bluuebunny/crossref_metadata_2025 huggingface dataset:
Image quality improvement in megavoltage cone beam CT using an imaging beam line and a sintered pixelated array system
Authors: Breitbach Elizabeth K. , Maltz Jonathan S. , Gangadharan Bijumon , Bani‐Hashemi Ali , Anderson Carryn M. , Bhatia Sudershan K. , Stiles Jared , Edwards Drake S. , Flynn Ryan T.
Published: October 2011

Purpose:

To quantify the improvement in megavoltage cone beam computed tomography (MVCBCT) image quality enabled by the combination of a 4.2 MV imaging beam line (IBL) with a carbon electron target and a detector system equipped with a novel sintered pixelated array (SPA) of translucent Gd2O2S ceramic scintillator. Clinical MVCBCT images are traditionally acquired with the same 6 MV treatment beam line (TBL) that is used for cancer treatment, a standard amorphous Si (a‐Si) flat panel imager, and the Kodak Lanex Fast‐B (LFB) scintillator. The IBL produces a greater fluence of keV‐range photons than the TBL, to which the detector response is more optimal, and the SPA is a more efficient scintillator than the LFB.

Methods:

A prototype IBL + SPA system was installed on a Siemens Oncor linear accelerator equipped with the MVisionTM image guided radiation therapy (IGRT) system. A SPA strip consisting of four neighboring tiles and measuring 40 cm by 10.96 cm in the crossplane and inplane directions, respectively, was installed in the flat panel imager. Head‐ and pelvis‐sized phantom images were acquired at doses ranging from 3 to 60 cGy with three MVCBCT configurations: TBL + LFB, IBL + LFB, and IBL + SPA. Phantom image quality at each dose was quantified using the contrast‐to‐noise ratio (CNR) and modulation transfer function (MTF) metrics. Head and neck, thoracic, and pelvic (prostate) cancer patients were imaged with the three imaging system configurations at multiple doses ranging from 3 to 15 cGy. The systems were assessed qualitatively from the patient image data.

Results:

For head and neck and pelvis‐sized phantom images, imaging doses of 3 cGy or greater, and relative electron densities of 1.09 and 1.48, the CNR average improvement factors for imaging system change of TBL + LFB to IBL + LFB, IBL + LFB to IBL + SPA, and TBL + LFB to IBL + SPA were 1.63 (p < 10− 8), 1.64 (p < 10− 13), 2.66 (p < 10− 9), respectively. For all imaging doses, soft tissue contrast was more easily differentiated on IBL + SPA head and neck and pelvic images than TBL + LFB and IBL + LFB. IBL + SPA thoracic images were comparable to IBL + LFB images, but less noisy than TBL + LFB images at all imaging doses considered. The mean MTFs over all imaging doses were comparable, at within 3%, for all imaging system configurations for both the head‐ and pelvis‐sized phantoms.

Conclusions:

Since CNR scales with the square root of imaging dose, changing from TBL + LFB to IBL + LFB and IBL + LFB to IBL + SPA reduces the imaging dose required to obtain a given CNR by factors of 0.38 and 0.37, respectively. MTFs were comparable between imaging system configurations. IBL + SPA patient image quality was always better than that of the TBL + LFB system and as good as or better than that of the IBL + LFB system, for a given dose.
Hubble’s law and faster than light expansion speeds
Authors: Kaya Ali
Published: October 2011

Naively applying Hubble’s law to a sufficiently distant object gives a receding velocity larger than the speed of light. We discuss a similar situation in special relativity and argue that Hubble’s law is meaningful only for nearby objects with non-relativistic receding speeds. To support this claim, we note that in a curved spacetime manifold it is not possible to directly compare tangent vectors at different points, and thus there is no natural definition of relative velocity between two spatially separated objects. We clarify the meaning of Hubble’s receding speed v by showing that in a Friedmann–Robertson–Walker spacetime, if the four-velocity vector of a comoving object is parallel transported along the straight line in flat comoving coordinates to the position of a second comoving object, v/c becomes the rapidity of the local Lorentz transformation, which maps the fixed four-velocity vector to the transported one.
Any classical description of nature requires classical electromagnetic zero-point radiation
Authors: Boyer Timothy H.
Published: October 2011

Any attempt to describe nature within classical physics requires the presence of Lorentz-invariant classical electromagnetic zero-point radiation to account for the Casimir forces between parallel conducting plates at low temperatures. This zero-point radiation leads to classical explanations for several phenomena that are usually regarded as requiring quantum physics. We provide a brief overview of classical electromagnetic theory including classical zero-point radiation and note the areas of agreement and disagreement between the classical and quantum theories, both of which contain Planck’s constant.
Agrobacterium
Counteracts Host-Induced Degradation of Its Effector F-Box Protein
Authors: Magori Shimpei , Citovsky Vitaly
Published: October 2011

A plant pathogen prevents degradation of its key virulence factor in infected host cells.
Evading Apoptosis to Promote Persistent Infection
Authors: Gough Nancy R.
Published: October 2011

By stimulating the production of an alternatively spliced antagonistic form of TRAIL, HIV-infected cells escape apoptotic death.
Ultrashort Peptide Bioconjugates Are Exclusively Antifungal Agents and Synergize with Cyclodextrin and Amphotericin B
Authors: Arnusch Christopher J. , Ulm Hannah , Josten Michaele , Shadkchan Yana , Osherov Nir , Sahl Hans-Georg , Shai Yechiel
Published: October 2011

Many natural broad-spectrum cationic antimicrobial peptides (AMPs) possess a general mode of action that is dependent on lipophilicity and charge. Modulating the lipophilicity of AMPs by the addition of a fatty acid has been an effective strategy to increase the lytic activity and can further broaden the spectrum of AMPs. However, lipophilic modifications that narrow the spectrum of activity and exclusively direct peptides to fungi are less common. Here, we show that short peptide sequences can be targeted to fungi with structured lipophilic biomolecules, such as vitamin E and cholesterol. The conjugates were active against
Aspergillus fumigatus
,
Cryptococcus neoformans
, and
Candida albicans
but not against bacteria and were observed to cause membrane perturbation by transmission electron microscopy and in membrane permeability studies. However, for
C. albicans
, selected compounds were effective without the perturbation of the cell membrane, and synergism was seen with a vitamin E conjugate and amphotericin B. Moreover, in combination with β-cyclodextrin, antibacterial activity emerged in selected compounds. Biocompatibility for selected active compounds was tested
in vitro
and
in vivo
using toxicity assays on erythrocytes, macrophages, and mice.
In vitro
cytotoxicity experiments led to selective toxicity ratios (50% lethal concentration/MIC) of up to 64 for highly active antifungal compounds, and no
in vivo
murine toxicity was seen. Taken together, these results highlight the importance of the conjugated lipophilic structure and suggest that the modulation of other biologically relevant peptides with hydrophobic moieties, such as cholesterol and vitamin E, generate compounds with unique bioactivity.
Identification of Hopanoid Biosynthesis Genes Involved in Polymyxin Resistance in Burkholderia multivorans
Authors: Malott Rebecca J. , Steen-Kinnaird Barbara R. , Lee Tracy D. , Speert David P.
Published: October 2011

A major challenge to clinical therapy of
Burkholderia cepacia
complex (Bcc) pulmonary infections is their innate resistance to a broad range of antimicrobials, including polycationic agents such as aminoglycosides, polymyxins, and cationic peptides. To identify genetic loci associated with this phenotype, a transposon mutant library was constructed in
B. multivorans
ATCC 17616 and screened for increased susceptibility to polymyxin B. Compared to the parent strain, mutant 26D7 exhibited 8- and 16-fold increases in susceptibility to polymyxin B and colistin, respectively. Genetic analysis of mutant 26D7 indicated that the transposon inserted into open reading frame (ORF) Bmul_2133, part of a putative hopanoid biosynthesis gene cluster. A strain with a mutation in another ORF in this cluster, Bmul_2134, was constructed and named RMI19. Mutant RMI19 also had increased polymyxin susceptibility. Hopanoids are analogues of eukaryotic sterols involved in membrane stability and barrier function. Strains with mutations in Bmul_2133 and Bmul_2134 showed increased permeability to 1-
N
-phenylnaphthylamine in the presence of increasing concentrations of polymyxin, suggesting that the putative hopanoid biosynthesis genes are involved in stabilizing outer membrane permeability, contributing to polymyxin resistance. Results from a dansyl-polymyxin binding assay demonstrated that polymyxin B does not bind well to the parent or mutant strains, suggesting that Bmul_2133 and Bmul_2134 contribute to polymyxin B resistance by a mechanism that is independent of lipopolysaccharide (LPS) binding. Through this work, we propose a role for hopanoid biosynthesis as part of the multiple antimicrobial resistance phenotype in Bcc bacteria.
Synthesis of Artemiside and Its Effects in Combination with Conventional Drugs against Severe Murine Malaria
Authors: Guo Jin , Guiguemde Armand W. , Bentura-Marciano Annael , Clark Julie , Haynes Richard K. , Chan Wing-Chi , Wong Ho-Ning , Hunt Nicholas H. , Guy R. Kiplin , Golenser Jacob
Published: October 2011

This research describes the use of novel antimalarial combinations of the new artemisinin derivative artemiside, a 10-alkylamino artemisinin. It is a stable, highly crystalline compound that is economically prepared from dihydroartemisinin in a one-step process. Artemiside activity was more pronounced than that of any antimalarial drug in use, both in
Plasmodium falciparum
culture and
in vivo
in a murine malaria model depicting cerebral malaria (CM).
In vitro
high-throughput testing of artemiside combinations revealed a large number of conventional antimalarial drugs with which it was additive. Following monotherapy in mice, individual drugs reduced parasitemias to nondetectable levels. However, after a period of latency, parasites again were seen and eventually all mice became terminally ill. Treatment with individual drugs did not prevent CM in mice with recrudescent malaria, except for piperaquine at high concentrations. Even when CM was prevented, the mice developed later of severe anemia. In contrast, most of the mice treated with drug combinations survived. A combination of artemiside and mefloquine or piperaquine may confer an optimal result because of the longer half life of both conventional drugs. The use of artemiside combinations revealed a significant safety margin of the effective artemiside doses. Likewise, a combination of 1.3 mg/kg of body weight artemiside and 10 mg/kg piperaquine administered for 3 days from the seventh day postinfection was completely curative. It appears possible to increase drug concentrations in the combination therapy without reaching toxic levels. Using the drug combinations as little as 1 day before the expected death of control animals, we could prevent further parasite development and death due to CM or anemic malaria. Earlier treatment may prevent cognitive dysfunctions which might occur after recovery from CM.
Resistance Emergence Mechanism and Mechanism of Resistance Suppression by Tobramycin for Cefepime for Pseudomonas aeruginosa
Authors: Drusano G. L. , Bonomo Robert A. , Bahniuk Nadzeya , Bulitta Juergen B. , VanScoy Brian , DeFiglio Holland , Fikes Steven , Brown David , Drawz Sarah M. , Kulawy Robert , Louie Arnold
Published: October 2011

The panoply of resistance mechanisms in
Pseudomonas aeruginosa
makes resistance suppression difficult. Defining optimal regimens is critical. Cefepime is a cephalosporin whose 3′ side chain provides some stability against AmpC β-lactamases. We examined the activity of cefepime against
P. aeruginosa
wild-type strain PAO1 and its isogenic AmpC stably derepressed mutant in our hollow-fiber infection model. Dose-ranging studies demonstrated complete failure with resistance emergence (both isolates). Inoculum range studies demonstrated ultimate failure for all inocula. Lower inocula failed last (10 days to 2 weeks). Addition of a β-lactamase inhibitor suppressed resistance even with the stably derepressed isolate. Tobramycin combination studies demonstrated resistance suppression in both the wild-type and the stably derepressed isolates. Quantitating the RNA message by quantitative PCR demonstrated that tobramycin decreased the message relative to that in cefepime-alone experiments. Western blotting with AmpC-specific antibody for
P. aeruginosa
demonstrated decreased expression. We concluded that suppression of β-lactamase expression by tobramycin (a protein synthesis inhibitor) was at least part of the mechanism behind resistance suppression. Monte Carlo simulation demonstrated that a regimen of 2 g of cefepime every 8 h plus 7 mg/kg of body weight of tobramycin daily would provide robust resistance suppression for
Pseudomonas
isolates with cefepime MIC values up to 8 mg/liter and tobramycin MIC values up to 1 mg/liter. For
P. aeruginosa
resistance suppression, combination therapy is critical.
Fluoride Excess in Coccidioidomycosis Patients Receiving Long-Term Antifungal Therapy: an Assessment of Currently Available Triazoles
Authors: Thompson George R. , Bays Derek , Cohen Stuart H. , Pappagianis Demosthenes
Published: October 2011

The use of voriconazole, a trifluorinated antifungal, has been associated with the development of fluoride excess and periostitis/exostoses. We evaluated a cohort of patients on long-term triazole therapy and found that other fluorinated triazoles (fluconazole and posaconazole) conferred no risk for the development of hyperfluorosis and its complications in our cohort.
Expansion of Paneth Cell Population in Response to Enteric Salmonella enterica Serovar Typhimurium Infection
Authors: Martinez Rodriguez Nadine R. , Eloi Marjannie D. , Huynh Alexandria , Dominguez Teresa , Lam Annie H. Cheung , Carcamo-Molina Dayana , Naser Zeina , Desharnais Robert , Salzman Nita H. , Porter Edith
Published: October 2011

Paneth cells residing at the base of the small intestinal crypts contribute to the mucosal intestinal first line defense by secreting granules filled with antimicrobial polypeptides including lysozyme. These cells derive from the columnar intestinal stem cell located at position 0 and the transit amplifying cell located at position +4 in the crypts. We have previously shown that
Salmonella enterica
serovar Typhimurium (ST), a leading cause of gastrointestinal infections in humans, effects an overall reduction of lysozyme in the small intestine. To extend this work, we examined small-intestinal tissue sections at various time points after ST infection to quantify and localize expression of lysozyme and assess Paneth cell abundance, apoptosis, and the expression of Paneth cell differentiation markers. In response to infection with ST, the intestinal Paneth cell-specific lysozyme content, the number of lysozyme-positive Paneth cells, and the number of granules per Paneth cell decreased. However, this was accompanied by increases in the total number of Paneth cells and the frequency of mitotic events in crypts, by increased staining for the proliferation marker PCNA, primarily at the crypt side walls where the transit amplifying cell resides and not at the crypt base, and by apoptotic events in villi. Furthermore, we found a time-dependent upregulation of first β-catenin, followed by EphB3, and lastly Sox9 in response to ST, which was not observed after infection with a
Salmonella
pathogenicity island 1 mutant deficient in type III secretion. Our data strongly suggest that, in response to ST infection, a Paneth cell differentiation program is initiated that leads to an expansion of the Paneth cell population and that the transit amplifying cell is likely the main progenitor responder. Infection-induced expansion of the Paneth cell population may represent an acute intestinal inflammatory response similar to neutrophilia in systemic infection.
New insights into the proximal tendons of adductor longus, adductor brevis and gracilis
Authors: Davis J A , Stringer M D , Woodley S J
Published: October 2011

Objective

The adductor muscles are implicated in the pathogenesis of groin strain, but the proximal morphology of this muscle group is poorly defined. The purpose of this study was to investigate the detailed anatomy of the entheses and proximal musculotendinous junctions (MTJs) of adductor longus (AL), adductor brevis (AB) and gracilis.

Methods

The adductors were dissected bilaterally in 10 embalmed cadavers (7 females, mean age at death 79 years (range 57–93 years)), focusing on the type of enthesis, and architecture of the proximal tendons and MTJs. Histology was used to determine if the entheses contained fibrocartilage and to semiquantitatively assess the vascularity of each proximal tendon.

Results

All entheses were fibrocartilaginous. The proximal tendons of AB and gracilis were fused, forming a common tendinous insertion in all specimens. AL and AB both contained extensive intramuscular tendons of variable length (AL 11.1 ± 1.5 cm; AB 5.4 ± 1.1 cm); this has not been recorded previously. The vascularity of AL and AB tendons decreased significantly towards the enthesis (p < 0.05), and their entheses were significantly less vascular than that of gracilis (p < 0.05).

Conclusions

The proximal anatomy of AL, AB and gracilis is more complex than previously described. The arrangement and fusion of these muscles, their fibrocartilaginous entheses and differences in vascularity of their proximal tendons may be important anatomical considerations in the pathogenesis and pattern of adductor-related groin pain.
Effect of q-nonextensive distribution of electrons on dust acoustic shock waves in strongly coupled dusty plasmas
Authors: Pakzad Hamid Reza
Published: October 2011

The reductive perturbation method is used to derive the Kordeweg – de Vries – Burgers equation in strongly coupled dusty plasmas containing Boltzmann distributed ions and q-nonextensive electrons. It is observed that the nonlinear propagation of the dust acoustic waves gives rise to shock structures when there is strong correlation among the dust grains. The effect of the q-nonextensive parameter on the shock waves is discussed.
FOURIER AND CAUCHY–STIELTJES TRANSFORMS OF POWER LAWS INCLUDING STABLE DISTRIBUTIONS
Authors: HASEBE TAKAHIRO
Published: October 2011

We introduce a class of probability measures whose densities near infinity are mixtures of Pareto distributions. This class can be characterized by the Fourier transform which has a power series expansion including real powers, not only integer powers. This class includes stable distributions in probability and also noncommutative probability theories. We also characterize the class in terms of the Cauchy–Stieltjes transform and the Voiculescu transform. If the stability index is greater than one, stable distributions in probability theory do not belong to that class, while they do in noncommutative probability.
NUCLEAR STRUCTURE OF 97Mo FROM THE (d, p) REACTION
Authors: CHOWDHURY M. S. , BOOTH W.
Published: October 2011

The reaction 96 Mo (d, p)97 Mo has been studied at 12 MeV using the tandem Van de Graaff accelerator and a multi-channel magnetic spectrograph at the Atomic Weapon Research Establishment, Aldermaston, England. Angular distributions of protons are measured at 12 different angles from 5° to 87.5° at an interval of 7.5° and the reaction products are detected in nuclear emulsion plates. Thirty levels in the energy range from 0.000 to 2.458 MeV have been observed and absolute differential cross-sections for these levels have been measured. The data are analyzed in terms of the distorted-wave Born approximation (DWBA) theory of the direct reactions, and spins, parities and spectroscopic factors are deduced for various levels. Ambiguity in the spin assignments of d5/2 and d3/2 which is allowed in ln = 2(d, p) transition is removed by using the corresponding L-value of the 95 Mo (t, p)97 Mo reaction at Et = 12 MeV . Determined value of the sum of spectroscopic factors for transfers of d5/2 neutrons suggests configuration mixing in the ground state of 96 Mo . The properties of the levels in 97 Mo are compared with previous experimental results and theoretical predictions.
Vision of the unseen
Authors: Rocha Anderson , Scheirer Walter , Boult Terrance , Goldenstein Siome
Published: October 2011

Digital images are everywhere—from our cell phones to the pages of our online news sites. How we choose to use digital image processing raises a surprising host of legal and ethical questions that we must address. What are the ramifications of hiding data within an innocent image? Is this an intentional security practice when used legitimately, or intentional deception? Is tampering with an image appropriate in cases where the image might affect public behavior? Does an image represent a crime, or is it simply a representation of a scene that has never existed? Before action can even be taken on the basis of a questionable image, we must detect something about the image itself. Investigators from a diverse set of fields require the best possible tools to tackle the challenges presented by the malicious use of today's digital image processing techniques.

In this survey, we introduce the emerging field of digital image forensics, including the main topic areas of source camera identification, forgery detection, and steganalysis. In source camera identification, we seek to identify the particular model of a camera, or the exact camera, that produced an image. Forgery detection's goal is to establish the authenticity of an image, or to expose any potential tampering the image might have undergone. With steganalysis, the detection of hidden data within an image is performed, with a possible attempt to recover any detected data. Each of these components of digital image forensics is described in detail, along with a critical analysis of the state of the art, and recommendations for the direction of future research.
CATCH
Authors: Kleanthous Marios , Sazeides Yiannakis
Published: October 2011

Cache-content-duplication (CCD) occurs when there is a miss for a block in a cache and the entire content of the missed block is already in the cache in a block with a different tag. Caches aware of content-duplication can have lower miss penalty by fetching, on a miss to a duplicate block, directly from the cache instead of accessing lower in the memory hierarchy, and can have lower miss rates by allowing only blocks with unique content to enter a cache.

This work examines the potential of CCD for instruction caches. We show that CCD is a frequent phenomenon and that an idealized duplication-detection mechanism for instruction caches has the potential to increase performance of an out-of-order processor, with a 16KB, 8-way, 8 instructions per block instruction cache, often by more than 10% and up to 36%.

This work also proposes CATCH, a hardware mechanism for dynamically detecting CCD for instruction caches. Experimental results for an out-of-order processor show that a duplication-detection mechanism with a 1.38KB cost captures on average 58% of the CCD's idealized potential.
Geographic Information Retrieval
Authors: Purves Ross , Jones Christopher
Published: October 2011

This special issue of SIGSPATIAL Special presents a series of notes describing the state of the art in Geographic Information Retrieval. The notes are intended to provide a review of some of the challenges presented as key research areas in Geographic Information Retrieval [Larson, Jones and Purves], and reflect progress in the field in the intervening years. The challenges as originally set out in [2] were the following:

• detecting geographical references in the form of place names and associated spatial natural language qualifiers within text documents and in users' queries;

• disambiguating place names to determine which particular instance of a name is intended;

• geometric interpretation of the meaning of vague place names, such as the 'Midlands' and of vague spatial language such as 'near';

• indexing documents with respect to their geographic context as well as their non-spatial thematic content;

• ranking the relevance of documents with respect to geography as well as theme;

• developing effective user interfaces that help users to find what they want; and

• developing methods to evaluate the success of GIR.
Detecting geographical references in the form of place names and associated spatial natural language
Authors: Leidner Jochen L. , Lieberman Michael D.
Published: October 2011

Recognizing spatial language in text documents, termed
geoparsing
, is useful for many applications, because together with mapping such language to lat/long values, also known as
geocoding
, it enables the connection of the unstructured textual realm with the structured realm of
Geographic Information Systems (GIS)
[11]. For example, news stories about events happening in a particular location can be explored on a map for a spatial understanding of these events, as implemented by applications like the
European Media Monitor (EMM)
[18] and
NewsStand
[13, 20]. Web pages, blogs, encyclopedia articles, news stories, tweets and travel reports can all benefit from such interlinking with maps, which requires the recognition of spatial language. Note that geoparsing can be considered as a more specific application of the task of
Named Entity Recognition and Classification (NERC):
NERC is concerned with automatically recognizing proper nouns of any kind, often meant to include monetary amounts, dates, and other types, while geoparsing is the NERC task applied to locations specifically. Geoparsing is also known by many names in the literature, including
geotagging, georecognition
, and
toponym recognition
, but for consistency, here we will refer only to geoparsing. In this paper, we provide an overview of the challenges related to geoparsing, several families of geoparsing methods, existing systems and data collections available for performing geoparsing, and open research questions related to geoparsing.
Spatial grounding with vague place models
Authors: Schlieder Christoph , Henrich Andreas
Published: October 2011

Vagueness arises as a problem in the context of grounding named entities, a central task in geographic information retrieval (GIR) which consists in establishing the entities' "denotation with respect to the world or a model" [8]. We use the term
spatial grounding
in a slightly more general sense to refer to the association of any type of
spatial descriptor
with a
place model
. In the simplest case, the descriptor consists of a toponym and the place model is provided by a (vague) geographic region. More complex descriptors make use of prepositional phrases or even a text span comprising many sentences, e.g. a travel blog entry. However, descriptors are in no way limited to natural language expressions. A frequently used descriptor in mobile GIR is the geographic position of the user as part of the specification of an information need. Furthermore, spatial activities such as taking photographs can also act as descriptors for places models ("tell me more about the focused object"). Different place models for representing the vagueness of regions have been proposed including supervaluation semantics and qualitatively augmented fuzzy footprints [12]. In this paper we concentrate on approaches to grounding that exploit diverse information sources, for instance, topographic data or the spatial behavior of a user community, to determine place models which are sometimes more complex than point sets.
Profiling CCK-mediated pancreatic growth: the dynamic genetic program and the role of STATs as potential regulators
Authors: Gurda Grzegorz T. , Wang Jackie Y. , Guo LiLi , Ernst Stephen A. , Williams John A.
Published: October 2011

Feeding mice with protease inhibitor (PI) leads to increased endogenous cholecystokinin (CCK) release and results in pancreatic growth. This adaptive response requires calcineurin (CN)-NFAT and AKT-mTOR pathways, but the genes involved, the dynamics of their expression, and other regulatory pathways remain unknown. Here, we examined the early (1–8 h) transcriptional program that underlies pancreatic growth. We found 314 upregulated and 219 downregulated genes with diverse temporal and functional profiles. Several new identifications include the following: stress response genes Gdf15 and Txnip, metabolic mediators Pitpnc1 and Hmges2, as well as components of growth factor response Fgf21, Atf3, and Egr1. The genes fell into seven self-organizing clusters, each with a distinct pattern of expression; a representative gene within each of the upregulated clusters (Egr1, Gadd45b, Rgs2, and Serpinb1a) was validated by qRT-PCR. Genes up at any point throughout the time course and CN-dependent genes were subjected to further bioinformatics-based networking and promoter analysis, yielding STATs as potential transcriptional regulators. As shown by PCR, qPCR, and Western blots, the active phospho-form of STAT3 and the Jak-STAT feedback inhibitor Socs2 were both increased throughout early pancreatic growth. Moreover, immunohistochemistry showed a CCK-dependent and acinar cell-specific increase in nuclear localization of p-STAT3, with >75% nuclear occupancy in PI-fed mice vs. <0.1% in controls. Thus, the study identified novel genes likely to be important for CCK-driven pancreatic growth, characterized and biologically validated the dynamic pattern of their expression and investigated STAT-Socs signaling as a new player in this trophic response.
Postmortem Demonstration of the Source of Pulmonary Thromboembolism: The Importance of the Autopsy
Authors: Elhammady Gina , Schubeck Andrew T. , El-Najjar Vicky , Robinson Morton J.
Published: October 2011

Periprostatic or paravaginal venous thromboses are rarely considered clinically as sites of clot origin in patients with pulmonary thromboembolism. The majority of emboli have been demonstrated to originate in the veins of the legs. This report raises awareness of pelvic vein thrombosis as a potential source of pulmonary embolism that is rarely considered or detected clinically, and which usually requires postmortem examination for recognition. It also reviews the possible routes emboli may take to reach the lungs.
Systemic Administration of CpG Oligodeoxynucleotide and Levamisole as Adjuvants for Gene-Gun-Delivered Antitumor DNA Vaccines
Authors: Šmahel Michal , Poláková Ingrid , Sobotková Eva , Vajdová Eva
Published: October 2011

DNA vaccines showed great promise in preclinical models of infectious and malignant diseases, but their potency was insufficient in clinical trials and is needed to be improved. In this study, we tested systemic administration of two conventional adjuvants, synthetic oligodeoxynucleotide carrying immunostimulatory CpG motifs (CpG-ODN) and levamisole (LMS), and evaluated their effect on immune reactions induced by DNA vaccines delivered by a gene gun. DNA vaccination was directed either against the E7 oncoprotein of human papillomavirus type 16 or against the BCR-ABL1 oncoprotein characteristic for chronic myeloid leukemia. High doses of both adjuvants reduced activation of mouse splenic CD8+T lymphocytes, but the overall antitumor effect was enhanced in both tumor models. High-dose CpG-ODN exhibited a superior adjuvant effect in comparison with any combination of CpG-ODN with LMS. In summary, our results demonstrate the benefit of combined therapy with gene-gun-delivered antitumor DNA vaccines and systemic administration of CpG-ODN or LMS.
A Single Centre Retrospective Evaluation of Laparoscopic Rectal Resection with TME for Rectal Cancer: 5-Year Cancer-Specific Survival
Authors: Quarati Raoul , Summa Massimo , Priora Fabio , Maglione Valeria , Ravazzoni Ferruccio , Lenti Luca Matteo , Marino Graziella , Grosso Federica , Spinoglio Giuseppe
Published: October 2011

Laparoscopic colon resection has established its role as a minimally invasive approach to colorectal diseases. Better long-term survival rate is suggested to be achievable with this approach in colon cancer patients, whereas some doubts were raised about its safety in rectal cancer. Here we report on our single centre experience of rectal laparoscopic resections for cancer focusing on short- and long-term oncological outcomes. In the last 13 years, 248 patients underwent minimally invasive approach for rectal cancer at our centre. We focused on 99 stage I, II, and III patients with a minimum follow-up period of 5 years. Of them 43 had a middle and 56 lower rectal tumor. Laparoscopic anterior rectal resection was performed in 71 patients whereas laparoscopic abdomino-perineal resection in 28. The overall mortality rate was 1%; the overall morbidity rate was 29%. The 5-year disease-free survival rate was 69.7%, The 5-year overall survival rate was 78.8%.
Geometric Programming Approach to an Interactive Fuzzy Inventory Problem
Authors: Mandal Nirmal Kumar
Published: October 2011

An interactive multiobjective fuzzy inventory problem with two resource constraints is presented in this paper. The cost parameters and index parameters, the storage space, the budgetary cost, and the objective and constraint goals are imprecise in nature. These parameters and objective goals are quantified by linear/nonlinear membership functions. A compromise solution is obtained by geometric programming method. If the decision maker is not satisfied with this result, he/she may try to update the current solution to his/her satisfactory solution. In this way we implement man-machine interactive procedure to solve the problem through geometric programming method.
Closed‐Form Equations for Contact Force and Moment in Elastic Contact of Rough Surfaces
Authors: Sepehri Ali , Farhang Kambiz
Published: October 2011

It is reasonable to expect that, when two nominally flat rough surfaces are brought into contact by an applied resultant force, they must support, in addition to the compressive load, an induced moment. The existence of a net applied moment would imply noneven distribution of contact force so that there are more asperities in contact over one region of the nominal area. In this paper, we consider the contact between two rectangular rough surfaces that provide normal and tangential contact force as well as contact moment to counteract the net moment imposed by the applied forces. The surfaces are permitted to develop slight angular misalignment, and thereby contact moment is derived. Through this scheme, it is possible to also define elastic contribution to friction since the half‐plane tangential contact force on one side of an asperity is no longer balanced by the half‐plane tangential force component on the opposite side. The elastic friction force, however, is shown to be of a much smaller order than the contact normal force. Approximate closed‐form equations are found for contact force and moment for the contact of rough surfaces.
On the Stabilization of the Inverted‐Cart Pendulum Using the Saturation Function Approach
Authors: Aguilar-Ibañez Carlos , Martínez-García Juan C. , Soria-López Alberto , Rubio José de Jesús
Published: October 2011

A simple stabilizing controller for the cart‐pendulum system is designed in this paper. Our control strategy describes the underactuated system as a chain of integrators with a high‐order smooth nonlinear perturbation and assumes initialization of the system in the upper half plane. The design procedure involves two sequentially associated control actions: one linear and one bounded quasilinear. The first control action brings the nonactuated coordinate near to the upright position and keeps it inside
of a well‐characterized small vicinity, whereas the second control action asymptotically brings the whole state of the system to the origin. The corresponding closed‐loop stability analysis uses standard linear stability arguments as well as the traditional Lyapunov method and the LaSalle′s theorem. Our proposed control law ensures global stability of the system in the upper half plane. We illustrate the effectiveness of the proposed control strategy via numerical simulations.
High Spatial Resolution Time-of-Flight Secondary Ion Mass Spectrometry for the Masses: A Novel Orthogonal ToF FIB-SIMS Instrument withIn SituAFM
Authors: Whitby James A. , Östlund Fredrik , Horvath Peter , Gabureac Mihai , Riesterer Jessica L. , Utke Ivo , Hohl Markus , Sedláček Libor , Jiruše Jaroslav , Friedli Vinzenz , Bechelany Mikhael , Michler Johann
Published: October 2011

We describe the design and performance of an orthogonal time-of-flight (TOF) secondary ion mass spectrometer that can be retrofitted to existing focused ion beam (FIB) instruments. In particular, a simple interface has been developed for FIB/SEM instruments from the manufacturer Tescan. Orthogonal extraction to the mass analyser obviates the need to pulse the primary ion beam and does not require the use of monoisotopic gallium to preserve mass resolution. The high-duty cycle and reasonable collection efficiency of the new instrument combined with the high spatial resolution of a gallium liquid metal ion source allow chemical observation of features smaller than 50 nm. We have also demonstrated the integration of a scanning probe microscope (SPM) operated as an atomic force microscope (AFM) within the FIB/SEM-SIMS chamber. This provides roughness information, and will also allow true three dimensional chemical images to be reconstructed from SIMS measurements.
c-Jun-N-Terminal Kinase Signaling Is Involved in Cyclosporine-Induced Epithelial Phenotypic Changes
Authors: Pallet Nicolas , Thervet Eric , Anglicheau Dany
Published: October 2011

Tubular epithelial cells play a central role in the pathogenesis of chronic nephropathies. Previous toxicogenomic studies have demonstrated that cyclosporine- (CsA-) induced epithelial phenotypic changes (EPCs) are reminiscent of an incomplete epithelial to mesenchymal transition (EMT) in a TGF-β-independent manner. Furthermore, we identified endoplasmic reticulum (ER) stress as a potential mechanism that may participate in the modulation of tubular cell plasticity during CsA exposure. Because c-jun-N-terminal kinase (JNK), which is activated during ER stress, is implicated in kidney fibrogenesis, we undertook the current study to identify the role of JNK signaling in EPCs induced by CsA. In primary cultures of human renal epithelial cells, CsA activates JNK signaling, and the treatment with a JNK inhibitor reduces the occurrence of cell shape changes, E-cadherin downregulation, cell migration, and Snail-1 expression. Our results suggest that CsA activates JNK signaling, which, in turn, may participate in the morphological alterations through the regulation of Snail-1 expression.
Management of Hypertension in the Elderly Patient at Abidjan Cardiology Institute (Ivory Coast)
Authors: Kramoh K. E. , Aké-Traboulsi E. , Konin C. , N'goran Y. , Coulibaly I. , Adoubi A. , Koffi J. , Anzouan-Kacou J. B. , Guikahue M.
Published: October 2011

Background. Since the treatment of hypertension is beneficial for the elderly, we have undertaken this study that aims to evaluate the management of hypertension in elderly patient in Côte d'Ivoire.Methods. A retrospective study was conducted among 854 hypertensive elderly patients of Abidjan Cardiology Institute who were followed for a minimum of one year, between January 2000 and December 2009.Results. The patients mean age was years, and 59% were women. At the first presentation, it was mostly systolic-diastolic hypertension (51.8%) and isolated systolic hypertension (38.5%). Mean blood pressure was  mmHg for systolic,  mmHg for diastolic, and  mmHg for pulse pressure. Pulse pressure was ≥60 mmHg in 80.4%. According to the European Guidelines stratification of the cardiovascular risk-excess attributable to high blood pressure, 82.1% of the sample had a very high added risk. The pharmacological therapy was prescribed in 93.5%. More than 66% of patients were receiving ≥2 antihypertensive drugs including fixed-dose combination drugs. The most common agents used were diuretics (63.5%) followed by angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in 61.3%. The most common agents used for monotherapy were calcium antagonists. When ≥2 drugs were used, diuretics and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were the most common. Blood pressure control was achieved in 42.6%.Conclusion. The control of elderly hypertension can be effective in Sub-Saharan Africa. He required at least two antihypertensive drugs to meet the recommended blood pressure target.
Blockade of TGF-β Signaling by the TGFβR-I Kinase Inhibitor LY2109761 Enhances Radiation Response and Prolongs Survival in Glioblastoma
Authors: Zhang Mengxian , Kleber Susanne , Röhrich Manuel , Timke Carmen , Han Na , Tuettenberg Jochen , Martin-Villalba Ana , Debus Juergen , Peschke Peter , Wirkner Ute , Lahn Michael , Huber Peter E.
Published: October 2011

Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor that tends to be resistant to the ionizing radiotherapy used to treat it. Because TGF-β is a modifier of radiation responses, we conducted a preclinical study of the antitumor effects of the TGF-β receptor (TGFβR) I kinase inhibitor LY2109761 in combination with radiotherapy. LY2109761 reduced clonogenicity and increased radiosensitivity in GBM cell lines and cancer stem–like cells, augmenting the tumor growth delay produced by fractionated radiotherapy in a supra-additive manner in vivo. In an orthotopic intracranial model, LY2109761 significantly reduced tumor growth, prolonged survival, and extended the prolongation of survival induced by radiation treatment. Histologic analyses showed that LY2109761 inhibited tumor invasion promoted by radiation, reduced tumor microvessel density, and attenuated mesenchymal transition. Microarray-based gene expression analysis revealed signaling effects of the combinatorial treatments that supported an interpretation of their basis. Together, these results show that a selective inhibitor of the TGFβR-I kinase can potentiate radiation responses in glioblastoma by coordinately increasing apoptosis and cancer stem–like cells targeting while blocking DNA damage repair, invasion, mesenchymal transition, and angiogenesis. Our findings offer a sound rationale for positioning TGFβR kinase inhibitors as radiosensitizers to improve the treatment of glioblastoma. Cancer Res; 71(23); 7155–67. ©2011 AACR.
Impact of Inflammatory Bowel Disease on Pubertal Growth
Authors: Mason A. , Malik S. , Russell R.K. , Bishop J. , McGrogan P. , Ahmed S.F.
Published: October 2011

Background: Puberty is thought to be commonly affected in adolescents with inflammatory bowel disease (IBD). Aims: To determine the impact of Crohn’s disease (CD) and ulcerative colitis (UC) on the pubertal growth spurt. Methods: Retrospective study of 30 boys with CD (CD-M), 11 girls with CD (CD-F), 14 boys with UC (UC-M) and 12 girls with UC (UC-F). Pubertal growth was assessed by calculating peak height velocity SDS (PHV SDS), height SDS at diagnosis (HtDiag) and height SDS at PHV (HtPHV) and age at PHV (AgePHV). Systemic markers of disease activity were also collected. Results: Altered parameters of pubertal growth were observed in the CD groups compared to the normal population: in the CD-M group, median HtDiag was –0.56 (p = 0.001) and median AgePHV was 14.45 years (p = 0.004), and in the CD-F group, median HtDiag was –1.14 (p = 0.007) and HtPHV was –0.79 (p = 0.039). Individually, 8/30 CD-M cases had one or more parameter affected: 2 boys had HtDiag <–2, 3 boys had HtPHV <–2, 2 boys had an AgePHV >2 years above population mean, and 2 boys had a PHV SDS <–2. In the whole group, AgePHV showed an association with erythrocyte sedimentation rate (r = 0.4; p = 0.005) and an inverse association with BMI (r = 0.4; p = 0.001). Conclusion: Disorders of pubertal growth are more likely to occur in CD and, particularly, in boys.
Moyamoya Syndrome after Radiation Therapy: Case Reports
Authors: Kim Tae-Gon , Kim Dong-Seok , Chung Sang-Sup , Choi Joong-Uhn
Published: October 2011

Potentially harmful effects of irradiation on the developing central nervous system have been well documented. We report 2 pediatric patients with moyamoya syndrome developed after irradiation. Case: A 3-year-old girl had received 4,860 cGy of postoperative radiation for optic pathway glioma. Cerebral angiography 7 months after completion of the radiation therapy revealed progressive cerebral arterial occlusive disease, involving the internal carotid artery on either side of the circle of Willis, with abnormal netlike vessels. Another 5-year-old girl had received 3,600 cGy of postoperative radiation on the cerebrum for a medulloblastoma. Two years later, she was diagnosed with moyamoya syndrome and treated with indirect revascularization. She died due to further progressive obstruction of the right M1 and A1 on the unoperated hemisphere, in spite of well-developed collateral circulation from the superficial temporal artery and middle meningeal artery on the operated left hemisphere. We suggest that radiation therapy with portals typically including carotid siphon may particularly cause vascular damage, regardless of the tumor pathology and lead to radiation-induced moyamoya syndrome. The prognosis may be poorer in case of poor collateral flow and rapid progression. The radiation therapy may cause fatal vascular damage so it should be taken into consideration when a treatment plan is being formulated for young patients.