life experiences. Lack of insight and dysfunctional health beliefs are both associated with patient noncompliance. Conclusion: Poor insight and dysfunctional health beliefs are separate clinical phenomena. Making this distinction is important for guiding research and patient care.
The Cyclin-Dependent Kinase Inhibitor, p27kip1, Has No Correlation with the Malignant Potential of GIST
Authors: Shirin Haim , Kravtsov Vladimir , Shahmurov Mark , Sehayek Shabat Vered , Krinshpon Ivgeni , Alin Avi , Avinoach Ilana , Avni Yona
Published: April 2007

Background: Tumor size and mitotic activity are characteristically associated with the malignant potential and prognosis of gastrointestinal stromal tumors (GIST). However, since neither small tumor size nor low mitotic activity can rule out malignancy, additional factors that may predict malignant behavior have been suggested. Aim: To evaluate the correlation between the cyclin-dependent kinase inhibitor (CDI), p27kip1, expression and the malignant potential of GIST. Methods: Serial sections were evaluated by immunohistochemistry after staining with antibodies against p27/Kip1 and Ki-67 in surgical material obtained from 36 patients with GIST. p27kip1 staining intensity and the percentage of positive cells were investigated for association with the malignancy risk, pathological features, overall survival, and disease-free survival. Histologic grade was assigned by spindle vs. epithelioid cell histology, mucosal invasion, tumor cell necrosis or atypia and the number of mitoses. Results: In the multivariate model, p27kip1 expression was not significantly associated with any of the variables examined except Kit protein-CD117 (r = 0.37, p = 0.03). Comparative evaluation of p27kip1 expression in GIST cells revealed higher levels of p27kip1 in patients who died compared to those who survived (2.04 ± 0.54 vs. 1.3 ± 0.99, p = 0.1). Conclusion: The CDI p27kip1 was not associated with malignancy of GISTs and did not serve as a predictor of survival.
Absence of Alveolar Tears in Rat Lungs with Significant Alveolar Instability
Authors: Pavone Lucio A. , DiRocco Joseph D. , Carney David E. , Gatto Louis A. , McBride Nils-Tomas D. , Norton Jillian A. , Hession Richard M. , Boubert Francoise , Hojnowski Katy A. , LaFollette Ryan L. , Dries David J. , Nieman Gary F.
Published: March 2007

Background: Lung injury associated with the acute respiratory distress syndrome can be exacerbated by improper mechanical ventilation creating a secondary injury known as ventilator-induced lung injury (VILI). We hypothesized that VILI could be caused in part by alveolar recruitment/derecruitment resulting in gross tearing of the alveolus. Objectives: The exact mechanism of VILI has yet to be elucidated though multiple hypotheses have been proposed. In this study we tested the hypothesis that gross alveolar tearing plays a key role in the pathogenesis of VILI. Methods: Anesthetized rats were ventilated and instrumented for hemodynamic and blood gas measurements. Following baseline readings, rats were exposed to 90 min of either normal ventilation (control group: respiratory rate 35 min–1, positive end-expiratory pressure 3 cm H2O, peak inflation pressure 14 cm H2O) or injurious ventilation (VILI group: respiratory rate 20 min–1, positive end-expiratory pressure 0 cm H2O, peak inflation pressure 45 cm H2O). Parameters studied included hemodynamics, pulmonary variables, in vivovideo microscopy of alveolar mechanics (i.e. dynamic alveolar recruitment/derecruitment) and scanning electron microscopy to detect gross tears on the alveolar surface. Results: Injurious ventilation significantly increased alveolar instability after 45 min and alveoli remained unstable until the end of the study (electron microscopy after 90 min revealed that injurious ventilation did not cause gross tears in the alveolar surface). Conclusions: We demonstrated that alveolar instability induced by injurous ventilation does not cause gross alveolar tears, suggesting that the tissue injury in this animal VILI model is due to a mechanism other than gross rupture of the alveolus.
The Initial Response to Inhaled Nitric Oxide Treatment for Intensive Care Unit Patients with Acute Respiratory Distress Syndrome
Authors: Hsu Chien-Wei , Lee David Lin , Lin Shoa-Lin , Sun Shu-Fen , Chang Hsueh-Wen
Published: March 2007

Background: Inhaled nitric oxide (INO) can improve hypoxemia and reduce pulmonary hypertension, but there is a wide range of response to INO. Objectives: The aim of this study was to evaluate the effect of different INO concentrations in acute respiratory distress syndrome (ARDS) patients. Methods: Thirty-two adult ARDS patients who were supported by mechanical ventilator were included. INO was given at a concentration of 1, 5, 10, 20 and 40 ppm, sequentially. Arterial blood gas and mean pulmonary artery pressure (MPAP) were measured 30 min after INO concentrations changed. Results: There was a significant increase in PaO2/FiO2 (p < 0.0001) and a decrease in pulmonary vascular resistance index and MPAP (p < 0.0001) after INO use. INO concentrations required for improving oxygenation were in the range of 1–20 ppm, whereas concentrations required for decreasing MPAP were in the range of 1–40 ppm. PaO2/FiO2 worsened when the INO dose was adjusted above 20 ppm. Sixty-nine percent of ARDS patients were responders; 31% of them were nonresponders. Among responders, 64% of patients responded at 1 ppm, 36% at 5 ppm. Conclusions: The optimal doses for improving oxygenation and reducing PAP differ. The maximum PaO2/FiO2 was observed at a lower INO concentration than that required for the minimal MPAP. There was no further improvement in PaO2/FiO2 when the INO dose was adjusted above 20 ppm. Higher doses of INO treatment worsened oxygenation.
Retreatment of Ruptured Cerebral Aneurysms in Patients Randomized by Coiling or Clipping in the International Subarachnoid Aneurysm Trial (ISAT)
Authors: Campi Adriana , Ramzi Najib , Molyneux Andrew J. , Summers Paul E. , Kerr Richard S.C. , Sneade Mary , Yarnold Julia A. , Rischmiller Joan , Byrne James V.
Published: March 2007

Background and Purpose—

Because the long-term security of endovascular treatments remains uncertain, a follow-up study of the patients treated in the International Subarachnoid Aneurysm Trial was performed to compare the frequency, timing, and consequences of aneurysm recurrence.

Methods—

Patient data were reclassified by actual treatment performed. Aneurysm and patient characteristics, including occlusion grades, time and type of retreatment, and clinical outcomes, were compared. The relationship between these variables and late retreatment as a surrogate for recurrence was analyzed by means of the Cox proportional hazards model.

Results—

Retreatment was performed in 191 of 1096 (17.4%) patients after primary endovascular coiling (EVT) and in 39 of 1012 patients (3.8%) after neurosurgical clipping. After EVT, 97 (8.8%) patients were retreated early and 94 (9.0%) late, 7 (0.6%) after rebleeding and 87 (8.3%) without. The mean time to late retreatment was 20.7 months. After neurosurgical clipping, 30 (2.9%) patients were retreated early and 9 (0.85%) late, 3 (0.3%) after rebleeding and 6 (0.6%) without. The mean time to late retreatment was 5.7 months. The hazard ratio (HR) for retreatment after EVT was 6.9 (95% CI=3.4 to 14.1) after adjustment for age (
P
=0.001, HR=0.97, 95% CI=0.95 to 0.98), lumen size (
P
=0.006, HR=1.1, 95% CI=1.03 to 1.18), and incomplete occlusion (
P
<0.001, HR=7.6, 95% CI=3.3 to 17.5).

Conclusions—

Late retreatment was 6.9 times more likely after EVT. Younger age, larger lumen size, and incomplete occlusion were risk factors for late retreatment after EVT. After neurosurgical clipping, retreatments were earlier; whereas EVT retreatments continued to be performed throughout the follow-up period. Short-term follow-up imaging is therefore insufficient to detect recurrences after EVT.
From Prediction to Learning: Opening Experts' Minds to Unfolding History
Authors: Herrmann Richard K. , Choi Jong Kun
Published: April 2007

Although it would be nice if the intelligence community's tradecraft or the academic community's theories could predict the future, it is essential that international security experts learn quickly and accurately from unfolding history. This article reports on a multiyear study of experts dealing with security on the Korean Peninsula. It examines how experts learn and what can derail rational updating. Three factors common to much of the work in security studies contribute to the problem: the tendency to treat the intentions of other actors as unknowable private information that is beyond empirical examination; the inclination to believe that power provides a parsimonious explanation, even though it is multifaceted and dependent on numerous components; and the penchant for engaging in “factor wars” over which causal factors are most important while paying little attention to the cumulative and interactive effect of multiple factors. Collectively, these three factors produce overconfidence in hindsight and leave experts prisoners to their preconceptions. The article investigates in the Korean case whether translating narrative expert beliefs systems (i.e., theories) into Bayesian networks can open minds and promote more appropriate updating, and suggests that it can.
The Winning Weapon? Rethinking Nuclear Weapons in Light of Hiroshima
Authors: Wilson Ward
Published: April 2007

This article reexamines the widely held presumption that nuclear weapons played a decisive role in winning the war in the Pacific. Based on new research from Japanese, Soviet, and U.S. archives, it concludes that the atomic bombing of Hiroshima on August 6, 1945, played virtually no role in this outcome. A comparison of the responses of high-level Japanese officials to the bombing and the Soviet invasion on August 9 makes clear that the Soviet intervention touched off a crisis, while the bombing of Hiroshima did not. The article examines the evidence that, to save face, Japanese leaders blamed the bomb for losing the war. Finally, it sketches the profound impact this reappraisal may have on how nuclear weapons will be viewed in the future.
From Pin Factories to Gold Farmers: Editorial Introduction to a Research Stream on Cognitive Capitalism, Immaterial Labour, and the General Intellect
Authors: Toscano Alberto
Published: April 2007

This article introduces a series of essays on the related concepts of cognitive capitalism, immaterial labour and the 'general intellect', which will feature in the pages of Historical Materialism from this issue onwards. It outlines the stakes of the theoretical discussion around these concepts and welcomes the recasting in Marxian terms of debates which have o en been monopolised by apologetic treatments of capitalist development. It also identifies five areas which future articles in this 'research stream' will be preoccupied with: (1) the interpretation of Marxian notions, especially arising from the Grundrisse; (2) the philosophy of history and the schemata of social change that underpin concepts such as cognitive capitalism; (3) the identification of hegemonic social figures (e.g. the immaterial labourer, the 'cognitariat'); (4) issues of philosophical anthropology bearing on the definition of knowledge and intellect; (5) the role of debates on value (and its possible crisis) in assessing the idea of knowledge as a productive force.
The Impact of Coastal Boundaries and Small Hills on the Precipitation Distribution across Southern Connecticut and Long Island, New York
Authors: Colle Brian A. , Yuter Sandra E.
Published: March 2007

The modification of precipitation by the coastal land areas of Long Island (LI), New York, and southern Connecticut (CT) is examined for an extratropical cyclone over the northeast United States on 1 December 2004, which produced strong southerly flow (15–30 m s−1) below 900 mb and heavy precipitation over LI. The differential surface roughness at the coast and the hills of LI (30–80 m) and southern CT (100–250 m) enhanced the surface precipitation by 30%–50% over these regions compared with the nearby water region of LI Sound. The three-dimensional precipitation structures are shown using composite Weather Surveillance Radar-1988 Doppler radar data interpolated to a Cartesian grid, which is compared with a 4-km simulation using the fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model (MM5). As the low-level stratification and flow increased at low levels, the MM5 produced a terrain-forced gravity wave over LI and CT upward through 6 km MSL. Precipitation enhancement (2–3 dBZ) occurred from the surface upward to around the freezing level (3 km MSL) across central LI and southern CT, while there was a localized precipitation minimum over LI Sound. A factor separation on a few sensitivity MM5 runs was performed to isolate the impact of small hills and differential friction across the LI coastline. Both the hills and frictional effects have similar contributions to the total precipitation enhancement and the vertical circulations below 3 km. The hills of LI enhanced the gravity wave circulations slightly more than the differential friction above 3 km, while there was little flow and precipitation interaction between the hills and differential friction. A sensitivity simulation without an ice/snow cloud above 3 km MSL revealed that the seeder-feeder process enhanced surface precipitation by about a factor of 4.
A Phase-Plot Method for Diagnosing Vorticity Concentration Mechanisms in Mesoscale Convective Vortices
Authors: Kirk James R.
Published: March 2007

Mesoscale convective vortex (MCV) analysis results show that these vortices form by way of different evolutionary paths. Rewriting the traditional form of the relative vertical vorticity equation in terms of momentum advection curl produces an alternative form of the equation containing two terms. When the terms are normalized and plotted on orthogonal axes, a phase-plot path depicting MCV evolutionary growth is created. Thermodynamics is included in the phase plot by correlating the path to the heating characteristics of the troposphere. The application of the phase-plot scheme to several cases shows that for MCV formation events, there are two interconnected regions that combine to produce the vortex. The upper-middle- and upper-troposphere vorticity growth is governed primarily by vertical motion, with heating driving the vorticity growth in the upper-middle region. The lower-middle and lower-troposphere vorticity growth is governed primarily by horizontal motion, with the vertical heating gradient driving the vorticity growth in the lower-middle region. Which regime leads the vorticity growth is found to be case dependent. In the middle troposphere, evolutionary paths are governed by the relative strengths of heating and heating gradient. Additional phase-plot and mesoscale analyses clarify the characteristics of two MCV formation modes. In some cases, heating drives the complete formation of the MCV, whereas in cases with lesser heating, tipping is vital to the MCV formation process. In total, these results help synthesize many of the various discoveries regarding the origin and formation of the MCV.
Ground-Based Velocity Track Display (GBVTD) Analysis of W-Band Doppler Radar Data in a Tornado near Stockton, Kansas, on 15 May 1999
Authors: Tanamachi Robin L. , Bluestein Howard B. , Lee Wen-Chau , Bell Michael , Pazmany Andrew
Published: March 2007

On 15 May 1999, a storm intercept team from the University of Oklahoma collected high-resolution, W-band Doppler radar data in a tornado near Stockton, Kansas. Thirty-five sector scans were obtained over a period of approximately 10 min, capturing the tornado life cycle from just after tornadogenesis to the decay stage. A low-reflectivity “eye”—whose diameter fluctuated during the period of observation—was present in the reflectivity scans. A ground-based velocity track display (GBVTD) analysis of the W-band Doppler radar data of the Stockton tornado was conducted; results and interpretations are presented and discussed. It was found from the analysis that the axisymmetric component of the azimuthal wind profile of the tornado was suggestive of a Burgers–Rott vortex during the most intense phase of the life cycle of the tornado. The temporal evolution of the axisymmetric components of azimuthal and radial wind, as well as the wavenumber-1, -2, and -3 angular harmonics of the azimuthal wind, are also presented. A quasi-stationary wavenumber-2 feature of the azimuthal wind was analyzed from 25 of the 35 scans. It is shown, via simulated radar data collection in an idealized Burgers–Rott vortex, that this wavenumber-2 feature may be caused by the translational distortion of the vortex during the radar scans. From the GBVTD analysis, it can be seen that the maximum azimuthally averaged azimuthal wind speed increased while the radius of maximum wind (RMW) decreased slightly during the intensification phase of the Stockton tornado. In addition, the maximum azimuthally averaged azimuthal wind speed, the RMW, and the circulation about the vortex center all decreased simultaneously as the tornado decayed.
Nocturnal Meso-Beta Basin and Katabatic Flows on a Midlatitude Island
Authors: Cuxart J. , Jiménez M. A. , Martínez D.
Published: March 2007

A mesoscale simulation for the island of Majorca, Spain, in the western Mediterranean Sea is used to study the nocturnal system of winds under weak synoptic pressure gradients. A very high vertical resolution is used in the first 500 m above ground level to characterize with large detail the thin circulations close to ground, namely, basin and katabatic flows. It is found that the island, the basin, and the slope scales interact strongly, especially when a quasi-steady state is reached in the second part of the night. A high mountain range creates a high pressure area upwind where local winds can develop. Katabatic flows converge to the valleys where they interact with a cold pool, which is advected slowly to sea by the land–sea night-breeze effect combined with a topographic forcing. The katabatic flows experience small entrainment at the top and have well-defined characteristics. The results are partially confirmed by the observations and some satellite images.
A Nonlinear Statistical Model of Turbulent Air–Sea Fluxes
Authors: Bourras Denis , Reverdin Gilles , Caniaux Guy , Belamari Sophie
Published: March 2007

Most of the bulk algorithms used to calculate turbulent air–sea fluxes of momentum and heat are iterative algorithms whose convergence is slow and not always achieved. To avoid these drawbacks that are critical when large datasets must be processed, a statistical model of bulk air–sea fluxes based on artificial neural networks was developed. It was found that classical bulk algorithms were slower than the statistical model, by a factor of 1.75–7 depending on the bulk algorithm selected for the comparison. A set of 12 global analyses of an operational meteorological model as well as in situ data corresponding to equatorial and midlatitude conditions were used to assess the accuracy of the proposed model. The wind stress, latent, and sensible heat fluxes calculated with neural networks have acceptable biases with respect to bulk fluxes, between 0.4% and 1% depending on the flux magnitudes. Moreover, the rms deviation between bulk fluxes and neural network flux estimates is only 0.003 N m−2 for the momentum flux, 0.5 W m−2 for the sensible heat flux, and 1.8 W m−2 for the latent heat flux, at global scale, which is small compared with the natural variability of these quantities or the expected error.
Nanotechnology and Public Interest Dialogue: Some International Observations
Authors: Bowman Diana M. , Hodge Graeme A.
Published: April 2007

This article examines nanotechnology within the context of the public interest. It notes that though nanotechnology research and development investment totalled US$9.6 billion in 2005, the public presently understands neither the implications nor how it might be best governed. The article maps a range of nanotechnology dialogue activities under way within the United Kingdom, the United States, Germany, and Australia. It explores the various approaches to articulating public interest matters and notes a shift in the way in which these governments, on the whole, appear to be attempting to manage nanotechnology “risks.” It argues that open and transparent policy deliberations and extensive public discourse will be pivotal to protecting the public interest, gaining public trust and acceptance of nanotechnologies. The article concludes that though governing emerging technologies in the public interest is not a new concept, nanotechnology does present additional challenges that must be addressed by the guardians of the public interest.
Knowledge and Attitudes of Ugandan Preservice Science and Mathematics Teachers Toward Global and Ugandan Science- and Technology-Based Problems and/or Threats
Authors: Robinson Michael , Tibanyendera Basil , Seltzer-Kelly Debbie
Published: April 2007

This article reports the effects of a science, technology, and society (STS) teaching approach on the knowledge and attitudes of preservice science and mathematics teachers in Uganda toward global science and technology-based problems and/or threats. The responses of a baseline or control group (N = 50) and an experimental group (N = 50) to five questions on the preassessment indicated how little knowledge these preservice teachers had regarding these issues; however, the responses of the experimental group on the postassessment also showed how quickly a short treatment using an STS teaching approach could improve their knowledge. These results also inform planning for science education in Uganda to achieve science literacy in general, and particularly the understanding of environmental science problems and/or threats facing Ugandan citizens.
Gene Expression Profile in Temporal Lobe Epilepsy
Authors: Aronica Eleonora , Gorter Jan A.
Published: April 2007

Epilepsy is one of the most common neurological disorders. Temporal lobe epilepsy (TLE) represents the most frequent epilepsy syndrome in adult patients with resistance to pharmacological treatment. In TLE, the origin of seizure activity typically involves the hippocampal formation, which displays major neuropathological features, described with the term hippocampal sclerosis (HS). The expansion of neurosurgical epilepsy programs has offered the possibility of disposing of clinically well-characterized hippocampal tissue, so that the analysis of molecular mechanisms underlying the structural and functional reorganization occurring in the hippocampus and neighboring areas in TLE patients can be done on a large scale. The recent development of molecular biological technologies permits the analysis of changes in the expression of a large number of genes. This has opened new perspectives for epilepsy research. However, the hippocampal specimens obtained from patients with TLE most often represent an advanced stage of the pathology. For this reason, animal models that reproduce the clinical and histopathological features of TLE are helpful in detecting the early development of the pathological cascade leading to TLE with HS. An overview of recent data of gene expression profiles in human and experimental TLE is presented along with a discussion of the relevance of functional genomics, to develop new hypotheses and to detect likely candidate genes involved in epileptogenesis, as well as possible target molecules for new therapeutic approaches. NEUROSCIENTIST 13(2):100—108, 2007.
The Nucleus Accumbens and Pavlovian Reward Learning
Authors: Day Jeremy J. , Carelli Regina M.
Published: April 2007

The ability to form associations between predictive environmental events and rewarding outcomes is a fundamental aspect of learned behavior. This apparently simple ability likely requires complex neural processing evolved to identify, seek, and use natural rewards and redirect these activities based on updated sensory information. Emerging evidence from both animal and human research suggests that this type of processing is mediated in part by the nucleus accumbens (NAc) and a closely associated network of brain structures. The NAc is required for a number of reward-related behaviors and processes specific information about reward availability, value, and context. In addition, this structure is critical for the acquisition and expression of most Pavlovian stimulus-reward relationships, and cues that predict rewards produce robust changes in neural activity in the NAc. Although processing within the NAc may enable or promote Pavlovian reward learning in natural situations, it has also been implicated in aspects of human drug addiction, including the ability of drug-paired cues to control behavior. This article provides a critical review of the existing animal and human literature concerning the role of the NAc in Pavlovian learning with nondrug rewards and considers some clinical ture concerning the role of the NAc in Pavlovian learning with nondrug implications of these findings. NEUROSCIENTIST 13(2):148—159, 2007.
Matching of Pre- and Postsynaptic Specializations during Synaptogenesis
Authors: Lardi-Studler Barbara , Fritschy Jean-Marc
Published: April 2007

Formation of chemical synapses in the central nervous system is a highly regulated, multistep process that requires bidirectional communication across the synaptic cleft. Neurotransmitter receptors, scaffolding proteins, and signaling molecules need to be concentrated in the postsynaptic density, a specialized membrane microdomain apposed to the active zone of presynaptic terminals, where transmitter release occurs. This precise, synapse-specific matching implicates that sorting and targeting mechanisms exist for the molecular constituents of different types of synapses to ensure correct formation of neuronal circuits in the brain. There is considerable evidence from in vitro and in vivo studies that neurotransmitter signaling is not required for proper sorting during synapse formation, whereas active neurotransmission is essential for long-term synapse maintenance. Here, the authors review recent studies on the role of cell adhesion molecules in synaptogenesis and on possible mechanisms ensuring correct matching of pre- and postsynaptic sites. They discuss the role of neurotransmitter receptors and scaffolding proteins in these processes, focusing on fundamental differences between synapse formation during development and synapse maintenance and plasticity in adulthood. NEUROSCIENTIST 13(2): formation during 115—126, 2007. D
Neural Systems for Error Monitoring
Authors: Taylor Stephan F. , Stern Emily R. , Gehring William J.
Published: April 2007

Complex behavior requires a flexible system that maintains task performance in the context of specific goals, evaluating behavioral progress, adjusting behavior as needed, and adapting to changing contingencies. Generically referred to as performance monitoring, a key component concerns the identification and correction of differences between an intended and an executed response (i.e., an error). Brain mapping experiments have now identified the temporal and spatial components of a putative error-processing system in the large-scale networks of the human brain. Most of this work has focused on the medial frontal cortex and an associated electrophysiological component known as the error-related negativity (or error negativity). Although the precise role, or roles, of this region still remain unknown, investigations of error processing have identified a cluster of modules in the medial frontal cortex involved in monitoring/maintaining ongoing behavior and motivating task sets. Other regions include bilateral anterior insula/inferior operculum and lateral prefrontal cortex. Recent work has begun to uncover how individual differences might affect the modules recruited for a task, in addition to the identification of associations between pathological states and aberrant error signals, leading to insights about possible mechanisms of neuropsychiatric illness. NEUROSCIENTIST 13(2):160—172, 2007.
Astroglial Cells in Development, Regeneration, and Repair
Authors: Vaccarino Flora M. , Fagel Devon M. , Ganat Yosif , Maragnoli Maria E. , Ment Laura R. , Ohkubo Yasushi , Schwartz Michael L. , Silbereis John , Smith Karen M.
Published: April 2007

Three main cellular components have been described in the CNS: neurons, astrocytes, and oligodendrocytes. In the past 10 years, lineage studies first based on retroviruses in the embryonic CNS and then by genetic fate mapping in both the prenatal and postnatal CNS have proposed that astroglial cells can be progenitors for neurons and oligodendrocytes. Hence, the population of astroglial cells is increasingly recognized as heterogeneous and diverse, encompassing cell types performing widely different roles in development and plasticity. Astroglial cells populating the neurogenic niches increase their proliferation after perinatal injury and in young mice can differentiate into neurons and oligodendrocytes that migrate to the cerebral cortex, replacing the cells that are lost. Although much remains to be learned about this process, it appears that the up-regulation of the Fibroblast growth factor receptor is critical for mediating the injury-induced increase in cell division and perhaps for the neuronal differentiation of astroglial cells. NEUROSCIENTIST 13(2):173—185, 2007.
Impact of psychiatric disorders on health-related quality of life: general population survey
Authors: Saarni Samuli I. , Suvisaari Jaana , Sintonen Harri , Pirkola Sami , Koskinen Seppo , Aromaa Arpo , Lönnqvist Jouko
Published: March 2007

Background

Measurement of health-related quality of life (HRQoL) with generic preference-based instruments enables comparisons of severity across different conditions and treatments. This is necessary for rational public health policy.

Aims

To measure HRQoL decrement and loss of quality-adjusted life-years (QALYs) associated with pure and comorbid forms of depressive and anxiety disorders and alcohol dependence.

Method

A general population survey was conducted of Finns aged 30 years and over. Psychiatric disorders were diagnose with the Composite International Diagnostic Interview and HRQoL was measured with the 15D and EQ–5D questionnaires.

Results

Dysthymia, generalised anxiety disorder and social phobia were associated with the largest loss of HRQoL on the individual level before and after adjusting for somatic and psychiatric comorbidity. On the population level, depressive disorders accounted for 55%, anxiety disorders 30%, and alcohol dependence for 15% of QALY loss identified in this study.

Conclusions

Chronic anxiety disorders and dysthymia are associated with poorer HRQoL than previously thought.
Significant Coexpression of GLUT‐1, Bcl‐xL, and Bax in Colorectal Cancer
Authors: WINCEWICZ ANDRZEJ , SULKOWSKA MARIOLA , KODA MARIUSZ , KANCZUGA‐KODA LUIZA , WITKOWSKA EWA , SULKOWSKI STANISLAW
Published: April 2007

Abstract:  Hypoxic cancer cells overexpress Glucose transporter 1 (GLUT‐1) to accelerate glucose intake mainly for low effective, anaerobic respiration, so that they would not die of oxygen deficiency. Ischemic cell injury triggers apoptosis. Regulators of cell suicide like Bax and Bcl‐xL combine their functions to cause apoptosis or to rescue cells from death. GLUT‐1, Bax, and Bcl‐xL are of prognostic significance in colorectal cancer but they have not been compared, yet. Thus, we aimed to determine eventual correlations between GLUT‐1, Bax, and Bcl‐xL in association with different clinicopathological features of colorectal cancer patients. Expressions of the proteins were evaluated in specimens of 150 colorectal patients by immunohistochemistry. The levels of tissue expressions were statistically analyzed with Spearman's correlation test. As in group of all the patients, GLUT‐1 matched Bcl‐xL and Bax in statistically significant manner regardless of different node status, grade of histological differentiation, histopathological type, tumor site, gender and age of patients. GLUT‐1 correlated highly with Bcl‐xL in both groups of various tumor growth extent: pT1 + pT2 and pT3 + pT4 tumors (P < 0.016, r= 0.6340, P < 0.0001, r= 0.5204, respectively). Bax correlated with GLUT‐1 (P < 0.0001, r= 0.4284) and Bcl‐xL (P < 0.0001, r= 0.5233) in pT3 and pT4 tumors without any statistical significance in a homologous comparison at pT1 and pT2 stage (P > 0.173, r= 0.1078, P > 0.744, r= 0.1, respectively). Significant coexpression of GLUT‐1, Bcl‐xL, and Bax could point to cooperation of these regulatory proteins in elimination due to irreversible injury, adaptation to hypoxia, reduction of further damage, and survival of colorectal cancer cells.
Akt Involvement in Paclitaxel Chemoresistance of Human Ovarian Cancer Cells
Authors: KIM SU‐HYEONG , JUHNN YONG‐SUNG , SONG YONG‐SANG
Published: April 2007

Abstract:  Paclitaxel (taxol) is extensively used for chemotherapy of various cancers including ovarian cancer. Although paclitaxel induces apoptosis in cancer cells, its exact mechanism of action still remains to be determined. Akt mediates survival signals which preserve various cancer cells from apoptosis pathway. Thus, Akt is considered an exciting target for therapeutics. Here, we demonstrated that inhibition of Akt increases the efficacy of the paclitaxel‐induced apoptosis in SKOV3 and PA‐1 human ovarian cancer cells. The sensitivity to paclitaxel of SKOV3 and PA‐1 cells was examined using the MTT assay. At a concentration of 30 nM, PA‐1 cells were more sensitive to paclitaxel than SKOV3 cells. Apoptosis was accompanied by the release of cytochrome c into the cytoplasm and cleavage of poly (ADP‐ribose) polymerase (PARP). To further elucidate the mechanism of apoptosis by paclitaxel, we compared the levels of phosphorylation of Akt between paclitaxel‐resistant SKOV3 cells and paclitaxel‐sensitive PA‐1 cells.
The higher level of phosphorylated Akt was shown in SKOV3 cells than in PA‐1 cells. Interestingly, the treatment of paclitaxel decreased the amount of phosphorylated Akt in a time‐dependent manner in both cell lines. Furthermore, inhibition of Akt by specific phosphatidyinositol‐3‐kinase (PI3K)‐Akt inhibitors (Wortmannin, and LY294002) synergistically increased the efficacy of the paclitaxel‐induced apoptosis in both cell lines. These results suggest that the addition of the Akt inhibitor may increase the therapeutic efficacy of paclitaxel for patients with ovarian cancer.