bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural analysis of the CHO‐derived interleukin‐4 by liquid‐chromatography/electrospray ionization mass spectrometry
Authors: Tsarbopoulos Anthony , Pramanik Birendra N. , Nagabhushan Tattanahalli L. , Covey Thomas R.
Published: May 2005

Electrospray (ES) ionization mass spectrometric analysis of CHO‐derived recombinant interleukin‐4 (IL‐4) before and after deglycosylation with peptide: N‐glycosidase F is described. That proved useful not only in deriving the size of the attached carbohydrate components but also in identifying the major glycoforms as the mono‐and disialylated complex‐type N‐linked oligosaccharides. Additional signals arising from glycoforms containing carbohydrate components with more extended or higher branching were also detected. Further mapping of CHO IL‐4 was carried out by combining proteolytic digestion and chromatographic separation of the resulting peptide mixture with on‐line ES mass spectrometric detection. Comparative analysis of the V8 protease digests of CHO IL‐4 and its deglycosylated product revealed the Asn38 N‐glycosylation site. Glycopeptide‐containing fractions were identified by searching the resulting raw ES data for signal pairs whose m/z values differ by the mass of various carbohydrate units adjusted for the signal's charge state (e.g. 97 u difference for a triply charged ES signal of a glycopeptide containing NeuAc units). Furthermore, ES mass spectrometric analysis at elevated orifice potentials allowed the rapid location of the glycopeptides in the total ion current chromatogram by monitoring several carbohydrate‐specific fragment ions. This high orifice‐induced fragmentation is a highly sensitive method for generating sugar diagnostic ions in chromatographically separated components, even when glycopeptide and peptide fragments are co‐eluting.
Poly(ADP‐ribose) polymerase‐1 activation in a primate model of multiple sclerosis
Authors: Kauppinen Tiina M. , Suh Sang Won , Genain Claude P. , Swanson Raymond A.
Published: June 2005

Multiple sclerosis (MS) is an immune‐mediated disabling neurological disorder involving inflammation, demyelination, axonal damage, and neurodegeneration. Poly(ADP‐ribose)polymerase‐1 (PARP‐1), a nuclear enzyme linked to DNA repair, has been shown to regulate the cellular inflammatory response through interactions with nuclear factor‐κB. Extensive PARP‐1 activation can, by separate mechanisms, also cause cell death. PARP‐1 activation in brain occurs in several settings associated with oxidative stress and DNA damage, and PARP‐1 inhibition has been shown to attenuate inflammation and improve neuronal survival in these settings. Here we studied the pattern of PARP‐1 activation in a nonhuman primate model of MS, marmoset (Callithrix jacchus) experimental allergic encephalomyelitis (EAE). Characteristic of this model is relapsing and remitting focal demyelination typical of human MS. Immunostaining for poly(ADP‐ribose), the enzymatic product of PARP‐1, showed PARP‐1 activation specifically in plaque areas of EAE brains. Robust immunostaining was found in astrocytes surrounding demyelinated EAE plaques and in scattered nearby microglia, oligodendrocytes, and neurons. The immunostaining also suggested PARP‐1 activation in occasional endothelial cells surrounded by microglia or infiltrating peripheral blood cells. Given the importance of PARP‐1 in both inflammation and cell death processes, these findings suggest that PARP‐1 activation may be a significant factor in the pathogenesis of MS. © 2005 Wiley‐Liss, Inc.
Biochemical and morphologic evidence of the interaction of oligodendrocyte membrane rafts with actin filaments
Authors: Taguchi Katsutoshi , Yoshinaka Koji , Yoshino Ken‐ichi , Yonezawa Kazuyoshi , Maekawa Shohei
Published: June 2005

Cytoskeletal structures under the cell membrane carry out pivotal roles in the maintenance and remodeling of the cell structures. Reforming of the cytoskeletal networks after partial extraction of membrane components could be a good clue to identify molecular components pertaining the interaction of cytoskeleton with membrane. A detergent extract from 3‐week‐old rat brain membrane fraction was found to make an actin‐based gel upon incubation at 25°C. Some protein components of the gelation products were recovered in a Triton‐insoluble low‐density microdomain fraction (raft) after depolymerization of actin filaments. Some of these proteins were identified as 2′,3′‐cyclic nucleotide‐3′‐phosphodiesterase (CNPase), proteolipid protein (PLP), and myelin oligodendrocyte glycoprotein (MOG) through electrospray time‐of‐flight (ESI‐TOF) analysis and Western blotting. Because these proteins are well‐known marker proteins of oligodendrocytes, localization of these proteins and cholesterol, a raft‐localized lipid, with actin filaments was studied using cultured oligodendrocytes. Clear colocalization of these proteins and cholesterol with actin filaments was observed after Triton treatment at 4°C before fixation. These results indicate that raft microdomains participate in the formation of cell shape through interaction with microfilaments in oligodendrocytes. © 2005 Wiley‐Liss, Inc.
PI3K/Akt‐dependent regulation of the transcription factor myocyte enhancer factor‐2 in insulin‐like growth factor‐1‐ and membrane depolarization‐mediated survival of cerebellar granule neurons
Authors: Wiedmann M. , Wang X. , Tang X. , Han M. , Li M. , Mao Z.
Published: June 2005

Survival signals such as insulin‐like growth factor‐1 (IGF‐1) or membrane depolarization convey their neuronal protective effects through the activation of signaling networks and nuclear factors. In cerebellar granule neurons, IGF‐1 mediates survival primarily through the PI3K/Akt pathway. The function of the transcription factor myocyte enhancer factor‐2 (MEF2) is required for mediating membrane depolarization‐dependent neuronal survival. However, whether PI3K/Akt regulates MEF2 and the role of MEF2 in IGF‐1‐mediated survival of neurons are unknown. In addition, the contribution of the PI3K/Akt pathway in membrane depolarization‐induced neuronal survival remains undefined. We show here that the PI3K/Akt pathway promotes the survival of cerebellar granule neurons derived from Long‐Evans rats following IGF‐1 stimulation or membrane depolarization through regulation of MEF2 activity. IGF‐1 stimulated the gene transactivation activity of MEF2 and its DNA binding potential. Moreover, regulation of MEF2 function by IGF‐1 was dependent on the activity of the PI3K/Akt signaling pathway. Blocking MEF2 function reduced IGF‐1‐induced survival of cerebellar granule neurons. Membrane depolarization stimulated phosphorylation of Akt in cerebellar granule neurons. Blocking of the PI3K/Akt pathway with either a pharmacological inhibitor of PI3K, LY294002, or dominant negative mutants of PI3K and Akt inhibited the membrane depolarization‐induced increase in MEF2 transactivation as well as its DNA binding activity and reduced neuronal survival. Together, these findings provide clear evidence to support an important role of the PI3K/Akt pathway in the regulation of nuclear survival factor MEF2 upon either IGF‐1 stimulation or membrane depolarization, thus placing MEF2 as a novel downstream effector of the PI3K/Akt pathway in neurons. © 2005 Wiley‐Liss, Inc.
Role of heat treatment in childhood cancers: Distinct resistance profiles of solid tumor cell lines towards combined thermochemotherapy
Authors: Debes Anette , Willers Reinhart , Göbel Ulrich , Wessalowski Rüdiger
Published: June 2005

Background

Since information on the efficacy of hyperthermia in combination with chemotherapy on pediatric tumors is limited, we performed a systematic analysis on the synergistic effects of a combined application of heat and chemotherapy on 20 tumor cell lines derived from patients with neuroblastomas, Ewing tumors, germ cell tumors (GCT), and osteosarcomas.

Methods

Cisplatin (cDDP), a cross‐linking agent, and etoposide (VP‐16), a topoisomerase II inhibitor, were examined either alone or in combination with heat (42°C, 43°C) by using the XTT‐assay 1.

Results

Our data demonstrate that heat stress at 43°C for 1 hr, but not at 42°C, leads to a notable cytotoxic effect on the different tumor cells. The comparison of mean survival fractions reveals values between 62% for neuroblastoma cells and 76% for Ewing tumor cells. Analyzing the sensitivity to chemotherapy alone, our results show that cDDP (5 μg/ml) reduces cell growth to 47% in Ewing tumor cells, to 61% in neuroblastoma cells, to 75% in GCT cells, and to 76% in osteosarcoma cells. Treatment with VP‐16 (10 μg/ml) decreases cell survival to mean values between 58% (neuroblastomas) and 77% (osteosarcomas). Simultaneous application of heat and chemotherapy enhances synergistically cDDP cytotoxicity in all tumor types tested, whereas the efficacy of VP‐16 is only slightly influenced by additional application of hyperthermia. The cytotoxicity of cDDP (5 μg/ml) can be increased by a factor of between 1.5 and 2.5 at 42°C and from 2.6 to 14.0 at 43°C. Furthermore, the results show that the sensitivity to heat (43°C) as well as the sensitivity to chemotherapy and combined thermochemotherapy varies considerably between cell lines of the same tumor group.

Conclusions

Simultaneous application of hyperthermia synergistically enhances the cytotoxicity of the alkylating agent cDDP, but not of the topoisomerase II inhibitor VP‐16, in a defined spectrum of cell lines from different pediatric tumor entities. © 2005 Wiley‐Liss, Inc.
Cord blood transplant in childhood ALL
Authors: Sawczyn Kelly K. , Quinones Ralph , Malcolm Janet , Foreman Nicholas , Garrington Tim , Gore Lia , Gao Dexiang , Giller Roger
Published: June 2005

Background

Optimal therapy for high risk and relapsed acute lymphoblastic leukemia (ALL) remains uncertain. Wider availability of cord blood from related and unrelated donors has prompted studies of its use for hematopoeitic stem cell transplant (HSCT).

Procedure

We evaluated 26 consecutive cord blood transplants (CBT) for ALL performed at our center from 1996 to 2002 on studies using consistent conditioning therapy and graft‐versus‐host disease (GVHD) prophylaxis. Median patient age was 8.5 years (range, 0.5–24 year). Cord blood (CB) was from unrelated donors in 25/26 cases. Median CB nucleated cell dose was 3.26e7/kg (range, 0.8–12.9).

Results

With median follow‐up of 548 days, 16/26 patients (62%) are event‐free survivors. Acute GVHD developed in 14/24 evaluable patients, reaching grade III–IV in 7 patients. Chronic GVHD occurred in 10/22 evaluable patients. Multivariate analysis showed higher total nucleated cell dose per kilogram to be the strongest predictor of event‐free survival.

Conclusions

We conclude that CBT can effectively treat ALL in children with high risk features and following relapse. © 2005 Wiley‐Liss, Inc.
Phase II study of gemcitabine in children with relapsed acute lymphoblastic leukemia or acute myelogenous leukemia (ADVL0022): A Children's Oncology Group Report
Authors: Angiolillo Anne L. , Whitlock J. , Chen Z. , Krailo M. , Reaman G.
Published: June 2005

Background

To determine the response rate and toxicity to gemcitabine administered as 10 mg/m2/min × 360 min weekly for 3 weeks in children with relapsed acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML). Gemcitabine is a deoxycytidine analog that inhibits DNA synthesis and repair and has a broad spectrum of antitumor activity.

Procedure

From April 2001 to April 2003, 23 male and 9 female eligible patients were recruited for the Children's Oncology Group (COG) phase II study of Gemcitabine (ADVL0022).

Results

One of 20 evaluable patients with ALL and none of 10 evaluable patients with AML had complete responses to gemcitabine; there were no partial responses. Grade 3 or 4 hematologic toxicity and liver toxicity were common during therapy. Only one patient was alive 1 year after entry. The estimated 1‐year overall survival probability for the 32 patients was 4% (SE = 3%).

Conclusions

Gemcitabine at the dose and schedule in this trial was not effective for children with relapsed AML or ALL. Pediatr Blood Cancer © 2005 Wiley‐Liss, Inc.
Conservative surgical approach for thyroid and lymph‐node involvement in papillary thyroid carcinoma of childhood and adolescence
Authors: Massimino Maura , Collini Paola , Leite Silvia Fagundes , Spreafico Filippo , Zucchini Nicola , Ferrari Andrea , Mattavelli Franco , Seregni Ettore , Castellani Maria Rita , Cantù Giulio , Fossati‐Bellani Franca , Rosai Juan
Published: May 2005

Background

Prior to 1990s, papillary thyroid carcinomas (PTCs) in childhood/adolescence underwent a standard therapeutic approach (total thyroidectomy plus elective neck dissection, followed by radioactive iodine (RAI) ablation), with an overall survival of about 100%. The aim of this study is to outline the possibility of a conservative approach (hemithyroidectomy plus selective neck dissection of clinically involved nodes, followed by TSH‐suppressive therapy) in a selected group of patients.

Procedure

From 1968 to 2001, 42 pediatric PTC patients were treated at our institution. Absence of distant metastases and a tumor clinically limited to one lobe were both present in 28 cases that underwent a radical (20 cases) or a conservative (8 cases) surgical approach at the thyroid level. At cervical node level, 10 patients underwent a radical and 32 a conservative surgical approach. Clinicopathologic features at onset, type of therapy (radical vs. conservative), post‐operative complications, and outcome till May 31, 2004 were recorded. The impact of the type of surgery on outcome was evaluated.

Results

Overall and progression‐free survival (PFS) curves were found to be independent of the type of therapy (radical vs. conservative) in subgroups of patients matched for extent of disease at onset. Post‐operative complications occurred only with radical surgical approaches.

Conclusions

Childhood and adolescence PTCs show a high rate of spread but an excellent outcome independent of the type of therapy (radical vs. conservative). Taking into account the marked responsiveness to TSH‐suppression and the complications after radical therapy, in selected cases, a conservative approach should be considered, reserving more aggressive therapies in case of metastases or relapse. © 2005 Wiley‐Liss, Inc.
Relationship between mechanical properties and exfoliation degree of clay in polyurethane nanocomposites
Authors: Xia Hesheng , Shaw Stephen J , Song Mo
Published: June 2005

Exfoliated and intercalated polyurethane (PU) nanocomposites were prepared by in situ polymerization of polyol/organoclay mixture, chain extender and diisocyanate. Wide‐angle X‐ray diffraction and transmission electron microscopy confirmed an exfoliated structure for clay C30B and an intercalated structure for C20A in polyol and PU. The realization of exfoliated state for clay C30B in polyol during the mixing stage can provide an effective approach for controlling the exfoliation degrees by adjusting the content of intercalated and exfoliated organoclay C20A and C30B before polymerization. The effect of exfoliation degree on the mechanical and viscoelastic properties of PU was investigated. The addition of organoclay improved the tensile strength, modulus and elongation, but the hysteresis loss ratio and relaxation rate increased, and the relaxation time distribution became broad. The effect of organoclay on PU properties varied with the hard segment content. By increasing the exfoliation degree, the tensile strength and modulus increased, whereas the elongation decreased. The exfoliated PU nanocomposite had a lower relaxation rate and hysteresis loss ratio than the intercalated PU. Copyright © 2005 Society of Chemical Industry
Comparison of protein expression in human deltoideus and vastus lateralis muscles using two‐dimensional gel electrophoresis
Authors: Capitanio Daniele , Viganò Agnese , Ricci Enzo , Cerretelli Paolo , Wait Robin , Gelfi Cecilia
Published: June 2005

We have used two‐dimensional gel electrophoresis (2‐DE) and mass spectrometry (MS) to study the expression of contractile and regulatory proteins in human vastus lateralis and deltoideus muscles, in order to understand protein turnover and isoform switching in muscles with the same fiber‐type composition but different functional properties. We demonstrate a two‐ to six‐fold overexpression of enzymes associated with glycolysis, the tricarboxylic acid cycle, oxidative phosphorylation, and substrate transport in vastus lateralis compared to deltoideus. Expression levels of contractile protein isoforms correlated to the proportion of slow‐twitch fibers in deltoideus compared to vastus lateralis are consistent with the different contractile properties of the two muscles. Two proteins involved in free radical homeostasis were differentially expressed, suggesting a direct relationship between radical scavenging and the muscle function. The application of 2‐DE and MS to studies of muscle physiology thus offers a more comprehensive assessment of the molecular determinants of muscle function than traditional approaches.
Cancer‐related relationship communication in couples coping with early stage breast cancer
Authors: Manne Sharon L. , Ostroff Jamie S. , Norton Tina R. , Fox Kevin , Goldstein Lori , Grana Generosa
Published: May 2005

This longitudinal study examined the association between three types of communication strategies couples may use to handle stressors they experience during and after breast cancer treatment and psychological distress and relationship satisfaction of women with early stage breast cancer and their partners. Mutual constructive communication, mutual avoidance, and demand–withdraw communication strategies as well as psychological distress and marital satisfaction were rated by 147 patients and 127 partners during cancer treatment and 9 months later. Mutual constructive communication was associated with less distress and more relationship satisfaction for both patient and partner. Demand–withdraw communication was associated with higher distress and lower relationship satisfaction for both patient and partner. Mutual avoidance was associated with more distress for patient and partner but was not associated with relationship satisfaction. The negative association between mutual constructive communication and patient distress was stronger for patients with more physical impairment. Patients' perceptions of mutual constructive communication and mutual avoidance were associated with partners' distress, and patients' perceptions of mutual constructive and demand/withdraw communication were associated with partners' marital satisfaction. Clinical implications for couple‐focused communication skills training for cancer patients and their partners are discussed. Copyright © 2005 John Wiley & Sons, Ltd.
Water balance modelling of (Sub‐)Arctic rivers and freshwater supply to the Barents Sea Basin
Authors: Koster Eduard , Dankers Rutger , Linden Sandra van der
Published: June 2005

Recently, changes in the freshwater supply by rivers to the Arctic Ocean have attracted a great deal of attention. However, quantitative assessments of changes in the annual and seasonal discharge regime of (Sub‐)Arctic rivers resulting from climate change are still far from accurate. The sensitivity of discharge to potential changes in climate in two river catchments of intermediate size (104–105 km2), the Tana River in northern Fennoscandia and the Usa River in northern Russia, both draining into the Barents Sea Basin, was evaluated using a spatially distributed water balance model. The tentative results show that discharge amounts during peak flow might remain more or less the same or show a slight increase. However, peakflow events are expected to occur about 20 days or more earlier in spring. Concerning annual discharge amounts a strong increase of 25% for the Usa River and even 39% for the Tana River is simulated in conformity with projected increases in precipitation. Obviously, the resulting increases of the annual freshwater influx from the Tana River (from 5.3 to 7.3 km3) and that of the Usa River (from 42 to 52 km3) into the Barents Sea are insignificant in absolute terms. But in relative terms they agree remarkably well with earlier estimates of changes in freshwater inflow by the very large (Sub‐)Arctic rivers. Copyright © 2005 John Wiley & Sons, Ltd.
Dielectric and pyroelectric properties of BaTiO3–PVC composites
Authors: Olszowy M. , Pawlaczyk Cz. , Markiewicz E. , Kułek J.
Published: June 2005

Dielectric relaxation and pyroelectric response of the barium titanate–poly (vinyl chloride) BaTiO3–PVC composites of 0–3 connectivity and volume fraction of ceramics ϕ from 0.0 to 0.4 were investigated. Dielectric properties of the composites were found to be a combination of those of pure PVC polymer and BaTiO3 ceramics: the value of dielectric permittivity increases with increasing volume fraction of the ceramics but the temperature dependence is determined by two relaxation processes in the polymer (at ∼270 K – the local motion of the small groups in the chain and at ∼350 K – the segmental molecular motion) and in the ceramics (dielectric anomaly at the phase transitions). The value of the pyroelectric coefficient p of poled composites increases with ϕ and depends on the light modulation frequency fm as p ∼ f–nm with n ≈ 0.9 to 1.1, dependently on ϕ. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Growth of Ni–B films on n‐silicon
Authors: Mondal Anup , Nath Sabyashachi , Mondal Ashok , Bandopadhyay Sikha , Gangopadhyay Utpal , Saha Hiranmay
Published: June 2005

Electroless deposition of Ni–B films on n‐silicon has been developed, using sodium borohydride as the reducing agent. The deposition has been studied by varying the temperature, time of deposition and the concentration of the reducing agent used, keeping the pH of the solution unchanged. Sheet resistance of the deposited films were measured to confirm the growth. Preliminary studies on contact resistance between Ni–B film and n‐Si have been carried out. Results are found to be similar to contact resistance between Ni–B and p‐silicon, suggesting that ohmic contacts to n‐Si can be achieved even with Ni–B. This has been done with a view to deposit Ni simultaneously on both the front and back sides of a silicon solar cell, from the same solution. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Highly efficient all‐nitride phosphor‐converted white light emitting diode
Authors: Mueller‐Mach Regina , Mueller Gerd , Krames Michael R. , Höppe Henning A. , Stadler Florian , Schnick Wolfgang , Juestel Thomas , Schmidt Peter
Published: June 2005

The development and demonstration of a highly efficient warm‐white all‐nitride phosphor‐converted light emitting diode (pc‐LED) is presented utilizing a GaN based quantum well blue LED and two novel nitrogen containing luminescent materials, both of which are doped with Eu2+. For color conversion of the primary blue the nitridosilicates M2Si5N8 (orange‐red) and MSi2O2N2 (yellow‐green), with M = alkaline earth, were employed, thus achieving a high luminous efficiency (25 lumen/W at 1 W input), excellent color quality (correlated color temperature CCT = 3200 K, general color rendering index Ra > 90) and the highest proven color stability of any pc‐LED obtained so far. Thus, these novel all‐nitride LEDs are superior to both incandescent and fluorescent lamps and may therefore become the next generation of general lighting sources. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Influence of diabetes on the survival of patients hospitalized with heart failure: A 12‐year study
Authors: Varela‐Roman Alfonso , Shamagian Lilian Grigorian , Caballero Eduardo Barge , Ramos Pilar Mazon , Veloso Pedro Rigueiro , Gonzalez‐Juanatey Jose Ramon
Published: June 2005

Aim

To investigate the influence of diabetes mellitus (DM) on the prognosis of heart failure (HF) patients, focussing specifically on aetiology and patients with preserved left ventricular systolic function (LVSF), which to date has not been fully investigated.

Method and results

1659 Patients hospitalized for HF between 1991 and 2002 in the Cardiology Department of a tertiary hospital, aged 69±12years, 60% male were studied prospectively. Arterial hypertension was present in 54% of patients, DM in 26% and ischaemic cardiomyopathy in 51%. A survival analysis performed in April 2003 showed that DM worsens the prognosis of the whole group (median survival (MS):3.6 vs. 5.4 years; p<0.001), of ischaemic and non‐ischaemic patients (MS: 3.8 vs. 4.9 years; p=0.13 and 3.6 vs. 6.0 years; p<0.001, respectively). A similar effect of DM was shown in patients with preserved LVSF (MS: 3.8 vs. 5.8 years; p=0.03) and in patients with impaired LVSF (3.6 vs. 6.3 years; p<0.0001).

Conclusion

DM increases mortality among HF patients with preserved and impaired LVSF and those without ischaemic cardiomyopathy.
Different prognostic impact of systolic function in patients with heart failure and/or acute myocardial infarction
Authors: Thune Jens Jakob , Carlsen Christian , Buch Pernille , Seibæk Marie , Burchardt Hans , Torp‐Pedersen Christian , Køber Lars ,   on behalf of the DIAMOND investigators
Published: June 2005

Aims

To study the prognostic importance of left ventricular systolic function in patients with heart failure (HF) and acute myocardial infarction (AMI) with respect to the presence of prior heart failure and known ischemic heart disease.

Methods

In 13,084 consecutive patients diagnosed with either AMI or HF, a medical history and an echocardiographic assessment of left ventricular systolic function by wall motion index (WMI) were obtained. Patients were divided into four groups: AMI with or without a history of HF, and primary HF (no recent AMI) with or without a history of ischemic heart disease (IHD). Mortality was assessed after nine years of follow‐up.

Results

WMI stratified patients according to all‐cause mortality in all four groups of patients (p< 0.0001). For a decrease in WMI of 0.3 (corresponding to a decrease in left ventricular ejection fraction of 0.1), the hazard ratio was 1.61 (95% CI:1.48–1.76) for AMI patients without prior HF, 1.43 (1.38–1.48) for AMI patients with prior HF, 1.26 (1.22–1.30) for primary HF patients with IHD and 1.23 (1.18–1.27) for HF patients without IHD.

Conclusion

WMI stratifies patients with IHD and/or HF according to risk of all‐cause death. The presence of HF attenuates the prognostic power of WMI.
Kinetics of inclusion body formation studied in intact cells by FT‐IR spectroscopy
Authors: Ami Diletta , Natalello Antonino , Gatti-Lafranconi Pietro , Lotti Marina , Doglia Silvia Maria
Published: June 2005

The aggregation of a recombinant lipase as inclusion bodies (IBs) was studied directly within intact Escherichia coli cells by FT‐IR microspectroscopy. Through this approach, it was possible to monitor in real time the different kinetics of IB formation at 37 and 27 °C, in excellent agreement with the results of the SDS–PAGE analysis. Furthermore, insights on the residual native‐like structure of the expressed protein within IB – both isolated and inside cells – were obtained by the secondary structure analysis of the Amide I band in the IB FT‐IR spectra.
Saccharomyces cerevisiae Pex14p contains two independent Pex5p binding sites, which are both essential for PTS1 protein import
Authors: Williams Chris , van den Berg Marlene , Distel Ben
Published: June 2005

Pex14p is a peroxisomal membrane‐associated protein involved in docking of both Pex5p and Pex7p to the peroxisomal membrane. Previous studies have shown that, in humans, the N‐terminal region of Pex14p interacts with WxxxF/Y motifs in Pex5p. Here, we report that Saccharomyces cerevisiae Pex14p contains two independent Pex5p binding sites, one in the N‐ and one in the C‐terminus. Using deletion analysis we show that, in vivo, both of these interactions are needed for PTS1 import. Furthermore, we show that the characterized WxxxF/Y motifs of Pex5p are not essential for binding to the N‐terminus of Pex14p but do play a role in the interaction with the Pex14 C‐terminus. Thus, the data suggest that the mechanism of the Pex14p–Pex5p interaction in yeast is different from that previously reported for humans.
Grifolin, a potential antitumor natural product from the mushroom Albatrellus confluens, inhibits tumor cell growth by inducing apoptosis in vitro
Authors: Ye Mao , Liu Ji-kai , Lu Zhong-xin , Zhao Yan , Liu Su-fang , Li Li-li , Tan Ming , Weng Xin-xian , Li Wei , Cao Ya
Published: June 2005

Grifolin is a natural biologically active substance isolated from the fresh fruiting bodies of the mushroom Albatrellus confluens. Here, for the first time, we describe a novel activity of grifolin, namely its ability to inhibit the growth of tumor cells by the induction of apoptosis. Grifolin strongly inhibited the growth of tumor cell lines: CNE1, HeLa, MCF7, SW480, K562, Raji and B95‐8. Analysis of acridine orange (AO)/ethidium bromide (EB) staining and flow cytometry showed that grifolin possessed apoptosis induction activity to CNE1, HeLa, MCF7 and SW480. Furthermore, the cytochrome c release from mitochondria was detected by confocal microscopy in CNE1 cells after a 12 h treatment with grifolin. The increase of caspase‐8, 9, 3 activities revealed that caspase was a key mediator of the apoptotic pathway induced by grifolin, and the underexpression of Bcl‐2 and up‐regulation of Bax resulted in the increase of Bax: Bcl‐2 ratio, suggesting that Bcl‐2 family involved in the control of apoptosis. Owing to the combination of the significant antitumor activity by inducing apoptosis and natural abundance of the compound, grifolin holds the promise of being an interesting antitumor agent that deserves further laboratory and in vivo exploration.
Zinc in lipase L1 fromGeobacillus stearothermophilusL1 and structural implications on thermal stability
Authors: Choi Won-Chan , Kim Myung Hee , Ro Hyeon-Su , Ryu Sang Ryeol , Oh Tae-Kwang , Lee Jung-Kee
Published: June 2005

Lipase L1 fromGeobacillus stearothermophilusL1 contains an unusual extra domain, making a tight intramolecular interaction with the main catalytic domain through a Zn2+‐binding coordination. To elucidate the role of the Zn2+, we disrupted the Zn2+‐binding site by mutating the zinc‐ligand residues (H87A, D61A/H87A, and D61A/H81A/H87A/D238A). The activity vs. temperature profiles of the mutant enzymes showed that the disruption of the Zn2+‐binding site resulted in a notable decrease in the optimal temperature for maximal activity from 60 to 45–50 °C. The mutations also abolished the Zn2+‐induced thermal stabilization. The wild‐type enzyme revealed a 34.6‐fold increase in stabilization with the addition of Zn2+at 60 °C, whereas the mutant enzymes exhibited no response to Zn2+. Additional circular dichroism spectroscopy studies also confirmed the structural stabilizing role of Zn2+on lipase L1 at elevated temperatures.
Prediction of protein subcellular location using a combined feature of sequence
Authors: Gao Qing-Bin , Wang Zheng-Zhi , Yan Chun , Du Yao-Hua
Published: June 2005

To understand the structure and function of a protein, an important task is to know where it occurs in the cell. Thus, a computational method for properly predicting the subcellular location of proteins would be significant in interpreting the original data produced by the large‐scale genome sequencing projects. The present work tries to explore an effective method for extracting features from protein primary sequence and find a novel measurement of similarity among proteins for classifying a protein to its proper subcellular location. We considered four locations in eukaryotic cells and three locations in prokaryotic cells, which have been investigated by several groups in the past. A combined feature of primary sequence defined as a 430D (dimensional) vector was utilized to represent a protein, including 20 amino acid compositions, 400 dipeptide compositions and 10 physicochemical properties. To evaluate the prediction performance of this encoding scheme, a jackknife test based on nearest neighbor algorithm was employed. The prediction accuracies for cytoplasmic, extracellular, mitochondrial, and nuclear proteins in the former dataset were 86.3%, 89.2%, 73.5% and 89.4%, respectively, and the total prediction accuracy reached 86.3%. As for the prediction accuracies of cytoplasmic, extracellular, and periplasmic proteins in the latter dataset, the prediction accuracies were 97.4%, 86.0%, and 79.7, respectively, and the total prediction accuracy of 92.5% was achieved. The results indicate that this method outperforms some existing approaches based on amino acid composition or amino acid composition and dipeptide composition.
First report of sablefish in spawning condition off the coast of Kamchatka and the Kuril Islands
Authors: Orlov Alexei M. , Biryukov Igor A.
Published: June 2005

The population status of sablefish Anoplopoma fimbria (Anoplopomatidae) inhabiting the Asian coast of the western North Pacific is still uncertain, with no direct observations of sablefish spawning. This paper describes the first capture of pre-spawning and spawning individuals in Pacific waters off the Kuril Islands and Kamchatka, suggesting that sablefish spawning may occur on the southwestern edge of their range. Traditionally these areas have not been considered as suitable sablefish habitat. The spatial distribution of sablefish during pre-spawning periods suggests the use of quasistationary eddies. Further study of juvenile sablefish presence and survival will require ichthyoplankton surveys, and elucidation of population status of sablefish inhabiting the study area will require genetic investigation.
Central diabetes insipidus in five cats: Clinical presentation, diagnosis and oral desmopressin therapy
Authors: Aroch Itamar , Mazaki-Tovi Michal , Shemesh Oved , Sarfaty Havi , Segev Gilad
Published: June 2005

Five cases of central diabetes insipidus (CDI) in domestic shorthair cats are described. All cats were under 3 years of age at the onset of clinical signs, and outdoor or outdoor/indoor cats, in which a prior trauma was either present or possible. The history included polydipsia and polyuria, and physical examination abnormalities included urinary bladder distention and dehydration. All cats had hyposthenuria with a urine specific gravity between 1.003 and 1.006. The diagnosis was confirmed by an observed inability to concentrate urine during a water deprivation test or compatible serum osmolality, followed by an increase in urine concentration after desmopressin administration. All cats in this report were treated successfully with oral desmopressin. The dose (25–50 μg q8–12h) and the response to therapy were variable. Oral desmopressin administration may serve as an effective alternative route for cat owners who find the conjunctival or nasal application of the solution an inconvenient mode of therapy.
Surgical Management of Hypothenar and Thenar Hammer Syndromes: A Retrospective Study of 31 Instances in 28 Patients
Authors: DETHMERS R. S. M. , HOUPT P.
Published: June 2005

This retrospective study assessed the results of treatment of 29 cases of hypothenar hammer syndrome and two cases of thenar hammer syndrome. Three hands were symptom free, 15 were improved, 11 were unchanged and two were worse at a mean follow-up of 43 (range 4–60) months. Follow-up colour-coded Duplex sonography of revascularizations ( n = 27) revealed 13 patent, five occluded and one partially thrombosed grafts, seven grafts with aneurysmal dilatations and one coiled graft. Colour-coded Duplex sonography results after venous interposition graft combined with endoscopic thoracic sympathectomy were no better than venous interposition graft alone. All three arterial interposition grafts and two end-to-end-reconstructions were patent. The Duplex outcomes of the revascularizations did not correspond well with the clinical outcomes. Endoscopic thoracic sympathectomy was associated with a high rate of inconvenient side effects.
A novel total knee arthroplasty infection model in rabbits
Authors: Craig Matthew R. , Poelstra Kornelis A. , Sherrell J. Christopher , Kwon Michael S. , Belzile Etienne L. , Brown Thomas E.
Published: June 2005

Infection of biomaterial implants is an expensive and devastating complication of orthopaedic surgery historically ranging from less than 1% in primary total knee arthroplasty (TKA) to 10% in revision TKA. An in vivo animal model was developed to test the efficacy of innovative therapies for the prevention of biomaterial centered infections caused by methicillin‐resistant Staphylococcus aureus bacteria (MRSA). Twenty‐two New Zealand White rabbits were used in this study. After proper anesthesia, a stainless‐steel screw with a high molecular weight polyethylene (UHMWPE) washer was cemented in a defect created in the intra‐articular, nonarticulating portion of the lateral femoral condyle of each knee. After closure of the joint capsule, each knee was inoculated with 0, 102, 103, or 104 colony forming units (CFU) of MRSA. Animals were sacrificed after 7 days at which time joint aspirate, tissues and biomaterial samples were examined for evidence of infection.

A total of 42 knees were used for analysis. When saline was injected into the knee, 0/10 of the knees demonstrated evidence of biomaterial centered infection (with the contralateral knee receiving 104 CFU MRSA). Four of 10 knees developed a biomaterial centered infection when 102 CFU MRSA was introduced. Seven out of 10 knees developed a biomaterial centered infection when either 103 or 104 CFU MRSA was injected. No evidence of septicemia (positive blood cultures) was found in any animal. This rabbit knee model utilizes commonly employed inexpensive orthopaedic implant materials in an in vivo milieu and provides an effective method for the evaluation of treatments for biomaterial centered infections. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Novel ultrasonic evaluation of tissue‐engineered cartilage for large osteochondral defects—non‐invasive judgment of tissue‐engineered cartilage
Authors: Hattori Koji , Takakura Yoshinori , Ohgushi Hajime , Habata Takashi , Uematsu Kota , Ikeuchi Ken
Published: June 2005

Although numerous methods for regenerating articular cartilage have been investigated, the regenerated tissue showed various histological findings from hyaline‐like cartilage to fibrous tissue. Without biopsy, we are unable to know whether the cartilage regeneration method was histologically successful or not. We developed a new ultrasonic evaluation system for articular cartilage using the maximum magnitude (MM) from ultrasonic analysis. The purpose of this study was to investigate the usefulness of ultrasonic judgment of the cartilage regeneration procedure. Using our system we quantitatively evaluated tissue‐engineered cartilage in rabbit cartilage defects. The specimens were retrospectively divided into two groups on the basis of histological findings and investigated whether significant differences in ultrasonic analysis could be found between the two (group H: hyaline‐like cartilage group, successful; group F: fibrous tissue group, failure). In the ultrasonic findings, the MM was 1.11 ± 0.32 in group H and 0.65 ± 0.18 in group F and these differences were significant (P = 0.00061). Our results suggest that the ultrasonic evaluation system used in the present study is capable of judging the success or failure of cartilage regeneration procedures, and therefore, it could be a valuable tool arthroscopic diagnosis of cartilage regeneration. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
HOUSEHOLD AND COMMUNITY SOCIOECONOMIC INFLUENCES ON EARLY CHILDHOOD MALNUTRITION IN AFRICA
Authors: FOTSO JEAN-CHRISTOPHE , KUATE-DEFO BARTHELEMY
Published: June 2005

This paper uses multilevel modelling and Demographic and Health Survey data from five African countries to investigate the relative contributions of compositional and contextual effects of socioeconomic status and place of residence in perpetuating differences in the prevalence of malnutrition among children in Africa. It finds that community clustering of childhood malnutrition is accounted for by contextual effects over and above likely compositional effects, that urban–rural differentials are mainly explained by the socioeconomic status of communities and households, that childhood malnutrition occurs more frequently among children from poorer households and/or poorer communities and that living in deprived communities has an independent effect in some instances. This study also reveals that socioeconomic inequalities in childhood malnutrition are more pronounced in urban centres than in rural areas.
MIGRATION AS A DETERMINANT OF MARRIAGE PATTERN: PRELIMINARY REPORT ON CONSANGUINITY AMONG AFGHANS
Authors: WAHAB ABDUL , AHMAD MAHMUD , AKRAM SHAH SYED
Published: June 2005

Two sample populations, one refugee and one resident, were studied. The frequencies of consanguineous marriages came out to be 49·8% and 55·4%, respectively, for the refugees and the residents. Caste endogamy was dominant both in the residents and the refugees. The mean coefficient of inbreeding was calculated to be 0·0303 for the refugee population and 0·0332 for the resident population samples. First cousin marriage was the dominant type of marriage in both samples; father’s brother’s daughter (FBD) marriage was more frequent among the refugees while mother’s brother’s daughter (MBD) marriage was more frequent among the residents. Education has no decreasing effect on the incidence of consanguineous marriages. A significant difference in the pattern of marriages in the refugees is observed after the Saur Revolution of 1979.
IMPACT OF MATERNAL AGE ON BIRTH OUTCOMES: A POPULATION-BASED STUDY OF PRIMIPAROUS BRAZILIAN WOMEN IN THE CITY OF SÃO PAULO
Authors: JORGE MACHADO CARLA
Published: June 2005

The aim of this study is to analyse the impact of maternal age at first birth on low birth weight, preterm birth and low Apgar scores at one minute and at five minutes among live births delivered to primiparous Brazilian women in the city of São Paulo. Analyses were based on 73,820 birth records from the 1998 birth cohort. Logistic regression was used to assess the association between maternal age and each outcome variable, controlling for the following risk factors: delivery mode, plurality, sex, maternal education, number of prior losses, prenatal care, race, parity and community development. Maternal ages below 20 and above 30 years were significantly associated with the risks of low birth weight and preterm birth, but no association was found between maternal ages and Apgar score, with the exception that ages 15–19 reduced the odds of a low one-minute score. Even though this result seems to be inconsistent, low birth weight, preterm birth and low Apgar scores measure different dimensions of newborn well-being, and the association of each measure with maternal age is expected to diverge.
Special Issue High Performance Parallel Functional Programming
Authors: TRINDER P. W.
Published: June 2005

Engineering high-performance parallel programs is hard: not only must a correct, efficient and inherently-parallel algorithm be developed, but the computations must be effectively and efficiently coordinated across multiple processors. It has long been recognised that ideas and approaches drawn from functional programming may be particularly applicable to parallel and distributed computing (e.g. Wegner 1971). There are several reasons for this suitability. Concurrent stateless computations are much easier to coordinate, high-level coordination abstractions reduce programming effort, and declarative notations are amenable to reasoning, i.e. to optimising transformations, derivation and performance analysis.
VoDKA: Developing a Video-on-Demand Server using Distributed Functional Programming
Authors: GULIAS VICTOR M. , BARREIRO MIGUEL , FREIRE JOSE L.
Published: June 2005

In this paper, we present some experience of using the concurrent functional language Erlang to implement a distributed video-on-demand server. For performance reasons, the server is deployed in a cheap cluster made from off-the-shelf components. The demanding system requirements, in addition to the complex and ever-changing domain, suggested a highly flexible and scalable architecture as well as a quite sophisticated control software. Functional programming played a key role in the development, allowing us to identify functional abstractions throughout the system. Using these building blocks, large configurations can be defined using functional and process composition, reducing the effort spent on adapting the system to the frequent changes in requirements. The server evolved from a prototype that was the result of a project supported by a regional cable company, and it is currently being used to provide services for real-world users. Despite our initial concerns, efficiency has not been a major issue.
Shared memory multiprocessor support for functional array processing in SAC
Authors: GRELCK CLEMENS
Published: June 2005

Classical application domains of parallel computing are dominated by processing large arrays of numerical data. Whereas most functional languages focus on lists and trees rather than on arrays, SAC is tailor-made in design and in implementation for efficient high-level array processing. Advanced compiler optimizations yield performance levels that are often competitive with low-level imperative implementations. Based on SAC, we develop compilation techniques and runtime system support for the compiler-directed parallel execution of high-level functional array processing code on shared memory architectures. Competitive sequential performance gives us the opportunity to exploit the conceptual advantages of the functional paradigm for achieving real performance gains with respect to existing imperative implementations, not only in comparison with uniprocessor runtimes. While the design of SAC facilitates parallelization, the particular challenge of high sequential performance is that realization of satisfying speedups through parallelization becomes substantially more difficult. We present an initial compilation scheme and multi-threaded execution model, which we step-wise refine to reduce organizational overhead and to improve parallel performance. We close with a detailed analysis of the impact of certain design decisions on runtime performance, based on a series of experiments.
Effects of snow depth forcing on Southern Ocean sea ice simulations
Authors: Powell Dylan C. , Markus Thorsten , Stössel Achim
Published: May 2005

The aim of this study is to investigate the competing effects of a snow layer's insulation and snow‐ice formation on thermodynamic sea ice thickness growth in response to changes in precipitation. Using optimal interpolation to assimilate Special Sensor Microwave/Imager satellite‐derived snow depths into a dynamic‐thermodynamic sea ice model, we create a daily assimilated snow depth product for the years 1992–2003. The assimilated snow depths are used to adjust National Centers for Environmental Prediction/National Center for Atmospheric Research reanalysis precipitation rates which subsequently force the model's snow depths and freshwater input. These adjusted precipitation rates are used to create a best estimate snow depth climatology. This climatology provides the basis for a series of sensitivity experiments. Precipitation rates are varied from 0.0 to a doubling of the present day precipitation. Initially, sea ice volume decreases with increasing precipitation rate multiplying factor (PRMF) because of the insulation effects of a deeper snow layer. The turning point at which the insulation effect becomes balanced by the snow to ice conversion effect ranges from PRMF = 0.50 to PRMF = 0.75, depending upon the snow thermal conductivity and density. This suggests that with present‐day precipitation rates the snow effect on Southern Ocean sea ice is dominated by snow‐ice formation rather than the snow's insulation.