bluuebunny/crossref_metadata_2025 huggingface dataset:
Visualizing individual microtubules by bright field microscopy
Authors: Gutiérrez-Medina Braulio , Block Steven M.
Published: October 2010

Microtubules are slender (∼25 nm diameter), filamentous polymers involved in cellular structure and organization. Individual microtubules have been visualized via fluorescence imaging of dye-labeled tubulin subunits and by video-enhanced, differential interference-contrast microscopy of unlabeled polymers using sensitive CCD cameras. We demonstrate the imaging of unstained microtubules using a microscope with conventional bright field optics in conjunction with a webcam-type camera and a light-emitting diode illuminator. The light scattered by microtubules is image-processed to remove the background, reduce noise, and enhance contrast. The setup is based on a commercial microscope with a minimal set of inexpensive components, suitable for implementation in a student laboratory. We show how this approach can be used in a demonstration motility assay, tracking the gliding motions of microtubules driven by the motor protein kinesin.
Thermodynamic curvature measures interactions
Authors: Ruppeiner George
Published: October 2010

Thermodynamic fluctuation theory originated with Einstein, who inverted the relation S=kB ln Ω to express the number of states in terms of entropy: Ω=exp(S/kB). The theory’s Gaussian approximation is discussed in most statistical mechanics texts. I review work showing how to go beyond the Gaussian approximation by adding covariance, conservation, and consistency. This generalization leads to a fundamentally new object: The thermodynamic Riemannian curvature scalar R, a thermodynamic invariant. I argue that |R| is related to the correlation length and suggest that the sign of R corresponds to whether the interparticle interactions are effectively attractive or repulsive.
Strong coupling, energy splitting, and level crossings: A classical perspective
Authors: Novotny Lukas
Published: October 2010

Strongly interacting quantum systems are at the heart of many physical processes, ranging from photosynthesis to quantum information. We demonstrate that many characteristic features of strongly coupled systems can be derived classically for a simple coupled harmonic oscillator. This model system is used to derive frequency splittings and to analyze adiabatic and diabatic transitions between the coupled states. A classical analog of the Landau–Zener formula is derived. The classical analysis is intuitive and well suited for introducing students to the basic concepts of strongly interacting systems.
A physics department’s role in preparing physics teachers: The Colorado learning assistant model
Authors: Otero Valerie , Pollock Steven , Finkelstein Noah
Published: October 2010

In response to substantial evidence that many U.S. students are inadequately prepared in science and mathematics, we have developed an effective and adaptable model that improves the education of all students in introductory physics and increases the numbers of talented physics majors becoming certified to teach physics. We report on the Colorado Learning Assistant model and discuss its effectiveness at a large research university. Since its inception in 2003, we have increased the pool of well-qualified K–12 physics teachers by a factor of approximately three, engaged scientists significantly in the recruiting and preparation of future teachers, and improved the introductory physics sequence so that students’ learning gains are typically double the traditional average.
Reducing Glutamate Release
Authors: Foley John F.
Published: October 2010

Ketone bodies compete with chloride ions for binding to vesicular glutamate transporters, thus inhibiting glutamate release.
Overexpression of
patA
and
patB
, Which Encode ABC Transporters, Is Associated with Fluoroquinolone Resistance in Clinical Isolates of
Streptococcus pneumoniae
Authors: Garvey Mark I. , Baylay Alison J. , Wong Ryan L. , Piddock Laura J. V.
Published: October 2010

Fifty-seven clinical isolates of
Streptococcus pneumoniae
were divided into four groups based on their susceptibilities to the fluoroquinolones ciprofloxacin and norfloxacin and the dyes ethidium bromide and acriflavine. Comparative reverse transcription-PCR was used to determine the level of expression of the genes
patA
and
patB
, which encode putative ABC transporters. Overexpression was observed in 14 of the 15 isolates that were resistant to both fluoroquinolones and dyes and in only 3 of 24 of those resistant to fluoroquinolones only. Isolates overexpressing
patA
and
patB
accumulated significantly less of the fluorescent dye Hoechst 33342 than wild-type isolates, suggesting that PatA and PatB are involved in efflux. Inactivation of
patA
and
patB
by
in vitro mariner
mutagenesis conferred hypersusceptibility to ethidium bromide and acriflavine in all isolates tested and lowered the MICs of ciprofloxacin in the
patAB
-overproducing and/or fluoroquinolone-resistant isolates. These data represent the first observation of overexpression of
patA
and
patB
in clinical isolates and show that PatA and PatB play a clinically relevant role in fluoroquinolone resistance.
Plasma and Intracellular (Peripheral Blood Mononuclear Cells) Pharmacokinetics of Once-Daily Raltegravir (800 Milligrams) in HIV-Infected Patients
Authors: Moltó José , Valle Marta , Back David , Cedeño Samandhy , Watson Victoria , Liptrott Neill , Egan Deirdre , Miranda Cristina , Barbanoj Manuel J. , Clotet Bonaventura
Published: October 2010

The aim of this study was to evaluate the plasma and intracellular pharmacokinetics of raltegravir in HIV-infected patients receiving once-daily raltegravir. Five HIV-infected patients on stable therapy with lopinavir-ritonavir monotherapy whose HIV-1 RNA load was <50 copies/ml were included in this open-label, pilot study. Raltegravir was added to the antiretroviral regimen at a dose of 800 mg once daily from days 0 to 10. On day 10, a full pharmacokinetic profile was obtained for each participant. Raltegravir concentrations in plasma and peripheral blood mononuclear cells (PBMCs) were determined by high-performance liquid chromatography with a fluorescence detector and by liquid chromatography-tandem mass spectrometry (LC-MS/MS), respectively. The values of the raltegravir pharmacokinetic parameters in plasma and PBMCs were calculated by noncompartmental analysis. Raltegravir was well tolerated, and all participants completed the study. No differences in the times to the maximum concentration of raltegravir in plasma or the raltegravir half-lives were observed between plasma and PBMCs. The geometric mean raltegravir maximum concentration, the concentration at the end of the dosing interval, and the area under the concentration-time curve during the dose interval in plasma versus PBMCs were 2,640 ng/ml (range, 887 to 10,605 ng/ml) versus 199 ng/ml (range, 82 to 857 ng/ml) (geometric mean ratio [GMR], 13.30; 95% confidence interval [CI], 3.11 to 56.89;
P
= 0.003); 89 ng/ml (range, 51 to 200 ng/ml) versus 7 ng/ml (range, 2 to 15 ng/ml) (GMR, 13.21; 95% CI, 3.94 to 44.26;
P
= 0.001); and 12,200 ng·h/ml (range, 5,152 to 30,130 ng·h/ml) versus 909 ng·h/ml (range, 499 to 2,189 ng·h/ml) (GMR, 13.43; 95% CI, 5.13 to 35.16;
P
< 0.001), respectively. Raltegravir does not accumulate in PBMCs, with intracellular concentrations being about 1/10 of the concentrations in plasma. Despite once-daily dosing, mean raltegravir concentrations at the end of the dosing interval in plasma and PBMCs exceeded the reported protein-binding-adjusted 95% inhibitory concentration (IC
95
) and IC
50
for wild-type viral strains, respectively.
In Vivo
and
In Vitro
Efficacy of Chloroquine against
Plasmodium malariae
and
P. ovale
in Papua, Indonesia
Authors: Siswantoro H. , Russell B. , Ratcliff A. , Prasetyorini B. , Chalfein F. , Marfurt J. , Kenangalem E. , Wuwung M. , Piera K. A. , Ebsworth E. P. , Anstey N. M. , Tjitra E. , Price R. N.
Published: October 2010

Reports of potential drug-resistant strains of
Plasmodium malariae
in western Indonesia raise concerns that chloroquine resistance may be emerging in
P. malariae
and
P. ovale
. In order to assess this,
in vivo
and
in vitro
efficacy studies were conducted in patients with monoinfection in Papua, Indonesia. Consecutive patients with uncomplicated malaria due to
P. ovale
or
P. malariae
were enrolled in a prospective clinical trial, provided with supervised chloroquine treatment, and followed for 28 days. Blood from patients with
P. malariae
or
P. ovale
parasitemia greater than 1,000 per microliter underwent
in vitro
antimalarial drug susceptibility testing using a modified schizont maturation assay. Of the 57 evaluable patients in the clinical study (
P. malariae
,
n
= 46;
P. ovale
,
n
= 11), none had recurrence with the same species during follow-up. The mean parasite reduction ratio at 48 h was 86 (95% confidence interval [CI], 57 to 114) for
P. malariae
and 150 (95% CI, 54 to 245) for
P. ovale
(
P
= 0.18). One patient infected with
P. malariae
, with 93% of parasites at the trophozoite stage, was still parasitemic on day 4.
In vitro
drug susceptibility assays were carried out successfully for 40 isolates (34 infected with
P. malariae
and 6 with
P. ovale
). The
P. malariae
infections at trophozoite stages had significantly higher chloroquine 50% effective concentrations (EC
50
s) (median, 127.9 nM [range, 7.9 to 2,980]) than those initially exposed at the ring stage (median, 14.0 nM [range, 3.5 to 27.0];
P
= 0.01). The EC
50
for chloroquine in
P. ovale
was also higher in an isolate initially at the trophozoite stage (23.2 nM) than in the three isolates predominantly at ring stage (7.8 nM). Chloroquine retains adequate efficacy against
P. ovale
and
P. malariae
, but its marked stage specificity of action may account for reports of delayed parasite clearance times.
A Novel Insertion Sequence, IS
Aba10
, Inserted into IS
Aba1
Adjacent to the
bla
OXA-23
Gene and Disrupting the Outer Membrane Protein Gene
carO
in
Acinetobacter baumannii
Authors: Lee Yangsoon , Kim Chang-Ki , Lee Hyukmin , Jeong Seok Hoon , Yong Dongeun , Lee Kyungwon
Published: October 2010

We investigated an outbreak caused by carbapenem-resistant
Acinetobacter baumannii
carrying the
bla
OXA-23
gene. A novel insertion sequence (IS), named IS
Aba10
, was found to be inserted into the IS
Aba1
element preceding the
bla
OXA-23
gene in a group of isolates showing higher carbapenem MICs. The presence of IS
Aba10
was associated with increased OXA-23 expression, likely by providing additional promoter sequences. IS
Aba10
was also inserted into the
carO
outer membrane protein gene in most of these isolates.
Leukocytes Infiltrate the Skin and Draining Lymph Nodes in Response to the ProtozoanLeishmania infantum chagasi
Authors: Thalhofer Colin J. , Chen Yani , Sudan Bayan , Love-Homan Laurie , Wilson Mary E.
Published: October 2010

The vector-borne protozoanLeishmania infantum chagasicauses minimal inflammation after inoculation into skin but disseminates to cause fatal visceral leishmaniasis. To define the inflammatory response at the parasite inoculation site, we introduced metacyclicL. infantum chagasipromastigotes intradermally into BALB/c mouse ears and studied inflammatory cells over 7 days. Ly6G+neutrophils rapidly infiltrated the dermis, peaking after 6 to 24 h. Macrophages and NK cells next infiltrated the dermis, and NK followed by B cells expanded in draining lymph nodes. Parasite-containing phagocytes were tracked with fluorescent mCherry-labeledL. infantum chagasi.Ly6G+neutrophils contained the greatest proportion of intracellular parasites 6 to 24 h after inoculation, whereas dermal macrophages harbored the majority of intracellular parasites after 2 to 7 days. These observations were validated microscopically. Low doses of antibody transiently depleted mice of neutrophils, leaving other cells intact. Combined results ofin vivoimaging, flow cytometry, and quantitative PCR showed that neutrophil depletion slowed the clearance of extracellular (luciferase-positive) promastigotes during the first 24 h after inoculation yet decreased the numbers of leukocytes containing intracellular (mCherry-positive) parasites. From 3 days onward, totalL. infantum chagasi-containing dermal leukocytes and totalL. infantum chagasiparasites in draining lymph nodes were similar in both groups. Nonetheless, a second wave ofL. infantum chagasi-containing neutrophils occurred 7 days after parasite inoculation into neutrophil-depleted mice, corresponding to the time of neutrophil recovery. Thus, neutrophils were recruited to the dermis even late after inoculation, andL. infantum chagasitrafficked through neutrophils in both neutrophil-depleted and control mice, albeit with different kinetics. Recruitment of neutrophils and transient parasite residence in neutrophils may play a role in nonulcerative forms of leishmaniasis.
Vets in changing times
Authors: Tiffin Ross
Published: October 2010

The environment in which practices must operate has changed dramatically over the past 30 years, with major shifts in the way clients behave, the retail environment and the expectations of vets themselves. Ross Tiffin looks at some of the changes that have occurred and the implications for business.
Measuring and monitoring reproductive performance in dairy herds
Authors: Cook John
Published: October 2010

As herds continue to increase in size, traditional indicators for measuring and monitoring reproductive performance, such as calving interval, calving to conception interval, conception rate, submission rate and days open, are becoming less appropriate markers for assessing the performance of modern dairy herds. The definitions used to describe these parameters often vary, which can make it difficult to know which cows are eligible for analysis and hence benchmark true herd performance. The use of averages is also likely to miss the true impact of management changes on the reproductive capability of the herd. This article suggests the use of some alternative measures of reproductive performance and considers their role in the management of larger dairy herds.
Prepurchase examination in horses: detection and significance of heart murmurs
Authors: Patteson Mark
Published: October 2010

By requesting a prepurchase examination, potential purchasers are asking the veterinary surgeon to provide an opinion on the suitability of a particular horse for a specified intended purpose. The identification and significance of cardiac murmurs is one element of such examinations. Diagnosis of cardiac murmurs can be challenging – for example, a murmur could be due to normal physiology or it may be the result of disease, which may or may not limit a horse's performance or safety, and, furthermore, the relevance of this will depend on the intended use of the animal. However, the ground rules for a prepurchase examination are similar to those of any clinical evaluation – the key is to establish a specific diagnosis, which must then be put into context in terms of a prospective purchaser's requirements. To regard all horses with abnormal murmurs as unsuitable for purchase would not be in the interests of possible buyers. This article describes the clinical approach to detecting and assessing the significance of heart murmurs in horses as part of a prepurchase examination. It also highlights the importance of recording the findings accurately and providing a thorough explanation of all the issues, including any potential for progression of a condition and how abnormal results may or may not affect the safety, performance, resale and insurance of an animal.
Enhancing the fairness of pandemic critical care triage
Authors: Kirby Jeffrey
Published: October 2010

Historically, the triage of temporarily scarce health resources has served narrow utilitarian ends. The recent H1N1 pandemic experience provided an opportunity for expanding the theoretical foundations/understandings of critical care triage in the context of declared infectious pandemics. This paper briefly explores the ethics-related challenges associated with the development of modern critical care triage protocols and provides descriptions of some ‘enhanced fairness’ features which were developed through the use of an inclusive deliberative engagement process by a Canadian provincial Department of Health.
Surgeons' opinions and practice of informed consent in Nigeria
Authors: Ogundiran Temidayo O , Adebamowo Clement A
Published: October 2010

Background

Informed consent is perhaps more relevant to surgical specialties than to other clinical disciplines. Fundamental to this concept is the provision of relevant information for the patient to make an informed choice about a surgical intervention. The opinions of surgeons in Nigeria about informed consent in their practice were surveyed.

Methods

A cross-sectional survey of surgeons in Nigeria was undertaken in 2004/5 using self-administered semistructured questionnaires.

Results

There were 102 respondents, 85.3% of whom were men and 58.8% were aged 31–40 years. 43.1% were consultants and 54.0% were surgical trainees. 27.4% were in surgical subspecialties, 26.5% in general surgery and 21.6% were obstetricians and gynaecologists. 54.9% agreed that sufficient information is not provided to patients while obtaining their consent for surgical procedures. They listed medicolegal reasons (70.6%), informing patients about benefits, risks and alternatives (64.7%) and hospital policy (50.0%) as some reasons for obtaining consent for surgical procedures. When patients decline to give consent for surgery, 84.3% of them thought that poor communication between surgeons and patients may be contributory. They identified taking a course in bioethics during surgical training and compulsory communication skills course as some ways to improve communication between surgeons and patients.

Conclusion

Most Nigerian surgeons seemed to have a good knowledge of the informed consent requirements and process but fall short in practice. There is a need to improve the surgeon–patient relationship in line with modern exigencies to provide interactive environments for fruitful patient communication and involvement.
BACKPROPAGATION THROUGH TIME TRAINING OF A NEURO-FUZZY CONTROLLER
Authors: KOPRINKOVA-HRISTOVA PETIA
Published: October 2010

The paper considers gradient training of fuzzy logic controller (FLC) presented in the form of neural network structure. The proposed neuro-fuzzy structure allows keeping linguistic meaning of fuzzy rule base. Its main adjustable parameters are shape determining parameters of the linguistic variables fuzzy values as well as that of the used as intersection operator parameterized T-norm. The backpropagation through time method was applied to train neuro-FLC for a highly non-linear plant (a biotechnological process). The obtained results are discussed with respect to adjustable parameters rationality. Conclusions are made with respect to the appropriate intersection operations too.
AUTOMATED NONLINEAR SYSTEM MODELING WITH MULTIPLE FUZZY NEURAL NETWORKS AND KERNEL SMOOTHING
Authors: YU WEN , LI XIAOOU
Published: October 2010

This paper, presents a novel identification approach using fuzzy neural networks. It focuses on structure and parameters uncertainties which have been widely explored in the literatures. The main contribution of this paper is that an integrated analytic framework is proposed for automated structure selection and parameter identification. A kernel smoothing technique is used to generate a model structure automatically in a fixed time interval. To cope with structural change, a hysteresis strategy is proposed to guarantee finite times switching and desired performance.
DESIGNING BOOSTING ENSEMBLE OF RELATIONAL FUZZY SYSTEMS
Authors: SCHERER RAFAŁ
Published: October 2010

A method frequently used in classification systems for improving classification accuracy is to combine outputs of several classifiers. Among various types of classifiers, fuzzy ones are tempting because of using intelligible fuzzy if-then rules. In the paper we build an AdaBoost ensemble of relational neuro-fuzzy classifiers. Relational fuzzy systems bond input and output fuzzy linguistic values by a binary relation; thus, fuzzy rules have additional, comparing to traditional fuzzy systems, weights — elements of a fuzzy relation matrix. Thanks to this the system is better adjustable to data during learning. In the paper an ensemble of relational fuzzy systems is proposed. The problem is that such an ensemble contains separate rule bases which cannot be directly merged. As systems are separate, we cannot treat fuzzy rules coming from different systems as rules from the same (single) system. In the paper, the problem is addressed by a novel design of fuzzy systems constituting the ensemble, resulting in normalization of individual rule bases during learning. The method described in the paper is tested on several known benchmarks and compared with other machine learning solutions from the literature.
ON THE POSSIBLE RANKS AMONG MATRICES WITH A GIVEN PATTERN
Authors: JOHNSON CHARLES R. , ZHANG YULIN
Published: October 2010

Given are tight upper and lower bounds for the minimum rank among all matrices with a prescribed zero–nonzero pattern. The upper bound is based upon solving for a matrix with a given null space and, with optimal choices, produces the correct minimum rank. It leads to simple, but often accurate, bounds based upon overt statistics of the pattern. The lower bound is also conceptually simple. Often, the lower and an upper bound coincide, but examples are given in which they do not.
ONLINE SCHEDULING OF PARALLEL JOBS WITH BOUNDED PROCESSING TIMES ON TWO MACHINES
Authors: LIU MING , XU YINFENG , CHU CHENGBIN , ZHENG FEIFENG
Published: October 2010

We study the problem of online scheduling parallel jobs with bounded processing times on 2 machines, and the objective is to minimize makespan. A parallel job requires simultaneous processing on a pre-specified, job-dependent number of machines. The problem is online in the sense that jobs are presented one by one. Once a job is presented, we must irrevocably assign it to some time slot before the next one shows up. We investigate the case where the processing times of jobs are bounded within interval [a, αa] where a > 0 and α > 1. We first prove a lower bound of competitive ratios for online algorithms equal [Formula: see text] when α ≥ 2 and [Formula: see text] when 1 < α < 2, respectively. We further prove that the Greedy algorithm proposed in Chan et al. (2008) is [Formula: see text]-competitive in the case but it cannot be better than [Formula: see text]-competitive. The results imply that when 1 < α < 2 Greedy has a competitive ratio better than 2, which is the competitive ratio of Greedy in the case without processing time bound.
What is eqDRC?
Authors: Pikus Fedor G.
Published: October 2010

Traditional design rule checking (DRC) uses one-dimensional measurements of features and geometries to determine rule compliance. As feature sizes decrease and design complexity increases, analysis and verification become increasingly difficult. Equation-based DRC (eqDRC) extends DRC technology with a programmable modeling engine. Using eqDRC, users can define multi-dimensional feature measurements with flexible mathematical expressions that can be used to develop, calibrate, and optimize models for design analysis and verification.
Lifting the Nebula: Novel Insights into Skeletal Muscle Contractility
Authors: Ottenheijm Coen A. C. , Granzier Henk
Published: October 2010

Nebulin is a giant protein and a constituent of the skeletal muscle sarcomere. The name of this protein refers to its unknown (i.e., nebulous) function. However, recent rapid advances reveal that nebulin plays important roles in the regulation of muscle contraction. When these functions of nebulin are compromised, muscle weakness ensues, as is the case in patients with nemaline myoptahy.
Gamma Oscillations in the Hippocampus
Authors: Colgin Laura Lee , Moser Edvard I.
Published: October 2010

Gamma oscillations are thought to temporally link the activity of distributed cells. We discuss mechanisms of gamma oscillations in the hippocampus and review evidence supporting a functional role for such oscillations in several key hippocampal operations, including cell grouping, dynamic routing, and memory. We propose that memory encoding and retrieval are coordinated by different frequencies of hippocampal gamma oscillations and suggest how transitions between slow and fast gamma may occur.
Ancient Atmospheres and the Evolution of Oxygen Sensing Via the Hypoxia-Inducible Factor in Metazoans
Authors: Taylor Cormac T. , McElwain Jennifer C.
Published: October 2010

Metazoan diversification occurred during a time when atmospheric oxygen levels fluctuated between 15 and 30%. The hypoxia-inducible factor (HIF) is a primary regulator of the adaptive transcriptional response to hypoxia. Although the HIF pathway is highly conserved, its complexity increased during periods when atmospheric oxygen concentrations were increasing. Thus atmospheric oxygen levels may have provided a selection force on the development of cellular oxygen-sensing pathways.
Recovery of Visual Function in a Patient with an Onodi Cell Mucocele Compressive Optic Neuropathy Who Had a 5-Week Interval between Onset and Surgical Intervention: A Case Report
Authors: Wu Wencan , Sun Michelle T. , Cannon Paul S. , Jianbo Shi , Selva Dinesh
Published: October 2010

Purpose. To report on a patient with compressive optic neuropathy secondary to an Onodi cell mucocele, who fully recovered visual function following surgery.Method. Case report.Results. A 28-year-old male was admitted with a right visual acuity of 20/100 following treatment for an initial diagnosis of optic neuritis. Subsequent examination suggested compressive optic neuropathy, and neuroimaging confirmed the presence of an Onodi mucocele compressing the optic nerve. The patient underwent a right endonasal sphenoethmoidectomy with decompression 5 weeks after the initial onset of symptoms. Three weeks following surgery, the visual acuity was 20/20, and there was complete resolution of the visual field defect, which has remained stable at 1 year.Conclusion. Onodi cell mucocele should be included in the differential diagnosis of a young patient with compressive optic neuropathy. Surgical decompression should be considered even when symptoms have been present for over a month.
Tumor Antigen Cross‐Presentation and the Dendritic Cell: Where it All Begins?
Authors: McDonnell Alison M. , Robinson Bruce W. S. , Currie Andrew J.
Published: October 2010

Dendritic cells (DCs) are professional antigen‐presenting cells (APCs) that are critical for the generation of effective cytotoxic T lymphocyte (CTL) responses; however, their function and phenotype are often defective or altered in tumor‐bearing hosts, which may limit their capacity to mount an effective tumor‐specific CTL response. In particular, the manner in which exogenous tumor antigens are acquired, processed, and cross‐presented to CD8 T cells by DCs in tumor‐bearing hosts is not well understood, but may have a profound effect on antitumor immunity. In this paper, we have examined the role of DCs in the cross‐presentation of tumor antigen in terms of their subset, function, migration, and location with the intention of examining the early processes that contribute to the development of an ineffective anti‐tumor immune response.
Low‐Complexity Gaussian Detection for MIMO Systems
Authors: Wo Tianbin , Hoeher Peter Adam
Published: October 2010

For single‐carrier transmission over delay‐spread multi‐input multi‐output (MIMO) channels, the computational complexity of the receiver is often considered as a bottleneck with respect to (w.r.t.) practical implementations. Multi‐antenna interference (MAI) together with intersymbol interference (ISI)
provides fundamental challenges for efficient and reliable data detection. In this paper, we carry out a systematic study on the interference structure of MIMO‐ISI channels, and sequentially deduce three different Gaussian approximations to simplify the calculation of the global likelihood function. Using factor graphs
as a general framework and applying the Gaussian approximation, three low‐complexity iterative detection algorithms are derived, and their performances are compared by means of Monte Carlo simulations. After a careful inspection of their merits and demerits, we propose a graph‐based iterative Gaussian
detector (GIGD) for severely delay‐spread MIMO channels. The GIGD is characterized by a strictly linear computational complexity w.r.t. the effective channel memory length, the number of transmit antennas, and the number of receive antennas. When the channel has a sparse ISI structure, the complexity of the
GIGD is strictly proportional to the number of nonzero channel taps. Finally, the GIGD provides a near‐optimum performance in terms of the bit error rate (BER) for repetition encoded MIMO systems.
Development of a Multicommutated Flow System with Chemiluminometric Detection for Quantification of Gentamicin in Pharmaceuticals
Authors: Santos Lúcia H. M. L. M. , Araújo A. N. , Reis Boaventura , Montenegro M. C. B. S. M.
Published: October 2010

A new flow procedure based on multicommutation with chemiluminometric detection was developed to quantify gentamicin sulphate in pharmaceutical formulations. This approach is based on gentamicin's ability to inhibit the chemiluminometric reaction between luminol and hypochlorite in alkaline medium, causing a decrease in the analytical signal. The inhibition of the analytical signal is proportional to the concentration of gentamicin sulphate, within a linear range of 1 to 4 μg mL-1with a coefficient variation <3%. A sample throughput of 55 samples h-1was obtained. The developed method is sensitive, simple, with low reagent consumption, reproducible, and inexpensive, and when applied to the analysis of pharmaceutical formulations (eye drops and injections) it gave results with RSD between 1.10 and 4.40%.
The Microstructure of Ni Layer on Single-Walled Carbon Nanotubes Prepared by an Electroless Coating Process
Authors: Li Weixue , Jin Hui , Hao Yuan , Chen Tijun , Dai Jianfeng , Wang Qing
Published: October 2010

The single-walled carbon nanotubes (SWNTs, diameter: 2~3 nm), which were obtained in the suspension of purification solution, with Ni-P coating layers were obtained by an electroless deposition process. The SWNTs before and after coating were characterized by transmission electron microscopy (TEM) and energy dispersive spectrometry (EDS). An Ni-P layer on individual nanotube with thickness of 20 nm can be obtained after the deposition process. The X-ray diffraction (XRD) and selected area electron diffraction (SAED) analysis of Ni-P SWNTs before and after heat treatment show that the heat treatment caused the transformation of the amorphous Ni-P layer to the nanocrystalline Ni-P (crystalline Ni andNi3P intermetallic compound) layer. The XRD pattern of SWNTs with Ni-P layers after heat treatment revealed that the crystal structures of Ni in plating layer contained: hexagonal close-packed (hcp) structure and face-centered cubic (fcc) structure. The lattice parameters of Ni (fcc) andNi3P are larger than the bulk's, indicting that the lattice expansion has taken place. However, the lattice parameter of Ni (hcp) has no difference from the bulk's.
Isolation of Specific Clones from Nonarrayed BAC Libraries through Homologous Recombination
Authors: Nefedov Mikhail , Carbone Lucia , Field Matthew , Schein Jacquie , de Jong Pieter J.
Published: October 2010

We have developed a new approach to screen bacterial artificial chromosome (BAC) libraries by recombination selection. To test this method, we constructed an orangutan BAC library using an E. coli strain (DY380) with temperature inducible homologous recombination (HR) capability. We amplified one library segment, induced HR at 42∘C to make it recombination proficient, and prepared electrocompetent cells for transformation with a kanamycin cassette to target sequences in the orangutan genome through terminal recombineering homologies. Kanamycin‐resistant colonies were tested for the presence of BACs containing the targeted genes by the use of a PCR‐assay to confirm the presence of the kanamycin insertion. The results indicate that this is an effective approach for screening clones. The advantage of recombination screening is that it avoids the high costs associated with the preparation, screening, and archival storage of arrayed BAC libraries. In addition, the screening can be conceivably combined with genetic engineering to create knockout and reporter constructs for functional studies.
Potential of Complementary and Alternative Medicine in Preventive Management of Novel H1N1 Flu (Swine Flu) Pandemic: Thwarting Potential Disasters in the Bud
Authors: Arora Rajesh , Chawla R. , Marwah Rohit , Arora P. , Sharma R. K. , Kaushik Vinod , Goel R. , Kaur A. , Silambarasan M. , Tripathi R. P. , Bhardwaj J. R.
Published: October 2010

The emergence of novel H1N1 has posed a situation that warrants urgent global attention. Though antiviral drugs are available in mainstream medicine for treating symptoms of swine flu, currently there is no preventive medicine available. Even when available, they would be in short supply and ineffective in a pandemic situation, for treating the masses worldwide. Besides the development of drug resistance, emergence of mutant strains of the virus, emergence of a more virulent strain, prohibitive costs of available drugs, time lag between vaccine developments, and mass casualties would pose difficult problems. In view of this, complementary and alternative medicine (CAM) offers a plethora of interesting preventive possibilities in patients. Herbs exhibit a diverse array of biological activities and can be effectively harnessed for managing pandemic flu. Potentially active herbs can serve as effective anti influenza agents. The role of CAM for managing novel H1N1 flu and the mode of action of these botanicals is presented here in an evidence‐based approach that can be followed to establish their potential use in the management of influenza pandemics. The complementary and alternative medicine approach deliberated in the paper should also be useful in treating the patients with serious influenza in non pandemic situations.
Ewing's Sarcoma and Second Malignancies
Authors: Schiffman Joshua D. , Wright Jennifer
Published: October 2010

Ewing's sarcoma (ES) is a rare tumor that is most common in children and young adults. Late effects of ES therapy include second cancers, a tragic outcome for survivors of such a young age. This paper will explore the frequencies and types of malignancies that occur after ES. Additionally, it will review how second malignancies have changed with the shift in treatment from high-dose radiation to chemotherapy regimens including alkylators and epipodophyllotoxins. The risk of additional cancers in ES survivors will also be compared to survivors of other childhood cancers. Finally, the possible genetic contribution to ES and second malignancies will be discussed.
Ecosystem-Based Management in Fiji: Successes and Challenges after Five Years of Implementation
Authors: Jupiter Stacy D. , Egli Daniel P.
Published: October 2010

In 2005, a network of 3 large, district-wide marine protected areas (MPAs) and 17 village-managed closures (tabu) was established in Kubulau District, Fiji. Underwater visual census (UVC) data of fish biomass and benthic cover were collected between 2007 and 2009 and analysed with PERMANOVA and ANOSIM to assess differences between closed and open areas. High reef fish biomass (>1000 kg/ha) within closures, significantly elevated over open areas, was consistently observed from: (1) tabu areas on naturally productive reefs within visual distance from villages; and (2) the large, long-term permanent closure located away from fishing pressure. Factors that may have contributed to low fish biomass within closures include small size of closures; noncompliance with management rules; and disclosure of management success to fishers from villages with high reliance on fisheries products. Future success of the network depends on improving awareness of management rules and ensuring implementation within a broader ecosystem framework.
Targeting the Mechanisms of Resistance to Chemotherapy and Radiotherapy with the Cancer Stem Cell Hypothesis
Authors: Morrison Ryan , Schleicher Stephen M. , Sun Yunguang , Niermann Kenneth J. , Kim Sungjune , Spratt Daniel E. , Chung Christine H. , Lu Bo
Published: October 2010

Despite advances in treatment, cancer remains the 2nd most common cause of death in the United States. Poor cure rates may result from the ability of cancer to recur and spread after initial therapies have seemingly eliminated detectable signs of disease. A growing body of evidence supports a role for cancer stem cells (CSCs) in tumor regrowth and spread after initial treatment. Thus, targeting CSCs in combination with traditional induction therapies may improve treatment outcomes and survival rates. Unfortunately, CSCs tend to be resistant to chemo- and radiation therapy, and a better understanding of the mechanisms underlying CSC resistance to treatment is necessary. This paper provides an update on evidence that supports a fundamental role for CSCs in cancer progression, summarizes potential mechanisms of CSC resistance to treatment, and discusses classes of drugs currently in preclinical or clinical testing that show promise at targeting CSCs.
Enhanced Genetic Instability and Dasatinib Sensitivity in Mammary Tumor Cells Lacking NEDD9
Authors: Singh Mahendra K. , Izumchenko Eugene , Klein-Szanto Andres J. , Egleston Brian L. , Wolfson Marina , Golemis Erica A.
Published: October 2010

Elevated expression of the NEDD9/HEF1/Cas-L scaffolding protein promotes tumor cell invasion and metastasis in multiple cancer cell types. Conversely, generation of mammary tumors in the mouse mammary tumor virus (MMTV)-polyoma virus middle T (PyVT) genetic model is delayed by a Nedd9−/− genotype. These activities arise from the role of NEDD9 in assembling complexes and supporting activity of cancer signaling proteins, including FAK, Src, Shc, and AKT, and would support evaluation of NEDD9 expression as an unambiguous biomarker for tumor aggressiveness. However, we here show that despite the initial delay in tumor growth, cells derived from MMTV-PyVT;Nedd9−/− tumors are characteristically hyperaggressive versus MMTV-PyVT;Nedd9+/+ cells in anchorage-independent growth, in growth on three-dimensional matrix produced by tumor-associated fibroblasts, and in formation of tumors after mammary orthotopic reinjection and of lung metastases after tail vein injection. This reversal suggests the specific selection of MMTV-PyVT;Nedd9−/− cells for growth in an in vivo microenvironment. Indeed, MMTV-PyVT;Nedd9−/− cells have increased cell cycle, centrosomal, and mitotic defects, phenotypes compatible with the increased selection of these cells for aggressive growth. Intriguingly, in spite of their aggressive phenotype, MMTV-PyVT;Nedd9−/− cells persistently have low levels of Src activation and are hypersensitive to the Src kinase inhibitor dasatinib. These studies identify NEDD9 as a complex modulator of different aspects of mammary tumor growth. Cancer Res; 70(21); 8907–16. ©2010 AACR.
BRCA1-IRIS Overexpression Promotes Cisplatin Resistance in Ovarian Cancer Cells
Authors: Chock Kerri L. , Allison Jamie M.S. , Shimizu Yoshiko , ElShamy Wael M.
Published: October 2010

Evasion of apoptosis plays a key role in cancer development, drug resistance, and recurrence. The BRCA1 locus product protein BRCA1-IRIS is overexpressed in several cisplatin-resistant ovarian cancer cell lines, but its relationship to resistance is uncertain. Here, we show that in human ovarian surface epithelial (HOSE) cells, overexpression of BRCA1-IRIS triggers expression of the antiapoptotic protein survivin. Negative modulation of phosphatidylinositol 3-kinase (PI3K) signaling or AKT silencing reduced survivin expression in this setting. Conversely, silencing BRCA1-IRIS in ovarian cancer cell lines derepressed PTEN expression along with the antiapoptotic AKT targets FOXO1 and FOXO3a, suppressing survivin expression. Cisplatin (≤50 μmol/L) exposure was sufficient to activate expression of the BRCA1-IRIS-AKT-survivin cascade in HOSE cells, whereas under similar conditions cisplatin failed to induce apoptosis in ovarian cancer cell lines expressing this regulatory cascade. Mechanistic investigations indicated that BRCA1-IRIS triggers survivin expression through a PI3K/AKT-dependent pathway involving NF-κB, but also through a PI3K/AKT-independent pathway involving PTEN, FOXO1, and FOXO3a. Our findings indicate how BRCA1-IRIS overexpression prevents chemotherapy-induced cell death by upregulating expression of survivin, and they highlight this regulatory cascade as a candidate focus to improve treatment of advanced drug-resistant ovarian cancers. Cancer Res; 70(21); 8782–91. ©2010 AACR.
Prostate Cancer Radiosensitization through Poly(ADP-Ribose) Polymerase-1 Hyperactivation
Authors: Dong Ying , Bey Erik A. , Li Long-Shan , Kabbani Wareef , Yan Jingsheng , Xie Xian-Jin , Hsieh Jer-Tsong , Gao Jinming , Boothman David A.
Published: October 2010

The clinical experimental agent, β-lapachone (β-lap; Arq 501), can act as a potent radiosensitizer in vitro through an unknown mechanism. In this study, we analyzed the mechanism to determine whether β-lap may warrant clinical evaluation as a radiosensitizer. β-Lap killed prostate cancer cells by NAD(P)H:quinone oxidoreductase 1 (NQO1) metabolic bioactivation, triggering a massive induction of reactive oxygen species, irreversible DNA single-strand breaks (SSB), poly(ADP-ribose) polymerase-1 (PARP-1) hyperactivation, NAD+/ATP depletion, and μ-calpain–induced programmed necrosis. In combination with ionizing radiation (IR), β-lap radiosensitized NQO1+ prostate cancer cells under conditions where nontoxic doses of either agent alone achieved threshold levels of SSBs required for hyperactivation of PARP-1. Combination therapy significantly elevated SSB level, γ-H2AX foci formation, and poly(ADP-ribosylation) of PARP-1, which were associated with ATP loss and induction of μ-calpain–induced programmed cell death. Radiosensitization by β-lap was blocked by the NQO1 inhibitor dicoumarol or the PARP-1 inhibitor DPQ. In a mouse xenograft model of prostate cancer, β-lap synergized with IR to promote antitumor efficacy. NQO1 levels were elevated in ∼60% of human prostate tumors evaluated relative to adjacent normal tissue, where β-lap might be efficacious alone or in combination with radiation. Our findings offer a rationale for the clinical utilization of β-lap (Arq 501) as a radiosensitizer in prostate cancers that overexpress NQO1, offering a potentially synergistic targeting strategy to exploit PARP-1 hyperactivation. Cancer Res; 70(20); 8088–96. ©2010 AACR.
Cell Signaling by Urokinase-type Plasminogen Activator Receptor Induces Stem Cell–like Properties in Breast Cancer Cells
Authors: Jo Minji , Eastman Boryana M. , Webb Drue L. , Stoletov Konstantin , Klemke Richard , Gonias Steven L.
Published: October 2010

Signaling by urokinase-type plasminogen activator receptor (uPAR) can cause epithelial-mesenchymal transition (EMT) in cultured breast cancer cells. In this report, we show that uPAR signaling can also induce cancer stem cell (CSC)–like properties. Ectopic overexpression of uPAR in human MDA-MB-468 breast cancer cells promoted the emergence of a CD24−/CD44+ phenotype, characteristic of CSCs, while increasing the cell surface abundance of integrin subunits β1/CD29 and α6/CD49f that represent putative mammary gland stem cell biomarkers. uPAR overexpression increased mammosphere formation in vitro and tumor formation in an immunocompromized severe combined immunodeficient (SCID) mouse model of orthotopic breast cancer. Hypoxic conditions that are known to induce EMT in MDA-MB-468 cells also increased cell surface β1/CD29, mimicking the effects of uPAR overexpression. Antagonizing uPAR effector signaling pathways reversed the increase in cell surface integrin expression. Whereas uPAR overexpression did not induce EMT in MCF-7 breast cancer cells, CSC-like properties were nevertheless still induced along with an increase in tumor initiation and growth in the orthotopic setting in SCID mice. Notably, in MCF-7 cell mammospheres, which display a well-defined acinus-like structure with polarized expression of E-cadherin and β1-integrin, cell collapse into the central cavity was decreased by uPAR overexpression, suggesting that uPAR signaling may stabilize epithelial morphology. In summary, our findings show that uPAR signaling can induce CSC-like properties in breast cancer cells, either concomitantly with or separately from EMT. Cancer Res; 70(21); 8948–58. ©2010 AACR.
TRAIL-Induced Apoptosis Is Preferentially Mediated via TRAIL Receptor 1 in Pancreatic Carcinoma Cells and Profoundly Enhanced by XIAP Inhibitors
Authors: Stadel Dominic , Mohr Andrea , Ref Caroline , MacFarlane Marion , Zhou Shaoxia , Humphreys Robin , Bachem Max , Cohen Gerry , Möller Peter , Zwacka Ralf M. , Debatin Klaus-Michael , Fulda Simone
Published: October 2010

Purpose: We previously reported that small molecule X-linked inhibitor of apoptosis (XIAP) inhibitors synergize with soluble TRAIL to trigger apoptosis in pancreatic carcinoma cells. Because cancers may preferentially signal via 1 of the 2 agonistic TRAIL receptors, we investigated these receptors as a therapeutic target in pancreatic cancer in the present study.

Experimental Design: We examined TRAIL receptor expression and cytotoxicity of specific monoclonal antibodies to TRAIL-R1 (HGS-ETR1, mapatumumab) or TRAIL-R2 (HGS-ETR2, lexatumumab) and of TRAIL receptor selective mutants alone and in combination with small molecule XIAP inhibitors in pancreatic cancer cell lines, in primary specimens, and in a xenotransplant model in vivo.

Results: The majority of primary pancreatic carcinoma samples and all cell lines express one or both agonistic TRAIL receptors. Nine of 13 cell lines are more sensitive to mapatumumab-induced apoptosis, whereas lexatumumab requires cross-linking for maximal activity. Similarly, TRAIL-R1 selective mutants display higher cytotoxicity than TRAIL-R2 selective mutants. Small molecule XIAP inhibitors preferentially act in concert with mapatumumab to trigger caspase activation, caspase-dependent apoptosis, and suppress clonogenic survival. Also, primary cultured pancreatic carcinoma cells are more susceptible to mapatumumab than lexatumumab, which is significantly enhanced by a XIAP inhibitor. Importantly, combined treatment with mapatumumab and a XIAP inhibitor cooperates to suppress tumor growth in vivo.

Conclusions: Mapatumumab exerts antitumor activity, especially in combination with XIAP inhibitors against most pancreatic carcinoma cell lines, whereas lexatumumab requires cross-linking for optimal cytotoxicity. These findings have important implications for the design of TRAIL-based protocols for pancreatic cancer. Clin Cancer Res; 16(23); 5734–49. ©2010 AACR.