bluuebunny/crossref_metadata_2025 huggingface dataset:
The actin‐binding domain of cortactin is dynamic and unstructured and affects lateral and longitudinal contacts in F‐actin
Authors: Shvetsov Alexander , Berkane Emir , Chereau David , Dominguez Roberto , Reisler Emil
Published: December 2008

Cortactin is an F‐actin‐ and Arp2/3 complex‐binding protein, implicated in the regulation of cytoskeleton dynamics and cortical actin‐assembly. The actin‐binding domain of cortactin consists of a 6.5 tandem repeat of a 37‐amino acid sequence known as the cortactin repeat (residues 80–325). Using a combination of structure prediction, circular dichroism, and cysteine crosslinking, we tested a recently published three‐dimensional model of the cortactin molecule in which the cortactin repeat is folded as a globular helical domain [Zhang et al., 2007, Mol Cell 27:197–213]. We show that the cortactin repeat is unstructured in solution. Thus, wild type and mutant constructs of the cortactin repeat, containing pairs of cysteines at positions 112 and 246, 83 and 112, 83 and 246, and 83 and 306, could be readily crosslinked with reagents of varying lengths (0–9.6 Å). Using yeast actin cysteine mutants, we also show that cortactin inhibits disulfide and dibromobimane crosslinking across the lateral and longitudinal interfaces of actin subunits in the filament, suggesting a weakening of intersubunits contacts. Our results are in disagreement with the proposed model of the cortactin molecule and have important implications for our understanding of cortactin regulation of cytoskeleton dynamics. Cell Motil. Cytoskeleton 2009. © 2008 Wiley‐Liss, Inc.
Structural Modifications of DAPY Analogues with Potent Anti‐HIV‐1 Activity
Authors: Feng Xiao‐Qing , Liang Yong‐Hong , Zeng Zhao‐Sen , Chen Fen‐Er , Balzarini Jan , Pannecouque Christophe , De Clercq Erik
Published: December 2008

A novel series of diarylpyrimidine analogues (DAPYs) featuring a naphthyl moiety at the C4 position were designed, with all compounds exhibiting strong activity against wild‐type HIV‐1.

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A novel series of diarylpyrimidine analogues (DAPYs) featuring a naphthyl moiety at the C4 position were synthesized and evaluated for their in vitro activity against HIV in MT‐4 cells. All compounds exhibited strong activity against wild‐type HIV‐1. The most active compound showed activity against wild‐type HIV‐1 with an EC50 value of 2.35 nM and against the double mutant strain (K103N+Y181C) with an EC50 value of 6.6 μM, with a selectivity index greater than 60 000 against wild‐type HIV‐1. Additionally, some compounds also showed activity against HIV‐2 (EC50=5.82 μM).
Influence of compartmental involvement on the patterns of morbidity in soft tissue sarcoma of the thigh
Authors: Rimner Andreas , Brennan Murray F. , Zhang Zhigang , Singer Samuel , Alektiar Kaled M.
Published: December 2008

BACKGROUD:

The authors sought to determine whether differences existed in patterns of outcome and morbidity between the 3 thigh compartments after limb‐sparing surgery and postoperative radiation therapy (RT).

METHODS:

A total of 255 patients with primary soft tissue sarcoma (STS) of the thigh were identified in our sarcoma database (1982–2002). More than 80% of tumors were >5 cm, high grade, and deep; 33% had close or positive microscopic resection margins. Adjuvant RT consisted of brachytherapy alone (BRT; 63%), external beam RT alone (EBRT; 31%), or a combination of brachytherapy and EBRT (6%). There were 125 anterior, 58 medial, and 72 posterior lesions. The 3 compartments were balanced as to tumor grade, size, depth, margin status, and RT type.

RESULTS:

Overall local control (LC) was 89%, distant metastases‐free survival (DMFS) was 61%, and overall survival (OS) was 66% at 5 years (median follow‐up, 71 months). Overall rates for complications at 5 years were wound reoperation (10%), edema (13%), joint stiffness (12%), nerve damage (8%), and bone fractures (7%). Wound reoperation and edema were significantly higher for medial‐compartment tumors (P= .01 and .005, respectively), whereas nerve damage occurred more frequently in posterior‐compartment tumors (P< .001). There were no differences among bone fracture, joint stiffness, DMFS, or OS rates between compartments.

CONCLUSIONS:

Although tumor control was similar for all 3 compartments, more wound reoperation and edema were observed in the medial compartment, and more nerve damage was noted in the posterior compartment. These results may help guide decisions concerning current patients and improve the design of future treatments tailored to compartments. Cancer 2009. © 2008 American Cancer Society.
Mammary serine protease inhibitor inhibits epithelial growth factor‐induced epithelial‐mesenchymal transition of esophageal carcinoma cells
Authors: Cai Zhen , Zhou Yuan , Lei Ting , Chiu Jen‐Fu , He Qing‐Yu
Published: December 2008

BACKGROUND:

By using proteomic technology, the authors previously observed the substantial down‐regulation of mammary serine protease inhibitor (maspin) in esophageal squamous cell carcinoma and metastases. In the current study, they examined the effects of maspin re‐expression in a maspin‐null esophageal cancer cell line EC109 and also investigated the underlying mechanism.

METHODS:

A cell line with stable maspin expression was established. An epithelial growth factor (EGF)‐induced epithelial‐mesenchymal transition (EMT) model was used to mimic some aspects of the metastatic process in vitro. The effects of maspin reintroduction on EGF‐induced EMT and cell growth characteristics were evaluated. Comparative proteomic analysis of transfected cells versus parental cells was then performed to explore the potential mechanism.

RESULTS:

The introduction of maspin into EC109 cells was able to inhibit EGF‐induced EMT and altered cell growth characteristics, including the serum dependence, proliferative response to EGF stimulation, and colony formation ability in soft agar, indicating a conversion from a malignant phenotype to a benign phenotype. Proteomic analysis revealed a significant down‐regulation of a group of glycolytic enzymes in maspin‐transfected cells. In addition, maspin‐transfected cells expressed much lower levels of hypoxia‐inducible factor 1α than parental cells or empty vector transfected cells.

CONCLUSIONS:

Maspin exhibited a metastasis‐suppressive effect, which may be a consequence of the reversal of the malignant phenotype of EC109 cells. The switch of cellular metabolic phenotype to low glycolysis by the gain of maspin function may play a key role in the process. This finding provides additional evidence of the tumor metastasis‐suppressive activity of maspin and may indicate a new direction for future studies of the mechanism of maspin. Cancer 2009. © 2008 American Cancer Society.
Phase 1 and pharmacokinetic study of concurrent carboplatin and irinotecan in subjects aged 1 to 21 years with refractory solid tumors
Authors: Levy Adam S. , Meyers Paul A. , Wexler Leonard H. , Jakacki Regina , Angiolillo Anne , Ringuette Sarah N. , Cohen Marvin B. , Gorlick Richard ,   Other site principal investigators: Wayne Furman, MD (St. Jude Children's Research Hospital, Memphis, Tennessee); Rochelle Bagatell, MD (University of Arizona Health Sciences Center, Tucson, Arizona); Lori Luchtman‐Jones, MD (Washington University School of Medicine, St. Louis, Missouri); Luis Eduardo Garcia, MD (Hospital CIMA, San Jose, Costa Rica); and Eric Sandler, MD (Nemours Children's Clinic, Jacksonville, Florida).
Published: December 2008

BACKGROUND:

Preclinical testing suggests the combination of carboplatin and irinotecan has at least additive antitumor activity. The primary objectives of the current study were to determine the maximum tolerated doses (MTDs) and recommended phase 2 doses of carboplatin administered with irinotecan to pediatric patients with refractory solid tumors.

METHODS:

This was a multicenter, open‐label, single‐arm dose escalation study in which subjects with refractory solid tumors received 21‐day treatment cycles of intravenous carboplatin on Day 1 followed by intravenous irinotecan administered daily for 10 days within 2 consecutive weeks. The plasma pharmacokinetics of ultrafiltrable platinum, irinotecan, and 2 irinotecan metabolites were determined during Cycle 1. The interpatient plan for dose escalation at study initiation was to increase irinotecan first followed by increases in carboplatin.

RESULTS:

Twenty‐eight patients with a median age of 8.5 years (range, 1‐21 years) were enrolled with a variety of solid tumors. Two of 6 subjects at the first dose level (carboplatin target area under the curve [AUC], 4.0 mg/mL*min; irinotecan, 18 mg/m2/dose) experienced dose‐limiting gastrointestinal toxicities requiring a dose de‐escalation scheme (carboplatin AUC, 4.0 mg/mL*min; irinotecan, 15 mg/m2/dose). Three of 6 subjects at the second dose level experienced dose‐limiting gastrointestinal complications and bone marrow suppression. A further dose de‐escalation to carboplatin AUC of 4.0 mg/mL*min and irinotecan of 12 mg/m2/dose resulted in dose‐limiting bone marrow suppression in 1 of 13 patients treated at that dose, and therefore was determined to be the MTD. One complete response (in a patient with medulloblastoma) and 3 partial responses (in patients with neuroblastoma, medulloblastoma, and lymphoendothelial carcinoma, respectively) were observed.

CONCLUSIONS:

The recommended phase 2 dose in heavily pretreated pediatric patients is carboplatin (AUC, 4 mg/mL*min on Day 1) and irinotecan (12 mg/m2/ day × 10 days) given every 21 days. Cancer 2009. © 2008 American Cancer Society.
Timing of consent for the research use of surgically removed tissue
Authors: Hewitt Robert , Watson Peter H. , Dhir Rajiv , Aamodt Roger , Thomas Gerry , Mercola Dan , Grizzle William E. , Morente Manuel M.
Published: December 2008

Consent by patients to perform surgery (‘surgical consent’) and consent for the research use of residual tissue (‘research consent’) are desirable to respect individual autonomy and human dignity. In the past, documentation of these consents has been conveniently obtained before surgery by the same person using the same form. More recently, however, ethical concerns have forced a separation between the 2 consents so that they are now often obtained by different people using different forms, thus raising the possibility of obtaining the research consent postoperatively. The current study seeks to clarify the issues and explain why a postoperative informed consent process has distinct advantages in certain circumstances.
Tumor vasculature‐targeted delivery of tumor necrosis factor‐α*
Authors: Tandle Anita , Hanna Engy , Lorang Dominique , Hajitou Amin , Moya Catherine A. , Pasqualini Renata , Arap Wadih , Adem Asha , Starker Elizabeth , Hewitt Stephen , Libutti Steven K.
Published: December 2008

BACKGROUND: Recently, considerable efforts have been directed toward antivascular therapy as a new modality to treat human cancers. However, targeting a therapeutic gene of interest to the tumor vasculature with minimal toxicity to other tissues remains the objective of antivascular gene therapy. Tumor necrosis factor‐α (TNF‐α) is a potent antivascular agent but has limited clinical utility because of significant systemic toxicity. At the maximum tolerated doses of systemic TNF‐α, there is no meaningful antitumor activity. Hence, the objective of this study was to deliver TNF‐α targeted to tumor vasculature by systemic delivery to examine its antitumor activity. METHODS: A hybrid adeno‐associated virus phage vector (AAVP) was used that targets tumor endothelium to express TNF‐α (AAVP‐TNF‐α). The activity of AAVP‐TNF‐α was analyzed in various in vitro and in vivo settings using a human melanoma tumor model. RESULTS: In vitro, AAVP‐TNF‐α infection of human melanoma cells resulted in high levels of TNF‐α expression. Systemic administration of targeted AAVP‐TNF‐α to melanoma xenografts in mice produced the specific delivery of virus to tumor vasculature. In contrast, the nontargeted vector did not target to tumor vasculature. Targeted AAVP delivery resulted in expression of TNF‐α, induction of apoptosis in tumor vessels, and significant inhibition of tumor growth. No systemic toxicity to normal organs was observed. CONCLUSIONS: Targeted AAVP vectors can be used to deliver TNF‐α specifically to tumor vasculature, potentially reducing its systemic toxicity. Because TNF‐α is a promising antivascular agent that currently is limited by its toxicity, the current results suggest the potential for clinical translation of this strategy. Cancer 2009. Published 2008 by the American Cancer Society.
Validation of a new prognostic index for patients with chronic lymphocytic leukemia
Authors: Shanafelt Tait D. , Jenkins Greg , Call Timothy G. , Zent Clive S. , Slager Susan , Bowen Deborah A. , Schwager Susan , Hanson Curtis A. , Jelinek Diane F. , Kay Neil E.
Published: December 2008

BACKGROUND:

The clinical course of chronic lymphocytic leukemia (CLL) is highly variable. A prognostic index based on widely available clinical and laboratory features was recently developed to predict survival among patients with previously untreated CLL. This index requires validation in an independent series of patients before widespread use can be recommended.

METHODS:

The Mayo Clinic CLL database was used to evaluate the validity and reproducibility of the new prognostic index.

RESULTS:

A total of 440 patients with newly diagnosed CLL who were seen at the Mayo Clinic within 12 months of diagnosis and for whom data were available with which to calculate index score were identified. Patients were classified as low, intermediate, or high risk using the prognostic index. The estimated median survival times were: not reached for low risk, 10.1 years for intermediate risk, and 7.2 years for high risk. The estimated median and 5‐year survival by prognostic index risk category were similar to those originally reported. The prognostic index risk category added predictive value beyond that of Rai risk alone (P = .004). The prognostic index risk category remained a predictor of survival when analysis was limited to Rai stage 0 (P = .03) and nonreferred patients (P < .0001) and also predicted time to treatment (P < .0001).

CONCLUSIONS:

The results of the current study confirm the ability of a newly developed prognostic index to predict survival among patients with previously untreated CLL. The study also extended the utility of the index by demonstrating that it is useful at diagnosis, retains prognostic value when applied exclusively to Rai stage 0 patients, is effective in nonreferred patients, and predicts time to treatment. Cancer 2009. © 2009 American Cancer Society.
Acyclovir to prevent reactivation of varicella zoster virus (herpes zoster) in multiple myeloma patients receiving bortezomib therapy
Authors: Vickrey Eric , Allen Sharon , Mehta Jayesh , Singhal Seema
Published: December 2008

BACKGROUND:

Humoral‐mediated as well as cell‐mediated immunity is compromised in myeloma patients receiving treatment. Immunocompromised patients are at risk of developing herpes zoster. There is evidence from clinical trials that bortezomib therapy is associated with a significant risk of herpes zoster. It is the authors' clinical policy to administer long‐term acyclovir prophylactically to all symptomatic myeloma patients.

METHODS:

A retrospective review of the records of 125 myeloma patients who were treated with bortezomib and who also received routine acyclovir prophylaxis at the dose of 400 mg daily in >80% of patients was undertaken. Alternatives, used in <20% of patients, were 200 mg of acyclovir, 250/500 mg of valacyclovir, or 500 mg of famciclovir administered daily. This was accompanied by patient education regarding the importance of compliance with these prophylactic medications.

RESULTS:

The duration of bortezomib therapy was 1 to 164 weeks (median, 16 weeks). The total duration of exposure to bortezomib was 4150 weeks (80 patient‐years). Except for the occasional missed dose, the self‐reported compliance with antiviral prophylaxis was 100%. Not a single episode of herpes zoster was reported during this period. No adverse effects were noted that could be definitely attributed to acyclovir, valacyclovir, or famciclovir.

CONCLUSIONS:

Daily acyclovir (or a suitable alternative) appears to be effective at preventing herpes zoster virus in patients with myeloma who are receiving bortezomib, with or without corticosteroids. Cancer 2009. © 2008 American Cancer Society.
A QM/MM Investigation of Thymine Dimer Radical Anion Splitting Catalyzed by DNA Photolyase
Authors: Masson Fanny , Laino Teodoro , Rothlisberger Ursula , Hutter Jürg
Published: December 2008

On the mend: The repair reaction of the thymine dimer by DNA photolyase (see picture) is studied by hybrid quantum mechanical/molecular mechanical dynamics simulations based on the X‐ray structure of the enzyme–DNA complex. The dynamics of splitting of the thymine dimer radical anion within the DNA photolyase active site is characterized. The model includes the protein environment.

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DNA photolyase is a highly efficient light‐driven enzyme that repairs the UV‐induced cyclobutane pyrimidine dimer in damaged DNA. Herein, we investigate the repair reaction of the thymine dimer by means of hybrid quantum mechanical/molecular mechanical (QM/MM) dynamics simulations based on the X‐ray structure of an enzyme–DNA complex. In analogy to the self‐repair reaction, we find that the splitting mechanism of the cyclobutane ring is asynchronously concerted and is complete within a few picoseconds upon electron uptake. A few distinct processes characterize the dynamics of splitting of the thymine dimer radical anion within the DNA photolyase active site: continuous solvation reordering of the catalytic region, proton transfer from Glu283 to the dimer, as well as tight interactions of the cationic side chains of Arg232 and Arg350 with the thymine dimer. This points to the important role of the active‐site hydrogen bond and salt‐bridge patterns in stabilizing the thymine dimer anion and slowing down the electron back‐transfer process. Comparison of the repair efficiency with respect to the self‐repair reaction is also discussed.
Laser Microbeams and Optical Tweezers in Ageing Research
Authors: Grigaravičius Paulius , Greulich Karl Otto , Monajembashi Shamci
Published: December 2008

We show how a technique developed within the framework of physics and physical chemistry—in a true interdisciplinary approach—can answer questions in life sciences that are not solvable by using other techniques. Herein, we focus on blood‐pressure regulation and DNA repair in ageing studies. Laser microbeams and optical tweezers are now established tools in many fields of science, particularly in the life sciences. A short glimpse is given on the wide field of non‐age‐research applications in life sciences. Then, optical tweezers are used to show that exerting a vertical pressure on cells representing the inner lining of blood vessels results in bursts of NO liberation concomitant with large changes in cell morphology. Repeated treatment of such human umbilical vein endothelial cells (HUVEC) results in stiffening, a hallmark of manifest high blood pressure, a disease primarily of the elderly. As a second application in ageing research, a laser microbeam is used to induce, with high spatial and temporal resolution, DNA damages in the nuclei of U2OS human osteosarcoma cells. A pairwise study of the recruitment kinetics of different DNA repair proteins reveals that DNA repair starts with non‐homologous end joining (NHEJ), a repair pathway, and may only after several minutes switch to the error‐free homologous recombination repair (HRR) pathway. Since DNA damages—when incorrectly repaired—accumulate with time, laser microbeams are becoming well‐used tools in ageing research.
Index characterization of differential–algebraic equations in hybrid analysis for circuit simulation
Authors: Takamatsu Mizuyo , Iwata Satoru
Published: December 2008

Modern modeling approaches in circuit simulation naturally lead to differential–algebraic equations (DAEs). The index of a DAE is a measure of the degree of numerical difficulty. In general, the higher the index, the more difficult it is to solve the DAE. The modified nodal analysis (MNA) is known to yield a DAE with index at most two in a wide class of nonlinear time‐varying electric circuits.

In this paper, we consider a broader class of analysis method called the hybrid analysis. For linear time‐invariant RLC circuits, we prove that the index of the DAE arising from the hybrid analysis is at most one, and give a structural characterization for the index of a DAE in the hybrid analysis. This yields an efficient algorithm for finding an optimal hybrid analysis in which the index of the DAE to be solved attains zero. Finally, for linear time‐invariant electric circuits that may contain dependent sources, we prove that the optimal hybrid analysis by no means results in a higher index DAE than MNA. Copyright © 2008 John Wiley & Sons, Ltd.
Oxidovanadium Complexes for the Consumption of Alkylating Toxins (Eur. J. Inorg. Chem. 1/2009)
Authors: Fautch Jessica M. , Fanwick Phillip E. , Wilker Jonathan J.
Published: December 2008

The cover picture shows oxidovanadium complexes transforming alkylating toxins into alcohols. Variation of the electron‐donating ability of the ligand was found to permit a degree of control over the reactivity with alkylating agents. Kinetic studies revealed a small range of kobsd. values for this series of K[VO2(salhyph(R)2)] complexes (R = –NO2, –H, –CH3, –OCH3) examined. These experiments were carried out with an ultimate goal of developing compounds to consume toxins and prevent DNA alkylation damage. Details are discussed in the Short Communication by J. J. Wilker et al on p. 33 ff.
Asymmetric Hydrogenation of α‐Keto Phosphonates with Chiral Palladium Catalysts
Authors: Goulioukina Nataliya S. , Bondarenko Grigorii N. , Bogdanov Alexei V. , Gavrilov Konstantin N. , Beletskaya Irina P.
Published: December 2008

Under atmospheric hydrogen pressure, a catalytic amount of palladium(II) trifluoroacetate and (R)‐MeO‐BIPHEP in 2,2,2‐trifluoroethanol promoted the asymmetric hydrogenation of diisopropyl α‐keto phosphonates 1 to afford the corresponding α‐hydroxy phosphonates 2 in excellent yields and with a moderate enantioselectivities of up to 55 % ee. Racemic α‐aryl‐α‐hydroxy phosphonates can be prepared by using palladium on carbon as the catalyst. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Arsenic Release from a Natural Rock under Near‐natural Oxidizing Conditions
Authors: Noubactep C. , Chen‐Braucher D. , Schlothauer T.
Published: December 2008

The effects of carbonate concentration and the presence of iron hydroxide phases on the process of arsenic release from an ore material were investigated under experimental oxic conditions and in the pH range from 6.0 to 9.0. These experimental conditions are pertinent to arsenic leaching from tailings and mining wastes. The leaching tests lasted for ≤ 99 days and were performed with materials of five different particle sizes (≤ 2 mm). Carbonate ions were produced in‐situ by dolomite dissolution or were contained in used waters (0 to 30 mM as HCO3–). Iron hydroxide phases were formed in situ by oxidative dissolution of metallic iron (Fe0) or pyrite (FeS2). Non‐disturbed batch experiments and air‐homogenized experiments were conducted with a constant amount (10 g/L) of an arsenic‐bearing rock (ore material) of a given particle size and different types of water (deionized, tap and mineral water). For comparison, experiments were conducted with 0.1 M EDTA, 0.1 M Na2CO3, and 0.1 M H2SO4. Neither the use of dolomite nor the use of water containing various carbonate (HCO3–) concentrations could confirm the recent results on the favorable role of AsIII‐carbonate complexes on the arsenic transport in the environment. On the other hand, iron hydroxide phases (from Fe0 and FeS2) univocally delayed the As release in both experimental procedures. Furthermore, the theoretically expected effects of the particle size of the ore material was observed. If one takes into consideration that the used HCO3– concentrations were up to six times larger then those of natural surface waters (≤ 5.5 mM) but up to five times lower than those currently used in the literature (≥ 100 mM), it is concluded that the reported conflicting results for As leaching from sediments may be a misinterpretation of processes occurring in the sediment and yielding increased As release with increasing HCO3–/CO32– concentration.
Influence of Arsenic from Anthropogenic Loaded Soils on the Mine Water Quality in the Tin District Ehrenfriedersdorf, Erzgebirge (Germany)
Authors: Greif A. , Klemm W. , Klemm K.
Published: December 2008

The central part of the tin ore deposit Ehrenfriedersdorf/Erzgebirge, which was exploited from the 13th century to 1990, was flooded from 1994 to 1996. Since that time mine waters have flown through the gallery “Tiefer Sauberger Stolln” to the creek Wilisch in the Elbe river catchment area. The water at the mine portal shows high concentrations of arsenic and heavy metals. The average arsenic concentration is about 0.5 mg/L. Approximately two thirds of arsenic are transported dissolved. Where the mine water ascends from deeper levels, arsenic concentrations of about 0.4 mg/L were found. Here arsenic occurs predominantly particular. The mining gallery “Tiefer Sauberger Stolln” provides the unique opportunity of subsurface sampling for the identification of the arsenic sources under different hydrological conditions (normal and high water level). The sources of dissolved arsenic in the gallery part between the raise and the portal were determined and analyzed. Between these two monitoring points, many inflows of infiltration water were detected. The concentration of As in the infiltration water reaches up to 1.8 mg/L, which varies depending on the location in the gallery and the hydrological situation. The first part of the gallery was straightened, heightened and partly concreted with modern mining technique. The arsenic concentrations can decrease owing to high precipitation rates and snow melt events. The last part of the gallery was preserved due to low coverage. Here the arsenic concentrations in the infiltration waters increase with the surface water inflow. At a normal water level, 1 kg arsenic per day leaves the raise and 2.1 kg the gallery portal, which means that 50 % of the arsenic load comes from the infiltration water. At a high water level, 2.5 kg arsenic per day are transported through the raise and 8.2 kg per day through the gallery portal, which means that about 70 % of the arsenic load comes from infiltration water. The area of Ehrenfriedersdorf is characterized by a superposition of anthropogenic soil pollution over the geogenic inventory. There is a close connection between ancient soil contaminations by high amounts of water‐soluble arsenic compounds, e.g. arsenic trioxide formed by roasting the ores during ancient tin smelting, and high concentrations of dissolved arsenic in the infiltration water. The contamination of surface water and river sediments by arsenic is originating from an anthropogenic pollution of soils by ancient tailings via infiltration of water rich in arsenic into the mine gallery.
Separation of Organoarsenicals by Means of Zwitterionic Hydrophilic Interaction Chromatography (ZIC®‐HILIC) and Parallel ICP‐MS/ESI‐MS Detection
Authors: Xie D. , Mattusch J. , Wennrich R.
Published: December 2008

An analytical scheme was developed for the separation and detection of organoarsenicals using a zwitterionic stationary phase of hydrophilic interaction chromatography (ZIC®‐HILIC) coupled in parallel to electrospray ionization mass spectrometry (ESI‐MS) and to inductively coupled plasma mass spectroscopy (ICP‐MS). The optimization of separation and detection for organoarsenicals was mainly focused on the influence of the percentage of acetonitrile (MeCN) used as a major component of the mobile phase. Isocratic and gradient elution was applied by varying the MeCN percentage from 78 % to 70 % MeCN and 22 % to 30 % of an aqueous solution of ammonium acetate (125 mM NH4Ac; pH 8.3) on a ZIC®‐HILIC column (150 × 2.1 mm id, 3.5 μm), to allow for the separation and successful detection of nine organoarsenicals (i.e., 3‐nitro‐4‐hydroxyphenylarsonic acid (roxarsone, Rox), phenylarsonic acid (PAA), p‐arsanilic acid (p‐ASA), phenylarsine oxide (PAO), dimethylarsinate (DMA), methylarsonate (MMA), arsenobetaine (AsB), arsenocholine (AsC) and trimethylarsine oxide (TMAO)) within 45 min. All analytes were prepared in the mobile phase. The flow rate of the mobile phase, the splitting ratio between ICP‐MS and ESI‐MS detection, and the oxygen addition were adapted to ensure that there appeared a stably burning inductively coupled plasma. Furthermore, the analytical method was evaluated by the identification and quantification of AsB in the reference material DORM‐2 (dogfish muscle) resulting in a 95‐% recovery with respect to the AsB concentration in the extract.
A Two‐stage CSTR Cascade for Studying the Effect of Inhibitory and Toxic Substances in Bioprocesses
Authors: Hortsch R. , Löser C. , Bley T.
Published: December 2008

In some biotechnological processes like wastewater treatment and biotransformation, substances are involved which are inhibitory or even toxic to the microorganisms. Their presence changes the cell physiology or even acts lethal on the cells so that the process breaks down completely. For studying such processes, a two‐stage continuous‐flow stirred tank reactor (CSTR) cascade was developed where the toxic substance is only supplied to the second reactor. Mathematical modeling of the system showed that identical steady‐state conditions can be established in both bioreactors of the two‐stage CSTR cascade when the dilution rate of the second reactor is twice as high as the dilution rate in the first reactor, provided that both reactors are fed with the same culture medium and possess an identical working volume. The theoretically derived concept was verified by cultivating Saccharomyces cerevisiae CBS 8066 under glucose‐limited aerobic conditions. Independently of the dilution rates established (D1 in the range of 0.26 to 0.38 h–1 and D2 = 2·D1), the steady‐state values of the biomass, glucose and ethanol concentration were almost identical in both reactors. Moreover, the dynamic behavior after each stepwise change of the dilution rates was also identical in both reactors, which was detected by dissolved‐oxygen measurements. Finally, the system was applied to the whole‐cell biotransformation of ethyl 2‐chloro‐3‐oxo‐butanoate as an example.
Dynamics of Arsenic Species in Laboratory‐Scale Horizontal Subsurface‐Flow Constructed Wetlands Treating an Artificial Wastewater
Authors: Rahman K. Z. , Wiessner A. , Kuschk P. , Mattusch J. , Kästner M. , Müller R. A.
Published: December 2008

Knowledge regarding the dynamics of arsenic species and their interactions under gradient redox conditions in treatment wetlands is still insufficient. The aim of this investigation was to gain more information on the biotransformation of As and the dynamics of As species in horizontal subsurface‐flow constructed wetlands. Experiments were carried out in laboratory‐scale wetland systems, two planted with Juncus effusus and one unplanted, using an As‐containing artificial wastewater under defined organic C‐ and SO42–‐loading conditions. Immobilization of As was found in all systems under conditions of limited C, mainly due to adsorption and/or co‐precipitation. The removal efficiencies were substantially higher in the planted systems (60–70 %) as compared to the unplanted system (37 % on average). Immobilization under the conditions mentioned above appeared to decrease over time in all systems. At the beginning, the dosage of organic carbon immediately caused intensive microbial dissimilatory sulfate reduction in all systems (in the range of 85–95 %) and highly efficient removal of total arsenic (81–96 % on average). Later on, in this operation period, the intensity of sulfate reduction and simultaneous removal of As decreased, particularly in the planted wetlands (ranging from 30–46 %). One reason could be the re‐oxidation of reduced compounds due to oxygenation of the rhizosphere by the emergent wetland plants (helophytes). A significant amount of reduced As [As(III)] was found in the planted systems (> 75 % of total As) during the period of efficient microbial sulfate reduction, compared to the unplanted system (> 25 % of total As). The immobilization of arsenic was found to behave more stably in the planted beds than in the unplanted bed. Both systems (planted and unplanted) were suitable to treat wastewater containing As, particularly under sulfate reducing conditions. The unplanted system seemed to be more efficient regarding the immobilization of As, but the planted systems showed a better stability of immobilized As.
The anatomy of wood and bark of Scots Pine. A review of literature
Authors: Schultze‐Dewitz G. , Koch G.
Published: December 2008

Since one and a half century are known in the frame of an actual wood research a lot of investigations on wood of the European‐domestic tree species Norway Spruce [Picea abies (L.) Karst.] and Scots pine (Pinus sylvestris L.), that are with regard to their occurrence and utilization the most important ones. With a monographic treatment of Norway spruce 20 years ago there could be compiled characteristic structural features of wood and bark. But for the most distributed tree species Common or Scots pine it does not happen anything like that. Thus selected references shall inform on the relevant knowledge of its wooden and cortical tissues which could be held in recent times among others by 15 Fellows of the International Academy of Wood Science (IAWS). (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A dubious resurrection of Ochetophila Poepp. ex Endl. (Rhamnaceae)
Authors: Tortosa R. D.
Published: December 2008

The split off of Discaria nana and D. trinervis from the genus Discaria, recently made by Kellermann et al. (2005), is not accepted. The occurrence of specimens with morphological intermediacy between both species and D. chacaye, show that those species, that had been segregated into the genus Ochetophila, are closely related to the last species. Moreover, the entire margin of leaves and the petals well developed, considered synapomorphies of Ochetophila, are present in other species of Discaria. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Discrimination of Pinus eldarica Medw. and its two new species by epicuticular wax, lignin content, electrophoretic isozyme and activity of peroxidase
Authors: Shayanmehr F. , Jalali S. Gh. , Ghanati F. , Kartoolinejad D.
Published: December 2008

Mondell pine (Pinus eldarica Medw.) is a rare and drought resistant pine, found naturally only in semi desert environment southeast of Tbilisi, Georgia, and has been probably introduced to Iran more than 800 years ago. This species has gradually altered both in shape and growth rate in Nashtifan‐Khaf, and generated two species nova which so called as ball shaped and conical, according to characteristics of their shape and smaller stature. This study was conducted to discriminate these species nova using epicuticular wax features and certain biochemical characteristics i.e., peroxidase electrophoretic pattern (PAGE), the activity of soluble (SPO), ionically (IPO) and covalently (CPO) wall‐bound fractions of peroxidase, lignin and total protein content. Observation via scanning electron microspopy showed differences that in adaxial and abaxial surface of needles, and also seed surface, in ball shaped type with the others. But none of the biochemical characteristics had significant difference in these three types. The electrophoretic analysis showed that the peroxidase isozyme is not suitable marker for discriminating the species nova from wild type, in spite of obvious micro‐ and macromorphological differences. Results of current study, propose the use of molecular markers and cytogenetic studies in order to specify cause of species nova occurrence in the study area. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Morphology and environment: geographic distribution, ecological disjunction, and morphological variation in Actinocephalus polyanthus (Bong.) Sano (Eriocaulaceae)
Authors: Trovó M. , Sano P. T. , Winkworth R.
Published: December 2008

Most Brazilian Eriocaulaceae have highly restricted geographic distributions. Actinocephalus polyanthus (Bong.) Sano is one of the few widely distributed species; furthermore this distribution includes an interesting ecological disjunction. Actinocephalus polyanthus occurs in montane areas from northern Minas Gerais to Paraná, as well as coastal sand dune habitats in Santa Catarina and Rio Grande do Sul. In attempt to investigate whether there is any correlation between the ecological disjunction and the patterns of morphology exhibited by this species, eight populations were sampled covering the geographic distribution and the ecological disjunction. We used multivariate statistical methods (UPGMA, PCA and DF) to describe the morphology, and to verify its correlation with its distribution and habitat. We conclude that sand dune populations are morphologically different from the montane populations. The main difference in these plants is the robustness. The sand dune plants are significantly smaller than the plants from montane areas. We also verified that these populations have a morphological identity. The occurrence of this species in such diverse environments may reflect the morphological diversity of the various populations of the species, and may be the primary cause of the difference in these populations. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Insights on a sign‐preserving numerical method for the advection–diffusion equation
Authors: Sousa E.
Published: December 2008

In this paper we explore theoretically and numerically the application of the advection transport algorithm introduced by Smolarkiewicz to the one‐dimensional unsteady advection–diffusion equation. The scheme consists of a sequence of upwind iterations, where the initial iteration is the first‐order accurate upwind scheme, while the subsequent iterations are designed to compensate for the truncation error of the preceding step. Two versions of the method are discussed. One, the classical version of the method, regards the second‐order terms of the truncation error and the other considers additionally the third‐order terms. Stability and convergence are discussed and the theoretical considerations are illustrated through numerical tests. The numerical tests will also indicate in which situations are advantageous to use the numerical methods presented. Copyright © 2008 John Wiley & Sons, Ltd.
Effects of long‐term exposure to ramelteon, a melatonin receptor agonist, on endocrine function in adults with chronic insomnia
Authors: Richardson Gary , Wang‐Weigand Sherry
Published: December 2008

Objective

To evaluate the effects of ramelteon, an MT1/MT2 melatonin receptor agonist used to treat insomnia, on endocrine function in adults with chronic insomnia.

Methods

This was a double‐blind, placebo‐controlled, trial of adults (18–45 years) with chronic insomnia. Subjects received either ramelteon 16 mg or placebo nightly for 6 months. Hormonal measures of the thyroid, reproductive, and adrenal axes were analyzed monthly and compared with baseline and placebo values.

Results

While isolated changes were detected at some time points, there were no consistent statistically significant differences between treatments on measures of thyroid function (total T4, free T4, TSH, and total T3), adrenal function (AM cortisol, and ACTH), or on most reproductive endocrine measures [LH, FSH, estradiol (women), total, and free testosterone (men)]. Prolactin concentrations were increased overall in women in the ramelteon group compared with placebo (p = 0.003). No clinical effects of elevated prolactin were reported; average menstrual cycle length, duration of menses, and ovulation probability did not differ between groups.

Conclusions

Long‐term exposure to ramelteon 16 mg, a potent melatonin receptor agonist, resulted in mild, transient increase in prolactin, in women only, that were not associated with measurable reproductive effects. There were no consistent changes in other endocrine measures. Copyright © 2008 John Wiley & Sons, Ltd.
Hydrologic response of the Greenland ice sheet: the role of oceanographic warming
Authors: Hanna E. , Cappelen J. , Fettweis X. , Huybrechts P. , Luckman A. , Ribergaard M. H.
Published: December 2008

The response of the Greenland ice sheet to ongoing climate change remains an area of great uncertainty, with most previous studies having concentrated on the contribution of the atmosphere to the ice mass‐balance signature. Here we systematically assess for the first time the influence of oceanographic changes on the ice sheet. The first part of this assessment involves a statistical analysis and interpretation of the relative changes and variations in sea‐surface temperatures (SSTs) and air temperatures around Greenland for the period 1870–2007. This analysis is based on HadISST1 and Reynolds OI.v2 SST analyses, in situ SST and deeper ocean temperature series, surface‐air‐temperature records for key points located around the Greenland coast, and examination of atmospheric pressure and geopotential height from NCEP/NCAR reanalysis. Second, we carried out a novel sensitivity experiment in which SSTs were perturbed as input to a regional climate model, and document the resulting effects on simulated Greenland climate and surface mass balance. We conclude that sea‐surface/ocean temperature forcing is not sufficient to strongly influence precipitation/snow accumulation and melt/runoff of the ice sheet. Additional evidence from meteorological reanalysis suggests that high Greenland melt anomalies of summer 2007 are likely to have been primarily forced by anomalous advection of warm air masses over the ice sheet and to have therefore had a more remote atmospheric origin. However, there is a striking correspondence between ocean warming and dramatic accelerations and retreats of key Greenland outlet glaciers in both southeast and southwest Greenland during the late 1990s and early 2000s. Copyright © 2008 John Wiley & Sons, Ltd.
Glacier change in western North America: influences on hydrology, geomorphic hazards and water quality
Authors: Moore R. D. , Fleming S. W. , Menounos B. , Wheate R. , Fountain A. , Stahl K. , Holm K. , Jakob M.
Published: December 2008

The glaciers of western Canada and the conterminous United States have dominantly retreated since the end of the Little Ice Age (LIA) in the nineteenth century, although average rates of retreat varied from strong in the first‐half of the twentieth century, with glaciers stabilizing or even advancing until 1980, and then resuming consistent recession. This retreat has been accompanied by statistically detectable declines in late‐summer streamflow from glacier‐fed catchments over much of the study area, although there is some geographical variation: over recent decades, glaciers in northwest BC and southwest Yukon have lost mass dominantly by thinning with relatively low rates of terminal retreat, and glacier‐fed streams in that region have experienced increasing flows. In many valleys, glacier retreat has produced geomorphic hazards, including outburst floods from moraine‐dammed lakes, mass failures from oversteepened valley walls and debris flows generated on moraines. In addition to these hydrologic and geomorphic changes, evidence is presented that glacier retreat will result in higher stream temperatures, possibly transient increases in suspended sediment fluxes and concentrations, and changes in water chemistry. With climate projected to continue warming over the twenty‐first century, current trends in hydrology, geomorphology and water quality should continue, with a range of implications for water resources availability and management and hydroecology, particularly for cool and cold‐water species such as salmonids. Copyright © 2008 John Wiley & Sons, Ltd.
Genetic variation in SIPA1 in relation to breast cancer risk and survival after breast cancer diagnosis
Authors: Gaudet Mia M. , Hunter Kent , Pharoah Paul , Dunning Alison M. , Driver Kristy , Lissowska Jolanta , Sherman Mark , Peplonska Beata , Brinton Louise A. , Chanock Stephen , Garcia‐Closas Montserrat
Published: December 2008

Genetic variation inSIPA1,signal‐induced proliferation‐associated gene 1, has been proposed to be associated with aggressive breast tumor characteristics related to metastasis and worse prognosis in humans and rodents. To test this hypothesis, we genotyped 3 single nucleotide polymorphisms (SNP) located at −3092 (AT, rs3741378), and exon 14 + 14 (C>T, rs746429), and examined them in relation to breast cancer risk and overall survival, stratified by tumor characteristics in 2 independent case–control studies conducted in Poland (1,995 cases, 2,296 controls) and in Britain (2,142 cases, 2,257 controls). Vital status (n= 396 deaths) was available for 911 Polish and 1,919 British breast cancer cases with an average follow‐up time of 5.5 years. Overall, we found no significant associations between genetic variants ofSIPA1SNPs and breast cancer risk (per allele odds ratios, 95% confidence intervals (CI): rs931127–0.99, 0.93–1.06; rs3741378–1.03, 0.94–1.13; and, rs74642–0.98, 0.92–1.04). In both studies,SIPA1polymorphisms were not related to overall mortality (per allele hazard ratios, 95% CI: 1.02, 0.88–1.17; 0.90, 0.72–1.11; 1.04, 0.90–1.21, respectively). Our results do not support a relationship betweenSIPA1polymorphisms and breast cancer risk or subsequent survival. Published 2008 Wiley‐Liss, Inc.
Two‐photon laser confocal microscopy of micropermeability of resin‐dentin bonds made with water or ethanol wet bonding
Authors: Sauro Salvatore , Watson Timothy F. , Mannocci Francesco , Miyake Katsuya , Huffman Bradford P. , Tay Franklin R. , Pashley David H.
Published: December 2008

This study evaluated the micropermeability of six etch‐and‐rinse adhesives bonded to dentin. There were two principal groups: wet bonding with water or wet bonding with absolute ethyl alcohol. After bonding and the creation of composite build‐ups, the pulp chambers were filled with 0.1% lucifer yellow. The contents of the pulp chamber were kept under 20 cm H2O pressure to simulate pulpal pressure for 3 h. The specimens were vertically sectioned into multiple 0.5‐mm thick slabs that were polished and then examined using a two‐photon confocal laser scanning microscope (TPCLSM). The results showed that specimens bonded with adhesives using the water wet‐bonding condition all showed tracer taken up uniformly by the hybrid layer. This uptake of fluorescent tracer into the hybrid layer was quantified by computer software. The most hydrophobic experimental resins showed the highest fluorescent tracer uptake (ca. 1800 ± 160 arbitrary fluorescent units/std. surface area). The most hydrophilic experimental resins showed the lowest tracer uptake into water‐saturated hybrid layers. When ethanol wet‐bonding was used, significantly less fluorescent tracer was seen in hybrid layers. The most hydrophilic experimental resins and Single Bond Plus showed little micropermeability. Clearly, ethanol wet‐bonding seals dentin significantly better than water‐wet dentin regardless of the adhesive in etch‐and‐rinse systems. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009