bluuebunny/crossref_metadata_2025 huggingface dataset:
On the growth and propagation of linear instability waves in compressible turbulent jets
Authors: Ray Prasun K. , Cheung Lawrence C. , Lele Sanjiva K.
Published: May 2009

The linear instability of compressible axisymmetric unheated jets is investigated numerically. Solutions to the linear parabolized stability equations with Reynolds-averaged Navier–Stokes mean flows are used to describe the streamwise evolution of instability waves. For transonic jets, helical (azimuthal mode number m=1) instability waves tend to exhibit the largest gain over the jet potential core followed by the m=2 and axisymmetric modes. At higher frequencies, the disparity in energy growth between the different azimuthal modes decreases, and there is a progressive reduction in energy growth as azimuthal mode number is increased from two to four. The entropic and pressure components of the total energy are compared to the kinetic energy. We find that the pressure term tends to be small, while the importance of the entropic component increases with frequency and decreases with azimuthal mode number. It is shown that the helical mode growth rates exhibit similarity when a local “mixing layer” scaling is adopted. This similarity is then used to concisely illustrate the stabilizing effect of compressibility over a broad range of frequencies and Mach numbers. Computed phase velocities are compared to measured convective velocities for unforced turbulent jets with Mach numbers Mj=0.51 and Mj=1.41. Good agreement is observed provided that the appropriate azimuthal mode number is selected.
Integrated and dispersed photon echo studies of nitrile stretching vibration of 4-cyanophenol in methanol
Authors: Ha Jeong-Hyon , Lee Kyung-Koo , Park Kwang-Hee , Choi Jun-Ho , Jeon Seung-Joon , Cho Minhaeng
Published: May 2009

By means of integrated and dispersed IR photon echo measurement methods, the vibrational dynamics of C–N stretch modes in 4-cyanophenol and 4-cyanophenoxide in methanol is investigated. The vibrational frequency-frequency correlation function (FFCF) is retrieved from the integrated photon echo signals by assuming that the FFCF is described by two exponential functions with about 400 fs and a few picosecond components. The excited state lifetimes of the C–N stretch modes of neutral and anionic 4-cyanophenols are 1.45 and 0.91 ps, respectively, and the overtone anharmonic frequency shifts are 25 and 28 cm−1. At short waiting times, a notable underdamped oscillation, which is attributed to a low-frequency intramolecular vibration coupled to the CN stretch, in the integrated and dispersed vibrational echo as well as transient grating signals was observed. The spectral bandwidths of IR absorption and dispersed vibrational echo spectra of the 4-cyanophenoxide are significantly larger than those of its neutral form, indicating that the strong interaction between phenoxide and methanol causes large frequency fluctuation and rapid population relaxation. The resonance effects in a paradisubstituted aromatic compound would be of interest in understanding the conjugation effects and their influences on chemical reactivity of various aromatic compounds in organic solvents.
Relaxation and Prigogine–Defay ratio of compressed glasses with negative viscosity-pressure dependence
Authors: Wondraczek Lothar , Krolikowski Sebastian , Behrens Harald
Published: May 2009

Differential scanning calorimetry and density measurements were employed to study relaxation processes in compressed NaAlSi3O8 and Na0.34Ca0.31Al0.96Si3.04O8 glasses with negative dependence of viscosity (η) on pressure (p). Isobaric configurational heat capacities, coefficients of thermal expansion and compressibility of the melts, and real and apparent fictive temperatures are reported for the pressure regime from 0.1 to 700 MPa and cooling rates from 0.1 to 400 K/min. The onset of glass transition, measured on the compressed glass under normal pressure, is found to shift with increasing pressure of freezing in accordance with in situ viscosity data. Based on the pressure-derivative of the compression-induced excess enthalpy (or apparent fictive temperature), a condition for which a negative dependence of fictive temperature on pressure occurs is developed. It is further shown that in this case, also dη/dp is negative. We suggest that in the region of glass transition, glasses with large Prigogine–Defay (PD) ratio have a high probability to also exhibit a negative dependence of viscosity on pressure. However, the criterion cannot be applied inversely: particularly glasses with a high sensitivity of short-range structural parameters to pressure may exhibit a relatively low PD ratio, but negative dη/dp.
Subnanosecond time response of large-area superconducting stripline detectors for keV molecular ions
Authors: Casaburi A. , Zen N. , Suzuki K. , Ejrnaes M. , Pagano S. , Cristiano R. , Ohkubo M.
Published: May 2009

A large-area (200×200 μm2) superconducting stripline detector based on a parallel configuration of superconducting Nb nanowires is presented. We show that the parallel configuration provides a smart way to control the physical nonequilibrium state induced by the molecular impacts, which allows realizing large sensitive area and subnanosecond response at the same time. The experiments were carried out with molecular ions radiation in a keV energy range. The observed rise time was below 400 ps and the relaxation time was 500 ps, the best in this class of superconducting molecular detectors.
Separation algorithm for a 2D refractive index distribution and thickness profile of a phase object by laser diode-based multiwavelength interferometry
Authors: Lee Kwangchun , Ryu Sung Yoon , Kwak Yoon Keun , Kim Soohyun , Lee Yun Woo
Published: May 2009

A separation algorithm that uses three wavelengths for the simultaneous measurement of the two-dimensional refractive index distribution and thickness profile of transparent samples is proposed. The optical system is based on a Mach–Zehnder interferometer with laser diode-based multiwavelength sources. A liquid crystal retarder is used to obtain interference images at four states with phases, and the optical phase of the object is then calculated with a four-bucket algorithm. A glass rod and several samples, including a slide glass, a glass wafer, and a cover glass are used to obtain experimental results at wavelengths of 635, 660, and 675 nm. The refractive indices of the sample are distributed with an accuracy of less than 0.0003 and the thickness profile is calculated on the basis of the measured refractive index. This result demonstrates that the proposed algorithm can be used to separate the refractive index distribution and thickness profile of samples in two dimensions.
Single chain dynamics in polymer networks: A Monte Carlo study
Authors: Nedelcu S. , Sommer J.-U.
Published: May 2009

We investigated the dynamics of single chains diffusing in cross-linked polymer networks using the three-dimensional bond fluctuation method. We considered single chain dynamics in dry polymer networks, at monomer density of 0.51, and similarly, in networks swollen up to the maximum degree of swelling. In order to compare time scales at different degrees of network swelling we calculated the single monomer relaxation time τ0, which showed a strong decrease with swelling. The scaling laws of terminal relaxation times τd and the diffusion coefficients D as function of renormalized chain length covered both the Rouse and the entangled regime. We found that the entanglement length Ne as function of monomer density of the network has similar values to those calculated for polymer melts, at the same concentration. The effect of fixed topological constraints in polymer networks on the concentration dependence of the entanglement length is discussed.
Dissociation and preservation of preantral follicles and immature oocytes from female dasyurid marsupials
Authors: Czarny N. A. , Harris M. S. , Rodger J. C.
Published: May 2009

The mammalian ovary contains numerous immature preantral follicles that are not dependent on endocrine support, unlike the more mature hormone-dependant antral follicles. Preantral follicles can be enzymatically dissociated to yield immature oocytes that survive sub-zero preservation better as they lack a temperature-sensitive meiotic spindle. These techniques are highly applicable to gamete banking, which is an urgent requirement for Australian carnivorous marsupials as several species have rapidly declining populations and risk extinction. The present study developed protocols for the transport, dissociation, preservation and culture of granulosa cell-oocyte complexes (GOC) from the ovaries of dasyurid marsupials. High viability of GOC following enzymatic dissociation is reported and it was demonstrated that GOC are of significantly better quality following refrigerated storage for 24 h compared with storage at room temperature. Oocytes from primary follicles were not damaged by cold shock or the toxicity of vitrification media and following vitrification in liquid nitrogen 69.42 ± 2.44% of oocytes were viable. However, the surrounding granulosa cells demonstrated significant damage post-thaw. These granulosa cells proliferated during a 48-h culture period resulting in significant improvements in GOC quality. The present study is a valuable step towards cryostorage of dasyurid gametes and represents fundamentally important methods by which we can contribute to the conservation of Australia’s native predators.
The evolution of color vision in nocturnal mammals
Authors: Zhao Huabin , Rossiter Stephen J. , Teeling Emma C. , Li Chanjuan , Cotton James A. , Zhang Shuyi
Published: May 2009

Nonfunctional visual genes are usually associated with species that inhabit poor light environments (aquatic/subterranean/nocturnal), and these genes are believed to have lost function through relaxed selection acting on the visual system. Indeed, the visual system is so adaptive that the reconstruction of intact ancestral opsin genes has been used to reject nocturnality in ancestral primates. To test these assertions, we examined the functionality of the short and medium- to long-wavelength opsin genes in a group of mammals that are supremely adapted to a nocturnal niche: the bats. We sequenced the visual cone opsin genes in 33 species of bat with diverse sensory ecologies and reconstructed their evolutionary history spanning 65 million years. We found that, whereas the long-wave opsin gene was conserved in all species, the short-wave opsin gene has undergone dramatic divergence among lineages. The occurrence of gene defects in the short-wave opsin gene leading to loss of function was found to directly coincide with the origin of high-duty-cycle echolocation and changes in roosting ecology in some lineages. Our findings indicate that both opsin genes have been under purifying selection in the majority bats despite a long history of nocturnality. However, when spectacular losses do occur, these result from an evolutionary sensory modality tradeoff, most likely driven by subtle shifts in ecological specialization rather than a nocturnal lifestyle. Our results suggest that UV color vision plays a considerably more important role in nocturnal mammalian sensory ecology than previously appreciated and highlight the caveat of inferring light environments from visual opsins and vice versa.
The first Korean genome sequence and analysis: Full genome sequencing for a socio-ethnic group
Authors: Ahn Sung-Min , Kim Tae-Hyung , Lee Sunghoon , Kim Deokhoon , Ghang Ho , Kim Dae-Soo , Kim Byoung-Chul , Kim Sang-Yoon , Kim Woo-Yeon , Kim Chulhong , Park Daeui , Lee Yong Seok , Kim Sangsoo , Reja Rohit , Jho Sungwoong , Kim Chang Geun , Cha Ji-Young , Kim Kyung-Hee , Lee Bonghee , Bhak Jong , Kim Seong-Jin
Published: May 2009

We present the first Korean individual genome sequence (SJK) and analysis results. The diploid genome of a Korean male was sequenced to 28.95-fold redundancy using the Illumina paired-end sequencing method. SJK covered 99.9% of the NCBI human reference genome. We identified 420,083 novel single nucleotide polymorphisms (SNPs) that are not in the dbSNP database. Despite a close similarity, significant differences were observed between the Chinese genome (YH), the only other Asian genome available, and SJK: (1) 39.87% (1,371,239 out of 3,439,107) SNPs were SJK-specific (49.51% against Venter's, 46.94% against Watson's, and 44.17% against the Yoruba genomes); (2) 99.5% (22,495 out of 22,605) of short indels (< 4 bp) discovered on the same loci had the same size and type as YH; and (3) 11.3% (331 out of 2920) deletion structural variants were SJK-specific. Even after attempting to map unmapped reads of SJK to unanchored NCBI scaffolds, HGSV, and available personal genomes, there were still 5.77% SJK reads that could not be mapped. All these findings indicate that the overall genetic differences among individuals from closely related ethnic groups may be significant. Hence, constructing reference genomes for minor socio-ethnic groups will be useful for massive individual genome sequencing.
Impairments in fear conditioning in mice lacking the nNOS gene
Authors: Kelley Jonathan B. , Balda Mara A. , Anderson Karen L. , Itzhak Yossef
Published: May 2009

The fear conditioning paradigm is used to investigate the roles of various genes, neurotransmitters, and substrates in the formation of fear learning related to contextual and auditory cues. In the brain, nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) functions as a retrograde neuronal messenger that facilitates synaptic plasticity, including the late phase of long-term potentiation (LTP) and formation of long-term memory (LTM). Evidence has implicated NO signaling in synaptic plasticity and LTM formation following fear conditioning, yet little is known about the role of the nNOS gene in fear learning. Using knockout (KO) mice with targeted mutation of the nNOS gene and their wild-type (WT) counterparts, the role of NO signaling in fear conditioning was investigated. Plasma levels of the stress hormone corticosterone were measured to determine the relationship between physiological and behavioral response to fear conditioning. Contextual fear learning was severely impaired in male and female nNOS KO mice compared with WT counterparts; cued fear learning was slightly impaired in nNOS KO mice. Sex-dependent differences in both contextual and cued fear learning were not observed in either genotype. Deficits in contextual fear learning in nNOS KO mice were partially overcome by multiple trainings. A relationship between increase in plasma corticosterone levels following footshock administration and the magnitude of contextual, but not cued freezing was also observed. Results suggest that the nNOS gene contributes more to optimal contextual fear learning than to cued fear learning, and therefore, inhibition of the nNOS enzyme may ameliorate context-dependent fear response.
Expression of KAI1/CD82 in distant metastases from estrogen receptor‐negative breast cancer
Authors: Christgen Matthias , Christgen Henriette , Heil Charlotte , Krech Till , Länger Florian , Kreipe Hans , Lehmann Ulrich
Published: May 2009

The tetraspanin protein superfamily member KAI1 suppresses tumor growth and metastasis in animal models and is downregulated in various human malignancies. In breast cancer, KAI1 is preferentially lost in estrogen receptor (ER)‐positive tumors. Interestingly, most ER‐negative primary breast cancers retain KAI1 expression. This study aimed to evaluate whether or not KAI1 is downregulated during progression to metastasis of these carcinomas. Expression of KAI1, ER, progesterone receptor, c‐ErbB2, and Ki67 was analyzed in tissue microarrays comprising a large collection of distant organ metastases from human breast cancers (n = 92) by immunohistochemistry. Results were compared with a previously characterized set of primary breast tumors (n = 209). Immunoreactivity for KAI1 was observed in one‐third of the metastases and was associated with lack of ER expression (P = 0.005). The high frequency of KAI1‐positive cases in ER‐negative primary tumors was maintained in ER‐negative metastases. Expression of KAI1 was also observed in MDA‐MB‐468 and SK‐BR‐3, two ER‐negative breast cancer cell lines of metastatic origin. Moreover, a reanalysis of independent microarray gene expression data indicated maintenance of KAI1 mRNA expression in metastases from ER‐negative breast cancers. Furthermore, in a series of matched pairs of mammary carcinomas and metachronous distant metastases, all metastases from KAI1‐positive/ER‐negative primary tumors were KAI1‐positive as well. Collectively, these findings demonstrate that the expression of KAI1 is maintained during progression to metastasis in a large proportion of ER‐negative mammary carcinomas. This has significant implications for the use of KAI1 as a clinical marker and the understanding of the metastatic process in human breast cancer. (Cancer Sci 2009; 100: 1767–1771)
Acne prevalence and beyond: acne disability and its predictive factors among Chinese late adolescents in Hong Kong
Authors: Law M. P. M. , Chuh A. A. T. , Lee A. , Molinari N.
Published: May 2009

Background. Data are lacking on the prevalence of acne, its effects on quality of life (QOL) and the treatment usage among Chinese patients in late adolescence.

Aim. To derive data about the prevalence and predictive factors of acne, the disability caused by acne and choice of treatment used by Chinese late adolescents in Hong Kong.

Methods. This was a cross-sectional study of a random sample of 389 entrants in a university in Hong Kong, using the Global Acne Grading System (GAGS) to measure the clinical severity of acne and the Cardiff Acne Disability Index (CADI) to measure QOL.

Results. The response rate was 99.3%. The prevalence of acne was of 81.5% (95% CI 77.6–85.4%) and coexisted with a high frequency of acne disability at a rate of 81.8% (95% CI 78.1–85.6%). Assessment of the clinical severity of acne did not correlate strongly with the effect on QOL (γs = 0.445, P < 0.001). Over the previous 6 months, 30.3% of subjects had used topical treatments, 3.9% had taken systemic conventional western drugs and 3.2% of the subjects had used traditional Chinese medicine. Multivariate logistic regression was used to explore the predictive factors for acne disability. Female gender (P = 0.002), higher GAGS score (P < 0.001), higher perceived stress (P = 0.01) and willingness to pay Hong Kong$15 000 (£970) for a hypothetical permanent cure (P = 0.03) were positive predictors.

Conclusions. Acne is prevalent in Hong Kong and has considerable psychological effects. The association between clinical severity and impaired QOL is not strong.
Does sulphate enrichment promote the expansion of Typha domingensis (cattail) in the Florida Everglades?1
Authors: LI SHUWEN , MENDELSSOHN IRVING A. , CHEN HONGJUN , OREM WILLIAM H.
Published: May 2009

1. The expansion of Typha domingensis into areas once dominated by Cladium jamaicense in the Florida Everglades has been attributed to altered hydrology and phosphorus enrichment, although increased concentrations of sulphate and phosphorus often coincide. The potential importance of hydrogen sulphide produced from sulphate in the expansion of Typha has received little attention. The present study aimed to quantify the comparative growth and photosynthetic responses of Cladium and Typha to sulphate/sulphide.

2. Laboratory experiments showed that Cladium is less tolerant of sulphide than Typha. Cladium was adversely affected at sulphide concentrations of approximately 0.22 mm, while Typha continued to grow well and appeared healthy up to 0.69 mm sulphide.

3. Experiments in field mesocosms provided strong support for species‐specific differences in physiology and growth. Regardless of interstitial sulphide concentrations attained, Typha grew faster and had a higher photosynthetic capacity than Cladium. However, sulphide concentrations in the mesocosms reached only 0.18 mm which, based on the hydroponic study, was insufficient to affect the growth or photosynthetic responses of either species. Nevertheless, the upper range of sulphide (0.25–0.375 mm) in Everglades’ soil is high enough, based on our results, to impact Cladium but not Typha.

4. This research supports the hypothesis that sulphide accumulation could affect plant species differentially and modify species composition. Consequently, the role of sulphate loading should be considered, in conjunction with hydroperiod, phosphorus availability and disturbances, in developing future management plans for the Everglades.
Fine root responses of mature deciduous forest trees to free air carbon dioxide enrichment (FACE)
Authors: Bader Martin , Hiltbrunner Erika , Körner Christian
Published: May 2009

1. Elevated atmospheric carbon dioxide (CO2) concentrations have often been reported to increase carbon allocation below‐ground, particularly to fine root production. However, for trees these responses have primarily been studied in young expanding systems while the evidence for late successional systems that have reached steady state above‐ and below‐ground is very limited.

2. At the Swiss Canopy Crane (SCC) experimental site, we assessed whether elevated CO2 affects fine root biomass, fine root expansion and fine root C and N concentration under mature deciduous trees (c. 100 years) exposed to 7 years of free air CO2 enrichment (FACE) in a typical near‐natural central European forest.

3. After 5 and 6 years of CO2 enrichment, both, the soil core and ingrowth core method yielded similar reductions in biomass of c. –30% under elevated CO2 for live fine roots < 1 mm diameter. In year 7 of the experiment, when fine root biomass was re‐assessed at peak season, there was no significant CO2‐effect detectable. C and N concentrations in newly produced fine roots remained unaffected by elevated CO2. Soil moisture under CO2‐exposed trees was significantly increased during rainless periods.

4. The isotopic label introduced into the system by canopy enrichment with 13C‐depleted CO2 allowed us to trace the newly assimilated carbon. After 6 years of growth at 550 ppm CO2, recent fine roots (< 1 mm, ingrowth cores) of CO2‐enriched trees consisted of 51% new carbon, suggesting a rather slow root turnover and/or slow mixing of old and new carbon in these trees.

5. Reduced tree water consumption under elevated CO2 and resultant soil water savings might cause these trees to reduce their fine root investments in a future CO2‐enriched atmosphere.

6. Our findings and those from other multi‐year experiments indicate that fine root mass in late successional systems may also be unaffected or even suppressed instead of being stimulated by elevated CO2.
Enhancement of haemostatic efficacy of plasma‐derived FVIII by formulation with PEGylated liposomes
Authors: DAYAN I. , ROBINSON M. , BARU M.
Published: May 2009

Summary.  We have shown previously that PEGylated liposomes (PEGLip) bind recombinant FVIII (rFVIII) with high affinity and specificity. This binding resulted in a significant extension of the biological activity of rFVIII as demonstrated in animal models and in clinical trials. In the present study we found that PEGLip bind plasma‐derived factor VIII (pdFVIII). PEGLip binding did not affect potency or stability in vitro and did not alter levels of FVIII activity in vivo immediately after injection. However, formulation of pdFVIII with PEGLip led to several important improvements. Twenty‐four and 30 hours after injection, FVIII activity levels were significantly higher in haemophilic mice injected with PEGLip‐pdFVIII than in mice injected with standard pdFVIII. Half life, area under the curve and mean residence time were increased while clearance was decreased. In vivo efficacy was evaluated in a tail vein transection assay performed in haemophilic mice. Prophylactic treatment with PEGLip‐pdFVIII was much more effective in prolonging survival in this assay than similar treatment with standard pdFVIII. These results suggest that formulation of pdFVIII with PEGLip has the potential to improve patient care by prolonging the biological efficacy of pdFVIII and reducing the frequency of FVIII infusions.
Factor 5 mutation profile in German patients with homozygous and heterozygous factor V deficiency
Authors: DELEV D. , PAVLOVA A. , HEINZ S. , SEIFRIED E. , OLDENBURG J.
Published: May 2009

Summary.  Coagulation factor V (FV) plays an important role in the blood coagulation cascade as part of the prothrombinase complex. FV deficiency is a rare autosomal recessive bleeding disorder with variable phenotypic expression. Thus, our study reports 39 patients with FV deficiency. In 36 cases, we were able to identify a causative mutation. Of these, 20 patients were heterozygous for the identified mutation, nine were homozygous, six were compound heterozygous and one proband was pseudohomozygous. In the remaining patients, no mutation was found. A total of 42 genetic alterations (of which 33 were uniquely different mutations), comprising 19 missense mutations, eight nonsense mutations, four small deletions and two splice site mutations, were identified by this study. Twenty‐three of these were novel sequence variations not previously described in the literature. Interestingly, all changes found in exon 13 resulted in null alleles as either nonsense mutations or small deletions. The overall profile of these new mutations corresponds well with the data published in the F5 database. In those cases, where data were available, information on FV activity levels and/or bleeding history is given. Interestingly, some patients with mild FV deficiency (FV:C about 50% of normal) also exhibited bleeding episodes. Our data substantially contribute to the broadening and better understanding of the FV deficiency mutational spectrum. Identifying the molecular basis of mutations underlying this rare coagulation disorder will allow more insight into the mechanisms involved in the variable clinical phenotypes of patients with FV deficiency.
From malaria control to eradication: The WHO perspective
Authors: Mendis Kamini , Rietveld Aafje , Warsame Marian , Bosman Andrea , Greenwood Brian , Wernsdorfer Walther H.
Published: May 2009

Efforts to control malaria have been boosted in the past few years with increased international funding and greater political commitment. Consequently, the reported malaria burden is being reduced in a number of countries throughout the world, including in some countries in tropical Africa where the burden of malaria is greatest. These achievements have raised new hopes of eradicating malaria. This paper summarizes the outcomes of a World Health Organization’s expert meeting on the feasibility of such a goal. Given the hindsight and experience of the Global Malaria Eradication Programme of the 1950s and 1960s, and current knowledge of the effectiveness of antimalarial tools and interventions, it would be feasible to effectively control malaria in all parts of the world and greatly reduce the enormous morbidity and mortality of malaria. It would also be entirely feasible to eliminate malaria from countries and regions where the intensity of transmission is low to moderate, and where health systems are strong. Elimination of malaria requires a re‐orientation of control activity, moving away from a population‐based coverage of interventions, to one based on a programme of effective surveillance and response. Sustained efforts will be required to prevent the resurgence of malaria from where it is eliminated. Eliminating malaria from countries where the intensity of transmission is high and stable such as in tropical Africa will require more potent tools and stronger health systems than are available today. When such countries have effectively reduced the burden of malaria, the achievements will need to be consolidated before a programme re‐orientation towards malaria elimination is contemplated. Malaria control and elimination are under the constant threat of the parasite and vector mosquito developing resistance to medicines and insecticides, which are the cornerstones of current antimalarial interventions. The prospects of malaria eradication, therefore, rest heavily on the outcomes of research and development for new and improved tools. Malaria control and elimination are complementary objectives in the global fight against malaria.
Mycophenolate mofetil: effects on cellular immune subsets, infectious complications, and antimicrobial activity
Authors: Ritter M.L. , Pirofski L.
Published: May 2009

Abstract:Mycophenolate mofetil (MMF) is one of the most frequently used immunosuppressive drugs in solid organ transplant recipients. MMF is an inhibitor of inosine‐5′‐monophosphate, and is able to preferentially inhibit B‐cell and T‐cell function. The immunosuppressive abilities of MMF have made it one of the most successful anti‐rejection drugs in transplant patients, but patients also appear to have increased susceptibility to infections, specifically cytomegalovirus and BK virus. Despite its association with an increased risk of infection, MMF has also exhibited antimicrobial activity against pathogens including hepatitis C,Pneumocystis jirovecii, and human immunodeficiency virus. A thorough understanding of the functions of MMF on the immune system and interaction with infectious pathogens could be helpful in implementing preventative strategies against opportunistic infections in transplant patients.
Targeted monitoring of patients at high risk of post‐transplant lymphoproliferative disease by quantitative Epstein–Barr virus polymerase chain reaction
Authors: Omar H. , Hägglund H. , Gustafsson‐Jernberg Å. , LeBlanc K. , Mattsson J. , Remberger M. , Ringdén O. , Sparrelid E. , Sundin M. , Winiarski J. , Yun Z. , Ljungman P.
Published: May 2009

Background. Epstein–Barr virus (EBV)‐associated post‐transplantation lymphoproliferative disease (PTLD) is a serious complication after allogeneic stem cell transplantation (SCT). The likelihood of PTLD is increased in the presence of specific risk factors. Monitoring of EBV DNA load and early administration of rituximab in patients with high EBV loads is recommended for high‐risk patients.

Methods. Patients at high risk of EBV‐associated PTLD were defined as those showing an EBV serological mismatch between donor and recipient, those with lymphoma, those given cord blood grafts, and those with primary EBV disease before SCT. High‐risk patients were prospectively monitored by weekly measurement of EBV DNA by quantitative polymerase chain reaction assay, and rituximab was given when the EBV load reached 10,000 copies/mL or symptoms were suggestive of EBV disease. During the study period (July 2005 to the end of June 2007) 131 patients underwent SCT, of whom 53 had high risk factors. A historical control group transplanted between January 2003 to the end of June 2005 was retrospectively used to evaluate the effect of the prospective monitoring strategy.

Results. Of the patients, 30% were positive for EBV DNA at least once; 10% of patients with EBV DNAemia developed PTLD. Risk factors of EBV DNAemia were younger age (P=0.04), receiving transplants from mismatched family or unrelated donors (P=0.01), and acute graft‐versus‐host disease grades II–IV (P=0.001). The overall frequency of PTLD was 3%; 5.7% in the high‐risk group and 1.3% in the standard‐risk group. Previous splenectomy (P=0.046) was the only significant risk factor associated with PTLD. In the control group, 6 of 150 patients (4%) developed PTLD; 5/53 (9.4%) in the high‐risk group and 1/97 (1%) in the standard‐risk group. Human leukocyte antigen‐mismatched donors (P<0.01) and EBV‐positive donors/EBV‐negative recipients (P=0.01) had a significant impact on the risk of PTLD.

Conclusion. A targeted monitoring strategy among patients at a high risk of EBV‐associated PTLD might be helpful to decrease the risk of development of PTLD. However, larger prospective studies are needed to verify this hypothesis.
Lamprey GnRH‐III Releases Luteinizing Hormone but not Follicle Stimulating Hormone in Pigs
Authors: Barretero‐Hernandez R , Vizcarra JA , Bowen A , Galyean M
Published: May 2009

Contents

The effect of exogenous administration of lamprey GnRH‐III (IGnRH‐III) on gonadotropin secretion was evaluated in pigs. Six crossbred barrows (82.4 ± 3.5 kg body weight) were assigned randomly to a replicated 3 × 3 Latin square design to evaluate the effect of 0.1, 1.0 or 10.0 μg/kg body weight of exogenous IGnRH‐III on LH and FSH secretion. To facilitate blood collection and infusion of IGnRH‐III, barrows were catheterized in the jugular vein 1 day before initiation of experiments. Blood samples were taken at 10‐min intervals for 6 h, starting 2 h before treatments were applied. Relative concentrations of LH and FSH were calculated by obtaining the ratio of the average concentration of each hormone 2 h after infusion divided by the average concentration during the 2 h before infusion. Relative concentrations of FSH after IGnRH‐III infusion did not influence mean concentration of FSH at any of the doses; yet 10.0 μg/kg body weight had a significant effect on LH secretion (p < 0.01). Relative concentrations of LH averaged 1.2, 1.0 and 3.0 ng/ml (for doses of 0.1, 1.0 and 10.0 μg/kg body weight of IGnRH‐III respectively). Only a dose of 10 μg/kg body weight elicited a significant LH increase that was associated with exogenous IGnRH‐III infusion. We conclude that IGnRH‐III is a weak GnRH agonist and at high doses, IGnRH‐III has the ability to release LH but not FSH in barrows.
Anti‐hepatitis B virus treatment guided by long‐term virus kinetics stepwise tracing
Authors: Yang Jin , Cai Ting , Lou Guo‐Qiang
Published: May 2009

Background and Aims:  Biphasic modeling of viral kinetics provided valuable information to rapidly assess potential antiviral regimens during the beginning of therapy, but has not been performed over the long term.

Methods:  In 11 chronic hepatitis B patients with lamivudine treated per day, the model with delay time was applied to examine phase transition and analyze viral kinetics parameters.

Results:  Viral decay conformed to a biphasic mode during the first 4 weeks, with the complex profile appeared in the later period. Lamivudine treatment resulted in a mean log hepatitis B virus (HBV)‐DNA decline of 1.77 ± 0.55 after 4 weeks and 3.79 ± 1.70 log after 24 weeks. The median effectiveness of blocking viral replication was 96% (range, 89–99%). The median rate of free virus clearance and infected cell loss was 1.1/day and 0.03/day, respectively. Through phase transition determination and stepwise modeling process, viral kinetics were evaluated for complex decay profile during long‐term therapy. Moreover, with the abnormal kinetics tracked, an occasion of add‐on combined therapy was developed to treat patients with emerging virus mutants.

Conclusion:  The present study using mathematical modeling of viral decay may be a useful approach to evaluate optimal individualized therapy for HBV infection in a continuous long‐term manner.
IL‐18 serum level and IL‐18 promoter gene polymorphism in Iranian patients with gastrointestinal cancers
Authors: Haghshenas Mohammad Reza , Hosseini Seyed Vahid , Mahmoudi Mahmoud , Saberi‐Firozi Mehdi , Farjadian Shirin , Ghaderi Abbas
Published: May 2009

Background and Aim:  Interleukin (IL)‐18 level and association of its two promoter gene polymorphisms at −607C/A and −137G/C positions were investigated in Iranian patients with gastrointestinal (GI) cancers.

Methods:  232 cases of GI cancers and 312 healthy controls were enrolled. Serum level of IL‐18 was measured by enzyme linked immunosorbent assay (ELISA) and genotyping of IL‐18 gene polymorphisms were assessed by allele‐specific polymerase chain reaction (PCR).

Results:  There was a significant difference in the frequency of −137 G/C genotype between patients with stomach or colorectal cancers and control group. In patients with colorectal cancer, the frequency of the −607AA/−137GC genotype combination in unwell‐differentiated cases was more than those with well‐differentiated cancer. Haplotype analysis showed that in patients with stomach cancer −607C/−137C and −607A/−137G and in patients with colorectal cancer −607C/−137C were decreased compared with control group, and this difference reached statistical significance. Serum analysis revealed that the mean IL‐18 serum level in stomach and colorectal cancer before and after surgical operation was significantly higher than healthy volunteers. Postoperative IL‐18 level for all patients with colorectal cancer was significantly decreased compared with the levels before surgery.

Conclusion:  Results of this investigation suggests that Single Nucleotide Polymorphism (SNP) at position −137 G/C and haplotype frequency may play a role in predisposition of Iranian patients to stomach and colorectal cancers. In addition, increasing serum IL‐18 level may have clinical importance as a diagnostic marker in patients with stomach and colorectal cancer.
Dai‐kenchu‐to attenuates rat sinusoidal obstruction syndrome by inhibiting the accumulation of neutrophils in the liver
Authors: Narita Masato , Hatano Etsuro , Tamaki Nobuyuki , Yamanaka Kenya , Yanagida Atsuko , Nagata Hiromitsu , Asechi Hiroyuki , Takada Yasutsugu , Ikai Iwao , Uemoto Shinji
Published: May 2009

Background and Aim:  Sinusoidal obstruction syndrome (SOS) is drug‐induced liver injury that occurs in patients who receive hematopoietic cell transplantation and oxaliplatin‐contained chemotherapy. The aim of study was to investigate the pharmacological treatment of SOS using a traditional Japanese medicine, Dai‐kenchu‐to (DKT).

Methods:  Male Sprague‐Dawley rats were treated with monocrotaline (MCT) to induce SOS. The rats were divided into three groups: control, MCT and MCT+DKT groups. In the MCT+DKT group, DKT was gavaged at 12 h after MCT treatment and given every 12 h until the end of the protocol. The rats of MCT group were treated with water instead of DKT. At 48 h after MCT treatment, blood and liver samples were collected.

Results:  In the MCT+DKT group, the macroscopic and histological findings revealed liver congestion, sinusoidal alteration and the destruction of sinusoidal lining, which were comparable with those of the MCT group. However, the area of hepatic necrosis and serum AST levels significantly decreased in the MCT+DKT group compared with those of the MCT group. Treatment with DKT resulted in the reduction of neutrophil accumulation, myeloperoxidase activity and the expression of cytokine‐induced neutrophil chemoattractant (CINC) and intracellular adhesion molecule‐1 (ICAM‐1) mRNA in the liver compared with those of the MCT group. Treatment with processed ginger, one of the ingredients in DKT, resulted in similar effects to those shown by DKT.

Conclusions:  Dai‐kenchu‐to attenuates MCT‐induced liver injury by preventing neutrophil‐induced liver injury through blockage of upregulation of CINC and ICAM‐1 mRNA level.
Inhibition of oxidative stress and apoptosis enables extended maintenance of integrity and function of isolated hepatocytes in suspension
Authors: Wigg Alan J , Barritt Greg J , Young Graeme P , Phillips John W
Published: May 2009

Aims:  Isolated hepatocytes in suspension may offer an alternative culture system for bioartificial liver devices. However, maintenance of isolated hepatocyte suspensions in conventional media leads to rapid loss of cell integrity. The aim of this study was to develop a modified medium to better maintain hepatocyte integrity.

Methods:  Isolated rat hepatocytes were prepared by collagenase digestion. Hepatocytes were purified in a Percoll gradient, suspended in bicarbonate buffered isotonic saline supplemented with d‐α‐tocopherol succinate and glucose and medium changed at 24 h (modified medium). The properties of cells treated this way were compared with those prepared by collagenase digestion and suspension in bicarbonate buffered isotonic saline (basic medium). Both media were maintained at 30°C for 48 h on an orbital shaker. Markers for oxidative stress, apoptosis and metabolic function were measured enzymatically. Cell morphology was assessed by electron microscopy.

Results:  When compared to collagenase‐isolated hepatocytes maintained in basic medium, hepatocytes purified by Percoll (Amersham Biosciences, Castle Hill, Australia) and maintained in modified medium demonstrated significantly increased glutathione (GSH) and GSH : glutathione disulphide (GSSH) ratios, decreased lipid peroxidation product formation, decreased caspase‐3 protease activity, reduced uptake of trypan blue and loss of lactate dehydrogenase (LDH) and increase preservation of cellular adenosine triphosphate concentration ([ATP]), urea synthesis, ammonia removal and glycogen content. Cell morphology was substantially preserved following 48 h of maintenance in the modified medium.

Conclusions:  The use of Percoll and modified medium reduces cell injury and apoptosis and greatly improves maintenance of cell function and morphology. The modifications reported here and the use of isolated hepatocyte suspensions in bioartificial liver devices are worthy of further investigation.
Resumption of oral intake following percutaneous endoscopic gastrostomy
Authors: Paramsothy Sudarshan , Papadopoulos George , Mollison Lindsay C , Leong Rupert W L
Published: May 2009

Background and Aims:  Percutaneous endoscopic gastrostomy (PEG) provides enteral nutrition to patients who cannot swallow. Few studies have prospectively evaluated its long‐term outcomes or eventual resumption of oral intake.

Methods:  Consecutive PEG patients were prospectively recruited from a tertiary hospital over 12 months and followed until all had met the primary endpoints of death or resumption of oral diet with PEG extubation. Data was collected by standardised periodic phone interview.

Results:  Forty patients (24 males, median age 74 years) were followed for up to 8.4 years (median 5.3 months, interquartile range [IQR] 13.6 months). The end‐of‐study mortality rate was 70% (median 6.8 months, IQR 19.9 months) and the only predictor of mortality was head injury as the indication for PEG (Cox regression HR 5.90, 95% CI: 1.2–28.4). At two years following PEG, 30% of patients had resumed oral intake (median 2.9 months, IQR 7.2 months) and 19% remained on PEG‐feeding. Predictors of resumption of oral intake were the ability to tolerate some oral intake at 3 months (HR: 248.5, 95% CI: 8.7–7065.3) and 6 months (HR: 6.3, 95% CI: 1.03–38.9) but not at 12 months. Cumulative survival was highest for ear nose and throat (ENT) tumour and worst for acute head injury (log rank P = 0.048).

Conclusions:  Half of all PEG patients remained alive at 2 years using PEG or have resumed full oral intake. A supervised trial of oral intake at 3 or 6 months may help predict eventual resumption of per oral diet.
Effects of formula supplementation in breast‐fed infants with failure to thrive
Authors: Hren Irena , Mis Nataša Fidler , Brecelj Jernej , Čampa Andreja širca , Sedmak Marjeta , Kržišnik Ciril , Koletzko Berthold
Published: May 2009

Background:  The aim of the present study was to assess whether formula supplementation of infants with failure to thrive can improve underweight without jeopardizing breast‐feeding.

Methods:  In a prospective intervention study 31 term exclusively breast‐fed infants were studied, who were admitted to hospital at an age of 28–99 days with failure to thrive (≤40% expected weight gain for age and/or bodyweight ≤10th percentile for age) without underlying disease. Infant formula was offered ad libitum after each breast‐feeding, while continued breast‐feeding was supported.

Results:  Energy intake per day increased from 352 ± 111 kJ/kg (mean ± SD) at study start to 587 ± 115 kJ/kg (P < 0.001, days 1–3 of supplementation) and 501 ± 99 kJ/kg (days 29–31; P < 0.001 vs study entry). Twenty‐five infants continued to be partially (n = 21) or fully (n = 4) breast‐fed. Human milk intake decreased from 476 ± 163 g/day (study days 1–3) to 349 ± 285 g/day (study days 29–31; P < 0.01). The contribution of breast milk to total milk intake decreased from 100% to 42 ± 35% (P < 0.001). Supplementation over 31 days led to increased weight (0.98 [0.70], standard deviation scores [SDS]), length (+0.40 [0.41] SDS) and head circumference (+0.59 [0.93] SDS).

Conclusions:  One month of formula supplementation successfully improved growth in 72% of infants with failure to thrive on human milk feeding. Breast‐feeding was maintained in 81% of infants.
Effect of transfusion on the venous blood lactate level in very low‐birthweight infants
Authors: Takahashi Daijiro , Matsui Miyu , Shigematsu Reiko , Sato Tetsuji , Miyaji Ryosuke , Sakai Michio , Shirahata Akira
Published: May 2009

Background:  In recent years the blood lactate level can be easily and quickly measured with a small amount of blood, and the availability of an arterial blood lactate level has been reported as an indicator of oxygen deficit in adults. To determine whether venous blood lactate level can serve as such a marker for determining the indications for transfusion, blood lactate and hemoglobin level were monitored before and after transfusion.

Methods:  The study subjects consisted of 12 very low‐birthweight infants admitted to the neonatal intensive care unit and who had transfusion between June 2005 and June 2007. The data on the blood lactate and hemoglobin were collected retrospectively by referring to the clinical records.

Results:  A total of 18 transfusions was performed. There was no significant relationship between venous blood lactate and hemoglobin concentration before transfusion. The subjects were classified into two groups according to the lactate level before transfusion: 3.3 mmol/L and <3.3 mmol/L. In the high‐lactate group the lactate decreased significantly after transfusion (P < 0.01) and it continued to decrease thereafter. In the low‐lactate group, however, the lactate remained unchanged.

Conclusions:  Venous blood lactate measurements may offer some additional information regarding the optimal time for performing a transfusion. To the authors’ knowledge this is the first report to study the changes in lactate levels using venous blood sampling in red blood cell transfusion in very low‐birthweight infants.
The Rapoport effect is detected in a river system and is based on nested organization
Authors: Beketov Mikhail A.
Published: May 2009

Aim  To test two hypotheses: (i) the Rapoport effect is valid for a river continuum, particularly regarding the altitudinal distribution of mayflies over the large‐scale continuum from alpine stream to medium‐sized lowland river, and (ii) the observed Rapoport effect is based on high nestedness of the meta‐assemblage, implying the presence of a common species pool and species‐thinned nested subsets.

Location  Geometric centre of Eurasia, south‐western Siberia, Russia.

Methods  Regression analysis of breadth and midpoints of species altitudinal ranges, species richness and altitude. Comparison of the observed patterns with the null model predicted by the mid‐domain effect and conventional null hypothesis. Nestedness analysis.

Results  The Rapoport effect was explicitly demonstrated: species altitudinal ranges expanded with increase in the ranges’ midpoints and average per‐altitude ranges increased with increase in altitude and concurrent decrease in species richness. The significance of each trend was confirmed with respect to both the null models applied. Nestedness analysis has revealed that the observed Rapoport effect is based on nested organization of the meta‐assemblage over the river altitudinal/longitudinal gradient: a common species pool at low (but not the lowest) altitudes and nested subsets of this pool at higher altitudes.

Main conclusions  This study for the first time credibly shows the altitudinal Rapoport effect in freshwaters. This finding demonstrates cross‐habitat‐type consistency of the Rapoport effect, but does not suggest that the Rapoport effect is an obligatory attribute of river systems or lotic organisms. High nestedness underlying the observed Rapoport effect together with some previous studies indicate that the Rapoport effect in altitudinal and bathymetric gradients in general may be based on nested organization. The study highlights a deficiency of cross‐habitat‐type analyses of macroecological patterns (i.e. over terrestrial, freshwater and marine habitats).