bluuebunny/crossref_metadata_2025 huggingface dataset:
Lost in a World of Books: Reading and Identity in Pre‐War Japan
Authors: Townsend Susan C.
Published: June 2007

This paper forms part of a Literature Compass cluster on Modern Book History. The full cluster is made up of the following articles:

‘Between Then and Now: Modern Book History’, Kate Longworth, Literature Compass 4 (2007), 10.1111/j.1741‐4113.2007.00474.x.

‘Ezra Pound's Cantos: A Compact History of Twentieth‐Century Authorship, Publishing and Editing’, Mark Byron, Literature Compass 4 (2007), 10.1111/j.1741‐4113.2007.00475.x.

‘ “The Making of the Book”: Roy Fisher, the Circle Press and the Poetics of Book Art’, Matthew Sperling, Literature Compass 4 (2007), 10.1111/j.1741‐4113.2007.00476.x.

‘Bakhtinian “Journalization” and the Mid‐Victorian Literary Marketplace’, Dallas Liddle, Literature Compass 4 (2007), 10.1111/j.1741‐4113.2007.00477.x.

‘Manuscript in Print: The Materiality of Alternative Comics’, Emma Tinker, Literature Compass 4 (2007), 10.1111/j.1741‐4113.2007.00478.x.

‘Lost in a World of Books: Reading and Identity in Pre‐War Japan’, Susan C. Townsend, Literature Compass 4 (2007), 10.1111/j.1741‐4113.2007.00479.x.

***

This article considers the rapidly changing readership patterns in Japan during the late Meiji (1868–1912) and particularly the Taishō (1912–26) period, generally considered a brief interlude of cultural flowing and democratic promise. Paramount among the evidence is the autobiography of the Japanese philosopher Miki Kiyoshi (1897–1945), also an important source for historians of so‐called ‘Taishō democracy’. Miki's Wanderings through the World of Books (Dokusho Henreki), published in 1941, documents the social, cultural and political impact of Russian and Western European literature and philosophy upon a select and privileged group of young Japanese men and women born around the 1890s. Miki's lesser known, posthumously published confessional The Unspoken Philosophy (Katararezaru Tetsugaku) (1919), however, reveals the full emotional impact of Japan's encounter with foreign culture. Other essays and commentaries which Miki published in the mid‐1930s provide clues to the question of why the ‘Taishō generation’ failed to stem the rising tide of militarism in the 1930s. Through a detailed consideration of my translations of these Japanese texts, I argue that the acute anxiety and identity crisis which Miki's generation experienced before the Pacific War was a symptom of their immersion in and internalisation of Western European thought and culture.
A Tropical, Gregariously Semelparous Bamboo Shows No Seed Dormancy
Authors: Bellairs Sean M. , Franklin Donald C. , Hogarth Nicholas J.
Published: June 2007

Seed dormancy may be disadvantageous for gregariously semelparous plants because it disrupts the high levels of reproductive synchrony necessary for success. Alternately, it may provide a bet‐hedging option for an otherwise ‘all eggs in the one basket’ reproductive strategy. Rapid germination of seeds upon hydration has been demonstrated for a range of tropical, semelparous bamboos, but the fate of seeds that failed to germinate promptly has been inadequately investigated. We demonstrate prompt germination of seeds upon hydration and the absence of a dormant seedbank in a long‐lived, gregariously semelparous bamboo, Bambusa arnhemica, from monsoonal northern Australia. However, we refute the suggestion that seed dormancy is necessarily maladaptive in a gregariously semelparous plant. Rather, caryopsis dormancy may not be possible in a seasonally moist tropical climate. Given an inability to adjust or bet‐hedge their germination, bamboo germinants must cope with the vagaries of the monsoonal climate, a factor that may contribute to the general restriction of bamboos to regions with higher rainfall.
Successful Adoption of a School‐Based Telemedicine System
Authors: Mackert Michael , Whitten Pamela
Published: June 2007

Background:  Telemedicine, the provision of healthcare at a distance via telecommunication technology, has been used to address a wide range of health concerns in a variety of settings. Given the challenges schools face in keeping students healthy, telemedicine could be viewed as a mechanism to provide healthcare services directly to students in schools. This research focuses on a school‐based telemedicine project in Kansas, a project of the Kansas University Medical Center (KUMC) called TeleKidcare. TeleKidcare makes use of interactive television systems located in the school health office to let school nurses interact with KUMC physicians to provide consultations for sick children.

Methods:  A case study of the TeleKidcare system was conducted to investigate critical factors of success in the project; data was collected primarily through personal interviews (N = 23), with project documentation serving to corroborate the interview data.

Results:  Results point to factors to success both in the planning and operational phases of TeleKidcare. Examples of such factors include: (a) recognizing, and accounting for, the fact that different sites in a multisite telemedicine system might adopt the system in different ways; (b) the importance of involving actual users in the planning of the system, to ensure it could be built into the everyday work of school nurses; and (c) the importance of unintended appropriation of the technology by school nurses, using the system in ways that were completely unplanned.

Conclusion:  The lessons learned from TeleKidcare’s success can help researchers and practitioners considering similar systems in other schools.
Ultrafast Energy Delocalization and Electron Transfer Dynamics in 2‐Aminopurine‐Containing Trinucleotides†
Authors: Wang Qiang , Raytchev Milen , Fiebig Torsten
Published: June 2007

The fate of electronically excited states in DNA base stacks is of tremendous importance for subsequent photochemical damage reactions in the genome. In this study we present a femtosecond broadband pump‐probe study on the adenine isomer 2‐aminopurine (Ap) incorporated into trinucleotides. After selective excitation of Ap we can monitor energy delocalization between neighboring Ap moieties as well as excited state electron transfer, depending on the sequence of the trinucleotide. Our results establish the time scale for intrastand excimer formation and reveal the lifetime of the excimer state.
Loss of MSH2 protein expression is a risk factor in early stage cervical cancer
Authors: Nijhuis E R , Nijman H W , Oien K A , Bell A , ten Hoor K A , Reesink-Peters N , Boezen H M , Hollema H , van der Zee A G J
Published: June 2007

Background:Loss of mismatch repair (MMR) gene expression has been associated with fewer metastases and improved prognosis in various tumour types.

Aims:To evaluate the predictive and prognostic significance of loss of MMR protein MSH2 in early stage cervical cancer.

Methods:Specimens from 218 consecutive patients with early stage, surgically treated cervical cancer were analysed. Median age was 42 years (interquartile range 35–53). International Federation of Gynecology and Obstetrics (FIGO) stages were IB1 (57%), IB2 (25%) and IIA (18%). Histology was 70% squamous cell, 6% adenosquamous and 24% adenocarcinoma. Pelvic lymph node metastasis was present in 66 (30%) patients. Median follow-up was 5.2 years (interquartile range 2.5–7.9). Tissue microarrays (TMAs) were constructed containing three cores of paraffin-embedded tumour per case. MSH2 expression was assessed by immunohistochemistry on TMAs and full sections.

Results:In TMAs MSH2 expression could be analysed in 184/218 (84%) tumours. Loss of MSH2 was observed in 58/184 (32%) tumours, with a moderately strong concordance between TMAs and full sections (κ = 0.47). In tumours with loss of MSH2, pelvic lymph node metastasis and cancer invasion beyond 10 mm were more frequent (48% vs 25%, and 59% vs 37%, respectively). However, loss of MSH2 expression was not related to recurrence or survival.

Conclusion:TMAs are powerful tools for high throughput screening of biological markers for prognostic value in cervical cancer. Absence of MSH2 expression is associated with a high-risk profile in early stage cervical cancer, but does not predict lymph node status with sufficient accuracy to be used in the clinic.
ON A ROBUST ALGORITHM FOR HEART SOUND SEGMENTATION
Authors: ARI SAMIT , SAHA GOUTAM
Published: June 2007

The detection of heart diseases from heart sound signals needs an efficient segmentation algorithm to properly identify the location of the first and second heart sounds. This in turn helps in characterizing murmurs present in the cardiac cycles and the pathological condition by providing an appropriate time reference. The work presented here needs only the average heart rate as discrete auxiliary information that can be easily provided, unlike most of the methods which require the electrocardiography (ECG) signal as a continuous auxiliary signal in a complex setup. The algorithm was tested on 34 pathological cases and normal heart sound for a variety of sampling frequencies, recording environments, and age groups of subjects. It was found to give an overall accuracy of 95.51%. The robustness of the algorithm against additive white Gaussian noise contamination is also presented, and the noise immunity of various diseases for correct segmentation is established through this study.
SOME MATHEMATICAL TOOLS FOR THE ANALYSIS OF BIOLOGICAL SIGNALS
Authors: NICHELATTI MICHELE , PETTAZZONI PAOLO , PALLOTTI GIOVANNI
Published: June 2007

The paper presents an informal review of some techniques available for signal analysis. In the interpretation of biomedical signals, the individuation of hidden transient phenomena in the spectrum can have a crucial role for diagnostic purposes. Since most biological signals are nonstationary, the Fourier transform is not sufficient to detect possible transient phenomena in the spectrum; therefore, some improvements in the Fourier transform technique have been carried out by means of window functions in the transformation kernel. Some of the most important features of recent developments in signal analysis are discussed here, with special focus on the uncertainty principle governing any time–frequency analysis.
COMPUTER SIMULATION OF COTRANSMISSION BY EXCITATORY AMINO ACIDS AND ACETYLCHOLINE IN THE ENTERIC NERVOUS SYSTEM
Authors: MIFTAHOF ROUSTEM , AKHMADEEV N. R.
Published: June 2007

The role of cotransmission by α-amino-3-hydroxy-5-methyl-4-isoxalose propionic acid (AMPA), L-aspartate, N-methyl-D-aspartate (NMDA), and acetylcholine (ACh) as well as the coexpression of AMPA, NMDA, and nicotinic ACh (nACh) receptors on the electrophysiological activity of the primary sensory (AH) and motor (S) neurons of the enteric nervous system are numerically assessed. Results of computer simulations showed that AMPA and L-Asp alone can induce fast action potentials of short duration on AH and S neurons. Costimulation of nACh and AMPA receptors on the soma of the S neuron resulted in periodic spiking activity. A characteristic biphasic response was recorded from the AH neuron after coactivation of AMPA and NMDA receptors. Glutamate alone acting on NMDA receptors caused prolonged depolarization of the AH neuron and failed to depolarize the S neuron. Cojoint stimulation of the AMPA or nACh receptors was required to produce the effect of glutamate. The overall electrical response of neurons to the activation of NMDA receptors was long-term depolarization. Acetylcholine, AMPA, and glutamate acting alone or cojointly enhanced phasic contraction of the longitudinal smooth muscle. Treatment of neurons with AMPA, NMDA, and nACh receptor antagonists revealed intricate properties of the AH and S neurons. Application of MK-801, D-AP5, and CPP reduced the excitability of the AH neuron and totally abolished electrical activity in the S neuron. The information gained into the cotransmission by excitatory amino acids and acetylcholine in the enteric nervous system may be beneficial in the development of novel effective therapeutics to treat diseases associated with altered visceral nociception, i.e. irritable bowel syndrome.
2-ρ-DERIVATIONS ON A ρ-ALGEBRA AND APPLICATIONS TO THE QUATERNIONIC ALGEBRA
Authors: CIUPALĂ CĂTĂLIN
Published: June 2007

In this paper, we introduce 2-ρ-derivations on a ρ-algebra A, and define 2-linear connections on a ρ-bimodule M over A using these 2-derivations. Then we introduce and study the curvature of a linear connection. Our results are applied to the particular case of the quaternionic algebra ℍ.
ON THE RELATION BETWEEN MASS AND CHARGE: A PURE GEOMETRIC APPROACH
Authors: WANAS M. I.
Published: June 2007

A new solution to the field equations of the generalized field theory, constructed by Mikhail and Wanas in 1977, has been obtained. The geometric structure used, in the present application, is an absolute parallelism (AP)-space with spherical symmetry (type FIGI). The solution obtained represents a generalized field outside a charged massive central body. Two schemes have been used to get the physical meaning of the solution: The first is related to the metric of the Riemannian space associated with the AP-structure. The second is connected to a covariant scheme known as Type Analysis. It is shown that the dependence on both schemes for interpreting the results obtained, is better than the dependence on the metric of the Riemannian space associated with the AP-structure.

In general, if we consider the solution obtained as representing a geometric model for an elementary charged particle, then the results of the present work can be summarized in the following points. (i) It is shown that the mass of the particle is made up of two contributions: the first is the gravitational contribution, and the second is the contribution due to the existence of charge. (ii) The model allows for the existence of a charged particle whose mass is completely electromagnetic in origin. (iii) The model prevents the existence of a charged massless particle. (iv) The electromagnetic contribution, to the mass, is independent of the sign of the electric charge. (v) It is shown that the mass of the electron (or a positron) is purely made of its charge.
Tyrosine 687 Phosphorylated Alzheimer’s Amyloid Precursor Protein Is Retained Intracellularly and Exhibits a Decreased Turnover Rate
Authors: Rebelo Sandra , Vieira Sandra Isabel , Esselmann Hermann , Wiltfang Jens , da Cruz e Silva Edgar F. , da Cruz e Silva Odete A.B.
Published: June 2007

Tyrosine 687 (Y687) of the Alzheimer’s amyloid precursor protein (APP) was shown to be phosphorylated in the brains of Alzheimer’s disease patients. This residue lies within a typical endocytosis consensus motif commonly found in molecules with receptor functions, strongly suggesting a potential role for APP in signal transduction. Consequently, the work here described addressed how phosphorylation of Y687 may be affecting APP in terms of its proteolytic cleavage and subcellular distribution. Our data show that the APP mutant mimicking constitutive dephosphorylation of Y687 had a faster turnover rate, both in terms of maturation and metabolism, when compared to Wt-APP-GFP and even more so when compared to the mutant mimicking constitutive phosphorylation. Thus, the mutant mimicking constitutively phosphorylated Y687 had a much higher t1/2 and was significantly retained both in the ER and TGN. Additionally, this mutant was not incorporated into visible vesicular structures, with a concomitant dramatic decrease in Aβ production. Our findings point to the direct phosphorylation of APP on Y687 as an important regulatory mechanism in terms of determining the subcellular localization of APP and modulating its processing via different proteolytic pathways.
Signal Peptide Peptidases and Gamma-Secretase: Cousins of the Same Protease Family?
Authors: Fluhrer Regina , Haass Christian
Published: June 2007

Signal peptide peptidase (SPP) is an unusual aspartyl protease, which mediates clearance of signal peptides by proteolysis within the endoplasmic reticulum (ER). Like presenilins, which provide the proteolytically active subunit of the γ-secretase complex, SPP contains a conserved GxGD motif in its C-terminal domain which is critical for its activity. While SPP is known to be an aspartyl protease of the GxGD type, several presenilin homologues/SPP-like proteins (PSHs/SPPL) of unknown function have been identified by database searches. In contrast to SPP and SPPL3, which are both restricted to the endoplasmic reticulum, SPPL2b is targeted through the secretory pathway to endosomes/lysosomes. As suggested by the differential subcellular localization of SPPL2b and SPPL3 distinct phenotypes were found upon antisense gripNA-mediated knockdown in zebrafish. spp and sppl3 knockdowns in zebrafish result in cell death within the central nervous system, whereas reduction of sppl2b expression causes erythrocyte accumulation in an enlarged caudal vein. Moreover, expression of D/A mutants of the putative C-terminal active sites of spp, sppl2,and sppl3 produced phenocopies of the respective knockdown phenotypes. These data suggest that all investigated PSHs/SPPLs are members of the novel family of GxGD aspartyl proteases. More recently, it was shown that SPPL2b utilizes multiple intramembrane cleavages to liberate the TNFα intracellular domain into the cytosol and to release the C-terminal counterpart into the lumen. These findings suggest common principles of intramembrane proteolysis by GxGD type aspartyl proteases. In this article, we will review the similarities of SPPs and γ-secretase based on recent findings by us and others.
BACE1 and Mutated Presenilin-1 Differently Modulate Aβ40 and Aβ42 Levels and Cerebral Amyloidosis in APPDutch Transgenic Mice
Authors: Herzig Martin C. , Paganetti Paolo , Staufenbiel Matthias , Jucker Mathias
Published: June 2007

APPDutch transgenic (tg) mice develop cerebral amyloid angiopathy (CAA) that consists mainly of AβDutch40, with virtually no parenchymal amyloid plaques. To modulate cerebral amyloidosis, we crossbred APPDutch mice with either BACE1 tg mice to increase total AβDutch, or with G384A-mutated PS1 tg mice to elevate the ratio of AβDutch42 to AβDutch40. We analyzed all mice at 22 months of age. Compared to APPDutch mice, double-tg APPDutch/BACE1 mice revealed increased CAA mainly due to extensive vascular amyloid accumulation in the thalamus. In addition, they developed parenchymal amyloid in cortex and subiculum. In contrast, APPDutch/G384A-PS1 mice showed extensive, predominantly parenchymal amyloid throughout the entire brain, interestingly, even in the thalamus. The amyloid, composed largely of AβDutch42, was different compared to that in APPDutch/BACE1 mice which was composed mainly of AβDutch40. In summary, these mouse models reveal a broad variety and region-specificity of parenchymal versus vascular cerebral amyloid. This is partially explained by the absolute amount of neuronally produced AβDutch42 and AβDutch40 and ratio between the two. We conclude that the absolute levels of Aβ in combination with the ratio of Aβ42 to Aβ40 play a key role in determining the cerebral compartment and brain region in which Aβ is deposited.
A Systematic Review and Meta-Analysis of CSF Neurofilament Protein Levels as Biomarkers in Dementia
Authors: Petzold A. , Keir G. , Warren J. , Fox N. , Rossor M.N.
Published: June 2007

Background: Loss of cortical neurons is a key pathological feature in neurodegenerative dementias. Cerebrospinal fluid (CSF) neurofilaments (Nf) are a biomarker for neuronal death and axonal loss. Objective: To perform a meta-analysis to investigate the value of CSF Nf levels for the laboratory-supported differential diagnosis of neurodegenerative dementias. Methods: A systematic review and meta-analysis of studies on CSF Nf heavy (NfH) and light (NfL) levels in patients with dementia. The dementia subgroups analysed were Alzheimer (AD), frontotemporal lobe dementia (FTLD), vascular dementia (SVD), minimal cognitive deficit (MCI). Results: We identified 12 studies on CSF NfH and NfL levels which met the inclusion criteria and 11 were of a quality good enough to be used in this meta-analysis. CSF data was available on 818 patients (306 AD, 106 SVD, 98 FTLD, 25 MCI, 283 controls). Overall CSF NfH and NfL levels were higher in patients with AD, FTLD and SVD when compared to controls. The size of the effect ranged from 0.71 to 1.38. The strongest effect was observed for the comparison of FTLD patients with controls, both for NfL (1.38) and NfH (0.74). CSF NfL were also able to separate patients with FTLD from those with AD. Conclusion: At present we cannot recommend CSF NfH and NfL levels for use as a screening test in the diagnosis of dementia because of the rather small effect size. However, both neurofilament proteins may be of value for targeted investigation of some patients with FTLD, SVD and AD.
Glia Protects Neurons against Extracellular Human Neuromelanin
Authors: Depboylu Candan , Matusch Andreas , Tribl Florian , Zoriy Myroslav , Michel Patrick P. , Riederer Peter , Gerlach Manfred , Becker Sabine , Oertel Wolfgang H. , Höglinger Günter U.
Published: June 2007

Background: Neuromelanin-containing neurons of the substantia nigra are highly vulnerable to degenerate in Parkinson’s disease. Inhibition of the respiratory chain or formation of reactive oxygen species (ROS) by intracellular neuromelanin and triggering of inflammatory processes by extracellular neuromelanin emanating from melanized neurons after their demise are thought to be causally implicated in the high vulnerability of melanized neurons. Objective: We addressed the direct effect of purified neuromelanin on mitochondrial complex I activity, and its influence on ROS production and survival of primary mesencephalic neurons in the presence or absence of glia. Methods: Neuromelanin was isolated from midbrain of postmortem human brains. The content in iron and other elements was measured by inductively coupled mass spectrometry. The effect of neuromelanin on mitochondrial complex I activity was analyzed in post-nuclear extracts. Primary neuronal enriched and neuron-glia mixed cultures from midbrain were treated with different concentrations of neuromelanin. The generation of ROS was determined by fluorochrome detection. MAP2-positive and TH-positive neuronal viability was analyzed. Results: Neuromelanin did not affect complex I activity, but concentration-dependently increased ROS production in neurons and reduced the number of MAP2-positive and TH-positive cultured neurons. Glia protected neurons against the neuromelanin toxicity. Conclusion: Extracellular neuromelanin is detrimental to neurons implicating a mechanism of intracellular ROS production, but not complex I inhibition. ROS formation may be catalyzed by iron, which was sensitively identified in purified neuromelanin (3.3 mg/g). Importantly, we demonstrate that glial cells have the potential to mitigate the neurotoxic effect of neuromelanin.
Frontotemporal Lobar Degeneration with Ubiquitin-Positive Inclusions: A Molecular Genetic Update
Authors: van der Zee Julie , Gijselinck Ilse , Pirici Daniel , Kumar-Singh Samir , Cruts Marc , Van Broeckhoven Christine
Published: June 2007

Frontotemporal lobar degeneration (FTLD) is a clinically, pathologically and genetically highly complex disorder. In the last few years enormous progress has been made in dissecting the genetic etiology of FTLD. Mutations have been identified in the progranulin gene (PGRN), the charged multivesicular body protein 2B gene (CHMP2B) and the valosin-containing protein gene (VCP). Mutations in these genes all lead to FTLD pathology characterized by ubiquitin-immunoreactive neuronal cytoplasmic and intranuclear lentiform inclusions (FTLD-U). The similar pathology suggests that these genes may be connected trough a common disease pathway leading to neurodegeneration and the formation of these pathognomic inclusions. This review focuses on the molecular genetic processes underlying FTLD-U pathology.
Topographical Organization of the Facial Motor Nucleus in Florida Manatees (Trichechus manatus latirostris)
Authors: Marshall Christopher D. , Vaughn Susan D. , Sarko Diana K. , Reep Roger L.
Published: June 2007

Florida manatees (Trichechus manatus latirostris) possess modified vibrissae that are used in conjunction with specialized perioral musculature to manipulate vegetation for ingestion, and aid in the tactile exploration of their environment. Therefore it is expected that manatees possess a large facial motor nucleus that exhibits a complex organization relative to other taxa. The topographical organization of the facial motor nucleus of five adult Florida manatees was analyzed using neuroanatomical methods. Cresyl violet and hematoxylin staining were used to localize the rostrocaudal extent of the facial motor nucleus as well as the organization and location of subdivisions within this nucleus. Differences in size, length, and organization of the facial motor nucleus among mammals correspond to the functional importance of the superficial facial muscles, including perioral musculature involved in the movement of mystacial vibrissae. The facial motor nucleus of Florida manatees was divided into seven subnuclei. The mean rostrocaudal length, width, and height of the entire Florida manatee facial motor nucleus was 6.6 mm (SD 8 0.51; range: 6.2–7.5 mm), 4.7 mm (SD 8 0.65; range: 4.0–5.6 mm), and 3.9 mm (SD 8 0.26; range: 3.5–4.2 mm), respectively. It is speculated that manatees could possess direct descending corticomotorneuron projections to the facial motornucleus. This conjecture is based on recent data for rodents, similiarities in the rodent and sirenian muscular-vibrissal complex, and the analogous nature of the sirenian cortical Rindenkerne system with the rodent barrel system.
Natural History and Prognostic Factors of IgA Nephropathy Presented with Isolated Microscopic Hematuria in Chinese Patients
Authors: Shen Peicheng , He Liqun , Li Yi , Wang Yunman , Chan May
Published: June 2007

Background/Aims: IgA nephropathy (IgAN) with isolated microscopic hematuria (IMH) is prevalent in Asian countries including China. However, the natural history of IgAN with IMH has not yet been clarified. The aim of this study was to review the natural course and prognostic factors of IgAN with IMH in Chinese patients. Methods: We retrospectively studied 135 patients (43 males and 92 females) followed up for a mean period of 92 ± 28 months. In order to identify factors associated with renal progression, clinical and pathological data at onset were reviewed. Results: During the follow-up period, hematuria of 16 patients (12%) disappeared while persistent microscopic hematuria was seen in 119 patients (88%), and proteinuria was present in 39 patients (29%). The prevalence of hypertension was 32% (43 patients), and 20% (27 patients) developed renal insufficiency. The prevalence of proteinuria and hypertension in the microalbuminuria group was significantly higher than those in the normoalbuminuria group. Poor renal outcome is usually associated with hematuria, microalbuminuria, and tubulointerstitial lesions. Conclusion: IgAN with IMH may not imply favorable outcome, so early diagnosis and careful follow-up are clinically significant. Hematuria, microalbuminuria, and tubulointerstitial lesions are useful markers to identify those patients at high risk for renal progression.
Toward a Robust Canopy Hydrology Scheme with Precipitation Subgrid Variability
Authors: Wang Dagang , Wang Guiling
Published: June 2007

Representation of the canopy hydrological processes has been challenging in land surface modeling due to the subgrid heterogeneity in both precipitation and surface characteristics. The Shuttleworth dynamic–statistical method is widely used to represent the impact of the precipitation subgrid variability on canopy hydrological processes but shows unwanted sensitivity to temporal resolution when implemented into land surface models. This paper presents a canopy hydrology scheme that is robust at different temporal resolutions. This scheme is devised by applying two physically based treatments to the Shuttleworth scheme: 1) the canopy hydrological processes within the rain-covered area are treated separately from those within the nonrain area, and the scheme tracks the relative rain location between adjacent time steps; and 2) within the rain-covered area, the canopy interception is so determined as to sustain the potential evaporation from the wetted canopy or is equal to precipitation, whichever is less, to maintain somewhat wet canopy during any rainy time step. When applied to the Amazon region, the new scheme establishes interception loss ratios of 0.3 at a 10-min time step and 0.23 at a 2-h time step. Compared to interception loss ratios of 0.45 and 0.09 at the corresponding time steps established by the original Shuttleworth scheme, the new scheme is much more stable under different temporal resolutions.
Intimate Partner Homicide
Authors: Campbell Jacquelyn C. , Glass Nancy , Sharps Phyllis W. , Laughon Kathryn , Bloom Tina
Published: June 2007

Current rates of intimate partner homicide of females are approximately 4 to 5 times the rate for male victims, although the rates for both have decreased during the past 25 years. The major risk factor for intimate partner homicide, no matter if a female or male partner is killed, is prior domestic violence. This review presents and critiques the evidence supporting the other major risk factors for intimate partner homicide in general, and for intimate partner homicide of women (femicide) in particular, namely guns, estrangement, stepchild in the home, forced sex, threats to kill, and nonfatal strangulation (choking). The demographic risk factors are also examined and the related phenomena of pregnancy-related homicide, attempted femicide, and intimate partner homicide-suicide
A critical role for TNFα in the selective attachment of mononuclear leukocytes to angiotensin-II-stimulated arterioles
Authors: Mateo Teresa , Naim Abu Nabah Yafa , Losada Mercedes , Estellés Rossana , Company Chantal , Bedrina Begoña , Cerdá-Nicolás Jose Miguel , Poole Stephen , Jose Peter J. , Cortijo Julio , Morcillo Esteban J. , Sanz Maria-Jesus
Published: June 2007

Angiotensin II (Ang-II) exerts inflammatory activity and is involved in different cardiovascular disorders. This study has evaluated the involvement of tumor necrosis factor alpha (TNFα) in the leukocyte accumulation elicited by Ang-II. Ang-II (1 nM intraperitoneally in rats) induced TNFα release at 1 hour followed by neutrophil and mononuclear cell recruitment. The administration of an antirat TNFα antiserum had no effect on Ang-IIinduced neutrophil accumulation but inhibited the infiltration of mononuclear cells and reduced CC chemokine content in the peritoneal exudate. Pretreatment with either an anti-TNFα or an anti-IL-4 antiserum decreased Ang-II-induced arteriolar mononuclear leukocyte adhesion by 68% and 60%, respectively, in the rat mesenteric microcirculation. While no expression of TNFα was found in the postcapillary venules of Ang-II-injected animals, this cytokine was clearly up-regulated in the arterioles. Stimulation of human umbilical arterial endothelial cells (HUAECs) or isolated human mononuclear cells with 1 μM Ang-II caused increased TNFα mRNA expression and protein. Neutralization of TNFα activity reduced Ang-II-induced MCP-1, MCP-3, and RANTES release from HUAECs and MIP-1α from blood cells. In conclusion, the selective mononuclear leukocyte adhesion to Ang-II-stimulated arterioles is largely mediated by TNFα in cooperation with constitutive IL-4. Therefore, neutralization of TNFα activity may help to prevent mononuclear cell infiltration and the progression of the atherogenic process.
High-throughput identification of interacting protein-protein binding sites
Authors: Chung Jo-Lan , Wang Wei , Bourne Philip E
Published: June 2007

Background

With the advent of increasing sequence and structural data, a number of methods have been proposed to locate putative protein binding sites from protein surfaces. Therefore, methods that are able to identify whether these binding sites interact are needed.

Results

We have developed a new method using a machine learning approach to detect if protein binding sites, once identified, interact with each other. The method exploits information relating to sequence and structural complementary across protein interfaces and has been tested on a non-redundant data set consisting of 584 homo-dimers and 198 hetero-dimers extracted from the PDB. Results indicate 87.4% of the interacting binding sites and 68.6% non-interacting binding sites were correctly identified. Furthermore, we built a pipeline that links this method to a modified version of our previously developed method that predicts the location of binding sites.

Conclusion

We have demonstrated that this high-throughput pipeline is capable of identifying binding sites for proteins, their interacting binding sites and, ultimately, their binding partners on a large scale.
Characterization of protein-interaction networks in tumors
Authors: Platzer Alexander , Perco Paul , Lukas Arno , Mayer Bernd
Published: June 2007

Background

Analyzing differential-gene-expression data in the context of protein-interaction networks (PINs) yields information on the functional cellular status. PINs can be formally represented as graphs, and approximating PINs as undirected graphs allows the network properties to be characterized using well-established graph measures.

This paper outlines features of PINs derived from 29 studies on differential gene expression in cancer. For each study the number of differentially regulated genes was determined and used as a basis for PIN construction utilizing the Online Predicted Human Interaction Database.

Results

Graph measures calculated for the largest subgraph of a PIN for a given differential-gene-expression data set comprised properties reflecting the size, distribution, biological relevance, density, modularity, and cycles. The values of a distinct set of graph measures, namely Closeness Centrality, Graph Diameter, Index of Aggregation, Assortative Mixing Coefficient, Connectivity, Sum of the Wiener Number, modified Vertex Distance Number, and Eigenvalues differed clearly between PINs derived on the basis of differential gene expression data sets characterizing malignant tissue and PINs derived on the basis of randomly selected protein lists.

Conclusion

Cancer PINs representing differentially regulated genes are larger than those of randomly selected protein lists, indicating functional dependencies among protein lists that can be identified on the basis of transcriptomics experiments. However, the prevalence of hub proteins was not increased in the presence of cancer. Interpretation of such graphs in the context of robustness may yield novel therapies based on synthetic lethality that are more effective than focusing on single-action drugs for cancer treatment.
The Florey Adelaide Male Ageing Study (FAMAS): Design, procedures & participants
Authors: Martin Sean A , Haren Matthew T , Middleton Sue M , Wittert Gary A ,   Members of the Florey Adelaide Male Ageing Study (FAMAS)
Published: June 2007

Background

The Florey Adelaide Male Ageing Study (FAMAS) examines the reproductive, physical and psychological health, and health service utilisation of the ageing male in Australia. We describe the rationale for the study, the methods used participant response rates, representativeness and attrition to date.

Methods

FAMAS is a longitudinal study involving approximately 1200 randomly selected men, aged 35–80 years and living in the north – west regions of Adelaide. Respondents were excluded at screening if they were considered incapable of participating because of immobility, language, or an inability to undertake the study procedures. Following a telephone call to randomly selected households, eligible participants were invited to attend a baseline clinic measuring a variety of biomedical and socio-demographic factors. Beginning in 2002, these clinics are scheduled to reoccur every five years. Follow-up questionnaires are completed annually. Participants are also invited to participate in sub-studies with selected collaborators.

Results

Of those eligible to participate, 45.1% ultimately attended a clinic. Non-responders were more likely to live alone, be current smokers, have a higheevalence of self-reported diabetes and stroke, and lower levels of hypercholesterolemia. Comparisons with the Census 2001 data showed that participants matched the population for most key demographics, although younger groups and never married men were under-represented and elderly participants were over-represented. To date, there has been an annual loss to follow-up of just over 1%.

Conclusion

FAMAS allows a detailed investigation into the effects of bio-psychosocial and behavioural factors on the health and ageing of a largely representative group of Australian men.
Cloning and characterization of an adenoviral vector for highly efficient and doxycycline – suppressible expression of bioactive human single – chain interleukin 12 in colon cancer
Authors: Wulff Holger , Krieger Thorsten , Krüger Karen , Stahmer Ingrid , Thaiss Friedrich , Schäfer Hansjörg , Block Andreas
Published: June 2007

Background

Interleukin-12 (IL-12) is well characterized to induce cellular antitumoral immunity by activation of NK-cells and T-lymphocytes. However, systemic administration of recombinant human IL-12 resulted in severe toxicity without perceptible therapeutic benefit. Even though intratumoral expression of IL-12 leads to tumor regression and long-term survival in a variety of animal models, clinical trials have not yet shown a significant therapeutic benefit. One major obstacle in the treatment with IL-12 is to overcome the relatively low expression of the therapeutic gene without compromising the safety of such an approach. Our objective was to generate an adenoviral vector system enabling the regulated expression of very high levels of bioactive, human IL-12.

Results

High gene expression was obtained utilizing the VP16 herpes simplex transactivator. Strong regulation of gene expression was realized by fusion of the VP16 to a tetracycline repressor with binding of the fusion protein to a flanking tetracycline operator and further enhanced by auto-regulated expression of its fusion gene within a bicistronic promoter construct. Infection of human colon cancer cells (HT29) at a multiplicity of infection (m.o.i.) of 10 resulted in the production of up to 8000 ng/106cells in 48 h, thus exceeding any published vector system so far. Doxycycline concentrations as low as 30 ng/ml resulted in up to 5000-fold suppression, enabling significant reduction of gene expression in a possible clinical setting. Bioactivity of the human single-chain IL-12 was similar to purified human heterodimeric IL-12. Frozen sections of human colon cancer showed high expression of the coxsackie adenovirus receptor with significant production of human single chain IL-12 in colon cancer biopsies after infection with 3*107p.f.u. Ad.3r-scIL12. Doxycycline mediated suppression of gene expression was up to 9000-fold in the infected colon cancer tissue.

Conclusion

VP16 transactivator-mediated and doxycycline-regulated expression of the human interleukin-12 gene enables highly efficient and tightly controlled cytokine expression in human cancer. These data illustrate the potential of the described adenoviral vector system for the safe and superior expression of therapeutic genes in the treatment of colorectal cancer and other malignancies.
Comparison of marker gene expression in chondrocytes from patients receiving autologous chondrocyte transplantation versus osteoarthritis patients
Authors: Stoop Reinout , Albrecht Dirk , Gaissmaier Christoph , Fritz Jürgen , Felka Tino , Rudert Maximilian , Aicher Wilhelm K
Published: June 2007

Currently, autologous chondrocyte transplantation (ACT) is used to treat traumatic cartilage damage or osteochondrosis dissecans, but not degenerative arthritis. Since substantial refinements in the isolation, expansion and transplantation of chondrocytes have been made in recent years, the treatment of early stage osteoarthritic lesions using ACT might now be feasible. In this study, we determined the gene expression patterns of osteoarthritic (OA) chondrocytes ex vivo after primary culture and subculture and compared these with healthy chondrocytes ex vivo and with articular chondrocytes expanded for treatment of patients by ACT. Gene expression profiles were determined using quantitative RT-PCR for type I, II and X collagen, aggrecan, IL-1β and activin-like kinase-1. Furthermore, we tested the capability of osteoarthritic chondrocytes to generate hyaline-like cartilage by implanting chondrocyte-seeded collagen scaffolds into immunodeficient (SCID) mice. OA chondrocytes ex vivo showed highly elevated levels of IL-1β mRNA, but type I and II collagen levels were comparable to those of healthy chondrocytes. After primary culture, IL-1β levels decreased to baseline levels, while the type II and type I collagen mRNA levels matched those found in chondrocytes used for ACT. OA chondrocytes generated type II collagen and proteoglycan-rich cartilage transplants in SCID mice. We conclude that after expansion under suitable conditions, the cartilage of OA patients contains cells that are not significantly different from those from healthy donors prepared for ACT. OA chondrocytes are also capable of producing a cartilage-like tissue in the in vivo SCID mouse model. Thus, such chondrocytes seem to fulfil the prerequisites for use in ACT treatment.
A 1-year case-control study in patients with rheumatoid arthritis indicates prevention of loss of bone mineral density in both responders and nonresponders to infliximab
Authors: Marotte Hubert , Pallot-Prades Beatrice , Grange Laurent , Gaudin Philippe , Alexandre Christian , Miossec Pierre
Published: June 2007

The goal of the present study was to record changes in bone mineral density (BMD) and markers of bone turnover in patients with rheumatoid arthritis (RA) who were treated with methotrexate combined (or not combined) with infliximab. Included were 90 patients with RA who required anti-TNF-α therapy with infliximab because of persistent active disease despite treatment with methotrexate. The historical control group included 99 patients with RA who were treated with methotrexate at a time when anti-TNF-α treatment was not yet available. Lumbar and femoral neck BMD was measured using dual energy X-ray absorptiometry at baseline and 1 year later. Osteocalcin, C-terminal cross-linked telopeptide of type I collagen, parathyroid hormone and 25-hydroxycholecalciferol were measured in plasma at baseline and 1 year later. At 1 year BMD had decreased in the control group at spine (P < 0.01) and femoral neck (P < 0.001). In contrast, BMD at spine and femoral neck did not change after 1 year of infliximab treatment. At the same time point, no change in bone remodelling markers was observed. No association was observed between clinical response and changes in BMD, indicating that even those who did not respond clinically did not lose bone over a 1-year period. These data confirm the BMD decrease observed in RA patients treated with methotrexate alone. This bone loss was prevented by infliximab therapy. Importantly, this beneficial effect was also observed in apparent nonresponders.
Activation of Melanocortin 4 Receptors Reduces the Inflammatory Response and Prevents Apoptosis Induced by Lipopolysaccharide and Interferon-γ in Astrocytes
Authors: Caruso Carla , Durand Daniela , Schiöth Helgi B. , Rey Rodolfo , Seilicovich Adriana , Lasaga Mercedes
Published: June 2007

α-MSH exerts an immunomodulatory action in the brain and may play a neuroprotective role acting through melanocortin 4 receptors (MC4Rs). In the present study, we show that MC4Rs are constitutively expressed in astrocytes as determined by immunocytochemistry, RT-PCR, and Western blot analysis. α-MSH (5 μm) reduced the nitric oxide production and the expression of inducible nitric oxide synthase (iNOS) induced by bacterial lipopolysaccharide (LPS, 1 μg/ml) plus interferon-γ (IFN-γ, 50 ng/ml) in cultured astrocytes after 24 h. α-MSH also attenuated the stimulatory effect of LPS/IFN-γ on prostaglandin E2 release and cyclooxygenase-2 (COX-2) expression. Treatment with HS024, a selective MC4R antagonist, blocked the antiinflammatory effects of α-MSH, suggesting a MC4R-mediated mechanism in the action of this melanocortin. In astrocytes, LPS/IFN-γ treatment reduced cell viability, increased the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells and activated caspase-3. α-MSH prevented these apoptotic events, and this cytoprotective effect was abolished by HS024. LPS/IFN-γ decreased Bcl-2, whereas it increased Bax protein expression in astrocytes, thus increasing the Bax/Bcl-2 ratio. α-MSH produced a shift in Bax/Bcl-2 ratio toward astrocyte survival because it increased Bcl-2 expression and also prevented the effect of LPS/IFN-γ on Bax and Bcl-2 expression. In summary, these findings suggest that α-MSH, through MC4R activation, attenuates LPS/IFN-γ-induced inflammation by decreasing iNOS and COX-2 expression and prevents LPS/IFN-γ-induced apoptosis of astrocytes by modulating the expression of proteins of the Bcl-2 family.
Effects of Pituitary Hormone Deficiency on Growth and Glucose Metabolism of the Sheep Fetus
Authors: Fowden A. L. , Forhead A. J.
Published: June 2007

Pituitary hormones are essential for normal growth and metabolic responsiveness after birth, but their role before birth remains unclear. This study examined the effects of hypophysectomizing fetal sheep on their growth and glucose metabolism during the late normal and extended periods of gestation, and on their metabolic response to maternal fasting for 48 h near term. Fetal hypophysectomy reduced crown rump length (CRL), limb lengths, and body weight but increased ponderal index relative to controls near normal term. It also lowered the daily rate of crown rump length increment uniformly from 35 d before, to 20 d after normal term. Hypophysectomized (HX) fetuses had normal weight-specific rates of umbilical uptake, utilization, and oxidation of glucose but lower rates of umbilical oxygen uptake than controls near term. All these metabolic rates were significantly less in HX fetuses during the extended period of gestation than in HX and intact fetuses near normal term. In contrast to controls, glucogenesis was negligible in HX fetuses during maternal fasting. Consequently, the rate of glucose utilization decreased significantly in fasted HX but not intact fetuses. Conversely, the rate of CO2 production from glucose carbon decreased in fasted intact but not HX fetuses. Fetal hypophysectomy also prevented the fasting-induced increases in plasma cortisol and norepinephrine concentrations seen in controls. These findings demonstrate that the pituitary hormones are important in regulating the growth rate and adaptive responses of glucose metabolism to undernutrition in fetal sheep. They also suggest that fetal metabolism is altered when gestational length is extended.