bluuebunny/crossref_metadata_2025 huggingface dataset:
Activity of 9‐nitro‐camptothecin, an oral topoisomerase I inhibitor, in myelodysplastic syndrome and chronic myelomonocytic leukemia
Authors: Quintas‐Cardama Alfonso , Kantarjian Hagop , O'Brien Susan , Jabbour Elias , Giles Francis , Ravandi Farhad , Faderl Stefan , Pierce Sherry , Shan Jenny , Verstovsek Srdan , Cortes Jorge
Published: September 2006

BACKGROUND.

Topoisomerase I inhibitors, like topotecan, have activity in myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). 9‐Nitro‐camptothecin (9‐NC) is a new oral topoisomerase inhibitor with a good safety profile. The aims of the current study were to evaluate the activity and safety of 9‐NC in MDS and CMML.

METHODS.

Adults with a diagnosis of MDS (n = 12) and CMML (n = 32) received 9‐NC 2 mg/m2 orally daily 5 days a week, every 4 to 6 weeks.

RESULTS.

Overall, 5 (11%) patients achieved complete response (CR), 7 (16%) had a partial response (PR), and 6 (14%) had hematologic improvement (HI), for an overall response rate of 41%. The response rate was similar in MDS and CMML. Severe (Grade 3–4) side effects included nausea and vomiting (7%), diarrhea (18%), other gastrointestinal toxicities (5%), and genitourinary toxicities (12%).

CONCLUSIONS.

9‐NC is active in MDS and CMML. The paucity of available therapies in CMML makes 9‐NC a good candidate for further studies as a single agent, or in combination with decitabine, 5‐azacitidine or cytarabine. Cancer 2006. © 2006 American Cancer Society.
Treatment of metastatic sarcoma to the liver with bland embolization
Authors: Maluccio Mary A. , Covey Anne M. , Schubert Johanna , Brody Lynn A. , Sofocleous Constantinos T. , Getrajdman George I. , DeMatteo Ronald , Brown Karen T.
Published: September 2006

BACKGROUND.

The authors evaluated the impact of bland particle embolization on survival in patients with metastatic sarcoma to the liver.

METHODS.

Twenty‐four patients with liver‐dominant metastases from sarcoma were treated with particle embolization from 1996 to 2002. Primary tumors included 16 gastrointestinal stromal tumors (GISTs), 7 intestinal leiomyosarcomas, and 1 liposarcoma. Thirteen patients had known extrahepatic disease. Embolization was performed by using polyvinyl alcohol or trisacryl microspheres to effect stasis in the target vessel(s). Follow‐up images to assess response were obtained 4 weeks after the procedure. Decrease in the size of the target lesion by >25% or development of >50% necrosis on follow‐up imaging was considered a treatment response.

RESULTS.

Nineteen patients had metachronous liver metastases, and the median disease‐free interval was 22 months (range 10–156 months) from resection of the primary tumor. Ten patients underwent prior liver resection for metastatic disease. Of 15 evaluable patients, 9 patients (60%) had a radiographic response. The median follow‐up for all patients was 21 months. The median follow‐up for surviving patients was 59 months. Overall survival from the time of initial embolization was 62% at 1 year, 41% at 2 years, and 29% at 3 years. Patients who had radiographic evidence of response survived significantly longer than patients who did not respond (63 months vs. 19 months; P < .007). Patients with GIST survived significantly longer than patients with visceral leiomyosarcoma (median, 36 months vs. 18 months; P < .03).

CONCLUSIONS.

Bland embolization was efficacious in some patients with metastatic sarcoma to the liver. Radiographic evidence of response was correlated with improved survival. This regional therapy may enter the treatment algorithm for patients who have unresectable disease or disease that has failed conventional therapies. Cancer 2006. © 2006 American Cancer Society.
Squamous cell carcinoma of the lung compared with other histotypes shows higher messenger RNA and protein levels for thymidylate synthase
Authors: Ceppi Paolo , Volante Marco , Saviozzi Silvia , Rapa Ida , Novello Silvia , Cambieri Alberto , Lo Iacono Marco , Cappia Susanna , Papotti Mauro , Scagliotti Giorgio V.
Published: September 2006

BACKGROUND.

In patients with cancer, one of the main mechanism of resistance to antimetabolite drugs is related to higher levels of thymidylate synthase (TS) activity.

METHODS.

To investigate the association between TS expression and histopathologic data, 56 resection specimens from patients with nonsmall cell lung carcinoma (NSCLC) were collected consecutively. TS messenger RNA (mRNA) was evaluated in tumor specimens by using real‐time polymerase chain reaction (PCR) analysis; protein expression was evaluated by using immunohistochemistry (IHC) in formalin‐fixed, paraffin‐embedded (FFPE) specimens; and the analysis of TS transcriptional regulation activity was performed by using real‐time PCR analysis in snap‐frozen normal and tumor specimens.

RESULTS.

The amplification of the TS gene from FFPE tissues was obtained from all samples, with a median level (unit‐less ratio) of 1.45 (range, 0.34–5.24); whereas positive TS status at IHC (>10% positive cells) was detected in 56% of samples. It is noteworthy that TS expression was significantly higher in squamous cell carcinoma compared with adenocarcinoma when both mRNA levels (2.17 vs. 1.16; P < .0001) and protein levels (P = .0269) were considered in FFPE specimens, and a strong association was observed between mRNA and protein expression (P = .00017). Moreover, higher TS levels were observed in high‐grade tumors (P = .0389 and P = .0068 for mRNA and protein quantification, respectively). The analysis in snap‐frozen samples revealed that the TS gene was up‐regulated strongly in tumors (P = 3.8 × 10−12), and an 8‐fold increase (as a cut‐off value) in the TS mRNA ratio between tumor and corresponding normal tissue was detected in 32 of 56 patients (57%) bearing preferentially squamous cell tumors (P = .0022) and high‐grade tumors (P < .001).

CONCLUSIONS.

Data from the current study consistently indicated higher TS expression levels in squamous cell and in high‐grade carcinomas. This information may be useful in selecting which patients with NSCLC should receive treatment with TS‐inhibiting agents. Cancer 2006. © 2006 American Cancer Society.
Gliomatosis cerebri: 20 Years of experience at the Children's Hospital of Philadelphia
Authors: Armstrong Gregory T. , Phillips Peter C. , Rorke‐Adams Lucy B. , Judkins Alexander R. , Localio A. Russell , Fisher Michael J.
Published: September 2006

BACKGROUND.

Gliomatosis cerebri (GC) is a rare and typically fatal glial neoplasm of the central nervous system. In this report, the authors describe the largest cohort of children to date with GC and explore relations between potential prognostic factors, treatment, and survival.

METHODS.

Imaging, pathologic, and outcome data were reviewed from 13 patients who were diagnosed with GC and were treated at the Children's Hospital of Philadelphia (CHOP) between 1982 and 2005. All patients had GC confirmed by biopsy. Twelve patients received cranial irradiation, and 8 of those patients received adjuvant chemotherapy. A single patient age 1 year received chemotherapy alone. A review of the literature identified 51 pediatric patients with GC.

RESULTS.

The progression‐free survival rate in this study was 13% (range, 1.5–43 months), and the overall survival (OS) rate was 64% (range, 6.5–67 months) at 2 years. OS was significantly shorter for patients who presented in the first decade of life (P = .04). The time to progression was prolonged significantly for patients who had no evidence of tumor enhancement on imaging studies (P = .03). When survival data from patients reported in the literature were combined with the CHOP cohort, treatment prolonged OS significantly (P = .003).

CONCLUSIONS.

The outcome of pediatric patients with GC was extremely poor; however, the current results indicated that treatment may prolong OS. Age < 10 years and contrast enhancement on magnetic resonance imaging studies at diagnosis may be risk factors for shorter survival in pediatric patients with GC. Cancer 2006. © 2006 American Cancer Society.
Asymmetry Induction by Cooperative Intermolecular Hydrogen Bonds in Surface‐Anchored Layers of Achiral Molecules
Authors: Dmitriev Alexandre , Spillmann Hannes , Stepanow Sebastian , Strunskus Thomas , Wöll Christof , Seitsonen Ari P. , Lingenfelder Magali , Lin Nian , Barth Johannes V. , Kern Klaus
Published: September 2006

The mesoscale induction of two‐dimensional supramolecular chirality (formation of 2D organic domains with a single handedness) was achieved by self‐assembly of 1,2,4‐benzenetricarboxylic (trimellitic) acid on a Cu(100) surface at elevated temperatures. The combination of spectroscopic [X‐ray photoelectron spectroscopy (XPS) and near‐edge X‐ray absorption fine structure (NEXAFS)], real‐space‐probe [scanning tunneling microscopy (STM)], and computational [density functional theory (DFT)] methods allows a comprehensive characterization of the obtained organic adlayers, where details of molecular adsorption geometry, intermolecular coupling, and surface chemical bonding are elucidated. The trimellitic acid species, comprising three functional carboxylic groups, form distinct stable mirror‐symmetric hydrogen‐bonded domains. The chiral ordering is associated with conformational restriction in the domains: molecules anchor to the substrate with an ortho carboxylate group, providing two para carboxylic acid moieties for collective lateral interweaving through H bonding, which induces a specific tilt of the molecular plane. The ease of molecular symmetry switching in domain formation makes homochiral‐signature propagation solely limited by the terrace width. The molecular layer modifies the morphology of the underlying copper substrate and induces μm‐sized strictly homochiral terraces.
Intravenous iron requirement in adult hemodialysis patients
Authors: Nguyen Timothy V.
Published: September 2006

Objective.

Chronic hemodialysis patients often require maintenance intravenous iron, as iron is an essential component of effective erythropoiesis. The Anemia Work Group (NKF‐K/DOQI) anemia guidelines suggest a maintenance intravenous iron dose of 25–125 mg, but the optimal maintenance dose regimen remains difficult to determine. K/DOQI recommends these iron parameters: TSAT ≥ 20% and < 50%, ferritin ≥ 100 and < 800 ng/mL. An assessment of the maintenance dose regimen used in the present study is presented in this article.

Patients and Methods.

Data were collected retrospectively to evaluate clinical response in 40 adult chronic hemodialysis patients who received regular maintenance intravenous iron sucrose of 100 mg either every other week or every fourth week based on their ferritin and transferrin saturation (TSAT) levels. If ferritin level was between 100 and 500 ng/mL and TSAT level was 20% and 30%, then iron sucrose was administered every other week; if ferritin was 500–700 ng/mL or TSAT was 30%–45%, then iron sucrose was administered every fourth week. Ferritin and TSAT levels were monitored quarterly.

Results.

After the first quarter, 15 (38%) of the patients (n=15) remained on their original dosing regimen; 21 (53%) patients required adjustment to their regimen, either by discontinuing the regimen (n = 18) or decreasing the dosing interval (n = 3), 45% and 7.5% respectively; and 4 (10%) patients required additional intravenous iron supplementation.

Conclusion.

Iron sucrose administered at a dosage of 100 mg on a maintenance regimen either every other week or every fourth week exceeded most patients' requirements. Maximum intravenous iron maintenance doses for adult chronic hemodialysis patients remain difficult to determine, and the maintenance iron requirement varies from patient to patient.
Dialysis facility design—part II: Minimize costly plan changes
Authors: Bower Steven B.
Published: September 2006

During the development and construction of a dialysis clinic, there are decisions that influence the cost, building quality, and completion date of the project. Change orders—changes to the project after bidding and a contractor has been awarded—are often unavoidable. The owner, architect, and contractor, as well as outside agencies, will at times desire to make changes due to whim or necessity. Often, how you approach these changes has a larger impact on cost and schedule than the change itself. This article, the second of four installments focusing on dialysis clinic design, will review many of the issues that arise in successful project initiation and development from concept through construction, and will address several types of challenges that traditionally occur during the process.
cDNA cloning of myosin heavy chain genes from medaka Oryzias latipes embryos and larvae and their expression patterns during development
Authors: Ono Yosuke , Liang Chunshi , Ikeda Daisuke , Watabe Shugo
Published: September 2006

Several sarcomeric myosin heavy chains (MYHs) were cloned from embryos and larvae of medaka Oryzias latipes. Three genes encoding medaka MYHs (mMYHs) predominantly expressed in embryos (mMYHemb1) and larvae (mMYHL1 and mMYHL2), all belonged to fast skeletal MYHs, showing spatiotemporally different expression patterns during development. Besides these mMYHs, a few novel mMYHs were cloned from embryos and larvae at hatching. Whereas mMYHemb2, mMYHemb3, and mMYHL3 belonged to fast skeletal MYH, mMYHC1 and mMYHC2 did to slow/cardiac MYH. mMYHemb1 was expressed ahead of mMYHL1 and mMYHL2. In situ hybridization analysis demonstrated that the transcripts of mMYHemb1 and mMYHC1 were located in the horizontal myoseptum, whereas those of mMYHL1 and mMYHL2 in the inner part of myotomes and pharyngeal muscles, and those of mMYHC2 in the heart rudiment. In silico cloning based on the medaka genome database showed another mMYHs of the slow/cardiac types, mMYHC3 and mMYHC4. Developmental Dynamics 235:3092–3101, 2006. © 2006 Wiley‐Liss, Inc.
Gangliogenesis in the enteric nervous system: Roles of the polysialylation of the neural cell adhesion molecule and its regulation by bone morphogenetic protein‐4
Authors: Faure Christophe , Chalazonitis Alcmène , Rhéaume Catherine , Bouchard Guylaine , Sampathkumar S.‐Gopalan , Yarema Kevin J. , Gershon Michael D.
Published: September 2006

The neural crest–derived cells that colonize the fetal bowel become patterned into two ganglionated plexuses. The hypothesis that bone morphogenetic proteins (BMPs) promote ganglionation by regulating neural cell adhesion molecule (NCAM) polysialylation was tested. Transcripts encoding the sialyltransferases, ST8Sia IV (PST) and ST8Sia II (STX), which polysialylate NCAM, were detectable in fetal rat gut by E12 but were downregulated postnatally. PSA‐NCAM‐immunoreactive neuron numbers, but not those of NCAM, were developmentally regulated similarly. Circular smooth muscle was transiently (E16–20) PSA‐NCAM‐immunoreactive when it is traversed by migrating precursors of submucosal neurons. Neurons developing in vitro from crest‐derived cells immunoselected at E12 with antibodies to p75NTR expressed NCAM and PSA‐NCAM. BMP‐4 promoted neuronal NCAM polysialylation and clustering. N‐butanoylmannosamine, which blocks NCAM polysialylation, but not N‐propanoylmannosamine, which does not, interfered with BMP‐4‐induced neuronal clustering. Observations suggest that BMP signaling enhances NCAM polysialylation, which allows precursors to migrate and form ganglionic aggregates during the remodeling of the developing ENS. Developmental Dynamics 236:44–59, 2007. © 2006 Wiley‐Liss, Inc.
Sp5l is a mediator of Fgf signals in anteroposterior patterning of the neuroectoderm in zebrafish embryo
Authors: Sun Zhihui , Zhao Jue , Zhang Yu , Meng Anming
Published: September 2006

The neuroectoderm is patterned along the anterior‐posterior axis in vertebrate embryos. Fgf signals are required to induce the posterior neuroectodermal fates, but they repress the anterior fate. Sp5l/Spr2, an Sp1‐like transcription factor family member, has been shown to be required for development of mesoderm and posterior neuroectoderm. We demonstrate here that repression of the anterior neuroectodermal markers fez and otx1 by fgf17b or fgf3 coincides with induction of sp5l in the anterior neuroectoderm, and that this repression is efficiently rescued by simultaneous sp5l knockdown. On the other hand, sp5l knockdown is able to inhibit inductive activity of ectopic Fgf signals on the expression of the posterior neuroectodermal markers gbx2, hoxb1b, and krox20. Furthermore, effect of overexpression of a dominant negative Fgf receptor on anteroposterior patterning of the neuroectoderm is rescued by sp5l overexpression. Taken together, these data suggest that sp5l mediates the functions of Fgf signals in anteroposterior patterning of the neuroectoderm during zebrafish embryogenesis. Developmental Dynamics 235:2999–3006, 2006. © 2006 Wiley‐Liss, Inc.
A retrospective comparison of purging type disorders: Eating disorder not otherwise specified and bulimia nervosa
Authors: Wade Tracey D.
Published: September 2006

Objective:

In light of recent research indicating the clinical significance of eating disorder not otherwise specified‐purging only (EDNOS‐P), differences between women with lifetime bulimia nervosa purging subtype (BN‐P) and EDNOS‐P were examined.

Method:

Three groups of women were examined, a control group (n = 684) and two groups with lifetime eating disorders: BN‐P (n = 22), and EDNOS‐P (n = 53).

Results:

Women with lifetime BN‐P were significantly more likely to use vomiting than women with EDNOS‐P but the latter group relied more on laxative abuse. Compared with controls, women with both eating disorders had higher weight and shape concern, dietary restraint, lifetime major depression, and suicidality. The BN‐P group had significantly higher eating concern, dietary restraint, and suicidality than the EDNOS‐P group.

Conclusion:

In accordance with previous research examining women with current eating disorders, EDNOS‐P is indicated to be clinically significant. On the whole, the pattern of results indicated that EDNOS‐P lies somewhere between BN‐P and healthy controls in its clinical significance. © 2006 by Wiley Periodicals, Inc. Int J Eat Disord 2006
Evaluating binge eating disorder in children: Development of the children's binge eating disorder scale (C‐BEDS)
Authors: Shapiro Jennifer R. , Woolson Sandra L. , Hamer Robert M. , Kalarchian Melissa A. , Marcus Marsha D. , Bulik Cynthia M.
Published: September 2006

Objective:

Binge eating disorder (BED) may manifest itself differently in children than adults. Recently researchers have proposed provisional criteria for measuring BED in children. The purpose of this study was to develop a brief, simple, structured, interviewer‐administered scale (C‐BEDS) to measure BED in children according to the provisional criteria and to compare diagnostic results with SCID diagnoses.

Method:

A total of 55 children between the ages of 5 and 13 were interviewed with both the SCID and the C‐BEDS.

Results:

There was a significant association between the two measures (p = .001). Both measures adequately identified children with binge eating behaviors.

Conclusion:

Both the provisional criteria and the C‐BEDS may be developmentally appropriate for use with children, although the C‐BEDS may be a better screening instrument as it quickly identified children with subsyndromal BED. If used by physicians and other health providers, this brief measure may assist with identifying early onset binge eating behaviors and avoiding the associated consequences, including adult BED, obesity, and other comorbidities. © 2006 by Wiley Periodicals, Inc. Int J Eat Disord 2006
Facets of acculturation and their diverse relations to body shape concern in Fiji
Authors: Becker Anne E. , Fay Kristen , Gilman Stephen E. , Striegel‐Moore Ruth
Published: September 2006

Objective:

The present study examines the relation between acculturation and body shape concern in Fiji—a society undergoing rapid social change.

Method:

Data were from two cohorts of ethnic Fijian girls and women collected in 1998 (n = 115). A factor analysis was performed to identify dimensions of acculturation. The association of these with body shape concern was examined with linear regression.

Results:

Three dimensions of acculturation were identified. Multiple linear regression models demonstrated that each of these dimensions of acculturation had a unique relation to body shape concern. The adjusted R2 for the fully adjusted model relating acculturation to body concern was 0.63, indicating a substantial degree of shared variation between measures of body shape concern and measures of acculturation.

Conclusion:

Acculturation may have a strong impact on body shape concern in Fiji. However, acculturation is a multidimensional construct and does not likely have a monolithic relation to body shape concern. © 2006 by Wiley Periodicals, Inc. Int J Eat Disord 2006
Biosorption of Heavy Metals from Wastewater by Biosolids
Authors: Orhan Y. , Hrenovič J. , Büyükgüngör H.
Published: September 2006

In a study where the removal of heavy metals from wastewater is the primary aim, the biosorption of heavy metals onto biosolids prepared as Pseudomonas aeruginosa immobilized onto granular activated carbon was investigated in batch and column systems. In the batch system, adsorption equilibriums of heavy metals were reached between 20 and 50 min, and the optimal dosage of biosolids was 0.3 g/L. The biosorption efficiencies were 84, 80, 79, 59 and 42 % for Cr(VI), Ni(II), Cu(II), Zn(II) and Cd(II) ions, respectively. The rate constants of biosorption and pore diffusion of heavy metals were 0.013–0.089 min–1 and 0.026–0.690 min–0.5. In the column systems, the biosorption efficiencies for all heavy metals increased up to 81–100 %. The affinity of biosorption for various metal ions towards biosolids was decreased in the order: Cr = Ni > Cu > Zn > Cd.
Tissue Cultured Mountain Ginseng Adventitious Roots™: Safety and Toxicity Evaluation
Authors: Sivakumar G. , Yu K. W. , Lee J. S. , Kang J. K. , Lee H. L. , Kim W. J. , Paek K. Y.
Published: September 2006

Panax ginseng has strong anticancer, antidiabetic, antioxidant activity, various physiological functions, and is used as a nutritional and medicinal supplement. Tissue cultured mountain ginseng adventitious roots™ (TCMGARs) powder, which is derived from commercial scale bioreactor cultures, was tested for its consumption safety. The reverse mutation, chromosomal aberration and the micronucleus tests were found to show no significant mutagenicity. Furthermore, thirteen weeks of repeated dose toxicity of TCMGARs oral doses from 300–900 mg/kg, with a four‐week recovery period, did not produce mortality or significant changes in the general behavior and gross appearance of the internal organs of rats. The absolute body weight, urine test, haematology, blood chemistry, absolute organ weight and histopathological examination of both main and recovery groups revealed that there were no differences between the control and the treated rats. These results confirm that TCMGARs are safe and nontoxic at an average dietary consumption level.
Bioleaching of Heavy Metal Polluted Sediment: Influence of Temperature and Oxygen (Part 1)
Authors: Löser C. , Zehnsdorf A. , Görsch K. , Seidel H.
Published: September 2006

A remediation process for heavy metal polluted sediment has previously been developed in which the heavy metals are removed from the sediment by solid‐bed bioleaching using elemental sulfur (S0): the added S0 is oxidized by the indigenous microbes to sulfuric acid that dissolves the heavy metals which are finally extracted by percolating water. In this process, the temperature is a factor crucially affecting the rate of S0 oxidation and metal solubilization. Here, the effect of temperature on the kinetics of S0 oxidation has been studied: oxidized Weiße Elster River sediment (dredged near Leipzig, Germany) was mixed with 2 % S0, suspended in water and then leached at various temperatures. The higher the temperature was, the faster the S0 oxidized, and the more rapid the pH decreased. But temperatures above 35 °C slowed down S0 oxidation, and temperatures above 45 °C let the process – after a short period of acidification to pH 4.5 – stagnate. The latter may be explained by the presence of both neutrophilic to less acidophilic thermotolerant bacteria and acidophilic thermosensitive bacteria. Within 42 days, nearly complete S0 oxidation and maximum heavy metal solubilization only occurred at 30 to 45 °C. The measured pH(t) courses were used to model the rate of S0 oxidation depending on the temperature using an extended Arrhenius equation. Since molecular oxygen is another factor highly influencing the activity of S0‐oxidizing bacteria, the effect of dissolved O2 (controlled by the O2 content in the gas supplied) on S0 oxidation was studied in suspension: the indigenous S0‐oxidizing bacteria reacted quite tolerant to low O2 concentrations; the rate of S0 oxidation – measured as the specific O2 consumption – was not affected until the O2 content of the suspension was below 0.05 mg/L, i.e., the S0‐oxidizing bacteria showed a high affinity to O2 with a half‐saturation constant of about 0.01 mg/L. Stoichiometric coefficients describing the relationship between the mass of S0, O2 and CO2 consumed are scarcely available. The growth of S0‐oxidizing, obligate aerobic, autotrophic bacteria was, therefore, stoichiometrically balanced (by using a yield coefficient of YX/S = 0.146 g cells/g S0, calculated with data from the literature): 24.14 S0 + 29.21 O2 + 27.14 H2O + 5 CO2 + NO3–→ C5H7O2N + 24.14 SO42– + 47.28 H+, which resulted in Y = 1.21 g O2/g S0 and Y = 0.28 g CO2/g S0.
Bioleaching of Heavy Metal Polluted Sediment: Influence of Sediment Properties (Part 2)
Authors: Löser C. , Zehnsdorf A. , Hoffmann P. , Seidel H.
Published: September 2006

A remediation process for heavy metal polluted sediment has previously been developed, in which the heavy metals are removed from the sediment by solid‐bed bioleaching using sulfuric acid as a leaching agent arising from added elemental sulfur (S0). This process has been engineered with Weiße Elster River sediment (dredged near Leipzig, Germany), as an example. Here, six heavy metal polluted sediments originating from various bodies of water in Germany were subjected to bioleaching to evaluate the applicability of the developed process on sediment of different nature: each sediment was mixed with 2 % S0, suspended in water and then leached under identical conditions. The buffer characteristics of each sediment were mainly governed by its carbonate and Ca content, i.e., by its geological background, the redox potential and oxidation state depended on its pre‐treatment (e.g., on land disposal), while the pH value was influenced by both. The added S0 was quickly oxidized by the indigenous microbes even in slightly alkaline sediment. The microbially generated H2SO4 accumulated in the aqueous phase and was in part precipitated as gypsum. Significant acidification and heavy metal solubilization only occurred with sediment poor in buffer substances. With the exception of one sediment, the behavior in bioleaching correlated well with the behavior in titration with H2SO4. Since the content in carbonate seemed to be the most important factor deciding on the leachability of a sediment, oxic Weiße Elster River sediment was mixed with 2 % S0 and 0 to 100 g/kg of ground limestone to simulate various buffer capacities, suspended in water and then leached. The lime did not inhibit microbial S0 oxidation but generated a delay in acidification due to neutralization of formed H2SO4, where the pH only started to decrease when the lime was completely consumed. The more lime the sediment contained, the longer this lag period lasted, and the higher the pH and the lower the fraction of the solubilized heavy metals finally was. Since Cu requires stronger acidic conditions for its solubilization, it responded more sensitively to lime addition than Zn, Ni, and Cd. Heavy metal polluted sediment containing large amounts of carbonate may, in principle, also be remediated by bioleaching, but metal solubilization requires excessive amounts of the leaching agent and is thus uneconomical.
Use of Hydrocyclones for Mammalian Cell Retention: Separation Efficiency and Cell Viability (Part 1)
Authors: Elsayed E. A. , Medronho R. A. , Wagner R. , Deckwer W.‐D.
Published: September 2006

A hydrocyclone with a volume of 2.56 cm3 was studied as a potential cell retention device for mammalian cell cultures (6 L volume). For the feasible operation range (0.9 to 1.6 L/min flow corresponding to pressure drops of 0.4 to 1.3 bar) the hydrocyclone was characterized with regard to flow split (underflow‐to‐overflow ratio) and flow ratio (underflow to supply). Cultures of BHK and HeLa cells (with low cell concentrations) were applied to measure separation efficiency and cell viability for a hydrocyclone operation period of 3 min corresponding to a cell suspension throughput of 2.7 to 4.8 L. Cell separation efficiencies ranged from 0.77 to 0.97 and cell viability was not affected except for BHK cells in the overflow at the highest pressure drop (1.3 bar). As the overflow is commonly used for product harvest and cells are discarded, the application of the hydrocyclone has no detrimental effect on the reactor perfusion system. The results indicate that only cells passing from the primary vortex downwards into the inner secondary vortex and from there upwards could be damaged. Evidence for this hypothesis is obtained from operating the hydrocyclone with closed overflow (only centrifugal forces acting) for a period of 3 h. In these studies no significant effect on cell viability could be detected for HeLa and CHO cells. Hence, the results indicate that the hydrocyclone can be appropriately used for cell retention and separation in perfusion cultures. Application at higher pressures is recommended whereby separation efficiencies of 0.97 without any loss in viability can be achieved.
Inactivation Effects on Proteins in a Needle‐free Vaccine Injector
Authors: Ziegler A. S. , Schluecker E. , Reichel‐Lesnianski P. , Alt N. , Lee G.
Published: September 2006

Needle‐free powder injectors using a supersonic gas jet to force powder particles into the skin are suitable devices for the reliable delivery of powdered vaccines into viable epidermis. The peculiarities of the injection mechanism lead to a more comfortable injection for the patient, but in return to an increase in the stress on the pharmaceutical formulation in comparison to conventional injections with needle and syringe. As a lot of the conceivable drugs for needle‐free powder injection, particularly protein vaccines, are very sensitive bio‐molecules with an extremely fragile molecular structure, their resilience to the potential molecule damaging processes during the actuation with the device and the preservation of their biological activity are the crucial factors. Therefore it was the central aim of this work to identify and investigate the reasons for the loss of biological activity. The imaginable responsible process steps were investigated separately and the amounts of activity loss related to them. The manufacture of the powder and the loading of the cassette containing the formulation are examined. Moreover, the effects of static pressure exposition, the stress occurring because of the particle transport through the injector device, inevitably accompanied by impacts and shear stress and the influence of the particle impact with the target, were the focus of this investigation. Furthermore, different formulations of protein in combination with pharmaceutical excipients well‐known for their protein stabilizing effects during the powder manufacture process were examined in regard to their potential suitability to protect protein against the stress occurring throughout the needle‐free injection.
Effectiveness of Differently Designed Small‐Scale Constructed Wetlands to Decrease the Acidity of Acid Mine Drainage under Field Conditions
Authors: Kuschk P. , Wiessner A. , Buddhawong S. , Stottmeister U. , Kästner M.
Published: September 2006

Constructed wetlands are a near‐natural method for the treatment of acid mine drainages (AMD). Because of the different site‐specific wastewater qualities and the variability of the used constructed wetlands regarding design, it is difficult to compare their efficiencies on the basis of literature data (often specific removal rates are missing). The AMD treatment efficiencies (pH, acidity) of differently designed planted and unplanted small‐scale constructed wetlands (subsurface flow – SSF, surface flow – SF, and hydroponic – HP systems with an area of 0.55 m2 each) were compared under long‐term field conditions. The planted SF was found to be most effective, reaching mean acidity removal in the range of 80–90 %, and most resistant in view of external influences (i.e., heavy rain events). The planted SSF also showed high efficiency (50–90 %), but much more sensitivity to rain events. In both systems, the pH increased from 3.3 (mean of the inflows) to above 4.5 in the outflows. The efficiencies of the unplanted SF were insufficient and in the range of the (planted and unplanted) HP, i.e., smaller than 40 %. In general, the importance of plants for the success of the neutralization processes could be concluded.
Functional analysis of lung tumor suppressor activity at 3p21.3
Authors: ter Elst Arja , Hiemstra Bea E. , van der Vlies Pieter , Kamminga Wytske , van der Veen Anneke Y. , Davelaar Inge , Terpstra Peter , te Meerman Gerard J. , Gerbens Frans , Kok Klaas , Buys Charles H. C. M.
Published: September 2006

The early and frequent occurrence of deletions at 3p21.3 in lung cancer has led to the consideration of this chromosomal region as a lung cancer (LUCA) critical region with tumor suppressor activity. We covered this 19 genes‐containing region with overlapping P1 artificial chromosomes (PACs), in which genes are likely accompanied by their own promoters or other regulatory sequences. With these PACs we transfected cells from a small cell lung cancer (SCLC) cell line which readily caused tumors in nude mice. Per PAC we selected two cell clones with a low number of PAC copies integrated at a single genomic site. The selected clones were s.c. injected into nude mice to investigate whether the integrated genes suppressed the tumor‐inducing capacity of the original SCLC cell line. We could demonstrate PAC‐specific gene expression in the transfected cells. All of the PAC integration sites were different. It appeared that introduction of a PAC or even an empty PAC vector causes some chromosomal instability, which in principle may either promote or inhibit cell growth. However, both cell clones with integration of the same PAC from the centromeric part of the LUCA region in different genomic sites were the sole pair of clones that caused smaller tumors than did the original SCLC cell line. This suggests that rather than the induced chromosomal instability, the DNA sequence of that PAC, which in addition to two protein‐encoding genes contains at least one potential miRNA gene, is responsible for the tumor suppressor activity. © 2006 Wiley‐Liss, Inc.
Holocene paleogeographies of the Palairos coastal plain (Akarnania, northwest Greece) and their geoarchaeological implications
Authors: Vött Andreas , Brückner Helmut , Schriever Armin , Luther Jochen , Handl Mathias , van der Borg Klaas
Published: September 2006

Sediments from the Palairos coastal plain (Akarnania, northwest Greece) were studied to establish paleogeographical scenarios of Holocene landscape evolution. Near coast vibracore profiles revealed regressive sedimentary sequences, the base of which is dominated by marine sand and/or lagoonal mud. The middle and upper parts of the sequences are made up of lacustrine mud and fine‐ to coarse‐grained alluvial deposits reflecting the increased activity of torrential river systems. In the southern plain, marine sediments of the maximum incursion of the Ionian Sea were found 1 km inland and date from the seventh millennium B.C. This proves that the Lake Voulkaria in the northern plain does not represent the remains of a former marine embayment. Subsequently, a large lagoon developed and existed until the fourth millennium B.C. The central plain was mainly exposed to subaerial conditions when man started to colonize the area in the seventh millennium B.C. In the fifth millennium B.C., the Palairos lagoon turned into a freshwater lake. When ancient Palairos was founded in the 6th century B.C., shallow lakes and swamps dominated the southern and central parts of the plain. At that time, a narrow canal‐like connection between the Bay of Palairos‐Pogonia and the Lake Voulkaria existed and was possibly used as a slipway for ships. During the last 4000 years, the Palairos plain experienced strong input of fluvial sediments which finally filled up the coastal lake as well as the swampy grounds. © 2006 Wiley Periodicals, Inc.
Landscape and early farming settlement dynamics in central Greece
Authors: Bintliff John , Farinetti Emeri , Sarri Kalliope , Sebastiani Renato
Published: September 2006

Current hyperintensive surface survey in the Tanagra district of Boeotia, central Greece (J. L. Bintliff et al., 2002), together with a recent reanalysis of survey results from the Thespiae district (J. L. Bintliff et al., 1999), have led to a radical rethinking of how and where early farmers exploited the Greek landscape between earliest Neolithic and Early Bronze Age times. This new work is described, and its significance for the wider debates about the Greek landscape in this period is further discussed, to demonstrate that alongside widely spaced villages in earlier Neolithic times there were also small, short‐lived farms; both were associated with wetland hand cultivation. In later Neolithic and Early Bronze Age times, these locations remained, but vestigial traces discovered by hyperintensive survey methods have identified an explosion of small, short‐lived, and horizontally migrating farms across the newly cleared interfluve zones. A largely lost alluvial terrace provides a major resource for the earlier, wetland farming foci. © 2006 Wiley Periodicals, Inc.
Holocene environment and settlement on the Çarşamba alluvial fan, south‐central Turkey: Integrating geoarchaeology and archaeological field survey
Authors: Boyer Peter , Roberts Neil , Baird Douglas
Published: September 2006

The four‐dimensional geomorphological history of the Çarşamba fan in the Konya Basin, Turkey, has been reconstructed as part of integrated field research into the relations between Holocene environments and settlement history within a spatially well defined alluvial landscape, ∼500 km2in extent. This has involved on‐ and offsite study of alluvial sequences linked to a systematic archaeological site survey of multiperiod settlement mounds and to excavations at the Neolithic–Chalcolithic site of Çatalhöyük. Two principal alluvial units lie above Late Pleistocene lake marls and have been characterized using particle size, magnetic susceptibility, organic and carbonate content, and color. Based on a combination of14C, optically stimulated luminescence (OSL), and archaeological evidence, the lower unit dates primarily to the Neolithic–Chalcolithic, while the upper unit dates from Bronze Age to post‐Byzantine times. Counterintuitively, alluvial landscape changes have not necessarily led to the systematic burial —and, therefore, “loss”—of those archaeological sites that are smaller or shallower, earlier (i.e., prehistoric), and located closer to the fan apex. As well as being important in interpreting settlement distributions, this geomorphological history of alluviation, pedogenesis, and erosion also provides data on changing flood regimes and soil and water availability that have affected the suitability of individual areas for human occupation. © 2006 Wiley Periodicals, Inc.
Archaeology and climate: Settlement and lake‐level changes at the Aral Sea
Authors: Boroffka Nikolaus , Oberhänsli Hedi , Sorrel Philippe , Demory Francois , Reinhardt Christian , Wünnemann Bernd , Alimov Kamildzhan , Baratov Sergey , Rakhimov Kamildzhan , Saparov Nasbirgen , Shirinov Timur , Krivonogov Sergey K. , Röhl Ursula
Published: September 2006

New archaeological and geomorphologic data collected adjacent to the Aral Sea show lake‐level stands during the late Pleistocene and the past 5000 years. On the northern and southern shores, archaeological sites from the Palaeolithic through the Late Middle Ages contain evidence of various cultures and economies. Changes in settlement activity during the mid‐Holocene are related to several major lake‐level oscillations. Some of them, especially those which occurred at approximately 350–450 cal B.P. (during the Little Ice Age), 700–780 cal B.P., around 1400 cal B.P., and 1600–2000 cal B.P., were accompanied by lithological changes in sediment cores retrieved from the Aral Sea and were observed in shoreline shifts. We show that a maximum lake level at 72–73 m above sea level cannot be corroborated. The highest lake level, which was reached at the beginning of the 20th century, probably never exceeded 54–55 m a.s.l. Furthermore, we documented a previously unknown low‐level stand at 42–43 m a.s.l. that dated to the Bronze Age (∼4000–3000 B.P.). The regression during 1200–1300 cal A.D. was formerly underestimated and was lower than the present‐day lake level. The observed environmental changes, except those since the 1960s, are most probably driven by climate variability, though human activities (e.g., irrigation) can amplify the impact. © 2006 Wiley Periodicals, Inc.
Satellite imagery as a resource in the prospection for archaeological sites in central Syria
Authors: Wilkinson Keith N. , Beck Anthony R. , Philip Graham
Published: September 2006

Both IKONOS and CORONA satellite imagery are currently being employed by the research project Settlement and Landscape Development in the Homs Region, Syria, as the primary deskbased means of detecting non‐tell archaeological sites, a category that has generally been underrepresented in traditional tell‐centered surveys in the Middle East. Satellite imagery provides a highly effective means of prospecting for ancient settlement remains on the marl geologies of the project's Southern Study Area. The recent intense agricultural development of the area and a largely erosive landscape history since the Bronze Age mean that ancient settlements survive as “lags” in the present soils that display either highly reflective or (more rarely) absorptive signatures in the imagery. As a result, many previously unknown archaeological sites have been detected by the project. Laboratory analysis of transects of samples taken across four sites detected in the satellite imagery suggests that the reflectance/absorption spectra of the archaeological sites is largely a product of the grain‐size variations that result from occupation activities; geochemical and magnetic properties play a lesser role. The grain‐size properties of the site locations are likely to reflect the decomposition of mud‐brick, the dominant building material in the area for much of the past. © 2006 Wiley Periodicals, Inc.
Cellular iron status influences the functional relationship between microglia and oligodendrocytes
Authors: Zhang X. , Surguladze N. , Slagle‐Webb B. , Cozzi A. , Connor J. R.
Published: September 2006

Previously, we have reported that there is a spatiotemporal relationship between iron accumulation in microglia and oligodendrocytes during normal development and in remyelination following injury. This in vivo observation has prompted us to develop a cell culture model to test the relationship between iron status of microglia and survival of oligodendrocytes. We found that conditioned media from iron‐loaded microglia increases the survival of oligodendrocytes; but conditioned media from iron loaded activated microglia is toxic to oligodendrocytes. In the trophic condition, one of the proteins released by iron‐loaded microglia is H‐ferritin, and transfecting the microglia with siRNA for H‐ferritin blocks the trophic response on oligodendrocytes. Lipopolysaccharide (LPS) activation decreases the amount of H‐ferritin that is released from microglia and increases the release of the proinflammatory cytokines tumor necrosis factor‐α and interleukin‐1. LPS activation of iron‐enriched microglia results in the activation of NF‐kB and greater release of cytokines when compared with that of control microglia; whereas treating microglia with an iron chelator is associated with less NF‐kB activation and less release of cytokines. These results indicate that microglia play an important role in iron homoeostasis and that their iron status can influence how microglia influence growth and survival of oligodendrocytes. The results further indicate that ferritin, released by microglia, is a significant source of iron for oligodendrocytes. © 2006 Wiley‐Liss, Inc.
The TLR3 ligand polyI:C downregulates connexin 43 expression and function in astrocytes by a mechanism involving the NF‐κB and PI3 kinase pathways
Authors: Zhao Yongmei , Rivieccio Mark A. , Lutz Sarah , Scemes Eliana , Brosnan Celia F.
Published: September 2006

Toll‐like receptor 3 (TLR3) is a component of the innate immune response that responds to dsRNA viruses and virus replication intermediates. In this study we show that activation of astrocytes with the dsRNA mimetic polyinosinic‐cytidylic acid (pI:C) results in loss of expression of connexin43 (Cx43) mRNA and protein while upregulating the expression of the ionotropic P2 receptor P2X4R. Analysis of the signaling pathways involved failed to demonstrate a role for the p38 MAP kinase, ERK, or JNK signaling pathways whereas an inhibitor of the PI3 kinase/Akt pathway effectively blocked the action of pI:C. Using adenoviral vectors containing a super‐repressor of NF‐κB (NF‐κB SR) construct or a dominant negative interferon regulatory factor 3 (dnIRF3) construct showed that inhibition of both transcription factors also blocked the effects of pI:C. To explore the functional consequences of pI:C activation we used a pore‐forming assay for P2X4R activity and a scrape loading assay for gap junction intercellular communication (GJIC). No pore‐forming activity consistent with functional P2X4R expression was detected in either control or activated astrocytes. In contrast, robust Lucifer yellow transfer indicative of GJIC was detected in resting cells that was lost following pI:C activation. The dnIRF3 construct failed to restore GJIC whereas the NF‐κB SR or the NF‐κB inhibitor BAY11‐7082 and the PI3K inhibitor LY294002 all significantly reversed the effect of pI:C on GJ connectivity. We conclude that activation of the innate immune response in astrocytes is associated with functional loss of GJIC through a pathway involving NF‐κB and PI3 kinase. © 2006 Wiley‐Liss, Inc.