bluuebunny/crossref_metadata_2025_split huggingface dataset:
The application and limitations of mathematical modelling in the prediction of permeability across mammalian skin and polydimethylsiloxane membranes
Authors: Moss Gary P , Sun Yi , Wilkinson Simon C , Davey Neil , Adams Rod , Martin Gary P , Prapopopolou M , Brown Marc B 
Published: September 2011

Abstract

Objectives
Predicting the rate of percutaneous absorption of a drug is an important issue with the increasing use of the skin as a means of moderating and controlling drug delivery. One key feature of this problem domain is that human skin permeability (as Kp) has been shown to be inherently non-linear when mathematically related to the physicochemical parameters of penetrants. As such, the aims of this study were to apply and evaluate Gaussian process (GP) regression methods to datasets for membranes other than human skin, and to explore how the nature of the dataset may influence its analysis.

Methods
Permeability data for absorption across rodent and pig skin, and artificial membranes (polydimethylsiloxane, PDMS, i.e. Silastic) membranes was collected from the literature. Two quantitative structure–permeability relationship (QSPR) models were used to compare with the GP models. Further performance metrics were computed in terms of all predictions, and a range of covariance functions were examined: the squared exponential (SE), neural network (NNone) and rational quadratic (QR) covariance functions, along with two simple cases of Matern covariance function (Matern3 and Matern5) where the polynomial order is set to 1 and 2, respectively. As measures of performance, the correlation coefficient (CORR), negative log estimated predictive density (NLL, or negative log loss) and mean squared error (MSE) were employed.

Key findings
The results demonstrated that GP models with different covariance functions outperform QSPR models for human, pig and rodent datasets. For the artificial membranes, GPs perform better in one instance, and give similar results in other experiments (where different covariance parameters produce similar results). In some cases, the GP predictions for some of the artificial membrane dataset are poorly correlated, suggesting that the physicochemical parameters employed in this study might not be appropriate for developing models that represent this membrane.

Conclusions
While the results of this study indicate that permeation across rodent (mouse and rat) and pig skin is, in a statistical sense, similar, and that the artificial membranes are poor replacements of human or animal skin, the overriding issue raised in this study is the nature of the dataset and how it can influence the results, and subsequent interpretation, of any model produced for particular membranes. The size of the datasets, in both absolute and comparative senses, appears to influence model quality. Ideally, to generate viable cross-comparisons the datasets for different mammalian membranes should, wherever possible, exhibit as much commonality as possible.
Beta-
d
-Glucan Detection as a Diagnostic Test for Invasive Aspergillosis in Immunocompromised Critically Ill Patients with Symptoms of Respiratory Infection: an Autopsy-Based Study
Authors: De Vlieger Greet , Lagrou Katrien , Maertens Johan , Verbeken Eric , Meersseman Wouter , Van Wijngaerden Eric 
Published: September 2011

ABSTRACT

Beta-(1,3)-
d
-glucan (BG) detection is an emerging tool to diagnose invasive fungal infections (IFIs). Invasive aspergillosis (IA) is the second most common IFI in immunocompromised intensive care unit (ICU) patients. We retrospectively analyzed the serum BG concentration (Fungitell; Associates of Cape Cod) in immunocompromised ICU patients with proven IA and in immunocompromised ICU patients in whom autopsy failed to show IFI. The study was performed in a 17-bed medical ICU in a 1,900-bed referral hospital. Patients at risk for IA were eligible for inclusion when at least two additional clinical signs were present. Patients with other IFIs were excluded. Fourteen patients with IA and 33 patients who had no IFI were eligible for inclusion. Serum BG levels were significantly higher in patients with IA than patients without an IFI (
P
< 0.01). Using a cutoff of 140 pg/ml, the sensitivity and specificity were 85.7 and 69.7%, respectively; the positive and negative predictive values were 54.5 and 92.0%, respectively. The positive and negative likelihood ratios were 2.83 and 0.21, respectively. Although serum BG concentrations were higher in immunocompromised ICU patients with IA than in patients with the same risk factors who did not have IFI on autopsy, the moderate performance characteristics of this test limit its use as a diagnostic test for IA in this population.
First Report of Disseminated Mycobacterium Skin Infections in Two Liver Transplant Recipients and Rapid Diagnosis by
hsp65
Gene Sequencing
Authors: Lau Susanna K. P. , Curreem Shirly O. T. , Ngan Antonio H. Y. , Yeung Chi-Keung , Yuen Kwok-Yung , Woo Patrick C. Y. 
Published: September 2011

ABSTRACT

We present here the first report of disseminated skin
Mycobacterium
infections in two liver transplant recipients, in which
hsp65
gene sequencing was used for rapid species identification. Both patients had hepatitis B virus-related cirrhosis and diabetes mellitus and presented with progressive generalized, nodular skin lesions. In one patient, a 50-year-old woman who had frequent contact with marine fish, an acid-fast bacillus was isolated from skin biopsy tissue after 2 months of culture. While awaiting phenotypic identification results,
hsp65
gene sequencing showed that it was most closely related to that of
Mycobacterium marinum
with 100% nucleotide identity. The patient was treated with oral rifampin, ethambutol, and moxifloxacin. In the other patient, a 59-year-old woman, direct PCR for
Mycobacterium
using
hsp65
gene from skin biopsy tissue was positive, with the sequence most closely related to that of
M. haemophilum
with 100% nucleotide identity. Based on PCR results, the patient was treated with clarithromycin, ethambutol, moxifloxacin, and amikacin. A strain of
M. haemophilum
was only isolated after 3 months. Skin lesions of both patients resolved after 1 year of antimycobacterial therapy. Nontuberculous
Mycobacterium
infections should be considered in liver transplant recipients presenting with chronic, nodular skin lesions. This report highlights the crucial role of
hsp65
gene PCR and sequencing on both cultured isolates and direct clinical specimens for rapid diagnosis of slow-growing
Mycobacterium
infection.
Infection of Calves with Bovine Norovirus GIII.1 Strain Jena Virus: an Experimental Model To Study the Pathogenesis of Norovirus Infection
Authors: Otto Peter H. , Clarke Ian N. , Lambden Paul R. , Salim Omar , Reetz Jochen , Liebler-Tenorio Elisabeth M. 
Published: September 2011

ABSTRACT
The experimental infection of newborn calves with bovine norovirus was used as a homologous large animal model to study the pathogenesis of norovirus infection and to determine target cells for viral replication. Six newborn calves were inoculated orally with Jena virus (JV), a bovine norovirus GIII.1 strain, and six calves served as mock-inoculated controls. Following infection, calves were euthanized before the onset of diarrhea (12 h postinoculation [hpi]), shortly after the onset of diarrhea (18 to 21 hpi), and postconvalescence (4 days pi [dpi]). Calves inoculated with JV developed severe watery diarrhea at 14 to 16 hpi, and this symptom lasted for 53.5 to 67.0 h. Intestinal lesions were characterized by severe villus atrophy together with loss and attenuation of villus epithelium. Viral capsid antigen (JV antigen) was detected by immunohistochemistry in the cytoplasm of epithelial cells on villi. In addition, granular material positive for JV antigen was detected in the lamina propria of villi. Lesions first appeared at 12 hpi and were most extensive at 18 to 19 hpi, extending from midjejunum to ileum. The intestinal mucosa had completely recovered at 4 dpi. There was no indication of systemic infection as described for norovirus infection in mice. JV was found in intestinal contents by reverse transcription-PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) as early as 12 hpi. Fecal shedding of the virus started at 13 hpi and stopped at 23 hpi or at necropsy (4 dpi), respectively. Throughout the trial, none of the control calves tested positive for JV by ELISA or RT-PCR.
Increased Frequency of Regulatory T Cells Accompanies Increased Immune Activation in Rectal Mucosae of HIV-Positive Noncontrollers
Authors: Shaw Julia M. , Hunt Peter W. , Critchfield J. William , McConnell Delandy H. , Garcia Juan Carlos , Pollard Richard B. , Somsouk Ma , Deeks Steven G. , Shacklett Barbara L. 
Published: September 2011

ABSTRACTGut-associated lymphoid tissue (GALT) is a major site of HIV replication and CD4+T cell depletion. Furthermore, microbial translocation facilitated by mucosal damage likely contributes to the generalized immune activation observed in HIV infection. Regulatory T cells (Treg) help maintain homeostasis and suppress harmful immune activation during infection; however, in the case of persistent viral infections such as HIV, their role is less clear. Although a number of studies have examined Treg in blood during chronic infection, few have explored Treg in the gastrointestinal mucosa. For this study, paired blood and rectal biopsy samples were obtained from 12 HIV noncontrollers (viral load of >10,000 copies/ml plasma), 10 HIV controllers (viral load of <500 copies/ml plasma for more than 5 years), and 12 HIV seronegative control subjects. Noncontrollers had significantly higher percentages of Treg in rectal mononuclear cells (RMNC), but not in blood, compared to seronegative subjects (P= 0.001) or HIV controllers (P= 0.002). Mucosal Treg positively correlated with viral load (P= 0.01) and expression of immune activation markers by CD4+(P= 0.01) and CD8+(P= 0.07) T cells. Suppression assays indicated that mucosal and peripheral Treg of noncontrollers and controllers maintained their capacity to suppress non-Treg proliferation to a similar extent as Treg from seronegative subjects. Together, these findings reveal that rather than experiencing depletion, mucosal Treg frequency is enhanced during chronic HIV infection and is positively correlated with viral load and immune activation. Moreover, mucosal Treg maintain their suppressive ability during chronic HIV infection, potentially contributing to diminished HIV-specific T cell responses and viral persistence.
The Universally Conserved Prokaryotic GTPases
Authors: Verstraeten Natalie , Fauvart Maarten , Versées Wim , Michiels Jan 
Published: September 2011

SUMMARYMembers of the large superclass of P-loop GTPases share a core domain with a conserved three-dimensional structure. In eukaryotes, these proteins are implicated in various crucial cellular processes, including translation, membrane trafficking, cell cycle progression, and membrane signaling. As targets of mutation and toxins, GTPases are involved in the pathogenesis of cancer and infectious diseases. In prokaryotes also, it is hard to overestimate the importance of GTPases in cell physiology. Numerous papers have shed new light on the role of bacterial GTPases in cell cycle regulation, ribosome assembly, the stress response, and other cellular processes. Moreover, bacterial GTPases have been identified as high-potential drug targets. A key paper published over 2 decades ago stated that, “It may never again be possible to capture [GTPases] in a family portrait” (H. R. Bourne, D. A. Sanders, and F. McCormick, Nature348:125-132, 1990) and indeed, the last 20 years have seen a tremendous increase in publications on the subject. Sequence analysis identified 13 bacterial GTPases that are conserved in at least 75% of all bacterial species. We here provide an overview of these 13 protein subfamilies, covering their cellular functions as well as cellular localization and expression levels, three-dimensional structures, biochemical properties, and gene organization. Conserved roles in eukaryotic homologs will be discussed as well. A comprehensive overview summarizing current knowledge on prokaryotic GTPases will aid in further elucidating the function of these important proteins.
From Water and Ions to Crowded Biomacromolecules:In VivoStructuring of a Prokaryotic Cell
Authors: Spitzer Jan 
Published: September 2011

SUMMARYThe interactions and processes which structure prokaryotic cytoplasm (water, ions, metabolites, and biomacromolecules) and ensure the fidelity of the cell cycle are reviewed from a physicochemical perspective. Recent spectroscopic and biological evidence shows that water has no active structuring role in the cytoplasm, an unnecessary notion still entertained in the literature; water acts only as a normal solvent and biochemical reactant. Subcellular structuring arises from localizations and interactions of biomacromolecules and from the growth and modifications of their surfaces by catalytic reactions. Biomacromolecular crowding is a fundamental physicochemical characteristic of cellsin vivo. Though some biochemical and physiological effects of crowding (excluded volume effect) have been documented, crowding assays with polyglycols, dextrans, etc., do not properly mimic the compositional variety of biomacromoleculesin vivo.In vitrocrowding assays are now being designed with proteins, which better reflect biomacromolecular environmentsin vivo, allowing for hydrophobic bonding and screened electrostatic interactions. I elaborate further the concept of complex vectorial biochemistry, where crowded biomacromolecules structure the cytosol into electrolyte pathways and nanopools that electrochemically “wire” the cell. Noncovalent attractions between biomacromolecules transiently supercrowd biomacromolecules into vectorial, semiconducting multiplexes with a high (35 to 95%)-volume fraction of biomacromolecules; consequently, reservoirs of less crowded cytosol appear in order to maintain the experimental average crowding of ∼25% volume fraction. This nonuniform crowding model allows for fast diffusion of biomacromolecules in the uncrowded cytosolic reservoirs, while the supercrowded vectorial multiplexes conserve the remarkable repeatability of the cell cycle by preventing confusing cross talk of concurrent biochemical reactions.
Highways for internal virus spread: patterns of virus movement in the stoloniferous herb Trifolium repens
Authors: van Mölken Tamara , Sundelin Thomas , Snetselaar Reinier , Stuefer Josef F. 
Published: September 2011

Resource sharing between connected ramets can be advantageous for clonal plants. However, widespread vascular integration bears the risks of enhanced internal pathogen spread, which may be one of the most prominent disadvantages of clonal growth. In this paper we analyzed patterns of internal virus spread in ramet groups of the stoloniferous herb Trifolium repens L. (white clover) and investigated the effect of leaf ontogeny on intraclonal disease development. We inoculated single leaves of T. repens with White clover mosaic virus and analyzed the infection status of ramets at different distances from the point of infection and in leaves from different developmental stages. White clover mosaic virus infected all young developing plant parts positioned on basal branches or on the main stolon. Leaf ontogeny strongly affected disease development, and fully mature leaves on the main stolon remained virus free. The pattern of plant-internal virus spread was not affected by heterogeneous light conditions. Despite the well-described advantages of physiological integration, our data suggest that clonal integration may lead to negative selection pressures on clonal growth in pathogen-prone environments.
Assessing hydraulic conductivities of a compacted dam core using geostatistical analysis of construction control data
Authors: Smith M. , Konrad J.-M. 
Published: September 2011

The surveillance of a 94.5 m high embankment dam in northern Quebec, Canada, revealed the possibility of the existence of a zone of higher hydraulic conductivity in its till core. The spatial continuity of the measured fines content in the dam during construction was computed by geostatistical means to predict values at unsampled locations for the entire core volume. The hydraulic conductivities were inferred using the predicted fines content and in situ compaction conditions. The inferred hydraulic conductivities and their spatial representations were supported by thermal and seepage field monitoring data. This provided the necessary background information to interpret the surveillance data and determine the cause of the presence of a more pervious zone in the core, which was related to spatial variability of the fines content of the till, placement water content, and compaction procedures. The geostatistical approach complemented with laboratory and construction control data is an efficient tool to characterize dam heterogeneities permitting location of zones of more intensive seepage.
Precipitation frequency controls interannual variation of soil respiration by affecting soil moisture in a subtropical forest plantation
Authors: Wang Yidong , Li Qingkang , Wang Huimin , Wen Xuefa , Yang Fengting , Ma Zeqing , Liu Yunfen , Sun Xiaomin , Yu Guirui 
Published: September 2011

Despite the significance of interannual variation of soil respiration (RS) for understanding long-term soil carbon dynamics, factors that control the interannual variation of RS have not been sufficiently investigated. Interannual variation of RS was studied using a 6-year data set collected in a subtropical plantation dominated by an exotic species, slash pine (Pinus elliottii Engelm.), in China. The results showed that seasonal variation of RS was significantly affected by soil temperature and soil water content (SWC). RS in the dry season (July–October) was constrained by seasonal drought. Mean annual RS was estimated to be 736 ± 30 g C·m–2·year–1, with a range of 706–790 g C·m–2·year–1. Although this forest was characterized by a humid climate with high precipitation (1469 mm·year–1), the interannual variation of RS was attributed to the changes of annual mean SWC (R2 = 0.66, P = 0.03), which was affected by annual rainfall frequency (R2 = 0.80, P < 0.01) and not rainfall amount (P = 0.84). Consequently, precipitation pattern indirectly controlled the interannual variation of RS by affecting soil moisture in this subtropical forest. In the context of climate change, interannual variation of RS in subtropical ecosystems is expected to increase because of the predicted changes of precipitation regime.
Phase Space and Dynamical Fluctuations of Kaon-to-Pion Ratios
Authors: Tawfik Abdel 
Published: September 2011

Abstract
The dynamical fluctuations of kaon-to-pion ratios have been studied over a wide range of center-of-mass energies √s. On the basis of changing phase space volume which apparently is the consequence of phase transition from hadrons to quark-gluon plasma at large √s, the single-particle distribution function f is assumed to be rather modified. Varying f and phase space volume are implemented in the grand-canonical partition function, especially at large √s, so that the hadron resonance gas model, when taking into account the experimental acceptance and quark phase space occupation factor, turns to be able to reproduce the dynamical fluctuations of kaon-to-pion ratios over the entire range of √s.
Novel Insights into the Role of Interleukin-27 and Interleukin-23 in Human Malignant and Normal Plasma Cells
Authors: Giuliani Nicola , Airoldi Irma 
Published: September 2011

Abstract
Multiple myeloma is a monoclonal postgerminal center tumor that has phenotypic features of plasmablasts and/or plasma cells and usually localizes at multiple sites in the bone marrow. The pathogenesis of multiple myeloma is complex and dependent on the interactions between tumor cells and their microenvironment. Different cytokines, chemokines, and proangiogenic factors released in the tumor microenvironment are known to promote multiple myeloma cell growth. Here, we report recent advances on the role of 2 strictly related immunomodulatory cytokines, interleukin-27 (IL-27) and IL-23, in human normal and neoplastic plasma cells, highlighting their ability to (i) act directly against multiple myeloma cells, (ii) influence the multiple myeloma microenvironment by targeting osteoclast and osteoblast cells, and (iii) modulate normal plasma cell function. Finally, the therapeutic implication of these studies is discussed. Clin Cancer Res; 17(22); 6963–70. ©2011 AACR.
Mechanistic Contribution of Ubiquitous 15-Lipoxygenase-1 Expression Loss in Cancer Cells to Terminal Cell Differentiation Evasion
Authors: Moussalli Micheline J. , Wu Yuanqing , Zuo Xiangsheng , Yang Xiu L. , Wistuba Ignacio Ivan , Raso Maria G. , Morris Jeffrey S. , Bowser Jessica L. , Minna John D. , Lotan Reuben , Shureiqi Imad 
Published: September 2011

Abstract
Loss of terminal cell differentiation promotes tumorigenesis. 15-Lipoxygenase-1 (15-LOX-1) contributes to terminal cell differentiation in normal cells. The mechanistic significance of 15-LOX-1 expression loss in human cancers to terminal cell differentiation suppression is unknown. In a screen of 128 cancer cell lines representing more than 20 types of human cancer, we found that 15-LOX-1 mRNA expression levels were markedly lower than levels in terminally differentiated cells. Relative expression levels of 15-LOX-1 (relative to the level in terminally differentiated primary normal human–derived bronchial epithelial cells) were lower in 79% of the screened cancer cell lines than relative expression levels of p16 (INK4A), which promotes terminal cell differentiation and is considered one of the most commonly lost tumor suppressor genes in cancer cells. 15-LOX-1 was expressed during terminal differentiation in three-dimensional air–liquid interface cultures, and 15-LOX-1 expression and terminal differentiation occurred in immortalized nontransformed bronchial epithelial but not in lung cancer cell lines. 15-LOX-1 expression levels were lower in human tumors than in paired normal lung epithelia. Short hairpin RNA–mediated downregulation of 15-LOX-1 in Caco-2 cells blocked enterocyte-like differentiation, disrupted tight junction formation, and blocked E-cadherin and ZO-1 localization to the cell wall membrane. 15-LOX-1 episomal expression in Caco-2 and HT-29 colon cancer cells induced differentiation. Our findings indicate that 15-LOX-1 downregulation in cancer cells is an important mechanism for terminal cell differentiation dysregulation and support the potential therapeutic utility of 15-LOX-1 reexpression to inhibit tumorigenesis. Cancer Prev Res; 4(12); 1961–72. ©2011 AACR.