bluuebunny/crossref_metadata_2025 huggingface dataset:
Interception of the radicals produced in electrophilic fluorination with radical traps (Tempo, Dmpo) studied by electrospray ionization mass spectrometry
Authors: Zhang Xiang , Wang Haoyang , Guo Yinlong
Published: May 2006

The interaction of the nitroxide radical traps (Tempo and Dmpo) and radicals produced in the electrophilic fluorination of olefins (styrene and α‐methylstyrene) and Selectfluor (1‐chloromethyl‐4‐fluoro‐1,4‐diazoniabicyclo[2.2.2]octanebis(tetrafluoroborate) (F‐TEDA‐BF4) (1)) was investigated by electrospray ionization mass spectrometry (ESI‐MS). Tempo succeeded in intercepting the radical cationic intermediates and the radical adduct ions were detected at m/z 260 (for styrene) and m/z 274 (for α‐methylstyrene). Dmpo could also intercept the fluorine radical and radical adduct ions were detected at m/z 131, 132 and 152. The interception of the radical cationic intermediates and fluorine radical is good evidence for the presence of a single‐electron transfer mechanism in the electrophilic fluorination. Copyright © 2006 John Wiley & Sons, Ltd.
Respiratory Function after Laparoscopic Distal Gastrectomy—An Index of Minimally Invasive Surgery
Authors: Tanimura Shinya , Higashino Masayuki , Fukunaga Yosuke , Kishida Satoru , Ogata Akihito , Fujiwara Yushi , Osugi Harushi
Published: May 2006

Background

As the techniques of laparoscopic surgery have improved, various institutions have performed laparoscopic gastrectomies with regional lymph node dissection, as well as open surgery. Although alleviation of postoperative pain and prompt recovery have been reported in the literature, objective indexes of the minimal invasiveness of laparoscopic procedures are as yet very few.

Methods

We performed distal gastrectomy with regional lymph node dissection for gastric cancer patients using three kinds of procedures, namely, open gastrectomy, hand‐assisted laparoscopic surgery (HALS), and totally laparoscopic gastrectomy. Ablation of the stomach, lymph node dissection, and reconstruction of the digestive tract were all carried out intracorporeally with or without HALS in the laparoscopic procedures. The ordinary respiratory function test was performed pre‐ and postoperatively for 50 patients operated on by each procedure, and the reduced percentages of the measured values were calculated.

Results

Postoperative respiratory function was consistently excellent, with minimal loss of vital capacity and forced expiratory volume per second in the totally laparoscopic group compared to HALS or open cases.

Conclusions

Although it may be a complicated technique, totally laparoscopic distal gastrectomy is considered a minimally invasive procedure for gastric cancer from the viewpoint of postoperative respiratory function.
The Role of Whole‐Body Fluorine‐18‐FDG Positron Emission Tomography in the Detection of Recurrence in Symptomatic Patients with Stages II and III Breast Cancer
Authors: Wolfort Ryan M. , Li Benjamin D.L. , Johnson Lester W. , Turnage Richard H. , Lilien David , Ampil Fred , Burton Gary , Chu Quyen D.
Published: May 2006

Background

The role of whole‐body fluorine‐18‐FDG positron emission tomography (FDG‐PET) as an adjunct localize recurrence in stages II and III breast cancer patients who present with clinical suspicion for recurrence is not well established. We report our experience in such a patient population.

Methods

A retrospective review of all patients with stages II and III breast cancer who had a whole‐body FDG‐PET scan was performed.

Results

Of the 23 patients who fit the criteria, 9 had stage II and 14 had stage III breast cancer. Overall sensitivity, specificity, and accuracy were 81%, 100%, and 87%, respectively. Positive and negative predictive values for stages II and III were 100% and 83%, respectively, and 100% and 50%, respectively. FDG‐PET detected two recurrences that were missed by conventional imagings, but such recurrences were local and amenable for biopsy.

Conclusions

In patients with stages II and III breast cancer who present with a suspicion for recurrent disease, a whole‐body FDG‐PET scan may be a useful adjunct in the evaluation of recurrence. However, its added benefit over conventional imaging should be questioned.
Lack of Association between Microsatellite Instability and Benign Adrenal Tumors
Authors: Namour Fares , Ayav Ahmet , Lu Xiaohong , Klein Marc , Muresan Miahela , Bresler Laurent , Tramoy Denise , Guéant Jean‐Louis , Brunaud Laurent
Published: May 2006

Background

The adrenal gland may give rise to pheochromocytomas, which are catecholamine‐producing tumors originating from the adrenal medulla, or to adrenocortical tumors, which derive from the adrenocortical cortex and may be secreting or not. The genetic mechanisms underlying the formation of these tumors include somatic mutations in susceptibility genes, especially in the familial forms, and allelic loss, especially in chromosome 1.

Aim

The aim of this study was to investigate a third genetic mechanism by evaluating microsatellite instability using the reference markers (Bat25, Bat26, D2S123, D5S346, D17S250) validated by the National Cancer Institute. Microsatellite loci were analyzed in 32 benign tumors, including 11 pheochromocytomas and 21 adrenocortical tumors, in patients with and without familial syndrome.

Results

The different alleles of microsatellite loci were reliably detected by DNA fragments analysis, whereas data obtained after melting‐point analysis on the Lightcycler were inconsistent. No microsatellite instability was detected in any tumor. One patient with a unilateral pheochromocytoma showed a loss of heterozygosity for D17S250. A second patient with a MEN‐2A syndrome and a two‐sided pheochromocytoma exhibited a loss of heterozygosity for D2S123 in the right tumor only and a retention of heterozygosity for all markers in the left tumor.

Conclusions

These results suggest that microsatellite instability, evaluated by the five reference markers of the National Cancer Institute, is not a feature of benign adrenal tumors.
Feasibility of Primary Inguinal Hernia Repair with a New Mesh
Authors: Fei L. , Filippone G. , Trapani V. , Cuttitta D. , Iannuzzi E. , Iannuzzi M. , Galizia G. , Moccia F. , Signoriello G.
Published: May 2006

Background

The purpose of this study was to evaluate the feasibility of primary inguinal repair with open tension‐free and sutureless technique using a new polypropylene “patch and plug system” (Prolene 3D patch), and the quality of the treatment in terms of reduction of postoperative discomfort.

Methods

Fifty‐six consecutive patients, mean age 54.5 ± 11.2 years, with primary unilateral uncomplicated inguinal hernia, were treated in a day‐surgery setting. Collected data included: pain scores at 24 hours, 72 hours, and 7, 15, and 30 days after operation, analgesic medications, return to work and to heavy house and/or moderate sporting activities, and quality of life as measured by Short Form 36 health survey questionnaire (SF‐36) before the operation and at 6 months follow‐up.

Results

Postoperative pain was low: the mean visual analog scale (VAS) scores were 2.8 at 24 h, 1.8 at 72 h, and 0.9, 0.3, and 0.04 at 7, 15, and 30 days, respectively. Analgesic drugs were not used by 66.0% (n = 37) of the patients. The mean global time to return to work and to heavy activities was 9.9 ± 4.6 and 14.6 ± 7.0, days, respectively. Patient satisfaction showed a significant improvement in all SF‐36 domain scores at 6 months follow‐up (P < 0.001). There were no major complications, recurrences, or mortality.

Conclusions

The new mesh seems to satisfy all requirements of a feasible, reliable, and effective device for repairing primary inguinal hernia with high patient comfort.
Guidelines for Essential Trauma Care: Progress in India
Authors: Joshipura Manjul
Published: May 2006

The planning and development of trauma care systems in India has yet to gain attention and priority from the government, even though trauma is a major public health problem. Several efforts are under way to improve the delivery of trauma care for the injured. Guidelines for Essential Trauma Care has proved to be an ideal tool with which to begin the process of development for building a national system for the care of the injured in one of the most populous countries in the world, and one with a high burden of trauma deaths and disability. This article focuses on the impact of the Guidelines for Essential Trauma Care in efforts for improvement of the system in India.
Evaluation of Trauma Care Capabilities in Four Countries Using the WHO‐IATSIC Guidelines for Essential Trauma Care
Authors: Mock Charles , Nguyen Son , Quansah Robert , Arreola‐Risa Carlos , Viradia Ramesh , Joshipura Manjul
Published: May 2006

Background

We sought to identify affordable and sustainable methods to strengthen trauma care capabilities globally, especially in developing countries, using the Guidelines for Essential Trauma Care. These guidelines were created by the World Health Organization (WHO) and the International Society of Surgery and provide recommendations on elements of trauma care that should be in place at the range of health facilities globally.

Methods

The guidelines were used as a basis for needs assessments in 4 countries selected to represent the world’s range of geographic and economic conditions: Mexico (middle income; Latin America); Vietnam (low income; east Asia); India (low income; south Asia); and Ghana (low income; Africa). One hundred sites were assessed, including rural clinics (n = 51), small hospitals (n = 34), and large hospitals (n = 15). Site visits utilized direct inspection and interviews with administrative and clinical staff.

Results

Resources were partly adequate or adequate at most large hospitals, but there were gaps that could be improved, especially in low‐income settings, such as shortages of airway equipment, chest tubes, and trauma‐related medications; and prolonged periods where critical equipment (e.g., X‐ray, laboratory) were unavailable while awaiting repairs. Rural clinics everywhere had difficulties with basic supplies for resuscitation even though some received significant trauma volumes. In all settings, there was a dearth of administrative functions to assure quality trauma care, including trauma registries, trauma‐related quality improvement programs, and regular in‐service training.

Conclusions

This study identified several low‐cost ways in which to strengthen trauma care globally. It also has demonstrated the usefulness of the Guidelines for Essential Trauma Care in providing an internationally applicable, standardized template by which to assess trauma care capabilities.
Niche width and niche overlap: a method based on type‐2 fuzzy sets
Authors: Yimin Li , Xihao Sun , Chongying Gong
Published: May 2006

Complicated ecosystems and the high non‐linearity of evolution has made biology more adaptable to a variety of environments. The relationship between life and environment demands a dynamic definition of niche and its measurement. In this paper we propose a model of niche with dynamic character based on the “broad band” effect in type‐2 fuzzy sets. The niche in this definition is an interval in each ecological dimension which is dynamic in character and depends on the actual environment. We also give formulas for niche width and niche overlap. We compute the niche width and overlap for plants and animals and then compare these results with previous results. The results for niche width in this paper reflect the diversity of resources used by species or communities. The results for niche overlap demonstrate overlap under different environmental conditions. The results are, moreover, intervals, which could provide more information. The model in this paper could therefore be used to describe the state of every resource comprehensively, reflecting the interaction between species and environment.
Emergent multiple predator effects in an experimental microbial community
Authors: Jiang Lin , Krumins Jennifer Adams
Published: May 2006

Studies on multiple predator effects have typically focused on metazoans. Here we examined the effects of multiple consumers on bacteria. Specifically, we investigated the separate and combined effects of two common bacterivorous ciliates,Colpidium striatumandParamecium caudatum, on a simple bacterial assemblage. Non‐additive multiple predator effects emerged for all bacterial species significantly affected by grazing, where bacterial responses in the two‐consumer treatment cannot be predicted by summing the separate effects of the two consumers. Some species showed risk reduction (observed responses less than expected), whereas others showed risk enhancement (observed responses larger than expected). We attributed risk alteration to the interference between the two consumers. Contradictory to theoretical predictions, total bacterial abundance in the two‐consumer treatment did not differ from single‐consumer treatments and consumer‐free controls, due largely to risk reduction and compensatory responses within the bacterial assemblage. Decomposition of particulate organic matter was greater in the two‐consumer treatment than theParameciumsingle‐consumer treatment, but did not differ among other treatments. These results suggest that the presence of multiple consumers may have unexpected impacts on the structure and functioning of bacterial communities.
Family heritage and depression guides: Family and peer views influence adolescent attitudes about depression
Authors: Wisdom Jennifer P. , Agnor Chrystal
Published: May 2006

While adolescents tend to under‐use professional mental health services for depression, they informally seek health‐related information from parents and peers. In this study, we interviewed 15 adolescents to examine how the views and behaviours of others influence teens’ decisions about seeking care for depression. Using a grounded theory approach, we found that teens’ families, peers, and siblings contributed uniquely to teens’ decisions in seeking care for depression. Families may disclose a “heritage” of depression, and their choices about disclosing family mental health issues, previous treatment, and coping strategies affected teens’ understanding of depression. Peer “depression guides,” who had themselves experienced depression, provided teens with advice on recognizing depression, managing stigma, and seeking care. Siblings bridged the roles of peer and family, influencing teens’ choices about accessing treatment. These findings suggest that family and peers should be included during teens’ depression treatment.
Studying cellular architecture in three dimensions with improved resolution: Ta replicas revisited
Authors: Cabezas Pilar , Risco Cristina
Published: May 2006

Metal replicas have been used for surface analysis of biological structures with a variety of spatial resolutions. Platinum (Pt) has been the metal of choice because it provides very stable replicas and images of high contrast. Some other metals, such as tantalum (Ta) have been reported to provide better resolution on isolated macromolecular complexes and cellular structures. Our goal is to study the gain in detail with Ta and to evaluate if it provides enough detail and resolution to assist in the study of complex volumes of intact cellular structures obtained by methods that reach molecular resolution. To this purpose Pt and Ta replicas of cellular structures and viruses have been studied by transmission electron microscopy (TEM). Replicas of Ta show new details on the surface of two types of isolated viral particles such as 100 nm bunyaviruses and large, >300 nm, vaccinia virus (VV). Inside cells, the structural pieces that build VV immature particles are visualized only in Ta replicas. Looking for smaller intracellular complexes, new details are also seen in nuclear pores from Ta replicas. Additional masses, most likely representing the cargo during transport, are distinguished in some of the pores. Visualization of proteins in plasma membranes strongly suggests that detail and resolution of Ta replicas are similar to those estimated for 3D maps currently obtained by electron tomography of viruses and cells.
Long‐term effects of levosimendan infusion on inflammatory processes and sFas in patients with severe heart failure
Authors: Trikas Athanasios , Antoniades Charalambos , Latsios Giorgos , Vasiliadou Karmen , Karamitros Ioannis , Tousoulis Dimitris , Tentolouris Costantinos , Stefanadis Christodoulos
Published: May 2006

Background

The calcium sensitizer levosimendan improves myocardial contractility in patients with heart failure, although its effects on inflammation and apoptosis are unknown.

Aim

To examine the effects of levosimendan on markers of inflammation and apoptosis, over a period of 30 d following a 24 h infusion, in patients with heart failure.

Methods

Thirty four patients with severe heart failure were randomised to receive a 24 h infusion of levosimendan or placebo, in a double‐blind trial. Haemodynamic evaluation and blood sampling were performed at baseline, 24 h, 30 h, 48 h, 7 d and 30 d after the end of the infusion.

Results

Seven patients (1 levosimendan, 6 placebo), were excluded during follow‐up. In the remaining 27 patients, levosimendan decreased serum IL‐6 and sFAS, 24 h after the infusion (p<0.01 andp<0.05 vs baseline), an effect sustained for 7–30 d. Serum TNF‐α and sTNF‐R1 were decreased between 48 h (p<0.01 vs baseline for both) and 7 d (p<0.05 vs baseline for sTNF‐R1) after infusion. Serum sTNF‐R2 was decreased at 24 h (p<0.05 vs baseline) and remained lower than baseline for at least 7 d (p<0.05).

Conclusions

These findings indicate that levosimendan decreases the expression of proinflammatory cytokines, TNF‐α receptors and sFAS, immediately after infusion, an effect which persists for 7–30 d.
Interstitial nephritis in cats inoculated with Crandell Rees feline kidney cell lysates
Authors: Lappin Michael R. , Basaraba Randall J. , Jensen Wayne A.
Published: May 2006

Parenteral administration of Crandell Rees feline kidney (CRFK) cell lysates or feline herpesvirus 1, calicivirus, and panleukopenia virus-containing vaccines (FVRCP) grown on CRFK cells induces antibodies against CRFK cells. These antibodies also react with feline renal cell extracts. The purpose of this study was to determine whether interstitial nephritis would be detected in cats that were immunologically sensitized with CRFK lysates, boosted with CRFK lysates, and then biopsied 2 weeks after the booster. Cats (2 per group) were immunologically sensitized against CRFK lysates by administering 10 μg, 50 μg, or 50 μg plus alum 13 times (12 times in the first 50 weeks) over 2 years. Two cats were inoculated three times, 4 weeks apart with an FVRCP vaccine for intranasal administration as kittens, boosted 50 and 102 weeks later, and then renal biopsies taken 2 weeks after the last booster. Neither of the cats vaccinated with the FVRCP for intranasal administration had detectable renal inflammation. One cat in each of the three CRFK lysate sensitization groups had lymphocytic–plasmacytic interstitial nephritis.
Japanese production management: An evolution—With mixed success
Authors: Schonberger Richard J.
Published: May 2006

Japanese production management (JPM) became a dominant influence in the field of operations management when, in the early 1980s, knowledge of its main elements became known beyond Japan. Those elements – quick set‐up, small lots, cells, kanban, and so on – are well known. Rather than explaining them again, this paper's objective is to explore the sequence of events leading to JPM as a competitive force globally, as well as its impact on theory and practices in operations management. JPM's evolution includes shifting terminologies, fusions and adulterations; limited extensions from manufacturing into services and innovative enhancements, largely of Western origin. Longitudinal research data, based on inventory trends, provide insights on JPM's diffusions and its uneven results. Latter‐day puzzling lapses and disappointments, among Japanese as well as Western companies, raise questions about JPM's sustainability, as well as some of its changing manifestations. While the core of Japanese production management, now over three decades old, appears to have become solidly mainstream, its current and future states are problematic.
Alpine lake sediment records of the impact of glaciation and climate change on the biogeochemical cycling of soil nutrients
Authors: Filippelli Gabriel M. , Souch Catherine , Menounos Brian , Slater-Atwater Sara , Timothy Jull A.J. , Slaymaker Olav
Published: May 2006

Lake sediment cores from the Coast Mountains of British Columbia were analyzed using chemical sequential extractions to partition the dominant geochemical fractions of phosphorus (P). The P fractions include mineral P (the original source of bioavailable P), occluded P (bound to soil oxides), and organic P (remains of organic matter). By comparing P fractions of soil and recent lake sediment samples, these fractions are shown to be a valid proxy for landscape-scale nutrient status. Changes in soil development for an alpine watershed (Lower Joffre Lake) are inferred from the P fractions in the basin's outlet lake sediments. Glacially sourced mineral P dominates at the base of the core, but several rapid shifts in P geochemistry are evident in the first ∼3000 yr of the record. The latter indicates an interval of early and rapid soil nutrient maturation from ∼9600 to 8500 cal yr BP and a significant influx of slope-derived material into Lower Joffre Lake. A substantial increase in mineral P occurs at ca. 8200 cal yr BP, consistent with the cold event in the vicinity of the North Atlantic at that time. The more recent record reveals a continual increase in the proportion of mineral P from glacial sources to the lake, indicating a trend toward cooler conditions in the Coast Mountains.
Some useful tactics to modify, map and mine data from intelligent tutors
Authors: MOSTOW JACK , BECK JOSEPH
Published: May 2006

Mining data logged by intelligent tutoring systems has the potential to discover information of value to students, teachers, authors, developers, researchers, and the tutors themselves – information that could make education dramatically more efficient, effective, and responsive to individual needs. We factor this discovery process into tactics to modify tutors, map heterogeneous event streams into tabular data sets, and mine them. This model and the tactics identified mark out a roadmap for the emerging area of tutorial data mining, and may provide a useful vocabulary and framework for characterizing past, current, and future work in this area. We illustrate this framework using experiments that tested interventions by an automated reading tutor to help children decode words and comprehend stories.
Introduction
Authors: BURSTEIN JILL , LEACOCK CLAUDIA
Published: May 2006

Researchers and developers of educational software have experimented with natural language processing (NLP) capabilities and related technologies since the 1960's. Automated essay scoring was perhaps the first application of this kind (Page 1966). Over a decade later, Writer's Workbench, a text-editing application, was developed as a tool for classroom teachers (MacDonald, Frase, Gingrich and Keenan 1982). Intelligent tutoring applications, though more in the spirit of artificial intelligence, were also being developed during this time (Carbonell 1970; Brown, Burton and Bell 1974; Stevens and Collins 1977; Burton and Brown 1982; Clancy 1987).
Global compilation of variations in slab depth beneath arc volcanoes and implications
Authors: Syracuse Ellen M. , Abers Geoffrey A.
Published: May 2006

The location and motion of subducting plates relative to volcanic arcs provide a first‐order constraint on theories of arc magmagenesis. We compile volcano‐specific subduction parameters for 33,000 km of the global arc system at 839 volcanic centers, measuring the depth to the top of the slab (H) beneath each volcano. The compilation also includes estimates of slab strike and dip, incoming plate velocity, and age, all available in accompanying auxiliary material. The slab geometry is contoured from the top surface of Wadati‐Benioff zones (WBZs) for a variety of teleseismic and local seismicity catalogs, which provides a reference surface for evaluating the distribution of seismicity within subducting plates. The WBZ thickness exceeds that expected from hypocentral errors in a manner correlating with plate age, indicating that old plates have thicker regions in which earthquakes can occur. When averaged over 500‐km‐long arc segments, H ranges from 72 to 173 km with a global average of 105 km, increasing by 20 km when hypocentral error effects are taken into account. These depths correlate poorly with most subduction parameters, but significant correlations exist between H and slab dip (correlation coefficient is 0.54 for 45 arc segments). The dip correlation can be explained if the melting region is displaced from the Wadati‐Benioff zone by a constant‐thickness boundary layer. For the north Pacific, H varies inversely with descent rate; this trend may reflect the manner in which wedge thermal structure affects arc location. Over short distances some arc segments exhibit abrupt variations in arc location but not slab geometry, indicating that upper‐plate tectonic processes also exert control on H. These along‐strike trends in H also correlate with geochemical proxies for the degree of melting, at least in one test case. Thus slab geometry and kinematics provide an important control on the melting that produces arc volcanoes.
Large‐scale rigid‐body rotation in the mantle wedge and its implications for seismic tomography
Authors: Gorczyk Weronika , Gerya Taras V. , Connolly James A. D. , Yuen David A. , Rudolph Maxwell
Published: May 2006

Using a combined finite difference and marker‐in‐cell technique, we performed two‐dimensional coupled petrological‐thermomechanical numerical simulations of intraoceanic subduction. The simulations indicate that parts of the mantle wedge can become trapped between rheologically weak, hydrated, and partially molten upwellings (cold plumes) and the subducting slab. The structures form at various depths and develop circular, elliptic, or irregular shapes. The combined effect of the tractions caused by upwelling and subduction causes these regions to rotate. Our simulations investigate the parameters controlling the occurrence and long‐term stability of such rigid, rotating structures. Circular rotating structures like “subduction wheels” are characteristic of models with relatively young (20–30 Myr) slabs and intermediate (2–5 cm/yr) subduction rates. We propose that the development of such circular features may explain some of the isolated seismic velocity anomalies in the mantle wedge.
A model simulation on the circulation in the Sea of Okhotsk and the East Sakhalin Current
Authors: Simizu Daisuke , Ohshima Kay I.
Published: May 2006

Numerical model experiments have been conducted to clarify the circulation in the Sea of Okhotsk. The Princeton Ocean Model, which uses a vertical sigma coordinate, is adopted with the realistic topography. The East Sakhalin Current (ESC) is reproduced in the experiment forced by the annual mean wind stress. The ESC in the model consists of two components: a nearshore component on the shelf and an offshore one over the shelf slope, which is consistent with the drifter observations. The offshore component is interpreted as the western boundary current of the cyclonic circulation driven by the positive wind stress curl. The nearshore component is driven by the alongshore wind, regarded as an “arrested topographic wave” (ATW). The seasonal and interannual variations of the ESC transport are examined with the experiments forced by the daily wind stress for the period of 1985–1999. The model well reproduces the variabilities of the transport and structure of the ESC observed with the mooring array. Although a precise Sverdrup balance does not hold in the interior region, the amplitude of the monthly mean ESC transport corresponds roughly to one third of the Sverdrup transport with a phase lag of about a month. The transport variation of the nearshore component is explained well by integration of the onshore Ekman flux, which is consistent with the ATW theory. The circulation of the Okhotsk Sea and the transport of the ESC are affected only slightly by surface heat flux.
Evaluating aerosol nucleation parameterizations in a global atmospheric model
Authors: Lucas Donald D. , Akimoto Hajime
Published: May 2006

Numerically efficient parameterizations based on theories of binary, ternary and ion‐induced aerosol nucleation (BN, TN and IN) enable online calculations of new particle formation in high resolution atmospheric models. These parameterizations are evaluated interactively in a 3D global chemical transport model that simulates gaseous sulfuric acid, ammonia and the ion‐pair production rate. The BN and IN parameterizations produce new particles only in the cold upper troposphere, with IN giving relatively lower nucleation rates due to parameterization errors. In contrast, the TN parameterization predicts new particle formation throughout the troposphere, but gives unrealistically high nucleation rates. New and revised TN theories from recent studies instead give much lower rates and indicate that TN is not likely in the lower troposphere. Nucleation parameterizations can be useful for global modeling applications, but the current schemes should be used cautiously given their large uncertainties.
Changes in surface ozone levels due to convective downdrafts over the Bay of Bengal
Authors: Sahu L. K. , Lal S.
Published: May 2006

Simultaneous measurements of surface level ozone (O3) and meteorological parameters were made over the Bay of Bengal (BOB) during a cruise between 14 September and 12 October 2002. Variations in surface O3, equivalent potential temperature (θE) and associated meteorological parameters clearly show evidence of convective downdrafts during 18–19 September and 25–26 September. Sharp increase in O3 mixing ratio is coupled with decrease in θE value in the detrained air. The vertical wind velocity and satellite images also indicate significant convective activities during these periods. The maximum changes in O3 and θE were 26 ppbv and 12 K, respectively. These events comprise of both short and long time scale downdrafts.
Grateloupia longifolia polysaccharide inhibits angiogenesis by downregulating tissue factor expression in HMEC‐1 endothelial cells
Authors: Zhang Chao , Yang Fan , Zhang Xiong‐Wen , Wang Shun‐Chun , Li Mei‐Hong , Lin Li‐Ping , Ding Jian
Published: May 2006

The antiangiogenic and antitumor properties of Grateloupia longifolia polysaccharide (GLP), a new type of polysaccharide isolated from the marine alga, were investigated with several in vitro and in vivo models. Possible mechanisms underlying its antiangiogenic activity were also assessed.

GLP dose‐dependently inhibited proliferation of human microvascular endothelial cells (HMEC‐1) and human umbilical vein endothelial cells (HUVEC), with IC50 values of 0.86 and 0.64 mg ml−1, respectively. In tube formation and cell migration assays using HMEC‐1 cells, noncytotoxic doses of GLP significantly inhibited formation of intact tube networks and reduced the number of migratory cells. Inhibition by GLP was VEGF‐independent.

In the chick chorioallantoic membrane (CAM) assay, GLP (2.5 μg egg−1) reduced new vessel formation compared with the vehicle control. GLP (0.1 mg plug−1) also reduced the vessel density in Matrigel plugs implanted in mice.

The levels of pan and phosphorylated recptors for VEGF, VEGFR‐1 (flt‐1) and VEGFR‐2 (KDR) were not significantly altered by 5 mg ml−1 GLP treatment of HMEC‐1, although tissue factor (TF) showed significant decreases at both mRNA and protein levels following GLP treatment.

In mice bearing sarcoma‐180 cells, intravenous administration of GLP (200 mg kg−1) decreased tumor weight by 52% without obvious toxicity. Vascular density in sections of the tumor was reduced by 64% after GLP treatment.

Collectively, these results indicate that GLP has antitumor properties, associated at least, in part, with the antiangiogenesis induced by downregulation of TF.

British Journal of Pharmacology (2006) 148, 741–751. doi:10.1038/sj.bjp.0706741
Adrenomedullin actsvianitric oxide and peroxynitrite to protect against myocardial ischaemia‐induced arrhythmias in anaesthetized rats
Authors: Looi Yee Hoo , Kane Kathleen A , McPhaden Allan R , Wainwright Cherry L
Published: May 2006

The overall aim of this study was to determine if adrenomedullin (AM) protects against myocardial ischaemia (MI)‐induced arrhythmiasvianitric oxide (NO) and peroxynitrite.

In sham‐operated rats, the effects ofin vivoadministration of a bolus dose of AM (1 nmol kg−1) was assessed on arterial blood pressure (BP),ex vivoleukocyte reactive oxygen species generation and nitrotyrosine deposition (a marker for peroxynitrite formation) in the coronary endothelium.

In pentobarbitone‐anaesthetized rats subjected to ligation of the left main coronary artery for 30 min, the effects of a bolus dose of AM (1 nmol kg−1, i.v.;n=19) or saline (n=18) given 5 min pre‐occlusion were assessed on the number and incidence of cardiac arrhythmias. In a further series of experiments, some animals received infusions of the NO synthase inhibitorN(G)‐nitro‐L‐arginine (LNNA) (0.5 mg kg−1 min−1) or the peroxynitrite scavengerN‐mercaptopropionyl‐glycine (MPG) (20 mg kg−1 h−1) before AM.

AM treatment significantly reduced mean arterial blood pressure (MABP) and increasedex vivochemiluminescence (CL) generation from leukocytes in sham‐operated animals. AM also enhanced the staining for nitrotyrosine in the endothelium of coronary arteries.

AM significantly reduced the number of total ventricular ectopic beats that occurred during ischaemia (from 1185±101 to 520±74;P<0.05) and the incidences of ventricular fibrillation (from 61 to 26%;P<0.05). AM also induced a significant fall in MABP prior to occlusion. AM‐induced cardioprotection was abrogated in animals treated with the NO synthase inhibitor LNNA and the peroxynitrite scavenger MPG.

This study has shown that AM exhibits an antiarrhythmic effect through a mechanism that may involve generation of NO and peroxynitrite.

British Journal of Pharmacology(2006)148, 599–609. doi:10.1038/sj.bjp.0706771
Neuropeptide Y2receptors are involved in enhanced neurogenic vasoconstriction in spontaneously hypertensive rats
Authors: Gradin Kathryn A , Buus Carsten L , Li Jia‐Yi , Frøbert Ole , Simonsen Ulf
Published: May 2006

The present study addressed the role of neuropeptide (NPY) Y2receptors in neurogenic contraction of mesenteric resistance arteries from female spontaneously hypertensive rats (SHR). Arteries were suspended in microvascular myographs, electrical field stimulation (EFS) was performed, and protein evaluated by Western blotting and immunohistochemistry.

In vasopressin‐activated endothelium‐intact arteries, NPY and fragments with selectivity for Y1receptors, [Leu31,Pro34]NPY, Y2receptors, NPY(13–36), and rat pancreatic polypeptide evoked more pronounced contractions in segments from SHR than in Wistar Kyoto (WKY) arteries, even in the presence of the Y1receptor antagonist, BIBP3226 (0.3 μM, (R)‐N(2)‐(diphenacetyl)‐N‐[(4‐hydroxyphenyl)methyl]D‐arginineamide).

In the presence of prazosin and during vasopressin activation, EFS‐evoked contractions were larger in arteries from SHR compared to WKY. EFS contractions were enhanced by the Y2receptor selective antagonist BIIE0246TF (0.5μM, (S)‐N2‐[[1‐[2‐[4‐[(R,S)‐5,11‐dihydro‐6(6h)‐oxodibenz[b,e]azepin‐11‐y1]‐1‐piperazinyl]‐2‐oxoethyl]cyclo‐pentyl‐N‐[2‐[1,2‐dihydro‐3,5 (4H)‐dioxo‐1,2‐diphenyl‐3H‐1,2,4‐triazol‐4‐yl]ethyl]‐argininamide), reduced by BIBP3226, and abolished by the combination of BIBP3226 and BIIE0246TF.

Immunoblotting showed NPY Y1and Y2receptor expression to be similar in arteries from WKY and SHR, although a specific Y2receptor band at 80 kDa was detected only in arteries from WKY.

Immunoreaction for NPY was enhanced in arteries from SHR. In contrast to arteries from WKY, BIIE0246TF increased NPY immunoreactivity in EFS‐stimulated arteries from SHR.

The present results suggest that postjunctional neuropeptide Y1and Y2receptors contribute to neurogenic contraction of mesenteric small arteries. Moreover, both enhanced NPY content and altered neuropeptide Y1and Y2receptor activation apparently contribute to the enhanced neurogenic contraction of arteries from SHR.

British Journal of Pharmacology(2006)148, 703–713. doi:10.1038/sj.bjp.0706774
Sec14p-like proteins regulate phosphoinositide homoeostasis and intracellular protein and lipid trafficking in yeast
Authors: Mousley C.J. , Tyeryar K.R. , Ryan M.M. , Bankaitis V.A.
Published: May 2006

The major PI (phosphatidylinositol)/PC (phosphatidylcholine)-transfer protein in yeast, Sec14p, co-ordinates lipid metabolism with protein transport from the Golgi complex. Yeast also express five additional gene products that share 24–65% primary sequence identity with Sec14p. These Sec14p-like proteins are termed SFH (Sec Fourteen Homologue) proteins, and overexpression of certain individual SFH gene products rescues sec14-1ts-associated growth and secretory defects. SFH proteins are atypical in that these stimulate the transfer of PI, but not PC, between distinct membrane bilayer systems in vitro. Further analysis reveals that SFH proteins functionally interact with the Stt4p phosphoinositide 4-kinase to stimulate PtdIns(4,5)P2 synthesis which in turn activates phospholipase D. Finally, genetic analyses indicate that Sfh5p interfaces with the function of specific subunits of the exocyst complex as well as the yeast SNAP-25 (25 kDa synaptosome-associated protein) homologue, Sec9p. Our current view is that Sfh5p regulates PtdIns(4,5)P2 homoeostasis at the plasma membrane, and that Sec9p responds to that regulation. Thus SFH proteins individually regulate specific aspects of lipid metabolism that couple, with exquisite specificity, with key cellular functions.
Moving Ca2+ from the endoplasmic reticulum to mitochondria: is spatial intimacy enough?
Authors: Rutter G.A.
Published: May 2006

A number of studies in recent years have demonstrated that the ER (endoplasmic reticulum) makes intimate contacts with mitochondria, the latter organelles existing both as individual organelles and occasionally as a more extensive interconnected network. Demonstrations that mitochondria take up Ca2+ more avidly upon its mobilization from the ER than when delivered to permeabilized cells as a buffered solution also indicate that a shielded conduit for Ca2+ may exist between the two organelle types, perhaps comprising the inositol 1,4,5-trisphosphate receptor and mitochondrial outer membrane proteins including the VDAC (voltage-dependent anion channel). Although the existence of such intracellular ER–mitochondria ‘synapses’, or of an ER–mitochondria Ca2+ ‘translocon’, is an exciting idea, more definitive experiments are needed to test this possibility.
Interaction of the smooth endoplasmic reticulum and mitochondria
Authors: Goetz J.G. , Nabi I.R.
Published: May 2006

The ER (endoplasmic reticulum) is composed of multiple domains including the nuclear envelope, ribosome-studded rough ER and the SER (smooth ER). The SER can also be functionally segregated into domains that regulate ER–Golgi traffic (transitional ER), ERAD (ER-associated degradation), sterol and lipid biosynthesis and calcium sequestration. The last two, as well as apoptosis, are critically regulated by the close association of the SER with mitochondria. Studies with AMFR (autocrine motility factor receptor) have defined an SER domain whose integrity and mitochondrial association can be modulated by ilimaquinone as well as by free cytosolic calcium levels in the normal physiological range. AMFR is an E3 ubiquitin ligase that targets its ligand directly to the SER via a caveolae/raft-dependent pathway. In the present review, we will address the relationship between the calcium-dependent morphology and mitochondrial association of the SER and its various functional roles in the cell.
Phosphatidylinositol-transfer protein and its homologues in yeast
Authors: Griac P. , Holic R. , Tahotna D.
Published: May 2006

Yeast Sec14p acts as a phosphatidylinositol/phosphatidylcholine-transfer protein in vitro. In vivo, it is essential in promoting Golgi secretory function. Products of five genes named SFH1–SFH5 (Sec Fourteen Homologues 1–5) exhibit significant sequence homology to Sec14p and together they form the Sec14p family of lipid-transfer proteins. It is a diverse group of proteins with distinct subcellular localizations and varied physiological functions related to lipid metabolism and membrane trafficking.
The OSBP-related proteins (ORPs): global sterol sensors for co-ordination of cellular lipid metabolism, membrane trafficking and signalling processes?
Authors: Olkkonen V.M. , Johansson M. , Suchanek M. , Yan D. , Hynynen R. , Ehnholm C. , Jauhiainen M. , Thiele C. , Lehto M.
Published: May 2006

Protein families related to OSBP (oxysterol-binding protein) are present in eukaryotes from yeast to human. The functions of the ORPs (OSBP-related proteins) have remained largely enigmatic. Even though they have been implicated in the function of ERJs (endoplasmic reticulum junctions), it is evident that any single model for their mechanism of action is insufficient. The existing evidence points in many different directions, such as integration of sterol and sphingomyelin metabolism, regulation of neutral lipid metabolism, control of signalling cascades, regulation of secretory vesicle generation, and function in the microtubule-based motility of endo/lysosomes. Some of these functions could involve ERJ and non-vesicular transport of lipids, but this is unlikely to be the unifying feature. We believe, rather, that the common denominator for ORP function is acting as sterol sensors that relay information to a spectrum of cellular processes.
Macromolecular assemblies regulate nonvesicular phosphatidylserine traffic in yeast
Authors: Choi J.-Y. , Riekhof W.R. , Wu W.-I. , Voelker D.R.
Published: May 2006

PtdSer (phosphatidylserine) is synthesized in the endoplasmic reticulum and the related MAM (mitochondria-associated membrane), and transported to the PtdSer decarboxylases, Pds1p in the mitochondria, and Psd2p in the Golgi. Genetic and biochemical analyses of PtdSer transport are now revealing the role of specific protein and lipid assemblies on different organelles that regulate non-vesicular PtdSer transport. The transport of PtdSer from MAM to mitochondria is regulated by at least three genes: MET30 (encoding a ubiquitin ligase), MET4 (encoding a transcription factor), and one or more unknown genes whose transcription is regulated by MET4. MET30-dependent ubiquitination is required for the MAM to function as a competent donor membrane and for the mitochondria to function as a competent acceptor membrane. Non-vesicular transport of PtdSer to the locus of Psd2p is under the control of at least three genes, STT4 [encoding Stt4p (phosphatidylinositol 4-kinase)], PSTB2 (encoding the lipid-binding protein PstB2p) and PSD2 (encoding Psd2p). Stt4p is proposed to produce a pool of PtdIns4P that is necessary for lipid transport. PstB2p and Psd2p must be present on the acceptor membrane for PtdSer transport to occur. Psd2p contains a C2 (Ca2+ and phospholipid binding sequence) domain that is required for lipid transport. Reconstitution studies with chemically defined donor membranes demonstrate that membrane domains rich in the anionic lipids, PtdSer, PtdIns4P and phosphatidic acid function as the most efficient donors of PtdSer to Psd2p. The emerging view is that macromolecular complexes dependent on protein–protein and protein–lipid interactions form between donor and acceptor membranes and serve to dock the compartments and facilitate phospholipid transport.
The biological relevance of chemokine–proteoglycan interactions
Authors: Proudfoot A.E.I.
Published: May 2006

Chemokines exert their biological activity through high-affinity interactions with cell-surface receptors, thereby activating specific signalling pathways, and a second low-affinity interaction with proteoglycans. Proteoglycans consist of a protein core, to which GAG (glycosaminoglycan) chains are attached. The GAGs are long, linear, sulphated and highly charged heterogeneous polysaccharides that are expressed throughout the body in different forms depending on the developmental or pathological state of the organ/organism. Mechanistically, the GAG interaction is thought to facilitate the retention of chemokines on cell surfaces, thereby forming a high local concentration required for cell activation. Recently, we demonstrated that certain chemokines require interactions with GAGs for their in vivo function. Additionally we have shown that chemokines oligomerize on immobilized GAGs, and this ability to form higher order oligomers has also been shown to be essential for the activity of certain chemokines in vivo. We believe that interference with the chemokine–GAG interaction provides a novel anti-inflammatory strategy, exemplified by a variant of RANTES (regulated upon activation, normal T-cell expressed and secreted) that has abrogated GAG binding and oligomerization properties.
Protein–GAG interactions: new surface-based techniques, spectroscopies and nanotechnology probes
Authors: Yates E.A. , Terry C.J. , Rees C. , Rudd T.R. , Duchesne L. , Skidmore M.A. , Lévy R. , Thanh N.T.K. , Nichols R.J. , Clarke D.T. , Fernig D.G.
Published: May 2006

New approaches, rooted in the physical sciences, have been developed to gain a more fundamental understanding of protein–GAG (glycosaminoglycan) interactions. DPI (dual polarization interferometry) is an optical technique, which measures real-time changes in the mass of molecules bound at a surface and the geometry of the bound molecules. QCM-D (quartz crystal microbalance-dissipation), an acoustic technique, measures the mass and the viscoelastic properties of adsorbates. The FTIR (Fourier-transform IR) amide bands I, II and III, resulting from the peptide bond, provide insight into protein secondary structure. Synchrotron radiation CD goes to much shorter wavelengths than laboratory CD, allowing access to chromophores that provide insights into the conformation of the GAG chain and of β-strand structures of proteins. To tackle the diversity of GAG structure, we are developing noble metal nanoparticle probes, which can be detected at the level of single particles and so enable single molecule biochemistry and analytical chemistry. These new approaches are enabling new insights into structure–function relationships in GAGs and together they will resolve many of the outstanding problems in this field.
Computational approaches to the identification of heparin-binding sites on the surfaces of proteins
Authors: Forster M. , Mulloy B.
Published: May 2006

The identification of heparin-binding sites is important for understanding the physiological function of many secreted proteins. Most of the experimental techniques for mapping these sites do not define them to atomic resolution. The use of automated docking methods can aid this process by facilitating both the design of experiments and visualization of their results. A method designed for a systematic search over the whole protein surface for heparin-binding sites, using heparin oligosaccharide structures as ligands, is described, with its validation and details of several published applications. The scope and limitations of this crude but effective computational chemistry method are discussed.