bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards treatment planning and treatment of deep-seated solid tumors by electrochemotherapy
Authors: Miklavcic Damijan , Snoj Marko , Zupanic Anze , Kos Bor , Cemazar Maja , Kropivnik Mateja , Bracko Matej , Pecnik Tjasa , Gadzijev Eldar , Sersa Gregor
Published: February 2010

Background

Electrochemotherapy treats tumors by combining specific chemotherapeutic drugs with an intracellular target and electric pulses, which increases drug uptake into the tumor cells. Electrochemotherapy has been successfully used for treatment of easily accessible superficial tumor nodules. In this paper, we present the first case of deep-seated tumor electrochemotherapy based on numerical treatment planning.

Methods

The aim of our study was to treat a melanoma metastasis in the thigh of a patient. Treatment planning for electrode positioning and electrical pulse parameters was performed for two different electrode configurations: one with four and another with five long needle electrodes. During the procedure, the four electrode treatment plan was adopted and the patient was treated accordingly by electrochemotherapy with bleomycin. The response to treatment was clinically and radiographically evaluated. Due to a partial response of the treated tumor, the metastasis was surgically removed after 2 months and pathological analysis was performed.

Results

A partial response of the tumor to electrochemotherapy was obtained. Histologically, the metastasis showed partial necrosis due to electrochemotherapy, estimated to represent 40-50% of the tumor. Based on the data obtained, we re-evaluated the electrical treatment parameters in order to correlate the treatment plan with the clinical response. Electrode positions in the numerical model were updated according to the actual positions during treatment. We compared the maximum value of the measured electric current with the current predicted by the model and good agreement was obtained. Finally, tumor coverage with an electric field above the reversible threshold was recalculated and determined to be approximately 94%. Therefore, according to the calculations, a small volume of tumor cells remained viable after electrochemotherapy, and these were sufficient for tumor regrowth.

Conclusions

In this, the first reported clinical case, deep-seated melanoma metastasis in the thigh of the patient was treated by electrochemotherapy, according to a treatment plan obtained by numerical modeling and optimization. Although only a partial response was obtained, the presented work demonstrates that treatment of deep-seated tumor nodules by electrochemotherapy is feasible and sets the ground for numerical treatment planning-based electrochemotherapy.

Trial registration

EudraCT:2008-008290-54
Expression of the leukemic prognostic marker CD7 is linked to epigenetic modifications in chronic myeloid leukemia
Authors: Rogers Sally L , Zhao Yun , Jiang Xiaoyan , Eaves Connie J , Mager Dixie L , Rouhi Arefeh
Published: February 2010

Background

Expression levels of the cell surface glycoprotein, CD7, and the serine protease, elastase 2 (ELA2), in the leukemic cells of patients with chronic myeloid leukemia (CML) have been associated with clinical outcome. However, little is known about the mechanisms that underlie the variable expression of these genes in the leukemic cells.

Results

To address this question, we compared the level of their expression with the DNA methylation and histone acetylation status of 5' sequences of both genes in leukemic cell lines and primitive (lin-CD34+) leukemic cells from chronic phase CML patients. DNA methylation of theELA2gene promoter did not correlate with its expression pattern in lin-CD34+cells from chronic phase CML patient samples even though there was clear differential DNA methylation of this locus inELA2-expressing and non-expressing cell lines. In contrast, we found a strong relation between CD7 expression and transcription-permissive chromatin modifications, both at the level of DNA methylation and histone acetylation with evidence of hypomethylation of theCD7promoter region in the lin-CD34+cells from CML patients with high CD7 expression.

Conclusion

These findings indicate a link between epigenetic modifications and CD7 expression in primitive CML cells.
Phase I Pharmacokinetic and Pharmacodynamic Study of 17-dimethylaminoethylamino-17-demethoxygeldanamycin, an Inhibitor of Heat-Shock Protein 90, in Patients With Advanced Solid Tumors
Authors: Ramanathan Ramesh K. , Egorin Merrill J. , Erlichman Charles , Remick Scot C. , Ramalingam Suresh S. , Naret Cynthia , Holleran Julianne L. , TenEyck Cynthia J. , Ivy S. Percy , Belani Chandra P.
Published: February 2010

Purpose

To define the maximum tolerated dose, toxicities, pharmacokinetics, and pharmacodynamics of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17DMAG).

Methods

17DMAG was given intravenously over 1 hour daily for 5 days (schedule A) or daily for 3 days (schedule B) every 3 weeks. Plasma 17DMAG concentrations were measured by liquid chromatography/mass spectrometry. Heat-shock proteins (HSPs) and client proteins were evaluated at baseline and after treatment on day 1 in peripheral blood mononuclear cells (PBMCs) and in pre- and post-treatment (24 hours) biopsies done during cycle 1 at the recommended phase II dose (n = 7).

Results

Fifty-six patients were entered: 26 on schedule A; 30 on schedule B. The recommended phase II doses for schedules A and B were 16 mg/m2 and 25 mg/m2, respectively. Grade 3/4 toxicities included liver function test elevation (14%), pneumonitis (9%), diarrhea (4%), nausea (4%), fatigue (4%) and thrombocytopenia (4%). There were no objective responses. Four patients had stable disease. 17DMAG half-life was 24 ± 15 hours. 17DMAG area under the curve (range, 0.7 to 14.7 mg/mL × h) increased linearly with dose. The median HSP90, HSP70, and integrin-linked kinase levels were 87.5% (n = 14), 124% (n = 20), and 99.5% (n = 20) of baseline. Changes in HSPs and client proteins in tumor biopsies were not consistent between baseline and 24 hours nor did they change in the same direction as those in PBMCs collected at the time of biopsy.

Conclusion

The recommended phase II doses of 17DMAG (16 mg/m2 × 5 days or 25 mg/m2 × 3 days, every 3 weeks) are well tolerated and suitable for further evaluation.
HIV As a Risk Factor for Lung Cancer in Women: Data From the Women's Interagency HIV Study
Authors: Levine Alexandra M. , Seaberg Eric C. , Hessol Nancy A. , Preston-Martin Susan , Silver Sylvia , Cohen Mardge H. , Anastos Kathryn , Minkoff Howard , Orenstein Jan , Dominguez Geraldina , Watts D. Heather
Published: February 2010

Purpose

Prior reports of an increased risk of lung cancer in HIV-infected individuals have not always included control groups, nor considered other risk factors such as tobacco exposure. We sought to determine the role of HIV infection and highly active antiretroviral therapy (HAART) on lung cancer incidence in 2,651 HIV-infected and 898 HIV-uninfected women from the Women's Interagency HIV Study (WIHS).

Methods

A prospective study of the incidence rates of lung cancer was conducted, with cases identified through medical records, death certificates, and state cancer registries. Standardized incidence ratios (SIRs) were calculated to compare lung cancer incidence among HIV-infected and uninfected WIHS participants, with population-based expectations using the Surveillance, Epidemiology, and End Results registry. Behavioral characteristics in the WIHS were compared to US women by age and race adjusting the population-based data from the National Health and Nutritional Examination Survey (NHANES) III.

Results

Incidence rates of lung cancer were similar among HIV-infected and uninfected WIHS women. Lung cancer SIRs were increased in both HIV-infected and -uninfected women compared with population expectations, but did not differ by HIV status. Among HIV-infected women, lung cancer incidence rates were similar in pre-HAART and HAART eras. All WIHS women with lung cancer were smokers; the risk of lung cancer increased with cumulative tobacco exposure. WIHS women were statistically more likely to smoke than US women studied in NHANES III.

Conclusion

HIV infection is strongly associated with smoking behaviors that increase lung cancer risk. The role of HIV itself remains to be clarified.
Cross-Sectional Study of Imatinib Plasma Trough Levels in Patients With Advanced Gastrointestinal Stromal Tumors: Impact of Gastrointestinal Resection on Exposure to Imatinib
Authors: Yoo Changhoon , Ryu Min-Hee , Kang Byung Woog , Yoon Shin-Kyo , Ryoo Baek-Yeol , Chang Heung-Moon , Lee Jae-Lyun , Beck Mo Youl , Kim Tae Won , Kang Yoon-Koo
Published: February 2010

Purpose

Imatinib plasma trough levels (Cmin) have been reported to correlate with treatment outcomes in patients with gastrointestinal stromal tumors (GISTs). We therefore have evaluated the correlation between imatinib Cminand the clinical characteristics of patients with GIST.

Patients and Methods

Steady-state imatinib Cminin 107 patients with GIST who were taking imatinib 300 to 800 mg/d was measured.

Results

In patients treated with imatinib 400 (n = 92), 300 (n = 7), 600 (n = 2), or 800 (n = 11) mg/d, imatinib Cminwas 1,305 ± 633 ng/mL, 1,452 ± 830 ng/mL, 1,698 ± 725 ng/mL, and 3,330 ± 1,592 ng/mL, respectively. Of the 92 patients treated with 400 mg/d imatinib, 59 patients (63%) were men; the median age was 55 years (range, 28 to 76 years), and the median duration of imatinib use before sampling was 8.8 months (range, 0.5 to 67.6 months). The mean inter- and intrapatient variability rates were 44.7% and 26.5%, respectively. In univariate analyses, high Cminwas correlated with advanced age (P = .02), low creatinine clearance (P = .001), low hemoglobin (P = .03), and low albumin (P < .001) concentrations. Imatinib Cminwas also significantly lower in patients with (n = 18; 942 ± 330 ng/mL) than without (n = 74; 1,393 ± 659 ng/mL) major (ie, total or subtotal) gastrectomy (P = .002). In multivariate analysis, albumin (P = .001) concentrations, creatinine clearance (P = .002), and major gastrectomy (P = .003) were significantly correlated with Cmin.

Conclusion

In patients with GIST, imatinib Cminat steady state was significantly associated with albumin concentration, creatinine clearance, and previous major gastrectomy. Although its clinical impact is unclear at present time, monitoring of imatinib Cminmight be particularly important for optimal treatment with imatinib in patients who have undergone major gastrectomy.
Variations in the Response of Pituitary Lactotrophs to Oxytocin during the Rat Estrous Cycle
Authors: Tabak Joël , Gonzalez-Iglesias Arturo E. , Toporikova Natalia , Bertram Richard , Freeman Marc E.
Published: February 2010

Although removal of dopamine inhibition is established as a major factor in prolactin (PRL) release, a large body of evidence suggests that hypothalamic oxytocin (OT) may serve as a PRL-releasing hormone in the rat. PRL release is modulated by estradiol (E2), which rises between diestrus and proestrus of the estrous cycle, causing a PRL surge in the afternoon of proestrus. Given that E2 strongly modulates OT actions in both central and peripheral tissues, OT action on lactotrophs might also be modulated by the stage of the estrous cycle. To test this hypothesis, we have monitored PRL release and intracellular calcium levels ([Ca2+]i) induced by OT in pituitary lactotrophs obtained from female rats in either diestrus 1 or proestrus. We found that both secretory and [Ca2+]i responses to OT are significantly increased in lactotrophs obtained on proestrus. Moreover, we show that these differences are due to an increase in both the number of OT-responding lactotrophs and the magnitude of their individual [Ca2+]i responses. Both secretory and [Ca2+]i responses were abolished by a specific OT antagonist. Finally, dose-dependent studies show that the increased PRL-releasing effect of OT on proestrus is significant over a wide range of concentrations, particularly those observed in hypophyseal portal plasma. These results suggest that the rising E2 titers that culminate on proestrus facilitate the stimulatory action of OT on lactotrophs and support the notion that OT is a PRL-releasing hormone with an important role in the production of the proestrous surge of PRL.
On growth and form: a Cartesian coordinate system of Wnt and BMP signaling specifies bilaterian body axes
Authors: Niehrs Christof
Published: February 2010

The regulation of body axis specification in the common ancestor of bilaterians remains controversial. BMP signaling appears to be an ancient program for patterning the secondary, or dorsoventral, body axis, but any such program for the primary, or anteroposterior, body axis is debated. Recent work in invertebrates indicates that posterior Wnt/β-catenin signaling is such a mechanism and that it evolutionarily predates the cnidarian-bilaterian split. Here, I argue that a Cartesian coordinate system of positional information set up by gradients of perpendicular Wnt and BMP signaling is conserved in bilaterians, orchestrates body axis patterning and contributes to both the relative invariance and diversity of body forms.
LIN28 alters cell fate succession and acts independently of the let-7 microRNA during neurogliogenesis in vitro
Authors: Balzer Erica , Heine Christian , Jiang Qiang , Lee Vivian M. , Moss Eric G.
Published: February 2010

LIN28 is an RNA-binding protein that is expressed in many developing tissues. It can block let-7 (Mirlet7) microRNA processing and help promote pluripotency. We have observed LIN28 expression in the developing mouse neural tube, colocalizing with SOX2, suggesting a role in neural development. To better understand its normal developmental function, we investigated LIN28 activity during neurogliogenesis in vitro, where the succession of neuronal to glial cell fates occurs as it does in vivo. LIN28 expression was high in undifferentiated cells, and was downregulated rapidly upon differentiation. Constitutive LIN28 expression caused a complete block of gliogenesis and an increase in neurogenesis. LIN28 expression was compatible with neuronal differentiation and did not increase proliferation. LIN28 caused significant changes in gene expression prior to any effect on let-7, notably on Igf2. Furthermore, a mutant LIN28 that permitted let-7 accumulation was still able to completely block gliogenesis. Thus, at least two biological activities of LIN28 are genetically separable and might involve distinct mechanisms. LIN28 can differentially promote and inhibit specific fates and does not function exclusively by blocking let-7 family microRNAs. Importantly, the role of LIN28 in cell fate succession in vertebrate cells is analogous to its activity as a developmental timing regulator in C. elegans.
Contemporary discursive psychology: Issues, prospects, and Corcoran's awkward ontology
Authors: Potter Jonathan.
Published: February 2010

This paper is both an overview of the status of contemporary discursive psychology and a response to Corcoran's critical article. The first part of the paper reports on the main traditions that make up contemporary discursive psychology and how they relate to one another. Then it responds to Corcoran's claims that much of contemporary discursive psychology: (a) is over concerned with epistemic issues at the expense of ontological issues; (b) is too concerned with data purity while failing reflexively to address its own practices; (c) fails to address ethical, applied, and political issues in the way that a reformed ‘ontological’ discursive psychology would be able to; (d) fails to provide an adequate and rich account of relationality (of the kind offered by thinkers such as Bakhtin, Shotter, and Chouliaraki). The limitations of each point are addressed in turn, highlighting errors and confusions. The broadly epistemic focus is appropriate for the subject matter of discursive psychology; discursive psychology is less concerned with data purity than with pursuing the radical and empirically progressive possibilities in studying records of people living their lives in everyday and institutional settings (a surprising oversight in a discipline focused on the actions of human beings) and it has a reflexive tradition going back two decades; it has a strong and distinctive focus on ethical, applied, and political issues; it has an account of relationality that is grounded in conversational materials. A single example from interaction on a child protection helpline is analysed to illustrate the way relationality, knowledge, and intersubjectivity have been made analytically tractable in contemporary discursive research.
Social support and regular physical activity: Does planning mediate this link?
Authors: Molloy G. J. , Dixon D. , Hamer M. , Sniehotta F. F.
Published: February 2010

Objectives. Social support for physical activity is reliably associated with regular physical activity, however the social cognitive processes, particularly post‐intentional processes, that can explain this link have not been well characterized. In this study, we examined the extent to which the relationship between social support for physical activity and subsequent physical activity can be accounted for by planning processes.

Design and method. The design was prospective observational and the sample consisted of 903 university students. Participants completed standard theory of planned behaviour, planning, and physical activity measures at 2 time points, approximately 7 weeks apart. A gender stratified multiple mediation model was conducted to test the study hypotheses.

Results. A significant interaction between social support and gender was observed. This indicated that lower levels of social support for physical activity were associated with lower levels of physical activity at Time 2, for women only. In multiple mediation analysis, this was partly explained by the indirect effects of social support through perceived behavioural control and coping planning.

Conclusion. These findings highlight the importance of interpersonal processes in understanding the post‐intentional social cognitive determinants of regular physical activity. It is likely that planning processes relating to physical activity are often influenced by those in the ongoing immediate social environment who support this behaviour. Future development of theory and interventions should take account of the socially interactive nature of planning processes.
Il mare in tempesta nel De autexusio di Metodio d'Olimpo e nell'Hexaemeron di Giorgio di Pisidia
Authors: Franchi Roberta
Published: February 2010

The article offers a fundamental comparison between a passage in the dialogue of Methodius of Olympus calles De libero arbitrio, and one in the Hexaemeron of George of Pisidia. The starting point is represented by a description of the stormy sea, contained in the De libero arbitrio. After a poetical scene full of epical elements (high waves reach the sky and are like mountains), Methodius gives us an original representation of the sea: as the servant can't refuse to obey his master and mumbles by himself, so the sea has to restrain its anger and remain in its limits, even if it wants to be free. According to Job 38.11, it is forced to sacrifice its will, because there is a divine power that governs the universe. This passage may have influenced the composition of George of Pisidia. In fact, in his Hexaemeron the poet has come to personify the sea, first of all, with the image of a fugitive slave, then with a Bacchante who, taken by an impulse, wishes to go beyond the limits, and finally, with a female slave who is dragged away; this is created to support the conception that nature, in spite of natural impulse, is not independent and free, but is governed by God. Even if George of Pisidia inserts in his scene more details, the comparison of the sea with human subjects and the impossibility for it to be free refer to Methodius' passage. That the poet knew Methodius' writings is confirmed by one of his epigrams, in which he praises the bearing of the style of Methodius' works, based on evident lines of reasoning and divine inspiration.
Potassium – reference intervals for lithium-heparin plasma and serum from a population-based cohort / Kalium – Referenzbereiche für Lithium-Heparin-Plasma und Serum aus einer bevölkerungsbezogenen Studie
Authors: Drogies Tim , Ittermann Till , Lüdemann Jan , Klinke Doris , Kohlmann Thomas , Lubenow Norbert , Greinacher Andreas , Völzke Henry , Nauck Matthias
Published: February 2010

Background: Serum, as a standard material for the determination of numerous analytes, has disadvantages. The coagulation process leads to an artificial increase of the potassium concentration of approximately 0.3 mmol/L in serum samples compared to plasma. Consequently, plasma reflects the in vivo situation more accurately. The aim of the present analyses was to establish reference intervals (RIs) for potassium using data from a population-based study for serum (PS) and plasma (PP).

Methods: Serum was used from 2897 subjects aged 20–79 years, participating in the 5-year follow-up of the Study of Health in Pomerania (SHIP 1), a population-based study in northeast Germany. In addition, 2483 samples (serum and plasma) from a population of blood donors (DONOR-SHIP) were used. Finally, calculated RIs were reevaluated in 202,350 potassium values from hospitalized patients. All measurements were performed on a Siemens Dimension RxL Max HM with ion-selective electrodes. Using the sample pairs from DONOR-SHIP, a regression formula for the transformation of PS to PP was calculated. This formula was applied to the serum data from SHIP 1 to calculate corresponding plasma values. RIs (2.5th and 97.5th percentile) were defined with quantile regression and bootstrap method in SHIP 1.

Results: RIs for PS and PP were 3.7–5.1 mmol/L and 3.5–4.6 mmol/L, respectively. Clinically relevant age- or sex-specific tendencies were not detected. The difference between PS and PP is dependent on platelet count and potassium concentration.

Conclusions: The study permitted the establishment of RIs for PS and PP on a population-based study. For serum, the influence of platelet count and absolute potassium concentration on the results should be taken into account.
Performance Tests for the Selection of Fabrics and Additives When Used as Geotextile Bags, Containers, and Tubes
Authors: Koerner Robert M. , Koerner George R.
Published: February 2010

There are two performance tests available for the selection of fabrics and additives when contemplating a geotextile bag, container, or tube application. They are the “hanging bag test” and the “pillow test.” Both tests are described in this paper along with data generated by their use. While both can be used for selection purposes, the advantages of the pillow test over the hanging bag test are quite compelling. Items favoring the pillow test are much smaller size, need for less dredged or slurried infill material, better field simulated orientation, and the capability of monitoring hydraulic head versus time behavior. This last item is most important since dredging pressures are always involved and the simulated behavior of the pillow test gives good insight into the anticipated behavior of the full-scale application.
Randomized GH trial with two different dosages in combination with a GnRH analogue in short small for gestational age children: effects on metabolic profile and serum GH, IGF1, and IGFBP3 levels
Authors: van der Kaay Daniëlle , Bakker Boudewijn , van der Hulst Flip , Mul Dick , Mulder Jaap , Schroor Eelco , van Elswijk Denise , Rowaan Inge , Willeboer Merel , de Ridder Maria , Hokken-Koelega Anita
Published: February 2010

Background

GnRH analogue (GnRHa) combined with GH treatment has been proposed to increase adult height. Effect on metabolic profile and GH, IGF1, and IGFBP3 levels in short small for gestational age (SGA) children is unknown.

Objective

To assess fat mass and lean body mass SDS, percentage trunk fat, blood pressure (BP), insulin sensitivity (Si), β-cell function (disposition index, DI), lipid profile, and GH, IGF1, and IGFBP3 levels during 2 years of combined treatment.

Subjects

Forty-one pubertal short SGA children with a mean (±s.d.) age of 12.1 (±1.0) years.

Design

Children received 3.75 mg of leuprolide acetate depot subcutaneously every 4 weeks, and they were randomly assigned to receive 1 mg (group A) or 2 mg (group B) of GH/m2per day.

Results

Percentage trunk fat increased in both groups, but to a lower extent in group B. Lean body mass SDS increased only in group B. Changes in BP, Si, DI, and lipids were similar in both groups. Si significantly decreased, but DI remained unchanged. Lipids remained normal. GH and IGF1 levels were significantly higher in group B.

Conclusion

Our study is the first to report that 2 years of combined treatment with a GnRHa and either 1 or 2 mg GH/m2per day does not adversely affect body composition and metabolic profile of short SGA children who come under medical attention at the onset of puberty. There was a dose-dependent effect on fat mass SDSheight, percentage trunk fat, lean body mass SDSheight, and GH and IGF1 levels in favor of treatment with GnRHa and the higher GH dose of 2 mg/m2per day.
An Auxiliary Silencer and a Boundary Element Maintain High Levels of Silencing Proteins atHMRinSaccharomyces cerevisiae
Authors: Lynch Patrick J , Rusche Laura N
Published: February 2010

Heterochromatin is notable for its capacity to propagate along a chromosome. The prevailing model for this spreading process postulates that silencing proteins are first recruited to silencer sequences and then spread from these sites independently of the silencers. However, we found that in Saccharomyces cerevisiae silencers also influence the extent of silenced chromatin domains. We compared the abilities of two different silencers, HMR-E and a telomeric repeat, to promote silencing and found that the HMR-E silencer contributed to an increased steady-state association of Sir proteins over a region of several kilobase pairs compared to the telomeric repeat, even though both silencers recruited similar levels of Sir proteins. We also discovered that, although the HMR-E silencer alone was sufficient to block transcription of the HMR locus, a secondary silencer, HMR-I, boosted the level of Sir proteins at HMR, apparently beyond the level necessary to repress transcription. Finally, we discovered that a tRNAThr gene near HMR-I helped maintain silenced chromatin and transcriptional repression under conditions of reduced deacetylase activity. This study highlights the importance of auxiliary elements, such as HMR-I and the tRNAThr gene, in enhancing the association of Sir silencing proteins with appropriate genomic locations, thereby buffering the capacity of silenced chromatin to assemble under suboptimal conditions.
Regulation of Septum Formation by the Bud3–Rho4 GTPase Module inAspergillus nidulans
Authors: Si Haoyu , Justa-Schuch Daniela , Seiler Stephan , Harris Steven D
Published: February 2010

The ability of fungi to generate polarized cells with a variety of shapes likely reflects precise temporal and spatial control over the formation of polarity axes. The bud site selection system of Saccharomyces cerevisiae represents the best-understood example of such a morphogenetic regulatory system. However, the extent to which this system is conserved in the highly polarized filamentous fungi remains unknown. Here, we describe the functional characterization and localization of the Aspergillus nidulans homolog of the axial bud site marker Bud3. Our results show that AnBud3 is not required for polarized hyphal growth per se, but is involved in septum formation. In particular, our genetic and biochemical evidence implicates AnBud3 as a guanine nucleotide exchange factor for the GTPase Rho4. Additional results suggest that the AnBud3–Rho4 module acts downstream of the septation initiation network to mediate recruitment of the formin SepA to the site of contractile actin ring assembly. Our observations provide new insight into the signaling pathways that regulate septum formation in filamentous fungi.
Activation of Sterol Regulatory Element Binding Proteins in the Absence of Scap in Drosophila melanogaster
Authors: Matthews Krista A , Ozdemir Cafer , Rawson Robert B
Published: February 2010

The escort factor Scap is essential in mammalian cells for regulated activation of sterol regulatory element binding proteins (SREBPs). SREBPs are membrane-bound transcription factors. Cells lacking Scap cannot activate SREBP. They are therefore deficient in the transcription of numerous genes involved in lipid synthesis and uptake; they cannot survive in the absence of exogenous lipid. Here we report that, in contrast to mammalian cells, Drosophila completely lacking dscap are viable. Flies lacking dscap emerge at ∼70% of the expected rate and readily survive as homozygous stocks. These animals continue to cleave dSREBP in some tissues. Transcription of dSREBP target genes in dscap mutant larvae is reduced compared to wild type. It is greater than in mutants lacking dSREBP and remains responsive to dietary lipids in dscap mutants. Flies lacking dscap do not require the caspase Drice to activate dSREBP. This contrasts with ds2p mutants. ds2p encodes a protease that releases the transcription factor domain of dSREBP from the membrane. Larvae doubly mutant for dscap and ds2p exhibit phenotypes similar to those of ds2p single mutants. Thus, dScap and dS2P, essential components of the SREBP activation machinery in mammalian cells, are dispensable in Drosophila owing to different compensatory mechanisms.
Avaliação econômica em saúde: aplicações em doenças infecciosas
Authors: Vanni Tazio , Luz Paula Mendes , Ribeiro Rodrigo Antonini , Novaes Hillegonda Maria Dutilh , Polanczyk Carisi A.
Published: February 2010

O crescimento dos gastos em saúde, impulsionado pela incorporação de novas tecnologias diagnósticas e terapêuticas e pelo aumento da expectativa de vida da população, tem causado grande preocupação especialmente em países em desenvolvimento. A avaliação econômica em saúde visa a otimizar benefícios utilizando os recursos de maneira eficiente. O objetivo deste artigo é capacitar os leitores a identificar as características básicas, diferenciar os principais tipos e compreender as metodologias utilizadas nas avaliações econômicas em saúde, com enfoque nas doenças infecciosas. Assim sendo, revisamos os conceitos de perspectiva de estudo, horizonte analítico, custos e taxa de desconto. Além disso, identificamos as características dos estudos de custo-minimização, custo-efetividade, custo-utilidade e custo-benefício acompanhados de exemplos, descrevemos os principais desenhos de estudos econômicos, discutimos o uso de modelos matemáticos e examinamos a importância da análise de sensibilidade. Nas considerações finais, abordamos a incorporação da avaliação econômica em saúde no Brasil.
Eco-epidemiologia dos arbovírus na área de influência da rodovia Cuiabá-Santarém (BR 163), Estado do Pará, Brasil
Authors: Nunes Marcio Roberto Teixeira , Barbosa Taciana Fernandes Souza , Casseb Lívia Medeiros Neves , Nunes Neto Joaquim Pinto , Segura Nazaré de Oliveira , Monteiro Hamilton Antônio de Oliveira , Pinto Eliana Vieira , Casseb Samir Mansour , Chiang Jannifer de Oliveira , Martins Lívia Caricio , Medeiros Daniele Barbosa de Almeida , Vasconcelos Pedro Fernando da Costa
Published: February 2010

O presente estudo descreve os aspectos eco-epidemiológicos sobre arbovírus nos Municípios de Novo Progresso e Trairão, Estado do Pará, Brasil, na área de influência da BR 163. Anticorpos IH foram detectados para diferentes arbovírus, com reações monotípicas para os VMAY e VORO, dois importantes arbovírus associados a epidemias na Amazônia. Anticorpos IgM para o VORO e VMAY foram detectados em soros humanos, sugerindo infecção recente por esses arbovírus. Duas cepas do VDEN-3 foram isoladas de pacientes febris residentes em Novo Progresso e identificadas como genótipo III. Em termos gerais, os dados obtidos sugerem uma área propícia para a circulação e manutenção de arbovírus e uma população pouco imunizada. Portanto, é importante um monitoramento dinâmico das populações locais e de imigrantes e de animais silvestres quanto à presença de anticorpos e isolamentos de arbovírus, o que permitirá um efetivo controle das infecções por esses agentes virais em residentes da área da rodovia dentro do território paraense.
Vulnerabilidade social e risco ambiental: uma abordagem metodológica para avaliação de injustiça ambiental
Authors: Cartier Ruy , Barcellos Christovam , Hübner Cristiane , Porto Marcelo Firpo
Published: February 2010

O objetivo deste artigo é avaliar a vulnerabilidade sócio-ambiental por meio da seleção e análise de indicadores sócio-econômicos, demográficos e de infra-estrutura no entorno do Distrito Industrial Fazenda Botafogo, no Município do Rio de Janeiro, Brasil, utilizado neste trabalho como estudo de caso. Buscou-se verificar nesse espaço se existe alguma correlação entre grupos socialmente vulneráveis e risco ambiental, conformando um quadro de injustiça ambiental. O estudo caracteriza-se por ser uma análise quantitativa e espacial pautado na utilização de um Sistema de Informações Geográficas (SIG). As análises evidenciam uma forte correlação entre vulnerabilidade social e risco ambiental, tendo por referência a proximidade das indústrias na região escolhida. Os indicadores mostram que, na região analisada, as populações com as piores condições sócio-econômicas tendem a se localizar mais próximas às fontes industriais de riscos ambientais. De modo inverso, também foi verificado que os grupos populacionais com melhores condições sócio-econômicas tendem a se localizar mais distantes de tais espaços.
Prevalência e fatores associados a porte de arma e envolvimento em agressão física entre adolescentes de 15 a 18 anos: estudo de base populacional
Authors: Silva Ricardo Azevedo da , Jansen Karen , Godoy Russélia Vanila , Souza Luciano Dias Mattos , Horta Bernardo Lessa , Pinheiro Ricardo Tavares
Published: February 2010

Objetivo do estudo foi avaliar a prevalência e fatores associados a porte de arma e envolvimento em agressão física entre adolescentes de 15 a 18 anos na cidade de Pelotas, Rio Grande do Sul, Brasil. Estudo transversal de base populacional com uma amostra representativa de 960 adolescentes entre 15 e 18 anos, residentes na cidade de Pelotas. Sortearam-se, aleatoriamente, 90 setores censitários a partir dos 448 da cidade, e foram visitados 86 domicílios de cada setor. Para análise estatística utilizou-se a regressão de Poisson. A prevalência dos comportamentos estudados na presente amostra foi de 22,8% para participação em brigas com agressão física e 9,6% para porte de armas nos últimos 12 meses. Conclui-se que jovens do sexo masculino que utilizam álcool e/ou drogas ilícitas e apresentam transtornos psiquiátricos menores mostraram maior probabilidade de portar armas e de envolverem-se em brigas com agressão física.
Virtual toed‐in camera method to eliminate parallax distortions of stereoscopic images for stereoscopic displays
Authors: Deng Huan , Wang Qiong‐Hua , Li Da‐Hai , Wang Ai‐Hong
Published: February 2010

Abstract—The parallax images captured by a toed‐in camera have positive and negative horizontal parallax for stereoscopic displays, but they also have parallax distortions including horizontal and vertical distortions. The virtual toed‐in camera method can eliminate the horizontal distortion and reduce the vertical distortion. The parallax formulae for the corrected‐parallax images were deduced. The experiments were carried out and the results proved that the method was accurate. Good stereoscopic images without horizontal distortion and with little vertical distortion were presented on an autostereoscopic display.
Drivers for free‐form modular displays
Authors: Bauwens Pieter , Doutreloigne Jan
Published: February 2010

Abstract— When displays of different sizes and shapes are required, a modular display system seems to be a good solution. Many systems offer only a limited freedom of shapes. The display can be scaled, but no irregular shapes can be created. If those shapes can be created, the configuration is often manual. A more intelligent modular system allows all shapes to be created and configures automatically. This paper presents two drivers that can be used in such a modular system. The first driver ensures that the data finds its way to every module and is displayed, even if there are some “holes” in the display due to missing modules. The second driver adds some extra functionality. The precise display configuration can be detected, and in the graphical user interface (used for controlling the display) the user sees an updated view of the display configuration when modules are added or removed. Both drivers have been proven successful and results are presented in this paper.
Reducing the warp of sheet glass
Authors: Akilian Mireille , Schattenburg Mark L.
Published: February 2010

Abstract— Many leading technologies, such as flat‐panel displays and precision optics, require sheet glass with exceptional surface qualities. Commercially available sheet glass of <1 ‐mm thickness typically has a surface warp on the order of hundreds of microns, rendering it a challenge to utilize progressively thinner sheets. A novel method of shaping individual sheets and ribbons of glass is presented which utilizes porous mandrels. This method reduces the surface warp of the ribbon while in its hot state without contacting its surface. Sheet glass is inserted between two parallel porous mandrels spaced apart by a predefined distance. A thin layer of pressurized gas flows through each mandrel and out against the glass surfaces. The local gap between the warped glass sheet and the flat mandrel determines the local pressure on the glass. When in its heated and soft state, the glass sheet's surface is changed by this pressure with a strong restorative force proportional to the inverse of the gap cubed, which tends to flatten the sheet. By using flat mandrels and controlled pressurized gas at elevated temperatures, the outcome is a sheet of glass with a surface warp of a few microns while retaining its original pristine optical surface qualities.
Nitrogen deposition and its contribution to nutrient inputs to intensively managed agricultural ecosystems
Authors: He Chun-E. , Wang Xin , Liu Xuejun , Fangmeier Andreas , Christie Peter , Zhang Fusuo
Published: February 2010

Interest in nitrogen inputs via atmospheric deposition to agricultural ecosystems has increased recently, especially on the North China Plain because of extremely intensive agricultural systems and rapid urbanization in this region. Nitrogen deposition may make a significant contribution to crop N requirements but may also impose a considerable nutrient burden on the environment in general. We quantified total N deposition at two locations, Dongbeiwang near Beijing and Quzhou in Hebei province, over a two‐year period from 2005 to 2007 using an 15N tracer method, the integrated total N input (ITNI) system. Total airborne N inputs to a maize–wheat rotation system at both locations ranged from 99 to 117 kg N·ha−1·yr−1, with higher N deposition during the maize season (57–66 kg N/ha) than the wheat season (42–51 kg N/ha). Plant available N from deposition for maize and wheat was about 52 kg N·ha−1·yr−1, accounting for 50% of the total N deposition or 31% of total N uptake by the two crop species. In addition, a correction factor was derived for the maize season to adjust values obtained from small pots (0.057 m2) compared with field trays (0.98 m2) because of higher plant density in the pots. The results indicate that atmospheric N deposition is a very important N input and must be taken into account when calculating nutrient budgets in very intensively managed agricultural ecosystems.
Use of dynamic soil–vegetation models to assess impacts of nitrogen deposition on plant species composition: an overview
Authors: Vries W. De , Wamelink G. W. W. , Dobben H. van , Kros J. , Reinds G. J. , Mol-Dijkstra J. P. , Smart S. M. , Evans C. D. , Rowe E. C. , Belyazid S. , Sverdrup H. U. , Hinsberg A. van , Posch M. , Hettelingh J-P. , Spranger T. , Bobbink R.
Published: February 2010

Field observations and experimental data of effects of nitrogen (N) deposition on plant species diversity have been used to derive empirical critical N loads for various ecosystems. The great advantage of such an approach is the inclusion of field evidence, but there are also restrictions, such as the absence of explicit criteria regarding significant effects on the vegetation, and the impossibility to predict future impacts when N deposition changes. Model approaches can account for this. In this paper, we review the possibilities of static and dynamic multispecies models in combination with dynamic soil–vegetation models to (1) predict plant species composition as a function of atmospheric N deposition and (2) calculate critical N loads in relation to a prescribed protection level of the species composition. The similarities between the models are presented, but also several important differences, including the use of different indicators for N and acidity and the prediction of individual plant species vs. plant communities. A summary of the strengths and weaknesses of the various models, including their validation status, is given. Furthermore, examples are given of critical load calculations with the model chains and their comparison with empirical critical N loads. We show that linked biogeochemistry–biodiversity models for N have potential for applications to support European policy to reduce N input, but the definition of damage thresholds for terrestrial biodiversity represents a major challenge. There is also a clear need for further testing and validation of the models against long‐term monitoring or long‐term experimental data sets and against large‐scale survey data. This requires a focused data collection in Europe, combing vegetation descriptions with variables affecting the species diversity, such as soil acidity, nutrient status and water availability. Finally, there is a need for adaptation and upscaling of the models beyond the regions for which dose–response relationships have been parameterized, to make them generally applicable.
Estimating the effects of excess nutrients on stream invertebrates from observational data
Authors: Yuan Lester L.
Published: February 2010

Increased nutrient concentrations in streams and rivers have altered biological structure and function. Manipulative studies have provided insights into different mechanisms by which changes in nutrient concentrations influence aquatic biota, but these studies are limited in spatial scope and in their quantification of nutrient effects on aggregate measures of the invertebrate assemblage. Observational data provide a complementary source of information to manipulative studies, but these data must be analyzed such that the potential effects of spurious correlations are minimized. Propensity scores, a technique developed to analyze human health observational data, are applied here to estimate the effects of increased nutrients on the total taxon richness of stream invertebrates in a large observational data set collected from the western United States. The analysis indicates that increases in nutrient concentration are strongly associated with and cause decreases in invertebrate richness in large, but wadeable, open‐canopied streams. These decreases in invertebrate richness were not mediated by periphyton biomass, a commonly proposed mechanism by which nutrients influence invertebrates. In smaller, closed‐canopied streams, increases in nutrients were associated with small increases in total richness that were not statistically significant. Using propensity scores can greatly improve the accuracy of insights drawn from observational data by minimizing the potential that factors other than the factor of interest may confound the results.
Screening bioenergy feedstock crops to mitigate invasion risk
Authors: Davis Adam S , Cousens Roger D , Hill Jason , Mack Richard N , Simberloff Daniel , Raghu S
Published: February 2010

The cultivation of plants for the production of hydrocarbon fuels is gaining global momentum. These biofuels offer potential benefits as alternatives to fossil fuels, but mitigating any environmental risks posed by large‐scale cultivation of bioenergy feedstock (biofeedstock) species poses new challenges: some proposed biofuel crops have become naturalized, and even invasive; the relative risks and benefits of growing monocultures versus polycultures of biofeedstock species require more thorough examination; and prompt development of a robust ecological risk assessment framework and careful screening are needed before these biofuel species are widely cultivated. Greater collaboration between agronomists developing crops for biofeedstock production and invasion biologists could substantially lower the risk of new plant invasions.
Groundwater‐dependent ecosystems in Oregon: an assessment of their distribution and associated threats
Authors: Brown Jenny , Bach Leslie , Aldous Allison , Wyers Abby , DeGagné Julia
Published: February 2010

Effective protection and management of groundwater‐dependent ecosystems (GDEs) are hindered by inadequate information on their locations and the condition of associated groundwater supplies. We addressed this knowledge gap by developing a methodology that uses existing datasets to locate GDEs (including groundwater‐dependent springs, lakes, rivers, wetlands, and species) and assess threats to groundwater quantity and quality. Here we report on the application of this method across the US state of Oregon. Nearly 40% of watersheds in Oregon contain two or more types of GDEs – termed “GDE clusters” – indicating the widespread importance of groundwater to ecosystems. Documented problems may underestimate the threat to ecosystems from altered groundwater supply or quality. Although documented occurrences of water‐table declines are limited, high densities of permitted wells (for irrigation or other commercial purposes) pose a threat to groundwater availability in 18% of GDE clusters. Furthermore, although only 5% of GDE clusters have known groundwater contamination, our assessment indicates that 30% of GDE clusters are threatened with groundwater contamination by nitrates, 30% by industrial chemicals, and 70% by pesticides. This initial assessment of GDEs and threats to their groundwater supply highlights the ecological importance of groundwater and the need to incorporate protection of GDEs in water management policy.