bluuebunny/crossref_metadata_2025 huggingface dataset:
Melatonin promotes puromycin‐induced apoptosis with activation of caspase‐3 and 5′‐adenosine monophosphate‐activated kinase‐alpha in human leukemia HL‐60 cells
Authors: Koh Wonil , Jeong Soo‐Jin , Lee Hyo‐Jung , Ryu Ho‐Geon , Lee Eun‐Ok , Ahn Kyoo Seok , Bae Hyunsu , Kim Sung‐Hoon
Published: January 2011

Abstract:  Melatonin, a naturally occurring molecule, is produced by the pineal gland in a circadian manner to regulate biologic rhythms in humans. Recent studies report that melatonin may be an attractive candidate as an anticancer agent or for combined therapy because of its antioxidant, oncostatic and immunoregulatory activities. In this study, the potentiating effect of melatonin was evaluated on the apoptosis induced by puromycin as an anticancer drug in acute promyelocytic leukemia HL‐60 cells. Melatonin did not show significant cytotoxicity against HL‐60 cells compared to puromycin. However, melatonin significantly augmented the cytotoxicity of puromycin. Consistently, combined treatment of melatonin and puromycin reduced the expression of anti‐apoptotic proteins, such as bcl‐2 and bcl‐xL, and also induced caspase‐3 activation and poly (ADP‐ribose) polymerase (PARP) cleavage compared to puromycin treatment alone. Furthermore, cell cycle analysis revealed that melatonin promoted puromycin‐induced apoptosis by increasing the sub‐G1 population, but suppressing G2/M arrest in HL‐60 cells. Interestingly, melatonin activated the phosphorylation of 5′‐adenosine monophosphate‐activated kinase (AMPK) in combination with puromycin. Taken together, our results suggest that melatonin potentiates puromycin‐induced apoptosis with caspase‐3 and AMPK activation in HL‐60 cells, and thus, melatonin treatment can be effectively applied to leukemia treatment as a potential sensitizer for chemotherapeutic agents.
Oncogenetics of melanoma: basis for molecular diagnostics and therapy
Authors: Held Laura , Eigentler Thomas K. , Meier Friedegund , Held Marko , Röcken Martin , Garbe Claus , Bauer Jürgen
Published: January 2011

Our understanding of oncogenetics and of the molecular mechanisms involved in melanoma development and signaling has dramatically changed in recent years. Today, melanomas are also classified based on molecular alterations. Emerging molecular therapies are targeted against specific mutations in melanoma. An example of targeted therapies is the successful treatment of KIT‐mutant melanoma with the kinase inhibitor imatinib. Highly selective BRAF‐inhibitors are likewise under clinical development and show encouraging clinical responses. An increasing number of targeted drugs will emerge in the coming years, based on molecular diagnostics and classification. The present article reviews signaling pathways in melanocytes and alterations in melanoma that are a prerequisite to understanding modern cancer therapies in melanoma.
Effect of position on oxygen saturation and requirement in convalescent preterm infants
Authors: Elder Dawn E , Campbell Angela J , Galletly Duncan
Published: January 2011

Aims:  To document the effect of position on oxygen saturation and changes in oxygen requirement in convalescent preterm infants.

Methods:  Twelve infants born ≥24 and ≤32 weeks gestation, extubated and without congenital anomaly were studied using nap polysomnography in prone and supine, twice weekly until discharge. Mean oxygen saturation (SpO2), minimum SpO2, mean minimum SpO2 and time with SpO2 < 90% were measured in active sleep.

Results:  Eight male and four female infants [median gestation 28 (24–31) weeks and median birthweight 1059 (715–1840) g] had 39 studies. For 21 of 39 studies, the infant was on respiratory support. Four infants had chronic lung disease (CLD). SpO2 varied with postmenstrual age (PMA) (p = 0.003) but not with position (p = 0.36), and PMA did not influence the effect of position on SpO2 (p = 0.19). SpO2 was lower for those with CLD (p < 0.0001) and those on respiratory support (p < 0.001), but there was no effect of position (p = 0.97 and p = 0.67, respectively). From 36 weeks PMA, a change to supine did not increase oxygen requirement.

Conclusion:  In preterm infants, PMA and residual respiratory disease have greater effects on oxygenation than position. A supine sleep position is not disadvantageous for preterm infants at discharge.
Acute pancreatitis in children
Authors: Chang Yi‐Jung , Chao Hsun‐Chin , Kong Man‐Shan , Hsia Shao‐Hsuan , Lai Ming‐Wei , Yan Dah‐Chin
Published: January 2011

Aim:  To identify clinical, laboratory, and imaging characteristics associated with severe acute pancreatitis in children.

Methods:  This was a retrospective study of children under 18 years of age with acute pancreatitis between September 1993 and August 2008. Severity of pancreatitis was graded according to established criteria. Clinical, laboratory and radiological data for mild and severe pancreatitis were collected for analysis.

Results:  There were 180 cases of pancreatitis; 51 (28.3%) met criteria for severe disease. Severe pancreatitis was most commonly associated with systemic disease (22 of 51; 43.1%) and trauma (13 of 51; 25.4%). Patients with severe pancreatitis had significantly higher body weight, higher frequency of dyspnoea and pleural effusion, and lower serum calcium and albumin levels. Ten patients with systemic disease died; four of them had systemic lupus erythematosus (SLE). Computed tomography (CT) was more accurate than ultrasound in evaluation of the severity of pancreatitis.

Conclusions:  Acute pancreatitis in children is associated with significant morbidity and mortality. The severity of paediatric pancreatitis may be influenced by aetiology. CT is recommended for evaluation of severity of pancreatitis.
Mapping gradients of community composition with nearest‐neighbour imputation: extending plot data for landscape analysis
Authors: Ohmann Janet L. , Gregory Matthew J. , Henderson Emilie B. , Roberts Heather M.
Published: January 2011

Question:How can nearest‐neighbour (NN) imputation be used to develop maps of multiple species and plant communities?

Location:Western and central Oregon, USA, but methods are applicable anywhere.

Methods:We demonstrate NN imputation by mapping woody plant communities for >100 000 km2of diverse forests and woodlands. Species abundances on ∼25 000 plots were related to spatial predictors (rasters) describing climate, topography, soil and geographic location using constrained ordination (CCA). Species data from the nearest plot in multi‐dimensional CCA space were imputed to each map pixel. Maps of multiple individual species and community types were constructed from the single imputed surface. We computed a variety of diagnostics to characterize different qualities of the imputed (mapped) community data.

Results:Community composition gradients were strongly associated with climate and elevation, and less so with topography and soil. Accuracy of the imputation model for presence/absence of 150 species varied widely (kappa 0.00 to 0.80). Omission error rates were higher than commission rates due to low species prevalence, and areal representation of species was only slightly inflated. A map of 78 community types was 41% correct and 78% fuzzy correct. Errors of omission and commission were balanced, and areal representation of both rare and abundant communities was accurate. Map accuracy may be lower for some species than with other methods, but areal representation of species and communities across large landscapes is preserved. Because imputed vegetation surfaces are developed for all species simultaneously, map units contain suites of species known to co‐occur in nature. Maps of individual species, and of community types derived from them, will be internally consistent at map locations.

Conclusions:NN imputation is a useful modelling approach where maps of multiple species and plant communities are needed, such as in natural resource management and conservation planning or models that project landscape change under alternative disturbance or climate scenarios. More research is needed to evaluate other ordination methods for NN imputation of plant communities.
THE SWEET TYRANNY OF CREATING ONE'S OWN LIFE: RETHINKING POWER AND FREEDOM IN ENGLISH TEACHING
Authors: Brass Jory
Published: January 2011

In this historical study of English teaching, Jory Brass adopts a governmentality perspective to highlight the contingency and limits of pedagogical arguments that construct an oppositional relation between power and freedom. In the first part of the essay, Brass historicizes contemporary critiques of transmission pedagogies by comparing them with touchstone pedagogical texts of the 1890s through the 1920s. Next, he revisits two early twentieth‐century pedagogical frameworks to identify links among power, freedom, choice, and social norms that are obscured in contemporary pedagogical writing. Finally, Brass examines a popular contemporary text, Deborah Appleman's Critical Encounters in High School English, to highlight how its strategy to foster adolescents' freedom and empowerment inscribes social patterns of power and regulation. The study denaturalizes oppositional accounts of power and freedom so that scholars and teachers may scrutinize how power circulates when English is positioned to govern how students understand and conduct themselves as free, responsible, and empowered subjects.
SETTLEMENT‐FOCUSED PARENTING PLAN CONSULTATIONS: AN EVALUATIVE MEDIATION ALTERNATIVE TO CHILD CUSTODY EVALUATIONS
Authors: Pickar Daniel B. , Kahn Jeffrey J.
Published: January 2011

The divorce mediation field has recently seen the development of several “hybrid” alternative dispute resolution approaches to child custody disputes. The “settlement‐focused parenting plan consultation” (SFPPC) is a form of evaluative mediation, conducted by a “parenting plan consultant” (PPC), who possesses the combined expertise of a mediator and child custody evaluator. This hybrid model is a more expedient and considerably less expensive approach than a child custody evaluation, but preserves the hallmark mediation principle of self‐determination. The article describes the theory underlying the SFPPC, delineates the role requirements, procedures, and techniques of the parenting plan consultant, and addresses legal and ethical issues.
CONSULTANT CONDUCT IN ANTICIPATION OF A CHILD CUSTODY EVALUATION: ETHICAL AND SOCIAL DILEMMAS AND THE NEED FOR NEUTRAL PARENT EDUCATION
Authors: Barth Lauren
Published: January 2011

Mental health professionals are being retained with increasing frequency as “custody consultants” to prepare a parent for a child custody evaluation. While this practice may serve a legitimate function, no ethical guidelines clearly govern the conduct of a consultant in such circumstances. This lack of guidance has led to professional disagreement regarding the ethical implications of the practice. This ethical ambiguity is accompanied by social concern regarding the high cost of custody consulting, which has the practical effect of denying consulting services to low‐income or self‐represented litigants. This Note will describe the growing practice of custody consulting and the ethical and social unease currently associated with the practice. This Note will then propose that mandatory parent education programs be developed for parents preparing to undergo a custody evaluation. This type of educational program would provide many of the benefits of custody consulting in an ethically neutral fashion and would ensure that all parents have access to the benefits of this growing practice.
NIPPING IT IN THE BUD®: ADOPTING A FAMILY DRUG COURT APPROACH TO FIGHTING THE CYCLE OF ALCOHOL ADDICTION FOR CHILDREN WHEN PARENTS ARE CONVICTED OF DUI
Authors: Spataro Robert M.
Published: January 2011

Many states have implemented Drug Courts in recent years by combining drug and alcohol treatment with ongoing judicial supervision. Through the use of incentives such as reduced and dismissed charges and fines combined with supervised treatment, Drug Courts have been shown to be very effective in helping to break the cycle of addiction, crime, and repeat incarceration for those involved. However, these courts do little to address situations in which the addict is the custodial parent of a minor child, who is exponentially more at‐risk for future alcohol addiction simply by being the child of an alcoholic, due to both environmental and biological factors. Thus, while the parent's addiction is theoretically being addressed by the courts, little is being done, absent a showing of abuse or neglect, by the judicial system to combat the seeds of addiction that have already been planted in these children. Therefore, this Note advocates for states to include an alcohol education and counseling program aimed at children of alcohol‐related offenders based on the Drug Court Model. Participation in this program would then act as a mitigating factor for the addicted offender when receiving their final sentence. This proposed program would then serve as a model for other states to adopt in the near future.
DEVELOPMENT OF A MICROTITER ‐ BASED ASSAY FOR ASSESSMENT OF VIRULENCE RESPONSE IN SALMONELLA TYPHIMURIUM EXPOSED TO FRESH PRODUCE EXTRACTS
Authors: NUTT J.D. , LI X. , ZABALA‐DÍAZ I.B. , WOODWARD C.L. , RICKE S.C.
Published: January 2011

Abstract  The purpose of this research was to develop a microtiter‐based assay procedure for assessment of virulence gene response of Salmonella Typhimurium to fresh homogenized vegetables. The microtiter procedure was adapted from a assay for β‐galactosidase activity of a hilA fusion strain of S. Typhimurium with volumes of all reagents adjusted for microtiter plate wells. S. Typhimurium exposed to pH 7 saline yielded a higher level of hilA expression than responses after incubation in pH 4, 5 and 6 saline. Bacterial cells exposed to broccoli extracts yielded the higher levels of hilA expression while bell pepper and tomato yielded the overall lowest amounts of hilA expression. From this study, it appears that fresh produce extracts have different abilities to significantly alter virulence response in Salmonella. In conclusion, the hilA fusion stain assay can be successfully adapted to microtiter plates for testing Salmonella virulence response to vegetable extracts.
DETECTION OF VIABLE LISTERIA MONOCYTOGENES IN MILK USING AN ELECTROCHEMICAL METHOD
Authors: RUAN CHUANMIN , WANG HONG , YANG LIJU , LI YANBIN
Published: January 2011

Abstract  Growth of Listeria monocytogenes in a Listeria enrichment broth (LEB) was automatically monitored by electrochemical cyclic voltammetric scan using a gold working electrode. Changes in cyclic voltammograms were observed during growth of L. monocytogenes in LEB. The reduction peak at −0.4 V (vs Ag/AgCl) corresponding to the reduction of oxygen dissolved in LEB on cyclic voltammograms was decreasing with proliferation of L. monocytogenes, and disappeared eventually. A pair of reversible redox peaks appeared during growth of L. monocytogenes in LEB. These cyclic voltammetric characteristics can be used to detect L. monocytogenes in various samples. Threshold values (detection time) obtained from the oxygen consumption curves were inversely related to the concentrations of L. monocytogenes in the broth. A calibration curve was obtained by plotting initial cell concentrations (CFU/mL) determined by conventional plate counting, as a function of the detection time. A linear response was found on the calibration curve for L. monocytogenes between 1 ∼ 9 times 100 and 1 ∼ 9 times 105 cells/mL. The detection time was approximately 17 and 6 h for 1 ∼ 9 times 100 and 1 ∼ 9 × 105 cells/mL of viable L. monocytogenes in the broth, respectively. The method was evaluated in detection of L. monocytogenes in milk samples.
A RAPID AND EFFECTIVE METHOD FOR TOTAL RNA EXTRACTION FROM CONIDIA AND MYCELIUM OF SEPTORIA TRITICI
Authors: GUO JIAN‐RONG , ABD‐ELSALAM KAMEL A. , SCHNIEDER FRANK , VERREET JOSEPH‐ALEXANDER
Published: January 2011

Abstract  An effective and rapid method for RNA extraction from conidia and mycelium of S. tritici was developed, in which guanidinium isothiocyanate, CTAB and insoluble PVP were combined in one step, simplifying the extraction process greatly. The procedure can be completed in less than 6 h. Yield and purity of RNA could be estimated by electrophoresis on 1% formaldhyde‐denatured agarose gel and by measuring the absorbance at 280, 260, 230 and 210 nm by UV spectroscopy. The result of electrophoresis showed two clear bands of 18S and 28S rRNA and no DNA contamination in the isolated RNA solution. The ratios A260/A280, A260/A230, A260/A210 were 1.76–1.82, 2.79–3.21 and 0.81–0.86, respectively. A high yield with 532–881 ng total RNA per gram fresh conidia and mycelium of S. tritici was obtained. The RNA was of sufficient purity for RT‐PCR to detect the expression of β‐tubulin gene in S. tritici. This protocol may also be suitable for RNA extraction from spores and mycelium of other fungi.
DEVELOPMENT OF A MULTIPLEX PCR ASSAY FOR THE SPECIFIC DETECTION OF SALMONELLA, CAMPYLOBACTER JEJUNI, ESCHERICHIA COLI O157:H7, AND LISTERIA MONOCYTOGENES
Authors: GILBERT C. , O'LEARY A. , WINTERS D. , SLAVIK M.
Published: January 2011

Abstract  Detection of food‐associated bacterial pathogens has become a major focus of the food industry, regulatory agencies, and researchers. Multiple pathogens need to be rapidly detected with high specificity and as cost efficient as possible. In this research, a multiplex PCR assay for the specific detection of Listeria monocytogenes, Escherichia coli O157:‐H7, Salmonella, and Campylobacter jejuni was developed. The four bacteria were detectable at 104 CFU/PCR reaction. No cross‐reactivity with other bacteria commonly found associated with the four target organisms was found. This assay would simplify detection procedures for the target pathogens, reduce the time and labor necessary to acquire food safety results, and might allow one protocol to be used for bacterial detection on a wide variety of food products.
The effect of kurtosis on the power of two test statistics in covariance structure analysis
Authors: Foldnes Njål , Olsson Ulf Henning , Foss Tron
Published: January 2011

We study the effect of excess kurtosis on the non‐centrality parameters of the rescaled and the residual‐based test statistics for covariance structure models. The analysis is based on population matrices and parameters, which eliminates the sampling variability inherent in simulation studies. We show that the non‐centrality parameters, and consequently the asymptotic power, decrease as kurtosis in the data increases. Examples are provided to compare this decrease for the two test statistics, and to illustrate how substantial it is.
Bouyancy Effect on Forced Convection in Vertical Tubes at High Reynolds Numbers
Authors: Huang LiDong , Farrell Kevin J.
Published: January 2011

The complex interaction of forced and natural convections depends on flow regime and flow direction. Aiding flow occurs when both driving forces act in the same direction (heating upflow fluid and cooling downflow fluid), opposing flow occurs when they act in different directions (cooling upflow fluid and heating downflow fluid). To evaluate mixed convection methods, Heat Transfer Research, Inc. (HTRI) recently collected water and propylene glycol data in two vertical tubes of different tube diameters. The data cover wide ranges of Reynolds, Grashof, and Prandtl numbers and differing ratios of heated tube length to diameter in laminar, transition, and turbulent forced flow regimes. In this paper, we focus the buoyancy effect on forced convection of single-phase flows in vertical tubes with Reynolds numbers higher than 2000. Using HTRI data and experimental data in literature, we demonstrate that natural convection can greatly increase or decrease the convective heat transfer coefficient. In addition, we establish that natural convection should not be neglected if the Richardson number is higher than 0.01 or the mixed turbulent parameter Ra1/3/(Re0.8 Pr0.4) is higher than 0.05 even in forced turbulent flow with Reynolds numbers greater than 10,000. High resolution Reynolds-averaged Navier–Stokes simulations of several experimental conditions confirm the importance of the buoyancy effect on the production of turbulence kinetic energy. We also determine that flow regime maps are required to predict the mixed convection heat transfer coefficient accurately.
Applicability of molecular beam deposition for the growth of high-k oxides
Authors: Grube Matthias , Martin Dominik , Weber Walter M. , Mikolajick Thomas , Bierwagen Oliver , Geelhaar Lutz , Riechert Henning
Published: January 2011

Following the demand of replacing conventional dielectrics in the semiconductor industry, a material screening for new high-k dielectrics is necessary. In this article, the molecular beam deposition is presented as a versatile and valuable tool for growing dielectric films. ZrO2 was chosen as an example to demonstrate the capability of molecular beam deposition to grow thin high-k dielectrics in a metal-insulator-metal stack. A k-value from 21 to 26 could be achieved for as-grown films. This could be improved even further up to 30 by performing postdepositions anneals that result in a capacitance equivalent thickness of 1.5 nm at a leakage current density of 1.5×10−7 A/cm2. In addition, the crystallization behavior of ZrO2 was investigated.
Electrical analysis of three-stage passivated In0.53Ga0.47As capacitors with varying HfO2 thicknesses and incorporating an Al2O3 interface control layer
Authors: Monaghan S. , O’Mahony A. , Cherkaoui K. , O’Connor É. , Povey I. M. , Nolan M. G. , O’Connell D. , Pemble M. E. , Hurley P. K. , Provenzano G. , Crupi F. , Newcomb S. B.
Published: January 2011

The atomic layer deposition of high dielectric constant oxides like HfO2 on III-V substrates such as In0.53Ga0.47As leads to a poor interface, with the growth of In0.53Ga0.47As native oxides regardless of the surface pretreatment and passivation method. The presence of the native oxides leads to poor gate leakage current characteristics due to the low band gap of the native oxides and the presence of potential wells at the interface. In addition, the poor quality of this interface leads to very large interface state defect densities, which are detrimental to metal-oxide-semiconductor-based device performance. A wide band gap interlayer replacing the native oxide layer would remove the potential wells and provide a larger barrier to conduction. It may also assist in the improvement of the interface quality, but the problem remains as to how this native oxide interlayer cannot only be removed but prevented from regrowing. In this regard, the authors present electrical results showing that the atomic layer deposition (ALD) growth of a thin (∼1 nm) Al2O3 layer before the ALD growth of HfO2 causes a removal/reduction of the native oxides on the surface by a self-cleaning process without subsequent regrowth of the native oxides. As a result, there are significant improvements in gate leakage current densities, and significant improvements in the frequency dispersion of capacitance versus gate voltage, even when a defective In0.53Ga0.47As epitaxial layer on an InP substrate is employed. Measurements at different temperatures confirm that the frequency dispersion is mainly due to interface state defect responses and another weakly temperature dependent mechanism such as border traps, after accounting for the effects of nonideal In0.53Ga0.47As epitaxial layer growth defects where applicable.
MIAMI: Microscope and ion accelerator for materials investigations
Authors: Hinks J. A. , van den Berg J. A. , Donnelly S. E.
Published: January 2011

A transmission electron microscope (TEM) with in situ ion irradiation has been built at the University of Salford, U.K. The system consists of a Colutron G-2 ion source connected to a JEOL JEM-2000FX TEM via an in-house designed and constructed ion beam transport system. The ion source can deliver ion energies from 0.5 to 10 keV for singly charged ions and can be floated up to 100 kV to allow acceleration to higher energies. Ion species from H to Xe can be produced for the full range of energies allowing the investigation of implantation with light ions such as helium as well as the effects of displacing irradiation with heavy inert or self-ions. The ability to implant light ions at energies low enough such that they come to rest within the thickness of a TEM sample and to also irradiate with heavier species at energies sufficient to cause large numbers of atomic displacements makes this facility ideally suited to the study of materials for use in nuclear environments. TEM allows the internal microstructure of a sample to be imaged at the nanoscale. By irradiating in situ it is possible to observe the dynamic evolution of radiation damage which can occur during irradiation as a result of competing processes within the system being studied. Furthermore, experimental variables such as temperature can be controlled and maintained throughout both irradiation and observation. This combination of capabilities enables an understanding of the underlying atomistic processes to be gained and thus gives invaluable insights into the fundamental physics governing the response of materials to irradiation. Details of the design and specifications of the MIAMI facility are given along with examples of initial experimental results in silicon and silicon carbide.
Screencasts for Physics Students
Authors: Vondracek Mark
Published: January 2011

This paper outlines the use of “how to” videos, in the form of a screencast using a tablet computer, and posting the videos online. These videos are useful for when students miss a class, for those students who need to review a lesson or examples used in class when doing homework or reviewing for a test, for instructors of online classes, and also for instructors if they have to miss a day of class. Students overwhelmingly report this to be a useful and effective tool that has allowed them to catch up more easily after missing one or more days of class and for reviewing material from class.
When Does Air Resistance Become Significant in Free Fall?
Authors: Mohazzabi Pirooz
Published: January 2011

In introductory physics laboratories, students who experiment with freely falling objects frequently attribute any error in their experimental results to the presence of air resistance. It is, therefore, important to realize when and at what point during a free fall air resistance begins to play a significant role in the motion of the falling object. In this paper we address this question, and we show that blaming air resistance for errors in free-fall experiments in introductory physics laboratories is almost never justified.
Teaching Scientific Inquiry with Galaxy Zoo
Authors: Slater Stephanie J. , Slater Timothy F. , Lyons Daniel J.
Published: January 2011

The universe of topics to choose from when teaching an astronomy course is astronomically immense. This wide array of opportunity presents some inherently difficult choices for teachers at all levels on how to limit the scope of the course to make the syllabus manageable. As but one example, consider that even the most experienced astronomy teacher must choose between focusing on the astrophysics of stellar processes or on the nomenclature for stars and constellations because there is rarely time to give both justice. One might go as far as saying that planning an astronomy course is similar to the perspective offered by Michael Pollan in his book The Omnivore's Dilemma, which can be paraphrased as, “When entering a modern grocery store in the U.S. with unlimited choices, what is it that one chooses to eat and why?” Indeed, teaching about the entire universe in a single astronomy course involves some serious choices, as one can most certainly not teach everything.
The Hope of Audacity® (To Teach Acoustics)
Authors: Groppe Jennifer
Published: January 2011

When working on an oral history project, my brother recommended that I download a free audio recording and editing program called Audacity®. I have since discovered that it is a fantastic tool for students to visualize sound waves and to understand the meaning of amplitude, frequency, and superposition. This paper describes a collection of demonstrations, most of which require only a computer, a set of speakers, and a projector.
Stromal Endothelial Cells Directly Influence Cancer Progression
Authors: Franses Joseph W. , Baker Aaron B. , Chitalia Vipul C. , Edelman Elazer R.
Published: January 2011

Endothelial cells can serve as plastic paracrine regulators of cancer biology, modulating tumor growth and metastasis.
An Aptamer-siRNA Chimera Suppresses HIV-1 Viral Loads and Protects from Helper CD4
+
T Cell Decline in Humanized Mice
Authors: Neff Charles Preston , Zhou Jiehua , Remling Leila , Kuruvilla Jes , Zhang Jane , Li Haitang , Smith David D. , Swiderski Piotr , Rossi John J. , Akkina Ramesh
Published: January 2011

A dual-function aptamer that targets both a HIV-1 surface protein and a critical messenger RNA can inhibit HIV infection in humanized mice.
“Creating Hope” and Other Incentives for Drug Development for Children
Authors: Connor Edward , Cure Pablo
Published: January 2011

Proposed legislation would provide financial benefits for companies that develop drugs for treating rare pediatric diseases.
Excited to Madness
Authors: Minzenberg Michael J.
Published: January 2011

Faltering inhibitory interneurons in the prefrontal cortex lead to chaos in the schizophrenia brain.
Vaginal Microbicide Gel for Delivery of IQP-0528, a Pyrimidinedione Analog with a Dual Mechanism of Action against HIV-1
Authors: Mahalingam Alamelu , Simmons Adam P. , Ugaonkar Shweta R. , Watson Karen M. , Dezzutti Charlene S. , Rohan Lisa C. , Buckheit Robert W. , Kiser Patrick F.
Published: January 2011

Pyrimidinediones, a novel class of compounds, have previously been shown to possess antiviral activity at nanomolar concentrations. One member of this class of compounds, IQP-0528, was selected as the lead molecule for formulation development owing to its stability at physiologically relevant conditions, wide therapeutic window, and antiviral activity in the nanomolar range. Here, we report the development of two vaginal gels—3.0% hydroxyethyl cellulose (HEC) formulation and a 0.65% Carbopol formulation—for the sustained delivery of IQP-0528. Stability studies under accelerated conditions confirmed the chemical stability of IQP-0528 and mechanical stability of the gel formulation for 3 months.
In vitro
release studies revealed that diffusion-controlled release of IQP-0528 occurred over 6 h, with an initial lag time of approximately 1 h. Based on the drug release profile, the 3.0% HEC gel was selected as the lead formulation for safety and activity evaluations. The
in vitro
and
ex vivo
safety evaluations showed no significant loss in cell viability or significant inflammatory response after treatment with a 3.0% HEC gel containing 0.25% IQP-0528. In an
in vitro
HIV-1 entry inhibition assay, the lead formulation showed an 50% effective concentration of 0.14 μg/ml for gel in culture media, which corresponds to ∼0.001 μM IQP-0528. The antiviral activity was further confirmed by using polarized cervical explants, in which the formulation showed complete protection against HIV infection. In summary, these results are encouraging and warrant further evaluation of IQP-0528 gel formulations in
in vivo
models, as well as the development of alternative formulations for the delivery of IQP-0528 as a microbicide.
Process Analysis of Variables for Standardization of Antifungal Susceptibility Testing of Nonfermentative Yeasts
Authors: Zaragoza Oscar , Mesa-Arango Ana C. , Gómez-López Alicia , Bernal-Martínez Leticia , Rodríguez-Tudela Juan Luis , Cuenca-Estrella Manuel
Published: January 2011

Nonfermentative yeasts, such as
Cryptococcus
spp., have emerged as fungal pathogens during the last few years. However, standard methods to measure their antifungal susceptibility (antifungal susceptibility testing [AST]) are not completely reliable due to the impaired growth of these yeasts in standard media. In this work, we have compared the growth kinetics and the antifungal susceptibilities of representative species of nonfermentative yeasts such as
Cryptococcus neoformans
,
Cryptococcus gattii
,
Cryptococcus albidus
,
Rhodotorula
spp.,
Yarrowia lipolytica
,
Geotrichum
spp., and
Trichosporon
spp. The effect of the growth medium (RPMI medium versus yeast nitrogen base [YNB]), glucose concentration (0.2% versus 2%), nitrogen source (ammonium sulfate), temperature (30°C versus 35°C), shaking, and inoculum size (10
3
, 10
4
, and 10
5
cells) were analyzed. The growth rate, lag phase, and maximum optical density were obtained from each growth experiment, and after multivariate analysis, YNB-based media demonstrated a significant improvement in the growth of yeasts. Shaking, an inoculum size of 10
5
CFU/ml, and incubation at 30°C also improved the growth kinetics of organisms. Supplementation with ammonium sulfate and with 2% glucose did not have any effect on growth. We also tested the antifungal susceptibilities of all the isolates by the reference methods of the CLSI and EUCAST, the EUCAST method with shaking, YNB under static conditions, and YNB with shaking. MIC values obtained under different conditions showed high percentages of agreement and significant correlation coefficient values between them. MIC value determinations according to CLSI and EUCAST standards were rather complicated, since more than half of isolates tested showed a limited growth index, hampering endpoint determinations. We conclude that AST conditions including YNB as an assay medium, agitation of the plates, reading after 48 h of incubation, an inoculum size of 10
5
CFU/ml, and incubation at 30°C made MIC determinations easier without an overestimation of MIC values.
Virulence Inhibition by Zinc in Shiga-Toxigenic
Escherichia coli
Authors: Crane John K. , Byrd Isaac Wyatt , Boedeker Edgar C.
Published: January 2011

Previously, our laboratories reported that zinc inhibited expression of several important virulence factors in enteropathogenic
Escherichia coli
(EPEC) and reduced EPEC-induced intestinal damage
in vivo
. Since EPEC is genetically related to Shiga-toxigenic
E. coli
(STEC), we wondered whether the beneficial effects of zinc extended to STEC as well. Treatment options for STEC infection are very limited, since antibiotics tend to exacerbate disease via enhanced toxin production, so a safe intervention for this infection would be welcome. In this study, we report that in STEC strains zinc inhibits adherence to cultured cells as well as expression of EHEC secreted protein A (EspA). In addition, zinc inhibits the expression of Shiga toxin (Stx) at both the protein and the RNA level. Zinc inhibits basal and antibiotic-induced Stx production and inhibits both Stx1 and Stx2 by ≥90% at a concentration of 0.4 mM zinc. Rabbit EPEC strains were selected for acquisition of Stx-encoding bacteriophages, and these rabbit STEC strains (designated RDEC-H19A and E22-stx2) were used to test the effects of zinc
in vivo
in ligated rabbit intestinal loops.
In vivo
, zinc reduced fluid secretion into loops, inhibited mucosal adherence, reduced the amount of toxin in the loops, and reduced STEC-induced histological damage (villus blunting). Zinc has beneficial inhibitory effects against STEC strains that parallel those observed in EPEC. In addition, zinc strongly inhibits Stx expression; since Stx is responsible for the extraintestinal effects of STEC infection, such as hemolytic-uremic syndrome (HUS), zinc might be capable of preventing severe sequelae of STEC infection.
HIV-1/Mycobacterium tuberculosisCoinfection Immunology: How Does HIV-1 Exacerbate Tuberculosis?
Authors: Diedrich Collin R. , Flynn JoAnne L.
Published: January 2011

Human immunodeficiency virus type 1 (HIV) andMycobacterium tuberculosishave become intertwined over the past few decades in a “syndemic” that exacerbates the morbidity and mortality associated with each pathogen alone. The severity of the coinfection has been extensively examined in clinical studies. The extrapolation of peripheral evidence from clinical studies has increased our basic understanding of how HIV increases susceptibility to TB. These studies have resulted in multiple hypotheses of how HIV exacerbates TB pathology through the manipulation of granulomas. Granulomas can be located in many tissues, most prominently the lungs and associated lymph nodes, and are made up of multiple immune cells that can actively containM. tuberculosis. Granuloma-based research involving both animal models and clinical studies is needed to confirm these hypotheses, which will further our understanding of this coinfection and may lead to better treatment options. This review examines the data that support each hypothesis of how HIV manipulates TB pathology while emphasizing a need for more tissue-based experiments.
Toll-Like Receptor 5 Stimulation Protects Mice from Acute
Clostridium difficile
Colitis
Authors: Jarchum Irene , Liu Mingyu , Lipuma Lauren , Pamer Eric G.
Published: January 2011

Clostridium difficile
is a spore-forming bacterium that infects the lower intestinal tract of humans and is the most common known cause of diarrhea among hospitalized patients.
Clostridium difficile
colitis is mediated by toxins and develops during or following antibiotic administration. We have used a murine model of
C. difficile
infection, which reproduces the major features of the human disease, to study the effect of innate immune activation on resistance to
C. difficile
infection. We found that administration of purified
Salmonella
-derived flagellin, a Toll-like receptor 5 (TLR5) agonist, protects mice from
C. difficile
colitis by delaying
C. difficile
growth and toxin production in the colon and cecum. TLR5 stimulation significantly improves pathological changes in the cecum and colon of
C. difficile
-infected mice and reduces epithelial cell loss. Flagellin treatment reduces epithelial apoptosis in the large intestine, thereby protecting the integrity of the intestinal epithelial barrier during
C. difficile
infection. We demonstrate that restoring intestinal innate immune tone by TLR stimulation in antibiotic-treated mice ameliorates intestinal inflammation and prevents death from
C. difficile
colitis, potentially providing an approach to prevent
C. difficile
-induced pathology.
Maternal Microbe-Specific Modulation of Inflammatory Response in Extremely Low-Gestational-Age Newborns
Authors: Fichorova Raina N. , Onderdonk Andrew B. , Yamamoto Hidemi , Delaney Mary L. , DuBois Andrea M. , Allred Elizabeth , Leviton Alan
Published: January 2011

The fetal response to intrauterine inflammatory stimuli appears to contribute to the onset of preterm labor as well as fetal injury, especially affecting newborns of extremely low gestational age. To investigate the role of placental colonization by specific groups of microorganisms in the development of inflammatory responses present at birth, we analyzed 25 protein biomarkers in dry blood spots obtained from 527 newborns delivered by Caesarean section in the 23rd to 27th gestation weeks. Bacteria were detected in placentas and characterized by culture techniques. Odds ratios for having protein concentrations in the top quartile for gestation age for individual and groups of microorganisms were calculated. Mixed bacterial vaginosis (BV) organisms were associated with a proinflammatory pattern similar to those of infectious facultative anaerobes.PrevotellaandGardnerellaspecies, anaerobic streptococci, peptostreptococci, and genital mycoplasmas each appeared to be associated with a different pattern of elevated blood levels of inflammation-related proteins.Lactobacilluswas associated with low odds of an inflammatory response. This study provides evidence that microorganisms colonizing the placenta provoke distinctive newborn inflammatory responses and thatLactobacillusmay suppress these responses.

IMPORTANCEDespite improved intensive care, preterm and especially extremely low-gestation-age neonates continue to be at a considerably increased risk of morbidity, mortality, and developmental problems. The fetal inflammatory response appears to contribute to the onset of preterm labor, fetal injury, and complications, underlying lifetime health challenges facing these children. This study provides evidence that bacterial colonization of the very preterm placenta is associated with distinct microorganism-specific inflammatory protein profiles in the newborn blood specimens. We also provide evidence thatLactobacillusreduces inflammatory responses in newborns. Our data support the concept that targeting of placental colonization by specific drugs or probiotics during early pregnancy holds promise for preventing not only preterm birth but also subsequent and long-lasting, inflammation-provoked late sequelae.
Validation of a Sham Acupuncture Procedure in a Randomised, Controlled Clinical Trial of Chronic Pelvic Pain Treatment
Authors: Lee Shaun Wen Huey , Liong Men Long , Yuen Kah Hay , Leong Wing Seng , Khan Nurzalina Karim , Krieger John N
Published: January 2011

Background

Acupuncture is an attractive treatment option for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) that has proved refractory to conventional medical treatments. Unfortunately, it is difficult to determine the benefit of acupuncture because few studies have employed controls or had physiological outcome measures.

Objective

To determine the feasibility of a sham, or minimally invasive, acupuncture as a control for studies evaluating the efficacy of acupuncture treatment for chronic pelvic pain.

Methods

Participants were recruited from a double-blind randomised trial comparing acupuncture with a sham procedure for patients with CP/CPPS. Acupuncture or sham procedures were performed over a 10-week period. Sham acupuncture involved placement of short needles at sites 0.5 cm away from true acupuncture points (CV1, CV4, SP6 and SP9). Participants were asked to determine their procedure allocation at the end of treatment. A total of 35participants also agreed to have blood analyses for cortisol, β-endorphin and leucine-enkephalin.

Results

Thirty-five (78%) of the 45 participants randomised to the sham treatment thought they had received acupuncture compared with 27 (61%) of the 44 participants randomised to acupuncture (p=0.11). Biochemical data showed no differences between the groups immediately after treatment. Thirty-two (73%) of 44 acupuncture participants met the predefined clinical response criterion compared with 21 (47%) of 45 sham acupuncture participants (p=0.017, relative risk 1.81, 95% CI 1.3 to 3.1). At the end of the study, β-endorphin and leucine-enkephalin levels were both higher in the acupuncture group (p<0.01).

Conclusions

Minimally penetrating acupuncture was found to be a valid sham control and may prove useful for evaluating the efficacy of acupuncture for other conditions. (ClinicalTrials.gov number, NCT00260637)
Low Inter-Rater Reliability in Traditional Chinese Medicine for Female Infertility
Authors: Birkeflet Oddveig , Laake Petter , Vøllestad Nina
Published: January 2011

Background

Treatment of patients according to individual pattern diagnoses is an important feature of acupuncture rooted in traditional Chinese medicine (TCM). Little is known about the reliability of TCM pattern diagnoses.

Objective

To examine in a cross-sectional study the inter-rater reliability of TCM diagnoses and acupuncture point selection.

Methods

30 infertile and 24 previously pregnant women were examined for TCM patterns by two acupuncturists. An operational interview guide related to gynaecology was used. The acupuncturists independently decided on the TCM patterns (categorised as excess, deficiency and merged patterns) and the prescription of acupuncture points. Kappa Statistics were used in the analyses.

Results

39 different TCM patterns and 36 different acupuncture points were used. For the choice of acupuncture points, poor to no agreement was found. Moderate to fair agreement was seen in excess/deficiency and merged patterns. Perfect match to moderate agreement on treatment was obtained when choosing meridians given certain TCM patterns.

Conclusions

The low agreement on diagnoses indicates that acupuncturists follow individual pattern differentiation processes. The selection of acupuncture points seem to be closely related to the choice of TCM pattern diagnoses. The results indicate that the poor reliability in the diagnoses and thus treatment received by a patient will vary individually, which in turn is a challenge for clinical trials of acupuncture.
Paleomagnetic study of the Late Ordovician–Early Silurian platform sequence of Anticosti Island, Quebec
Authors: Seguin Maurice K. , Petryk Allen A.
Published: January 2011

Eighteen sites (152 samples, 441 specimens) from the Late Ordovician — Early Silurian sequence of Anticosti Island were studied paleomagnetically. Six sites were collected in the Vauréal Formation, seven in the Ellis Bay Formation, three in the Becscie Formation, and one each in the Gun River and Jupiter formations. The lithologies sampled consisted of limestones, sandy limestones, marls, and sandy calcareous shales drawn from a sedimentary platform sequence of predominantly inter-bedded limestones and shales. The specimens were demagnetized in alternating fields (AF) and thermally and were found to be quite stable. Two components of magnetization were isolated. The memory carrier is fine- to medium-grained magnetite; AF and thermal cleanings are about equally efficient. The average directions of residual magnetization are D = 167°, I = 37°, α95 = 18°; D = 315°, I = −24°, α95 = 17 °for components B and C, respectively. The corresponding paleopoles for the B and C components are 129°E, 19°N (dp = 12°, dm = 21°) and 341°E, 16°S (dp = 10°, dm = 18°).Component A is most probably composed of component C and the present Earth's field (PEF); it was chiefly observed in the more altered Vauréal Formation and in the altered top part of the cored samples. The most common component in the Ellis Bay, Becscie, Gun River, and Jupiter formations is component C. Component B is mainly found in the Becscie and Ellis Bay formations. Both components B and C are isolated in the 300–500 °C and 10–40 mT ranges. Component C is either older than component B or synchronous and of reverse polarity to component B. If this last alternative is correct, then the Ordovician and Silurian formations are overprinted by a pre-Kiaman magnetization. The more plausible scenario is the following: component B is secondary, of pre-Middle Carboniferous age, and overprinted on an older secondary magnetization (component C), the acquisition age of which is confined to the Silurian–Carboniferous time interval.
The age of igneous and metamorphic events in the western Cape Breton Highlands, Nova Scotia
Authors: Jamieson R. A. , Breemen O. van , Sullivan R. W. , Currie K. L.
Published: January 2011

Plutonic rocks of four different ages have been recognized in the Cape Breton Highlands on the basis of U–Pb dating of zircons. Two plutons, the North Branch Baddeck River leucotonalite [Formula: see text] and the Chéticamp pluton (550 ± 8 Ma), give dates that fall within the range of Late Proterozoic to Cambrian ages considered characteristic of the Avalon tectonostratigraphic zone of the eastern Appalachians. Late Ordovician to Silurian tonalite (Belle Côte Road orthogneiss, 433 ± 20 Ma) was metamorphosed, deformed, and incorporated into the central Highlands gneiss complex by approximately 370–395 Ma. High-level subvolcanic plutons (Salmon Pool pluton, [Formula: see text]) postdate all metamorphic rocks in the area. The presence of the older plutons is consistent with interpretation that the Cape Breton Highlands form part of the Avalon zone, but the presence of Ordovician–Silurian plutonic rocks and Devonian amphibolite-facies metamorphism is anomalous in comparison with the Avalon zone of Newfoundland and southeastern Cape Breton Island. Terranes with similar Late Proterozoic to mid-Paleozoic plutonic and metamorphic histories form a discontinuous belt along the northwest side of the Avalon zone southwest of Cape Breton Island. These rocks probably reflect events during and after the accretion of the Avalon zone to North America.