bluuebunny/crossref_metadata_2025 huggingface dataset:
Pediatric Hospital Dermatology: Experience with Inpatient and Consult Services at the Mayo Clinic
Authors: Storan Eoin R. , McEvoy Marian T. , Wetter David A. , el‐Azhary Rokea A. , Hand Jennifer L. , Davis Dawn M. R. , Bridges Alina G. , Camilleri Michael J. , Davis Mark D. P.
Published: February 2013

Data describing the management of pediatric patients admitted to a hospital under the care of a dermatologist and dermatology hospital consults for pediatric inpatients are limited. We aim to describe the role of an inpatient hospital service jointly run by dermatology and pediatrics and the activities of a pediatric dermatology hospital consult service. We retrospectively identified pediatric (age < 18 yrs) dermatology inpatients and hospital consult patients from January 1, 2009, through December 31, 2010. We examined patient demographics, indications for admission, length of stay, treatment provided, consult‐requesting service, and consult diagnosis. One hundred eight admissions were by a dermatologist. The mean age was 5.8 years; the median length of stay was 3 days. Indications for admission included atopic dermatitis (86.1%), psoriasis (3.7%), and eczema herpeticum (2.8%). The main treatment provided was wet dressings (97.2%). Eighty‐three dermatology hospital consults were requested. The mean age was 7.4 years. The main indications for dermatology consultation included drug rash (12.1%), cutaneous infections (12.1%), contact dermatitis (9.6%), psoriasis (8.4%), atopic dermatitis (6.0%), and hemangiomas (6.0%). This study describes the utility of the hospital pediatric dermatology inpatient and consult services in treating patients with severe skin disease.
Long‐term follow‐up of de novo allergy in pediatric liver transplantation – 10 yr experience of a single center
Authors: Lee Yoon , Lee Yoo Min , Kim Mi Jin , Lee Suk Koo , Choe Yon Ho
Published: February 2013

We conducted a study to clarify the incidence, clinical course, and risk factors of de novo allergies after liver transplantation. Ninety‐three patients who had been followed longer than one yr and who had no previous allergy history were included. Forty‐two patients (45.2%) developed de novo allergy. Of them, food allergy developed in 35 (37.6%). Respiratory allergy was observed in three (3.2%), and a patient (1.1%) had drug allergy. Fifty‐two (55.9%) of the 93 patients developed eosinophilia. The median age of patients with de novo allergy was 15 months (IR 11.3–20 months). De novo allergy developed five months after liver transplantation (IR 2.3–9.5 months) and lasted for 16 months (IR 8–34.5 months). Younger age at liver transplantation displayed statistically significant differences in development of allergy between allergy and non‐allergy groups. Twenty‐nine (69.0%) patients improved from allergy during the follow‐up period. No patient with de novo gastrointestinal allergy progressed to any respiratory allergy such as asthma. Older age at transplantation, EBV non‐risk, and CMV non‐risk had statistical significance in allergy improvement. Younger age at transplant predisposes to the development of allergy, while improvement of allergy is achieved more in older age.
Training and Experience of Nurses in Responding to Alcohol Misuse in Rural Communities
Authors: Kennedy Alison J. , Mellor David , McCabe Marita P. , Ricciardelli Lina A. , Brumby Susan A. , Head Alexandra , Mercer‐Grant Catherine
Published: February 2013

Objective

Alcohol misuse by farmers continues to challenge rural nurses. This article reports on the experiences of Australian nurses participating in the Alcohol Intervention Training Program (AITP).

Design and Sample

Qualitative interviews of 15 rural and remote nurses.

Measures

Semi‐structured phone interviews were utilized to assess the response to and implementation of the AITP—an intervention designed to build nurses' knowledge, confidence and skills when responding to alcohol misuse. It comprises practical and theoretical components and was designed for rural and remote settings where nurses encounter alcohol misuse.

Results

Nurses found the training provided new—or built on existing—knowledge of alcohol misuse and offered practical hands‐on “real life” skills. A range of workplace and personal situations where the content of the training was now being utilized were identified, and future use anticipated. Barriers to using the new knowledge and skills included both rural and generic issues. Constructive feedback to increasingly target the training to rural settings was recommended.

Conclusions

The AITP is an effective training program. It can be further tailored to meet common needs of rural and remote nurses working with farmers who misuse alcohol, while recognizing diversity in rural practice.
The Culture of Education in a Large Dialysis Organization: Informing Patient‐Centered Decision Making on Treatment Options for Renal Replacement Therapy
Authors: Mollicone Debra , Pulliam Joseph , Lacson Jr Eduardo
Published: February 2013

Challenged by the observation that newly admitted dialysis patients were often unaware of their treatment options, Fresenius Medical Care, North America developed a program to improve information delivered to chronic kidney disease (CKD) patients prior to their need for renal replacement therapy. Six years ago, the Treatment Options Program (TOPs) was established utilizing a standardized approach to educate individuals with CKD Stages 3 and 4. The program education focuses on modality and vascular access options. A key component includes follow‐up at predetermined intervals, offering additional education and patient reminders to continue to work with their physician in selecting a preferred renal replacement modality. Since program inception, over 73,000 individuals have been educated through TOPs. Home therapy utilization as first treatment is higher in the patient population that received TOPs education. Similarly, participants had a higher rate of permanent vascular access with decreased use of hemodialysis catheters upon admission. Avoiding hemodialysis catheter use and expanding home therapy utilization both offer potential benefits to all stakeholders: patients, providers, and payors, particularly as we move toward accountable healthcare systems. The ability to expand the TOPs program relies on seeing patients early enough to allow each patient time to process the information and work with their physician to select the modality and access that best meets their healthcare and lifestyle needs. Educating our patients facilitates empowerment and active participation in their therapy, a much coveted component of patient‐centered health care for the renal provider community as we look to the future.
Acute Start—Chronic Needs: Education and Support for Adults who have had Acute Start Dialysis
Authors: Watson Diane
Published: February 2013

For those patients with CKD followed in a pre‐dialysis environment, it is well appreciated that modality education leads to an informed decision regarding type of dialysis selected. However, for those individuals starting dialysis acutely and requiring chronic renal replacement therapy, modality education may be lacking. Because of the acuity of the dialysis start, and the intercurrent illness or event which precipitated and acute start, these patients require a specialized approach to education, and indeed, require a combination of education and support to learn about and choose a renal replacement therapy. The University Health Network, in Toronto, Canada, has developed a program and approach to education and support of this group of patients. The approach, results, and theoretical underpinnings of this program are reviewed, and a potential new “hybrid” educational framework is proposed.
Linking adaptation, delimitation of evolutionarily significant units (ESUs), and gene function: a case study using hemlock looper ecotypes
Authors: LUMLEY LISA M. , CUSSON MICHEL
Published: February 2013

Developing genetic markers for the identification of recently diverged groups, such as ecotypes or species complexes, remains difficult due to challenges with incomplete lineage sorting, hybridization and introgression. Genome‐wide scans of single nucleotide polymorphisms (SNPs) have proven useful for inferring patterns of genetic differentiation at the population level. In combination with a new analytical technique, the discriminant analysis of principal components (DAPC), and within the framework of iterative taxonomy, it may also be possible to extract a combination of SNPs as markers for the delimitation of closely related groups. In addition, since DAPC identifies the loci contributing the most to group clustering, it may be possible to link putative biological function to differences that define group boundaries. We tested this technique on two ecotypes of the hemlock looper (Lambdina fiscellaria), which differ in terms of number of larval stadia, developmental rate and fecundity. It was possible to separately cluster the two ecotypes with 95% correct assignment using 27 SNPs. We also determined that a storage hexamerin carried eight of these SNPs, including the two highest contributing loci, of which the top contributor was nonsynonymous. Other studies have found this protein to be highly expressed just before metamorphosis, pointing to a possible connection between its role in clustering ecotypes and its biological function. These SNP markers can now be further developed for high throughput delimitation of individuals of unknown ecotype identity.
Micro- and Nanoscale Conductive Tree-Structures for Cooling a Disk-Shaped Electronic Piece
Authors: Daneshi Masoud , Zare Marjan , Reza Salimpour Mohammad
Published: February 2013

In this research, we consider the generation of conductive heat trees at microscales and nanoscales for cooling electronics which are considered as heat-generating disk-shaped solids. With the advent of nanotechnology and the production of electronics in micro- and nanoscales in recent years, designing workable systems for cooling them is considered widely. Therefore, tree-shape conduction paths of highly conductive material including radial patterns, structures with one level of branching, tree-with-loop architectures, and combination of structures with branching and structures with loops are generated for cooling such electronic devices. Furthermore, constructal method which is used to analytically generate heat trees for cooling a disk-shaped body is modified in the present work, that we call it modified analytical method. Moreover, every feature of the tree architectures is optimized numerically to make a comparison between numerical and analytical results and to generate novel architectures. Since there are some constructal tree architectures which are not possible to be generated analytically, numerical approach is used for optimization. When the smallest features of the internal structure are smaller than mean free path of the energy carriers, heat conductivity is no longer a constant and becomes a function of the smallest dimension of the structure. Therefore, we consider models which were proposed for estimating conductivity of small scale bodies.
A Revised Approach for One-Dimensional Time-Dependent Heat Conduction in a Slab
Authors: Caffagni A. , Angeli D. , Barozzi G. S. , Polidoro S.
Published: February 2013

Classical Green’s and Duhamel’s integral formulas are enforced for the solution of one dimensional heat conduction in a slab, under general boundary conditions of the first kind. Two alternative numerical approximations are proposed, both characterized by fast convergent behavior. We first consider caloric functions with arbitrary piecewise continuous boundary conditions, and show that standard solutions based on Fourier series do not converge uniformly on the domain. Here, uniform convergence is achieved by integrations by parts. An alternative approach based on the Laplace transform is also presented, and this is shown to have an excellent convergence rate also when discontinuities are present at the boundaries. In both cases, numerical experiments illustrate the improvement of the convergence rate with respect to standard methods.
Critical Scales Govern the Mechanical Fragmentation Mechanisms of Biomolecular Assemblies
Authors: Sullivan Matthew , Keten Sinan
Published: February 2013

Fragmentation mechanisms of peptide assemblies under shock deformation are studied using molecular dynamics simulations and are found to depend strongly on the relative magnitude of the shock front radius to the fibril length and the ratio of the impact energy to the fibril cohesive energy. The competition between size scaling of curvature and impact energy leads to a mechanism change at a critical impact velocity, developing a stark contrast in the size scaling of fragmentation at low and high strain rates. We show that the fragmentation mechanisms can be classified on the basis of the length and time scales of deformation and relaxation to provide new insight into experimental observations.
The Two-Dimensional Elasticity Solution for the Buckling of a Thick Orthotropic Ring Under External Pressure Loading
Authors: Ji Wooseok , Waas Anthony M.
Published: February 2013

This paper is concerned with the 2D elasticity solution for the buckling of a thick orthotropic ring under external hydrostatic pressure loading. The bifurcation buckling problem is first formulated using two methods, distinguished by the manner in which the external work done by the pressure loading during the buckling transition is treated. In doing so, the correct buckling equations and associated traction boundary conditions are derived. The resulting sets of equations and associated boundary conditions are then cast in a weak form, amenable to a numerical solution using the finite element method. The necessity of using the correct pairs of energetically conjugate stress and strain measures for the buckling problem is pointed out. Errors in using the incorrect traction boundary condition and terms that influence the buckling load and that have been omitted in popular commercial codes are pointed out and their significance in influencing the buckling load is identified. Results from the present two-dimensional analysis to predict the critical pressure are compared with previous theoretical results. The formulation and results presented here can be used as the correct benchmark solution to establish the accuracy in computing the buckling load of thick orthotropic composite structures, of contemporary interest, due to the increased use of thick-walled composite shell type structures in diverse engineering applications.
Surface and Thermal Effects on the Pull-In Behavior of Doubly-Clamped Graphene Nanoribbons Under Electrostatic and Casimir Loads
Authors: Rokni Hossein , Lu Wei
Published: February 2013

In this study, a comprehensive analytical model is established based on Euler–Bernoulli beam theory with von Kármán geometric nonlinearity to investigate the effect of residual surface tension, surface elasticity, and temperature on the static pull-in voltages of multilayer graphene nanoribbon (MLGNR) doubly-clamped beams under electrostatic and Casimir forces and axial residual stress. An explicit closed-form analytical solution to the governing fourth-order nonlinear differential equation of variable coefficients is presented for the static pull-in behavior of electrostatic nanoactuators using a Fredholm integral equation of the first kind. The high accuracy of the present analytical model is validated for some special cases through comparison with other existing numerical, analytical, and experimental models. The effects of the number of graphene nanoribbons (GNRs), temperature, surface tension, and surface elasticity on the pull-in voltage and displacement of MLGNR electrostatic nanoactuaotrs are investigated. Results indicate that the thermal effect on the pull-in voltage is significant especially when a smaller number of GNRs are used. It is found that the surface effects become more dominant as the number of GNRs decreases. It is also demonstrated that the residual surface tension exerts a greater influence on the pull-in voltage in comparison with the surface elasticity.
Mechanical Behavior and Structural Evolution of Carbon Nanotube Films and Fibers Under Tension: A Coarse-Grained Molecular Dynamics Study
Authors: Lu Weibang , Liu Xia , Li Qingwen , Byun Joon-Hyung , Chou Tsu-Wei
Published: February 2013

Coarse-grained molecular dynamics simulations have been performed to investigate the tensile behavior of CNT films. It is found that CNT entanglements greatly degrade the tensile load-bearing capability of CNT films. The effect of twisting on the tensile behavior of CNT fibers spun from CNT films has also been investigated. Results indicate that twisting can make either positive or negative contributions to the mechanical properties of the film, depending on the microstructure. The structural and energy evolution of CNT films and fibers, as well as the stress distributions of CNTs which cannot be easily determined experimentally, have been illustrated. This study provides an effective means of revealing the structure/property relationships of CNT films/fibers, which are essential in designing high performance CNT fibers.
Modified Maximum Mechanical Dissipation Principle for Rate-Independent Metal Plasticity
Authors: Xiao Yuzhong , Chen Jun , Zhu Xinhai , Cao Jian
Published: February 2013

The approach regarding the plastic process as a constrained optimization problem (Simo, J. C., and Hughes, T. J. R., 1998, Computational Inelasticity, Springer, New York) is discussed and found to be limited in considering nonlinear kinematic hardening and mechanical dissipation. These limitations are virtually common in elastoplastic modeling in both theoretical studies and industrial applications. A modified maximum mechanical dissipation principle is proposed to overcome the limitations and form an energy-based framework of nonlinear hardening laws. With the control functions introduced into the framework, not only are the relationships between existing hardening models clarified against their ad hoc origins, but modeling nonsaturating kinematic hardening behavior is also achieved. Numerical examples are presented to illustrate the capability of the nonsaturating kinematic hardening model to describe the phenomena of the permanent softening as well as the cyclic loading. These applications indicate the concept of the control function can be nontrivial in material modeling. Finally, the methodology is also extended to incorporate the multiterm approach.
Characterization of metal oxide layers grown on CVD graphene
Authors: Matsubayashi Akitomo , Abel Joseph , Prasad Sinha Dhiraj , Ung Lee Ji , LaBella Vincent P.
Published: February 2013

Growth of a fully oxidized aluminum oxide layer with low surface roughness on graphene grown by chemical vapor deposition is demonstrated. This is accomplished by the deposition of a 0.2 nm thick titanium seed layer on the graphene prior to the deposition of the aluminum under ultra high vacuum conditions, which was subsequently oxidized. The stoichiometry and surface roughness of the oxide layers were measured for a range of titanium and aluminum depositions utilizing ex situ x-ray photoelectron spectrometry and atomic force microscopy. These fully oxidized films are expected to produce good dielectric layers for use in graphene based electronic devices.
Surface reconstruction at the initial Ge adsorption stage on Si(114)-2 × 1
Authors: Duvjir Ganbat , Kim Hidong , Dugerjav Otgonbayar , Li Huiting , Motlak Moaaed , Arvisbaatar Amarmunkh , Seo Jae M.
Published: February 2013

By combined investigation of scanning tunneling microscopy and synchrotron core-level photoemission spectroscopy on the structural and chemical evolution at the initial stage of Ge adsorption on Si(114)-2 × 1, it has been observed that one-dimensional (1D) sawtooth-like nanostructures composed of (113) and (117) facets and 1D trenches adjacent to the (113) facets are readily formed without any wetting layer. Due to the absence of chain structures on the reconstructed Si(114)-2 × 1, enhanced Ge interdiffusion detected from Ge/Si(5 5 12)-2 × 1 has not been found. Instead, Si atoms originating from etched surfaces and arriving Ge atoms form the alloy facets with Ge-rich surfaces. These experimental results prove that, if the direction of the Ge overlayer corresponding to that of the substrate is unstable like the present case, the arriving atoms prefer to form facets covered with the species of lower surface free energies rather than a uniform wetting layer.
The feasibility of an inverse geometry CT system with stationary source arrays
Authors: Hsieh Scott S. , Heanue Joseph A. , Funk Tobias , Hinshaw Waldo S. , Wilfley Brian P. , Solomon Edward G. , Pelc Norbert J.
Published: February 2013

Purpose:

Inverse geometry computed tomography (IGCT) has been proposed as a new system architecture that combines a small detector with a large, distributed source. This geometry can suppress cone‐beam artifacts, reduce scatter, and increase dose efficiency. However, the temporal resolution of IGCT is still limited by the gantry rotation time. Large reductions in rotation time are in turn difficult due to the large source array and associated power electronics. We examine the feasibility of using stationary source arrays for IGCT in order to achieve better temporal resolution. We anticipate that multiple source arrays are necessary, with each source array physically separated from adjacent ones.

Methods:

Key feasibility issues include spatial resolution, artifacts, flux, noise, collimation, and system timing clashes. The separation between the different source arrays leads to missing views, complicating reconstruction. For the special case of three source arrays, a two‐stage reconstruction algorithm is used to estimate the missing views. Collimation is achieved using a rotating collimator with a small number of holes. A set of equally spaced source spots are designated on the source arrays, and a source spot is energized when a collimator hole is aligned with it. System timing clashes occur when multiple source spots are scheduled to be energized simultaneously. We examine flux considerations to evaluate whether sufficient flux is available for clinical applications.

Results:

The two‐stage reconstruction algorithm suppresses cone‐beam artifacts while maintaining resolution and noise characteristics comparable to standard third generation systems. The residual artifacts are much smaller in magnitude than the cone‐beam artifacts eliminated. A mathematical condition is given relating collimator hole locations and the number of virtual source spots for which system timing clashes are avoided. With optimization, sufficient flux may be achieved for many clinical applications.

Conclusions:

IGCT with stationary source arrays could be an imaging platform potentially capable of imaging a complete 16‐cm thick volume within a tenth of a second.
Analysis of a free‐running synchronization artifact correction for MV‐imaging with aSi:H flat panels
Authors: Mooslechner Michaela , Mitterlechner Bernhard , Weichenberger Harald , Huber Stefan , Sedlmayer Felix , Deutschmann Heinz
Published: February 2013

Purpose:

Solid state flat panel electronic portal imaging devices (EPIDs) are widely used for megavolt (MV) photon imaging applications in radiotherapy. In addition to their original purpose in patient position verification, they are convenient to use in quality assurance and dosimetry to verify beam geometry and dose deposition or to perform linear accelerator (linac) calibration procedures. However, native image frames from amorphous silicon (aSi:H) detectors show a range of artifacts which have to be eliminated by proper correction algorithms. When a panel is operated in free‐running frame acquisition mode, moving vertical stripes (periodic synchronization artifacts) are a disturbing feature in image frames. Especially for applications in volumetric intensity modulated arc therapy (VMAT) or motion tracking, the synchronization (sync) artifacts are the limiting factor for potential and accuracy since they become even worse at higher frame rates and at lower dose rates, i.e., linac pulse repetition frequencies (PRFs).

Methods:

The authors introduced a synchronization correction method which is based on a theoretical model describing the interferences of the panel's readout clocking with the linac's dose pulsing. Depending on the applied PRF, a certain number of dose pulses is captured per frame which is readout columnwise, sequentially. The interference of the PRF with the panel readout is responsible for the period and the different gray value levels of the sync stripes, which can be calculated analytically. Sync artifacts can then be eliminated multiplicatively in precorrected frames without additional information about radiation pulse timing.

Results:

For the analysis, three aSi:H EPIDs of various types were investigated with 6 and 15 MV photon beams at varying PRFs of 25, 50, 100, 200, and 400 pulses per second. Applying the sync correction at panels with gadolinium oxysulfide scintillators improved single frame flood field image quality drastically [improvement of the signal‐to‐noise ratio (SNR) up to 66.1 dB for 6 MV and 66.0 dB for 15 MV]. Also for the EPID with a caesium iodide scintillator, the noise for the lower PRFs could be reduced (SNR at 6 MV of up to 56.3 dB and at 15 MV up to 46.7 dB). However, the simplistic readout interference model fails at higher PRFs, where image lag and ghosting effects due to trapped charges in the thin film transistor and scintillator postglowing require additional corrections.

Conclusions:

The presented free‐running sync correction method improves SNR of single frames and enables imaging applications, like low‐dose rate imaging at increased image frame rates (e.g., to track moving gold fiducials in the lung). Adaptive image guided radiotherapy protocols become even feasible in VMAT plans. Also simultaneous kilovolt and MV imaging applications can benefit from new possibilities of MV scatter removal in x‐ray images.
Beyond Arms-Control Monitoring
Authors: Jeanloz Raymond , Fung Inez , Bowyer Theodore W. , Wofsy Steven C.
Published: February 2013

Environmental monitoring can become a useful long-term objective of arms-control treaty verification.
Response to Comment on "Evolutionary Trade-Offs, Pareto Optimality, and the Geometry of Phenotype Space"
Authors: Shoval Oren , Sheftel Hila , Shinar Guy , Hart Yuval , Ramote Omer , Mayo Avi , Dekel Erez , Kavanagh Kathryn , Alon Uri
Published: February 2013

Edelaar raises concerns about the way we tested our theory. Our mathematical theorem predicts that despite the high dimensionality of trait space, trade-offs between tasks leads to phenotypes in low-dimensional regions in trait space, such as lines and triangles. We address Edelaar's questions with statistical tests that eliminate pseudoreplication concerns, finding that our predictions remain convincingly supported.
Probing Allostery Through DNA
Authors: Kim Sangjin , Broströmer Erik , Xing Dong , Jin Jianshi , Chong Shasha , Ge Hao , Wang Siyuan , Gu Chan , Yang Lijiang , Gao Yi Qin , Su Xiao-dong , Sun Yujie , Xie X. Sunney
Published: February 2013

Allostery Across DNA

Proteins, such as transcription factors and RNA polymerase, bind close to each other on DNA and their function is coordinated.

Kim
et al.

(p.
816
; see the Perspective by

Crothers

) report single-molecule experiments that show that the DNA binding affinity of a protein is significantly altered by a second protein bound nearby. The effect oscillates between stabilizing and destabilizing the binding with a periodicity equal to the helical pitch of DNA. Allosteric coupling between a transcriptional repressor and RNA polymerase modulated gene expression in living bacteria.
Fine Tuning Gene Regulation
Authors: Crothers Donald M.
Published: February 2013

An allosteric effect in which distortion of the DNA duplex by one protein modulates the binding of another protein may be important in gene regulation.

[Also see Report by

Kim
et al.

]
The End of the Beginning for the Brain
How to Create a Mind
The Secret of Human Thought Revealed

by Ray Kurzweil

Viking, New York, 2012. 352 pp. $27.95, C$29.50. ISBN 9780670025299. Duckworth, London. €20. ISBN 9780715645376
Authors: Koch Christof
Published: February 2013

After romping through the history of artificial intelligence, Kurzweil presents hierarchical, hidden Markov models as the means to understanding of the mind.
Demonstrating Uncertainty
Authors: Milburn Gerard J.
Published: February 2013

Heisenberg's uncertainty principle is demonstrated with a vibrating macroscopic mirror.

[Also see Report by

Purdy
et al.

]
The Animal Tree of Life
Authors: Telford Maximilian J.
Published: February 2013

A molecular phylogeny of the animal kingdom published 25 years ago was the precursor to today's widely accepted phylogeny of all animal phyla.
Designing Scientific Meetings
Authors: Alberts Bruce
Published: February 2013

This issue of
Science
contains announcements for more than 100 different Gordon Research Conferences, on topics that range from atomic physics to developmental biology. The brainchild of Neil Gordon of Johns Hopkins University, these week-long meetings are designed to promote intimate, informal discussions of frontier science. Often confined to fewer than 125 attendees, they have traditionally been held in remote places with minimal distractions. Beginning in the early 1960s, I attended the summer Nucleic Acids Gordon Conference in rural New Hampshire, sharing austere dorm facilities in a private boys' school with randomly assigned roommates. As a beginning scientist, I found the question period after each talk especially fascinating, providing valuable insights into the personalities and ways of thinking of many senior scientists whom I had not encountered previously. Back then, there were no cellphones and no Internet, and all of the speakers seemed to stay for the entire week. During the long, session-free afternoons, graduate students mingled freely with professors. Many lifelong friendships were begun, and—as Gordon intended—new scientific collaborations began. Leap forward to today, and every scientist can gain immediate access to a vast store of scientific thought and to millions of other scientists via the Internet. Why, nevertheless, do in-person scientific meetings remain so valuable for a life in science?
NSF Opening Adds to Concerns About Obama's Second-Term Science Team
Authors: Mervis Jeffrey , Malakoff David
Published: February 2013

U.S. scientists are wondering who will lead several important science agencies after the director of the National Science Foundation became the latest top official to step down.
Evaluation of a Mycobacterium avium subsp. paratuberculosisleuDMutant as a Vaccine Candidate against Challenge in a Caprine Model
Authors: Faisal Syed M. , Chen Jenn-Wei , Yan Falong , Chen Tsai-Tzu , Useh Nicodemus M. , Yan Weiwei , Guo Shanguang , Wang Shih-Jon , Glaser Amy L. , McDonough Sean P. , Singh Bhupinder , Davis William C. , Akey Bruce L. , Chang Yung-Fu
Published: February 2013

Johne's disease (JD) is prevalent worldwide and has a significant impact on the global agricultural economy. In the present study, we evaluated the protective efficacy of aleuD(Δleud) mutant and gained insight into differential immune responses after challenge with virulentM. aviumsubsp.paratuberculosisin a caprine colonization model. The immune response and protective efficacy were compared with those of the killed vaccine Mycopar.In vitrostimulation of peripheral blood mononuclear cells with johnin purified protein derivative showed that Mycopar and ΔleuDgenerated similar levels of gamma interferon (IFN-γ) but significantly higher levels than unvaccinated and challenged phosphate-buffered saline controls. However, only with ΔleuDwas the IFN-γ response maintained. Flow cytometric analysis showed that the increase in IFN-γ correlated with proliferation and activation (increased expression of CD25) of CD4, CD8, and γδT cells, but this response was significantly higher in ΔleuD-vaccinated animals at some time points after challenge. Both Mycopar and ΔleuDvaccines upregulated Th1/proinflammatory and Th17 cytokines and downregulated Th2/anti-inflammatory and regulatory cytokines at similar levels at almost all time points. However, significantly higher levels of IFN-γ (at weeks 26 and 30), interleukin-2 (IL-2; week 18), IL-1b (weeks 14 and 22), IL-17 (weeks 18 and 22), and IL-23 (week 18) and a significantly lower level of IL-10 (weeks 14 and 18) and transforming growth factor β (week 18) were detected in theΔleuD-vaccinated group. Most importantly, ΔleuDelicited an immune response that significantly limited colonization of tissues compared to Mycopar upon challenge with wild-typeM. aviumsubsp.paratuberculosis. In conclusion, the ΔleuDmutant is a promising vaccine candidate for development of a live attenuated vaccine for JD in ruminants.
Genomic Sequencing Reveals Mutations Potentially Related to the Overattenuation of a Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus
Authors: Yu Xiuling , Chen Nanhua , Deng Xiaoyu , Cao Zhen , Han Wei , Hu Dongmei , Wu Jiajun , Zhang Shuo , Wang Baoyue , Gu Xiaoxue , Tian Kegong
Published: February 2013

Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) continues to evolve when serially passaged in Marc-145 cells. In this study, we analyzed the genomic and antigenic variants of HP-PRRSV strain JXA1 during
in vitro
passage. Protective efficacies of JXA1 from passages 100, 110, 120, 140, and 170 against the high-virulence parental virus were evaluated by inoculating pigs with each of these viruses and then challenging with JXA1 from passage 5 at 28 days postimmunization. We found that the antigenicities of JXA1 from passages after 110 were significantly reduced. Inoculation with JXA1 from passages after 110 provided only insufficient protection against the parental strain challenge, indicating that the immunogenicity of JXA1 is significantly decreased when it is
in vitro
passaged for 110 times and more. To identify the genomic variants that emerged during the overattenuation, eight complete genomes of highly passaged JXA1 were sequenced. One guanine deletion in the 5′ untranslated region (UTR), two nucleotide substitutions in the 3′ UTR, and 65 amino acid mutations in nonstructural and structural proteins that accompanied with the attenuation and overattenuation were determined. Genomic sequencing of
in vitro
serially passaged HP-PRRSV first identified the mutations potentially correlated with the overattenuation of a HP-PRRSV strain. These results facilitate the research aimed at elucidating the mechanisms for PRRSV genomic and antigenic changes and may also contribute to developing a safe and effective PRRSV vaccine.
Value of a Quality Assessment Program in Optimizing Cryopreservation of Peripheral Blood Mononuclear Cells in a Multicenter Study
Authors: Aziz Najib , Margolick Joseph B. , Detels Roger , Rinaldo Charles R. , Phair John , Jamieson Beth D. , Butch Anthony W.
Published: February 2013

Cryopreservation of peripheral blood mononuclear cells (PBMC) allows assays of cellular function and phenotype to be performed in batches at a later time on PBMC at a central laboratory to minimize assay variability. The Multicenter AIDS Cohort Study (MACS) is an ongoing prospective study of the natural and treated history of human immunodeficiency virus (HIV) infection that stores cryopreserved PBMC from participants two times a year at four study sites. In order to ensure consistent recovery of viable PBMC after cryopreservation, a quality assessment program was implemented and conducted in the MACS over a 6-year period. Every 4 months, recently cryopreserved PBMC from HIV-1-infected and HIV-1-uninfected participants at each MACS site were thawed and evaluated. The median recoveries of viable PBMC for HIV-1-infected and -uninfected participants were 80% and 83%, respectively. Thawed PBMC from both HIV-1-infected and -uninfected participants mounted a strong proliferative response to phytohemagglutinin, with median stimulation indices of 84 and 120, respectively. Expression of the lymphocyte surface markers CD3, CD4, and CD8 by thawed PBMC was virtually identical to what was observed on cells measured in real time using whole blood from the same participants. Furthermore, despite overall excellent performance of the four participating laboratories, problems were identified that intermittently compromised the quality of cryopreserved PBMC, which could be corrected and monitored for improvement over time. Ongoing quality assessment helps laboratories improve protocols and performance on a real-time basis to ensure optimal cryopreservation of PBMC for future studies.
Regional Immune Response to Immunization with Escherichia coli O157:H7-Derived Intimin in Cattle
Authors: Boland Kathryn G. , Hayles Andrea N. , Miller Claire B. , Kerr Tovah , Brown Wendy C. , Lahmers Kevin K.
Published: February 2013

Escherichia coliO157:H7 is an enteric pathogen of animals and humans that can result in deadly sequelae. Cattle are asymptomatic carriers and shedders of the bacteria and serve as an important reservoir of human infection.E. coliO157:H7 colonizes the gastrointestinal tract, most frequently at the rectoanal junction mucosa in cattle. Vaccination is a potentially highly effective means of decreasing cattle colonization and shedding and thereby decreasing human infections. Currently available vaccines are administered subcutaneously or intramuscularly, and immune responses have been evaluated solely by systemic immunoglobulin responses. This study evaluated local and systemic lymphoproliferative responses in addition to immunoglobulin responses following subcutaneous or mucosal (rectal) immunization withE. coliO157:H7 outer membrane protein intimin over three trials. In all three trials, significant local and systemic lymphoproliferative responses (P< 0.05) occurred following immunization in the majority of animals, as well as significant immunoglobulin responses (P< 0.001) in all animals. Surprisingly, local responses in the mesorectal lymph nodes were very similar between the subcutaneous and mucosal immunization groups. Moreover, the responses in mesorectal lymph nodes appeared targeted rather than generalized, as minimal or no significant responses were observed in the associated prescapular lymph nodes of subcutaneously immunized animals. The results indicate that both subcutaneous and mucosal immunizations are effective methods of inducing immune responses againstE. coliO157:H7 in cattle.
Development of an Immunochromatographic Assay Based on Dense Granule Protein 7 for Serological Detection of Toxoplasma gondii Infection
Authors: Terkawi Mohamad Alaa , Kameyama Kyohko , Rasul Nazim Hamza , Xuan Xuean , Nishikawa Yoshifumi
Published: February 2013

Dense granule antigen proteins derived fromToxoplasma gondii(TgGRAs) are potential antigens for the development of diagnostic tools. TgGRA7 and TgGRA14 were detected in the peritoneal fluid ofT. gondii-infected mice, suggesting that TgGRAs may be highly antigenic proteins. Here, TgGRA7 and TgGRA14 were evaluated as candidates for the development of a marker for a rapid diagnostic test. The specificity and sensitivity of purified recombinant proteins of TgGRA7 and TgGRA14 were compared in an indirect enzyme-linked immunosorbent assay (iELISA) using a series of serum samples fromT. gondii-experimentally infected mice and using recombinantT. gondiimajor surface antigen 2 (TgSAG2) as a reference control. The iELISA with TgGRA7 showed the greatest diagnostic accuracy and could detect anti-TgGRA7 antibody in acute and chronic infections. A total of 59 field samples from pigs were also examined by the iELISAs, and the results compared with those of the latex agglutination test (LAT). Among the three recombinant antigens, TgGRA7 had the highest rates of positivity, with significant concordance (88.14) and kappa value (0.76) in comparison with the results using LAT. Furthermore, an immunochromatographic test (ICT) based on recombinant TgGRA7 was developed for rapid detection of antibodies to the infection. The ICT differentiated clearly between sera fromT. gondii-infected mice and uninfected orNeospora caninum-infected mice. Pig sera were examined with the ICT, and the results compared favorably with those of LAT and iELISA for TgGRA7, with kappa values of 0.66 and 0.70 to 0.79, respectively. These data suggest that the ICT based on TgGRA7 is a promising diagnostic tool for routine testing in the clinic and mass screening of samples in the field.
Region of Difference 4 in Alpine Mycobacterium caprae Isolates Indicates Three Variants
Authors: Domogalla Janina , Prodinger Wolfgang M. , Blum Helmut , Krebs Stefan , Gellert Susanne , Müller Matthias , Neuendorf Erdmute , Sedlmaier Florian , Büttner Mathias
Published: February 2013

The lack of complete genome sequence information for
Mycobacterium caprae
complicates a robust differentiation of
M. caprae
and
Mycobacterium bovis
. In this study, the presence or absence of
M. caprae
-specific single nucleotide polymorphisms in
lepA
and
gyrB
genes was assessed. The region of difference 4 (RD4) was analyzed for the identification and characterization of
M. caprae
. Molecular characteristics were evaluated in 12 recent
M. caprae
isolates from livestock and wildlife collected over a 3-year period in Bavaria, Germany. Conventional PCR strategies, sequence analysis of PCR fragments, and data from a next-generation sequencing approach together with variable-number tandem-repeat genotyping were utilized. Single nucleotide polymorphisms in the
lepA
and
gyrB
genes indicating the presence of
M. caprae
were detected in all the isolates. At least three different RD4 variants were found for Alpine
M. caprae
isolates. The results demonstrate that the RD4 region is rather heterogeneous in
M. caprae
genomes. As assumed by others, the presence of RD4 is critical for PCR-based differentiation of
M. caprae
from
M. bovis
, but in addition, the observed variability of RD4 allows the identification of
M. caprae
genotypes and may be indicative of a geographical-type appearance.
CHD6, a Cellular Repressor of Influenza Virus Replication, Is Degraded in Human Alveolar Epithelial Cells and Mice Lungs during Infection
Authors: Alfonso Roberto , Rodriguez Ariel , Rodriguez Paloma , Lutz Thomas , Nieto Amelia
Published: February 2013

The influenza virus polymerase associates to an important number of transcription-related proteins, including the largest subunit of the RNA polymerase II complex (RNAP II). Despite this association, degradation of the RNAP II takes place in the infected cells once viral transcription is completed. We have previously shown that the chromatin remodeler CHD6 protein interacts with the influenza virus polymerase complex, represses viral replication, and relocalizes to inactive chromatin during influenza virus infection. In this paper, we report that CHD6 acts as a negative modulator of the influenza virus polymerase activity and is also subjected to degradation through a process that includes the following characteristics: (i) the cellular proteasome is not implicated, (ii) the sole expression of the three viral polymerase subunits from its cloned cDNAs is sufficient to induce proteolysis, and (iii) degradation is also observed
in vivo
in lungs of infected mice and correlates with the increase of viral titers in the lungs. Collectively, the data indicate that CHD6 degradation is a general effect exerted by influenza A viruses and suggest that this viral repressor may play an important inhibitory role since degradation and accumulation into inactive chromatin occur during the infection.
Galectin-9 Functionally Impairs Natural Killer Cells in Humans and Mice
Authors: Golden-Mason Lucy , McMahan Rachel H. , Strong Michael , Reisdorph Richard , Mahaffey Spencer , Palmer Brent E. , Cheng Linling , Kulesza Caroline , Hirashima Mitsuomi , Niki Toshiro , Rosen Hugo R.
Published: February 2013

Galectin-9 is a pleiotropic immune modulator affecting numerous cell types of innate and adaptive immunity. Patients with chronic infection with either hepatitis C virus (HCV) or HIV have elevated circulating levels. Limited data exist on the regulation of natural killer (NK) cell function through interaction with galectin-9. We found that galectin-9 ligation downregulates multiple immune-activating genes, including eight involved in the NK cell-mediated cytotoxicity pathway, impairs lymphokine-activated killing, and decreases the proportion of gamma interferon (IFN-γ)-producing NK cells that had been stimulated with interleukin-12 (IL-12)/IL-15. We demonstrate that the transcriptional and functional changes induced by galectin-9 are independent of Tim-3. Consistent with these results for humans, we find that the genetic absence of galectin-9 in mice is associated with greater IFN-γ production by NK cells and enhanced degranulation. We also show that in the setting of a short-term (4-day) murine cytomegalovirus infection, terminally differentiated NKs accumulate in the livers of galectin-9 knockout mice, and that hepatic NKs spontaneously produce significantly more IFN-γ in this setting. Taken together, our results indicate that galectin-9 engagement impairs the function of NK cells, including cytotoxicity and cytokine production.
Synergistic Effect of the PDZ and p85β-Binding Domains of the NS1 Protein on Virulence of an Avian H5N1 Influenza A Virus
Authors: Fan Shufang , Macken Catherine A. , Li Chengjun , Ozawa Makoto , Goto Hideo , Iswahyudi N. F. N. , Nidom Chairul A. , Chen Hualan , Neumann Gabriele , Kawaoka Yoshihiro
Published: February 2013

The influenza A virus NS1 protein affects virulence through several mechanisms, including the host's innate immune response and various signaling pathways. Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype continue to evolve through reassortment and mutations. Our recent phylogenetic analysis identified a group of HPAI H5N1 viruses with two characteristic mutations in NS1: the avian virus-type PDZ domain-binding motif ESEV (which affects virulence) was replaced with ESKV, and NS1-138F (which is highly conserved among all influenza A viruses and may affect the activation of the phosphatidylinositol 3-kinase [PI3K]/Akt signaling pathway) was replaced with NS1-138Y. Here, we show that an HPAI H5N1 virus (A/duck/Hunan/69/2004) encoding NS1-ESKV and NS1-138Y was confined to the respiratory tract of infected mice, whereas a mutant encoding NS1-ESEV and NS1-138F caused systemic infection and killed mice more efficiently. Mutation of either one of these sites had small effects on virulence. In addition, we found that the amino acid at NS1-138 affected not only the induction of the PI3K/Akt pathway but also the interaction of NS1 with cellular PDZ domain proteins. Similarly, the mutation in the PDZ domain-binding motif of NS1 altered its binding to cellular PDZ domain proteins and affected Akt phosphorylation. These findings suggest a functional interplay between the mutations at NS1-138 and NS1-229 that results in a synergistic effect on influenza virulence.