bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Clinically Relevant Factors on the Immediate Biomechanical Surrounding for a Series of Dental Implant Designs
Authors: Shunmugasamy Vasanth Chakravarthy , Gupta Nikhil , Pessoa Roberto Sales , Janal Malvin N. , Coelho Paulo G.
Published: December 2010

The objective of the present study was to assess the influence of various clinically relevant scenarios on the strain distribution in the biomechanical surrounding of five different dental implant macrogeometries. The biomechanical environment surrounding an implant, i.e., the cortical and trabecular bone, was modeled along with the implant. These models included two different values of the study parameters including loading conditions, trabecular bone elastic modulus, cortical/trabecular bone thickness ratio, and bone loss for five implant designs. Finite element analysis was conducted on the models and strain in the bones surrounding the implant was calculated. Bone volumes having strains in four different windows of 0–200 με, 200–1000 με, 1000–3000 με, and >3000 με were measured and the effect of each biomechanical variable and their two-way interactions were statistically analyzed using the analysis of variance method. This study showed that all the parameters included in this study had an effect on the volume of bones in all strain windows, except the implant design, which affected only the 0–200 με and >3000 με windows. The two-way interaction results showed that interactions existed between implant design and bone loss, and loading condition, bone loss in the 200–1000 με window, and between implant design and loading condition in the 0–200 με window. Within the limitations of the present methodology, it can be concluded that although some unfavorable clinical scenarios demonstrated a higher volume of bone in deleterious strain levels, a tendency toward the biomechanical equilibrium was evidenced regardless of the implant design.
Hydrodynamic Effects of Compliance Mismatch in Stented Arteries
Authors: Selvarasu N. K. C. , Tafti Danesh K. , Vlachos Pavlos P.
Published: December 2010

Cardiovascular diseases are the number one cause of death in the world, making the understanding of hemodynamics and development of treatment options imperative. The most common modality for treatment of occlusive coronary artery diseases is the use of stents. Stent design profoundly influences the postprocedural hemodynamic and solid mechanical environment of the stented artery. However, despite their wide acceptance, the incidence of stent late restenosis is still high (Zwart et al., 2010, “Coronary Stent Thrombosis in the Current Era: Challenges and Opportunities for Treatment,” Current Treatment Options in Cardiovascular Medicine, 12(1), pp. 46–57), and it is most prevailing at the proximal and distal ends of the stent. In this work, we focus our investigation on the localized hemodynamic effects of compliance mismatch due to the presence of a stent in an artery. The compliance mismatch in a stented artery is maximized at the proximal and distal ends of the stent. Hence, it is our objective to understand and reveal the mechanism by which changes in compliance contribute to the generation of nonphysiological wall shear stress (WSS). Such adverse hemodynamic conditions could have an effect on the onset of restenosis. Three-dimensional, spatiotemporally resolved computational fluid dynamics simulations of pulsatile flow with fluid-structure interaction were carried out for a simplified coronary artery with physiologically relevant flow parameters. A model with uniform elastic modulus is used as the baseline control case. In order to study the effect of compliance variation on local hemodynamics, this baseline model is compared with models where the elastic modulus was increased by two-, five-, and tenfold in the middle of the vessel. The simulations provided detailed information regarding the recirculation zone dynamics formed during flow reversals. The results suggest that discontinuities in compliance cause critical changes in local hemodynamics, namely, altering the local pressure and velocity gradients. The change in pressure gradient at the discontinuity was as high as 90%. The corresponding changes in WSS and oscillatory shear index calculated were 9% and 15%, respectively. We demonstrate that these changes are attributed to the physical mechanism associating the pressure gradient discontinuities to the production of vorticity (vorticity flux) due to the presence of the stent. The pressure gradient discontinuities and augmented vorticity flux are affecting the wall shear stresses. As a result, this work reveals how compliance variations act to modify the near wall hemodynamics of stented arteries.
Nonlinear Smooth Orthogonal Decomposition of Kinematic Features of Sawing Reconstructs Muscle Fatigue Evolution as Indicated by Electromyography
Authors: Segala David B. , Gates Deanna H. , Dingwell Jonathan B. , Chelidze David
Published: December 2010

Tracking or predicting physiological fatigue is important for developing more robust training protocols and better energy supplements and/or reducing muscle injuries. Current methodologies are usually impractical and/or invasive and may not be realizable outside of laboratory settings. It was recently demonstrated that smooth orthogonal decomposition (SOD) of phase space warping (PSW) features of motion kinematics can identify fatigue in individual muscle groups. We hypothesize that a nonlinear extension of SOD will identify more optimal fatigue coordinates and provide a lower-dimensional reconstruction of local fatigue dynamics than the linear SOD. Both linear and nonlinear SODs were applied to PSW features estimated from measured kinematics to reconstruct muscle fatigue dynamics in subjects performing a sawing motion. Ten healthy young right-handed subjects pushed a weighted handle back and forth until voluntary exhaustion. Three sets of joint kinematic angles were measured from the right upper extremity in addition to surface electromyography (EMG) recordings. The SOD coordinates of kinematic PSW features were compared against independently measured fatigue markers (i.e., mean and median EMG spectrum frequencies of individual muscle groups). This comparison was based on a least-squares linear fit of a fixed number of the dominant SOD coordinates to the appropriate local fatigue markers. Between subject variability showed that at most four to five nonlinear SOD coordinates were needed to reconstruct fatigue in local muscle groups, while on average 15 coordinates were needed for the linear SOD. Thus, the nonlinear coordinates provided a one-order-of-magnitude improvement over the linear ones.
Finite Element Analysis of Ramming in Ovis canadensis
Authors: Maity Parimal , Tekalur Srinivasan Arjun
Published: December 2010

The energy produced during the ramming of bighorn sheep (Ovis canadensis) would be expected to result in undesirable stresses in their frontal skull, which in turn would cause brain injury; yet, this animal seems to suffer no ill effects. In general, horn is made of an α-keratin sheath covering a bone. Despite volumes of data on the ramming behavior of Ovis canadensis, the extent to which structural components of horn and horn-associated structure or tissue absorb the impact energy generated by the ramming event is still unknown. This study investigates the hypothesis that there is a mechanical relationship present among the ramming event, the structural constituents of the horn, and the horn-associated structure. The three-dimensional complex structure of the bighorn sheep horn was successfully constructed and modeled using a computed tomography (CT) scan and finite element (FE) method, respectively. Three different three-dimensional quasi-static models, including a horn model with trabecular bone, a horn model with compact bone that instead of trabecular bone, and a horn model with trabecular bone as well as frontal sinuses, were studied. FE simulations were used to compare distributions of principal stress in the horn and the frontal sinuses and the strain energy under quasi-static loading conditions. It was noticed that strain energy due to elastic deformation of the complex structure of horn modeled with trabecular bone and with trabecular bone and frontal sinus was different. In addition, trabecular bone in the horn distributes the stresses over a larger volume, suggesting a mechanical link between the structural constituents and the ramming event. This phenomenon was elucidated through the principal stress distribution in the structure. This study will help designers in choosing appropriate material combinations for the successful design of protective structures against a similar impact.
Simulation of LV Pacemaker Lead in Marginal Vein: Potential Risk Factors for Acute Dislodgement
Authors: Zhao Xuefeng , Burger Mike , Liu Yi , Das Mithilesh K. , Combs William , Wenk Jonathan F. , Guccione Julius M. , Kassab Ghassan S.
Published: December 2010

Although left ventricular (LV) coronary sinus lead dislodgement remains a problem, the risk factors for dislodgement have not been clearly defined. In order to identify potential risk factors for acute lead dislodgement, we conducted dynamic finite element simulations of pacemaker lead dislodgement in marginal LV vein. We considered factors such as mismatch in lead and vein diameters, velocity of myocardial motion, branch angle between the insertion vein and the coronary sinus, degree of slack, and depth of insertion. The results show that large lead-to-vein diameter mismatch, rapid myocardial motion, and superficial insertion are potential risk factors for lead dislodgement. In addition, the degree of slack presents either a positive or negative effect on dislodgement risk depending on the branch angle. The prevention of acute lead dislodgment can be enforced by inducing as much static friction force as possible at the lead-vein interface, while reducing the external force. If the latter exceeds the former, dislodgement will occur. The present findings underscore the major risk factors for lead dislodgment, which may improve implantation criterion and future lead design.
Experimentally Validated Microstructural 3D Constitutive Model of Coronary Arterial Media
Authors: Hollander Yaniv , Durban David , Lu Xiao , Kassab Ghassan S. , Lanir Yoram
Published: December 2010

Accurate modeling of arterial response to physiological or pathological loads may shed light on the processes leading to initiation and progression of a number of vascular diseases and may serve as a tool for prediction and diagnosis. In this study, a microstructure based hyperelastic constitutive model is developed for passive media of porcine coronary arteries. The most general model contains 12 independent parameters representing the three-dimensional inner fibrous structure of the media and includes the effects of residual stresses and osmotic swelling. Parameter estimation and model validation were based on mechanical data of porcine left anterior descending (LAD) media under radial inflation, axial extension, and twist tests. The results show that a reduced four parameter model is sufficient to reliably predict the passive mechanical properties. These parameters represent the stiffness and the helical orientation of each lamellae fiber and the stiffness of the interlamellar struts interconnecting these lamellae. Other structural features, such as orientational distribution of helical fibers and anisotropy of the interlamellar network, as well as possible transmural distribution of structural features, were found to have little effect on the global media mechanical response. It is shown that the model provides good predictions of the LAD media twist response based on parameters estimated from only biaxial tests of inflation and extension. In addition, good predictive capabilities are demonstrated for the model behavior at high axial stretch ratio based on data of law stretches.
The Author's Report
Authors: Greenslade Thomas B.
Published: December 2010

The referee's report is a standard rite of passage for an author of articles in The Physics Teacher. Will the referee (and the editor) agree with the basic premise and the details of your carefully thought-out article? I have faced this moment of truth many times; the majority of them were during the editorship of Cliff Swartz. These reminiscences are as much about the journal as Cliff, for, to many of us, the two seemed inseparable.
Whole Class Laboratories with Google Docs
Authors: Bonham Scott
Published: December 2010

Interactive (reformed) instruction helps students develop a deeper understanding of physics,1 a component of which is letting students explore physical phenomena first and then building upon their experience. However, the time required for a single group to collect sufficient data and the likelihood of measurement errors are often obstacles to this. This paper describes an approach that overcomes those obstacles by using Google Docs to easily collect data during class from all student groups to use for class discussion. Each group takes three to five measurements and submits their data through a web form that goes straight into a Google spreadsheet. The instructor then uses this for plots or calculations and leads a class discussion.
Innovative Use of a Classroom Response System During Physics Lab
Authors: Walgren Jay
Published: December 2010

More and more physics instructors are making use of personal/classroom response systems or “clickers.” The use of clickers to engage students with multiple-choice questions during lecture and available instructor resources for clickers have been well documented in this journal.1–4 Newer-generation clickers, which I refer to as classroom response systems (CRS), have evolved to accept numeric answers (such as 9.81) instead of just single “multiple-choice” entries (Fig. 1). This advancement is available from most major clicker companies and allows for a greater variety of engaging questions during lecture. In addition, these new “numeric ready” clickers are marketed to be used for student assessments. During a test or quiz, students' answers are entered into their clicker instead of on paper or Scantron® and immediately absorbed by wireless connection into a computer for grading and analysis. I recognize the usefulness and benefit these new-generation CRSs provide for many instructors. However, I do not use my CRS in either of the aforementioned activities. Instead, I use it in an unconventional way. I use the CRS to electronically capture students' lab data as they are performing a physics lab (Fig. 2). I set up the clickers as if I were going to use them for a test, but instead of entering answers to a test, my students enter lab data as they collect it. In this paper I discuss my use of a classroom response system during physics laboratory and three benefits that result: 1) Students are encouraged to “take ownership of” and “have integrity with” their physics lab data. 2) Students' measuring and unit conversion deficiencies are identified immediately during the lab. 3) The process of grading students' labs is simplified because the results of each student's lab calculations can be pre-calculated for the instructor using a spreadsheet. My use of clickers during lab can be implemented with most clicker systems available to instructors today. The CRS I use is the eInstruction's® Classroom Performance System™ (CPS™).5 (Fig. 1)
On Defining Mass
Authors: Hecht Eugene
Published: December 2010

Though central to any pedagogical development of physics, the concept of mass is still not well understood. Properly defining mass has proven to be far more daunting than contemporary textbooks would have us believe. And yet today the origin of mass is one of the most aggressively pursued areas of research in all of physics. Much of the excitement surrounding the Large Hadron Collider at CERN is associated with discovering the mechanism responsible for the masses of the elementary particles. This paper will first briefly examine the leading definitions, pointing out their shortcomings. Then, utilizing relativity theory, it will propose—for consideration by the community of physicists—a conceptual definition of mass predicated on the more fundamental concept of energy, more fundamental in that everything that has mass has energy, yet not everything that has energy has mass.
Exploring Magnetic Fields with a Compass
Authors: Lunk Brandon , Beichner Robert
Published: December 2010

A compass is an excellent classroom tool for the exploration of magnetic fields. Any student can tell you that a compass is used to determine which direction is north, but when paired with some basic trigonometry, the compass can be used to actually measure the strength of the magnetic field due to a nearby magnet or current-carrying wire. In this paper, we present a series of simple activities adapted from the Matter & Interactions textbook1 for doing just this. Interestingly, these simple measurements are comparable to predictions made by the Bohr model of the atom. Although antiquated, Bohr's atom can lead the way to a deeper analysis of the atomic properties of magnets. Although originally developed for an introductory calculus-based course, these activities can easily be adapted for use in an algebra-based class or even at the high school level.
Following Michael Faraday's Footprints
Authors: Galeano Javier
Published: December 2010

Last fall I had the good fortune of receiving financial support to shoot a documentary about Michael Faraday.1 I took the opportunity to learn more about this great experimentalist and to visit the highlights of places in his life. In this paper, I would like to share a list and description of some of the most remarkable places in London suitable for following Michael Faraday's footprints. There are many other places in Europe of special interest for the physics teacher,2,3 and some useful guides to help us visit places as “scientific travelers,”4,5 but this paper focuses on Michael Faraday and London. I have personally visited most of the places described below and found the experience to be really worthwhile.
Measuring Systematic Error with Curve Fits
Authors: Rupright Mark E.
Published: December 2010

Systematic errors are often unavoidable in the introductory physics laboratory. As has been demonstrated in many papers in this journal, such errors can present a fundamental problem for data analysis, particularly when comparing the data to a given model.1–3 In this paper I give three examples in which my students use popular curve-fitting software and adjust the theoretical model to account for, and even exploit, the presence of systematic errors in measured data.
Demonstration of momentum and kinetic energy during an entire collision
Authors: Sawadthaisong Nattakit , Chitaree Ratchapak , Barufaldi James P.
Published: December 2010

A collision is a physical phenomenon commonly occurring in our daily life. In the classroom, the instructor usually demonstrates collision to enhance students' conceptual understanding of momentum conservation and kinetic energy conservation in collisions.1–3 The results of such demonstrations illustrate that the total linear momentum and the kinetic energy for elastic collisions in a system are similar both before and after the collision.4 Demonstrating the momentum and kinetic energy while the two objects are in the process of colliding can provide greater insight into these concepts. Such demonstration results during the collision are rarely described, however, because the time during the collision process is very brief, making the determination of the velocity or momentum of each object very difficult.5 In this paper, we intend to present an interactive demonstration6 proposed to illustrate the results of momentum conservation and kinetic energy conservation simultaneously for the entire collision.
“Make and Take” YouTube
Authors: Riendeau Diane
Published: December 2010

Special thanks to Jeff Wetherhold for his contribution to this month's column.
Stretching Dielectric Elastomer Performance
Authors: Carpi Federico , Bauer Siegfried , De Rossi Danilo
Published: December 2010

Devices using materials that deform in response to electricity are based on a phenomenon that was observed more than two centuries ago.
Ectopic Expression of Germline Genes Drives Malignant Brain Tumor Growth in
Drosophila
Authors: Janic Ana , Mendizabal Leire , Llamazares Salud , Rossell David , Gonzalez Cayetano
Published: December 2010

Curing Insect Brain Tumors

Mammalian tumors often show ectopic expression of genes that normally function only in the germ line. The possible contribution of cancer germline (CG) genes to malignancy is unknown.

Janic
et al.

(p.
1824
; see the Perspective by

Wu and Ruvkun

) found that CG genes are also expressed in
Drosophila
brain tumors caused by mutants in the gene
lethal (3) malignant brain tumor
. Moreover, inactivation of some of these genes suppressed fly tumor growth. Because some
Drosophila
CG genes are orthologs of human CG genes, it is possible that inactivation of germline genes may show human tumor suppressor activity.
Hsp90 and Environmental Stress Transform the Adaptive Value of Natural Genetic Variation
Authors: Jarosz Daniel F. , Lindquist Susan
Published: December 2010

Exploiting Variation

Molecular chaperones help newly synthesized proteins fold, protecting the macromolecular machinery of the cell from various stresses; for example, the highly conserved heat shock proteins (hsp) protect against elevated temperature. Hsp90 has also been suggested both to buffer against and to potentiate existing genetic variation in a population. To investigate the generality of these claims,
Jarosz and Lindquist
(p.
1820
) screened 96
Saccharomyces cerevisiae
strains from various ecological niches—soil, fruit, sake, beer, and infected humans—as well as assessed their adaptive value under different growth conditions. Hsp90 determined the adaptive value of ∼20% of the genetic variation in baker's yeast, with half of the traits being buffered, and half potentiated by hsp90.
Has the Microbiota Played a Critical Role in the Evolution of the Adaptive Immune System?
Authors: Lee Yun Kyung , Mazmanian Sarkis K.
Published: December 2010

A Gutsy Analysis

Efforts to sequence the human microbiome—the genomes of all the microbes that inhabit our bodies—have demonstrated its enormous diversity. Analyses to probe the various functions of the microbiota, particularly of those that reside in the gut, have revealed that our microbiota has a profound impact on the development and function of our immune systems.
Lee and Mazmanian
(p.
1768
) review how the microbiota influences the development of the adaptive immune system. Specific species and families of microbiota support the differentiation of particular populations of T cells, and alterations in intestinal microbiota affect the development of inflammation and autoimmunity.
Brownian Motion of Stiff Filaments in a Crowded Environment
Authors: Fakhri Nikta , MacKintosh Frederick C. , Lounis Brahim , Cognet Laurent , Pasquali Matteo
Published: December 2010

Movement in a Tight Squeeze

The motion of flexible polymer chains in a dense melt or concentrated solution is described by reptation theory, in which a single chain is considered to snake back and forth inside a virtual confining tube formed by all its neighboring chains. A number of theories have been proposed for stiffer molecules, but it has been hard to obtain experimental data to determine the thermal motion of stiff filaments.

Fakhri
et al.

(p.
1804
) visualized carbon nanotubes directly as a model system for stiff polymers diffusing in a gel, and found that even a slight increase in flexibility significantly sped up diffusion of stiff filaments under confinement. The rotational diffusion constant grew linearly with the flexibility and, counterintuitively, did not depend on the degree of crowding.
The Challenge of Feeding Scientific Advice into Policy-Making
Authors: Schenkel Roland
Published: December 2010

Three case studies illustrate general principles to guide scientists and policy-makers in interactions with each other and the public.
High-Flux Solar-Driven Thermochemical Dissociation of CO
2
and H
2
O Using Nonstoichiometric Ceria
Authors: Chueh William C. , Falter Christoph , Abbott Mandy , Scipio Danien , Furler Philipp , Haile Sossina M. , Steinfeld Aldo
Published: December 2010

Fuel from Heat

Plants grow by using energy from the Sun to convert carbon dioxide into sugar-based polymers and aromatics. These compounds in turn can be stripped of their oxygen, either through millennia of underground degradation to yield fossil fuels, or through a rather more rapid process of dissolution, fermentation, and hydrogenation to yield biofuels. Can we use sunlight to turn CO
2
into hydrocarbon fuel without relying on the intervening steps of plant growth and breakdown?

Chueh
et al.

(p.
1797
) demonstrate one possible approach, in which concentrated sunlight heats cerium oxide to a sufficiently high temperature (∼1500°C) to liberate some oxygen from its lattice. The material then readily strips O atoms from either water or CO
2
, yielding hydrogen or CO, which can then be combined to form fuels.
A Pollen Factor Linking Inter- and Intraspecific Pollen Rejection in Tomato
Authors: Li Wentao , Chetelat Roger T.
Published: December 2010

Reds Versus Greens

Self-incompatibility (SI) allows plants to prevent inbreeding. Crosses with distant relatives (outbreeding) can also be problematic and is prevented by unilateral interspecific incompatability (UI). In the nightshade family, SI functions within green-fruited species, whereas crosses between green-fruited and red-fruited species (which includes tomato) results in UI.
Li and Chetelat
(p.
1827
) found a gene, related to known SI genes within this family, that differs in transcript length and function between individuals that are red-fruited and those that are green-fruited. A survey of species shows that the green-fruited species have a functional allele of this gene, whereas the transcript of this gene in red-fruited species, which are self-compatible, produce a putatively nonfunctional protein. These findings suggest that cultivated tomato may have lost the ability to pollinate other species within the same family, owing to the loss of this protein.
Computational Physics in Film
Authors: Bridson Robert , Batty Christopher
Published: December 2010

Numerical modeling of how objects and fluids move, collide, and break up underlies spellbinding video animations.
At the Sesquicentennial of
Origin
Evolution Since Darwin
The First 150 Years

Michael A. Bell, Douglas J. Futuyma, Walter F. Eanes, and Jeffrey S. Levinton, Eds.

Sinauer, Sunderland, MA, 2010. 704 pp. Paper, $69.95. ISBN 9780878934133.
Authors: Mindell David P.
Published: December 2010

Collectively, these essays survey the current state and future prospects of the major areas within evolutionary biology.
A Natural History of the Brain
Brain
The Inside Story

Rob DeSalle, Joy Hirsch, and Margaret Zellner, curators

American Museum of Natural History, New York, through 14 August 2011. Guangdong Science Center, Guangzhou, China, 19 November 2011 to 30 April 2012. Parque de las Ciencias, Granada, Spain, 14 July 2012 to 6 January 2013. Codie Idee per la Cultura, Torino, Italy, 2 March 2013 to 18 August 2013. www.amnh.org/exhibitions/brain/
Authors: Rabinowitz Abigail , Schoonover Carl E.
Published: December 2010

Through displays that promote an intuitive understanding of the brain, this exhibition offers a compelling survey of current brain science.
Generating an Atmosphere
Authors: Cruikshank Dale P.
Published: December 2010

The oxygen and carbon dioxide atmosphere on Saturn's moon Rhea is produced by a photochemical reaction mechanism.
Ubiquitination Inhibits Neuronal Exit
Authors: Métin Christine , Luccardini Camilla
Published: December 2010

Newborn neurons shut down a protein destruction mechanism to migrate to their final destination.
Revealing the Dark Matter of the Genome
Authors: Blaxter Mark
Published: December 2010

Integrated data sets from two animal model organisms provide insights into the organization, structure, and function of their genomes.
Model Organisms and Human Health
Authors: Alberts Bruce
Published: December 2010

In this issue of
Science
, we highlight the impressive efforts to describe and analyze the genomes of the two organisms—the fly
Drosophila melanogaster
and the nematode worm
Caenorhabditis elegans
—that serve as the best models for understanding the biology of all animals, including humans. Hundreds of scientists have collaborated in these two major studies, which have moved us far beyond the complete descriptions of the DNA molecules that make up the fly and worm genomes published a little more than a decade ago, an accomplishment that seemed amazing then. As summarized in the Perspective on p. 1758, the new findings reveal essentially all of the tens of thousands of RNA and protein molecules that each of these organisms produces, as well as how their genetic information is packaged. Extensive Web-based databases built on these data are freely available to everyone, greatly accelerating future discoveries. Strange as it may seem, this research, aimed at reaching a deep molecular understanding of how the bodies of a fly and a worm are formed and maintained, will be critical for improving human health.
Can Bolden Banish NASA Blues?
Authors: Lawler Andrew
Published: December 2010

Obama's nominee for NASA administrator is trying to rally public support on the eve of the moon landing anniversary as an expert panel and Congress worry that NASA has lost its way.
Polio Outbreak Breaks the Rules
Authors: Roberts Leslie
Published: December 2010

Polio is a horrendous disease, but it is seldom fatal—except now. An explosive outbreak in the Republic of Congo is writing another chapter in the book on how this ancient scourge behaves.
Court to Weigh University's Decision Not to Hire Astronomer
Authors: Couzin-Frankel Jennifer
Published: December 2010

Early next year, a federal court will take up the case of Martin Gaskell, an astrophysicist who claims that the University of Kentucky denied him a job because he is an evangelical Christian.
What's Next for Disease Eradication?
Authors: Enserink Martin
Published: December 2010

Despite major setbacks, the idea of wiping entire diseases from the face of the planet hasn't lost its appeal. But the rules of the game have changed.
CIRM: The Good, the Bad, and the Ugly
Authors: Miller Greg
Published: December 2010

Having bolstered basic research, California's stem cell agency must choose a new leader and figure out how to develop therapies
Calreticulin Is the Dominant Pro-Phagocytic Signal on Multiple Human Cancers and Is Counterbalanced by CD47
Authors: Chao Mark P. , Jaiswal Siddhartha , Weissman-Tsukamoto Rachel , Alizadeh Ash A. , Gentles Andrew J. , Volkmer Jens , Weiskopf Kipp , Willingham Stephen B. , Raveh Tal , Park Christopher Y. , Majeti Ravindra , Weissman Irving L.
Published: December 2010

Calreticulin-induced phagocytosis of cancer cells can be counterbalanced by CD47 expression.
Academic/Industry Challenges for Medical Device Development
Authors: Linehan John H. , Chaney Ari
Published: December 2010

A session about the challenges that occur during medical device development was held at a 2010 NIH forum on promoting collaborations among academia, government, and industry.
Advancing Translational Research Collaborations
Authors: Portilla Lili M. , Evans Greg , Eng Benjamin , Fadem Terry J.
Published: December 2010

A 2010 NIH forum investigated how barriers to collaboration among academia, government, and industry must be identified and overcome to maximize the clinical return on investment in science (see also the five accompanying meeting reports).
Short-Term Monotherapy in HIV-Infected Patients with a Virus Entry Inhibitor Against the gp41 Fusion Peptide
Authors: Forssmann Wolf-Georg , The Yu-Han , Stoll Matthias , Adermann Knut , Albrecht Uwe , Tillmann Hanns-Christian , Barlos Kleomenis , Busmann Annette , Canales-Mayordomo Angeles , Giménez-Gallego Guillermo , Hirsch Jochen , Jiménez-Barbero Jesus , Meyer-Olson Dirk , Münch Jan , Pérez-Castells Javier , Ständker Ludger , Kirchhoff Frank , Schmidt Reinhold E.
Published: December 2010

An optimized derivative of a natural HIV-1 entry inhibitor targeting the gp41 fusion peptide shows antiviral potency and minimal side effects in a Phase I/II clinical trial.
2010: Awards Show What Translation Can Accomplish
Authors: Desmond-Hellmann Susan
Published: December 2010

Four of the most coveted awards in science celebrate truly translational research.
Targeting the Channel: CF Treatment Gets Personal
Authors: Ahmad Shama
Published: December 2010

A drug that targets a specific mutated form of the protein that causes cystic fibrosis improves the protein’s function and disease symptoms.
Internalization of IgG-Coated Targets Results in Activation and Secretion of Soluble CD40 Ligand and RANTES by Human Platelets
Authors: Antczak Adam J. , Vieth Joshua A. , Singh Navinderjit , Worth Randall G.
Published: December 2010

Platelets are crucial elements for maintenance of hemostasis. Other functions attributable to platelets are now being appreciated, such as their role in inflammatory reactions and host defense. Platelets have been reported to bind immunological stimuli like IgG complexes, and for nearly 50 years it has been speculated that platelets may participate in immunological reactions. Platelets have been reported to bind and internalize various substances, similar to other leukocytes, such as macrophages and dendritic cells. In the present study, we tested the hypothesis that human platelets can bind and internalize IgG-coated particles, similar to leukocytes. To this end, we observed that interaction with IgG-coated beads resulted in platelet activation (as measured by CD62P expression), internalization of targets, and significant soluble CD40 ligand (sCD40L) and RANTES (regulated uponactivation,normalTcellexpresses andsecreted) secretion. Blocking FcγRIIA with monoclonal antibody (MAb) IV.3 or inhibiting actin remodeling with cytochalasin D inhibited platelet activation, internalization, and cytokine production. These data suggest that platelets are capable of mediating internalization of IgG-coated particles, resulting in platelet activation and release of both sCD40L and RANTES.
Immunogenicity and Safety of a Multicomponent Meningococcal Serogroup B Vaccine and a Quadrivalent Meningococcal CRM
197
Conjugate Vaccine against Serogroups A, C, W-135, and Y in Adults Who Are at Increased Risk for Occupational Exposure to Meningococcal Isolates
Authors: Kimura Alan , Toneatto Daniela , Kleinschmidt Annett , Wang Huajun , Dull Peter
Published: December 2010

Laboratory staff who work with meningococcal isolates are at increased risk for developing invasive disease relative to the general population. This was the first study of laboratory workers who received both a conjugate vaccine against meningococcal serogroups A, C, W-135, and Y (Men ACWY-CRM, Menveo) and an investigational multicomponent vaccine against serogroup B containing factor H binding protein, neisserial adhesin A,
Neisseria
heparin binding antigen, and New Zealand strain outer membrane vesicles (4CMenB). Healthy adults (18 to 50 years of age) received three doses of 4CMenB at baseline, 2 months, and 6 months followed by a single dose of MenACWY-CRM 1 month later. Immunogenicity was assessed via serum bactericidal assay using human complement (hSBA) at 1 month postvaccination; solicited reactogenicity and adverse events were monitored. Fifty-four participants enrolled. Bactericidal immune responses were evident after each dose of 4CMenB, as assessed by hSBA geometric mean titers and percentages of subjects with hSBA titers of ≥4 against the test strains or a 4-fold rise in titer over baseline. At 1 month postvaccination, most MenACWY-CRM recipients had hSBA titers of ≥8 against serogroups A, C, W-135, and Y. Few participants discontinued due to an adverse event or vaccine reaction. Rates of solicited reactions were lower after MenACWY-CRM than after 4CMenB administration. Sequential administration of 4CMenB and MenACWY-CRM provided robust evidence of an immune response against serogroups A, B, C, W-135, and Y in laboratory workers routinely exposed to meningococcal isolates.
Evaluation ofSalmonella-VectoredCampylobacterPeptide Epitopes for Reduction ofCampylobacter jejuniin Broiler Chickens
Authors: Layton S. L. , Morgan M. J. , Cole K. , Kwon Y. M. , Donoghue D. J. , Hargis B. M. , Pumford N. R.
Published: December 2010

Campylobacteris a leading cause of bacterial gastroenteritis in humans and is often linked to contaminated poultry products. LiveSalmonellavectors expressing three linear peptide epitopes fromCampylobacterproteins Cj0113 (Omp18/CjaD), Cj0982c (CjaA), and Cj0420 (ACE393) were administered to chicks by oral gavage on the day of hatch, and the chicks were challenged withCampylobacter jejunion day 21. All three candidate vaccines produced consistent humoral immune responses with high levels of serum IgG and mucosal secretory IgA (sIgA), with the best response from the Cj0113 peptide-expressing vector.Campylobacterchallenge following vaccination of three candidate vaccine groups decreasedCampylobacterrecovery from the ileum compared to that for controls on day 32. The Cj0113 peptide-expressing vector reducedCampylobacterto below detectable levels. TheSalmonella-vectored Cj0113 subunit vaccine appears to be an excellent candidate for further evaluation as a tool for the reduction ofCampylobacterin poultry for improved food safety.
Increasing Incidence of
Streptococcus pneumoniae
Serotype 19A and Emergence of Two Vaccine Escape Recombinant ST695 Strains in Liguria, Italy, 7 Years after Implementation of the 7-Valent Conjugated Vaccine
Authors: Ansaldi Filippo , Canepa Paola , de Florentiis Daniela , Bandettini Roberto , Durando Paolo , Icardi Giancarlo
Published: December 2010

Two serotype 19A (ST695)
Streptococcus pneumoniae
vaccine escape recombinant strains attributable to capsular switching events were detected by a laboratory surveillance system that is an integral part of a vaccination program begun in Liguria, Italy, in May 2003, an Italian administrative region with long-lasting high coverage, an unusual occurrence in Europe. To our knowledge, this is the first detection of an occurrence of capsular switching outside the United States.
Induction of Foot-and-Mouth Disease Virus-Specific Cytotoxic T Cell Killing by Vaccination
Authors: Patch Jared R. , Pedersen Lasse E. , Toka Felix N. , Moraes Mauro , Grubman Marvin J. , Nielsen Morten , Jungersen Gregers , Buus Soren , Golde William T.
Published: December 2010

Foot-and-mouth disease (FMD) continues to be a significant threat to the health and economic value of livestock species. This acute infection is caused by the highly contagious FMD virus (FMDV), which infects cloven-hoofed animals, including large and small ruminants and swine. Current vaccine strategies are all directed toward the induction of neutralizing antibody responses. However, the role of cytotoxic T lymphocytes (CTLs) has not received a great deal of attention, in part because of the technical difficulties associated with establishing a reliable assay of cell killing for this highly cytopathic virus. Here, we have used recombinant human adenovirus vectors as a means of delivering FMDV antigens in a T cell-directed vaccine in pigs. We tested the hypothesis that impaired processing of the FMDV capsid would enhance cytolytic activity, presumably by targeting all proteins for degradation and effectively increasing the class I major histocompatibility complex (MHC)/FMDV peptide concentration for stimulation of a CTL response. We compared such a T cell-targeting vaccine with the parental vaccine, previously shown to effectively induce a neutralizing antibody response. Our results show induction of FMDV-specific CD8
+
CTL killing of MHC-matched target cells in an antigen-specific manner. Further, we confirm these results by MHC tetramer staining. This work presents the first demonstration of FMDV-specific CTL killing and confirmation by MHC tetramer staining in response to vaccination against FMDV.
Insight toward Early Diagnosis of Leprosy through Analysis of the Developing Antibody Responses of
Mycobacterium leprae
-Infected Armadillos
Authors: Duthie Malcolm S. , Truman Richard W. , Goto Wakako , O'Donnell Joanne , Hay Marah N. , Spencer John S. , Carter Darrick , Reed Steven G.
Published: December 2010

Leprosy is a debilitating chronic disease caused by infection with
Mycobacterium leprae
. A World Health Organization-directed control strategy based upon the identification and treatment of patients has resulted in a marked reduction in the number of registered worldwide leprosy cases over the last 20 years. Despite these efforts, the number of new leprosy cases detected each year now remains relatively stable, and
M. leprae
infection continues to pose a health problem. It is suggested that earlier diagnosis is required to strengthen control programs. In this study, we have examined the development of antigen-specific immunoglobulin responses within armadillos experimentally infected with
M. leprae
to identify those responses that develop most rapidly and robustly following infection. Antibody responses to the
M. leprae
-specific phenolic glycolipid I and several protein antigens previously demonstrated to have diagnostic potential were assessed. Our results identify several antigens that can provide early diagnosis of
M. leprae
infection but also indicate considerable variability in the development of antigen-specific antibodies. Our data suggest that a combination of antigens is likely required to provide accurate and early leprosy diagnosis.
Analysis of Antibody Responses to
Mycobacterium leprae
Phenolic Glycolipid I, Lipoarabinomannan, and Recombinant Proteins To Define Disease Subtype-Specific Antigenic Profiles in Leprosy
Authors: Spencer John S. , Kim Hee Jin , Wheat William H. , Chatterjee Delphi , Balagon Marivic V. , Cellona Roland V. , Tan Esterlina V. , Gelber Robert , Saunderson Paul , Duthie Malcolm S. , Reece Stephen T. , Burman William , Belknap Robert , Mac Kenzie William R. , Geluk Annemieke , Oskam Linda , Dockrell Hazel M. , Brennan Patrick J.
Published: December 2010

A simple serodiagnostic test based on the
Mycobacterium leprae
-specific phenolic glycolipid I(PGL-I), for individuals with leprosy is nearly universally positive in leprosy patients with high bacillary loads but cannot be used as a stand-alone diagnostic test for the entire spectrum of the disease process. For patients with early infection with no detectable acid-fast bacilli in lesions or with low or no antibody titer to PGL-I, as in those at the tuberculoid end of the disease spectrum, this diagnostic approach has limited usefulness. To identify additional
M. leprae
antigens that might enhance the serological detection of these individuals, we have examined the reactivity patterns of patient sera to PGL-I, lipoarabinomannan (LAM), and six recombinant
M. leprae
proteins (ML1877, ML0841, ML2028, ML2038, ML0380, and ML0050) by Western blot analysis and enzyme-linked immunosorbent assay (ELISA). Overall, the responses to ML2028 (Ag85B) and ML2038 (bacterioferritin) were consistently high in both multibacillary and paucibacillary groups and weak or absent in endemic controls, while responses to other antigens showed considerable variability, from strongly positive to completely negative. This analysis has given a clearer understanding of some of the differences in the antibody responses between individuals at opposite ends of the disease spectrum, as well as illustrating the heterogeneity of antibody responses toward protein, carbohydrate, and glycolipid antigens within a clinical group. Correlating these response patterns with a particular disease state could allow for a more critical assessment of the form of disease within the leprosy spectrum and could lead to better patient management.
Detection and Differentiation of Cryptosporidium spp. in Human Clinical Samples by Use of Real-Time PCR
Authors: Hadfield Stephen J. , Robinson Guy , Elwin Kristin , Chalmers Rachel M.
Published: December 2010

Real-time PCR has the potential to streamline detection and identification of
Cryptosporidium
spp. in human clinical samples. In the present article, we report the first such assay to allow not only detection and differentiation of the most common human pathogens,
Cryptosporidium hominis
and
Cryptosporidium parvum
, but also simultaneous amplification of a region of the small subunit (SSU) rRNA gene, permitting direct sequence analysis to identify any
Cryptosporidium
species. An internal control is incorporated to identify the presence of PCR inhibitors. Analytical sensitivity was determined to be as low as 200 oocysts per gram of feces processed, equivalent to 2 oocysts per PCR. The
C. hominis
and
C. parvum
PCRs specifically detected only species/genotypes in their respective target clades. Diagnostic sensitivity and specificity, evaluated against a widely used conventional nested SSU rRNA gene PCR as a nominated gold standard using a panel of 258 (151 positive and 107 negative) samples, were 100% and 99.1%, respectively. The assay agreed with PCR-restriction fragment length polymorphism analysis of the
Cryptosporidium
oocyst wall protein gene for 134 of 136 (98.5%) samples tested prospectively and typed two additional isolates. The real-time PCR assay was sensitive, specific, and reproducible and significantly improved laboratory work flow and turnaround times.
Identification of Pseudallescheria and Scedosporium Species by Three Molecular Methods
Authors: Lu Qiaoyun , Gerrits van den Ende A. H. G. , Bakkers J. M. J. E. , Sun Jiufeng , Lackner M. , Najafzadeh M. J. , Melchers W. J. G. , Li Ruoyu , de Hoog G. S.
Published: December 2010

The major clinically relevant species in
Scedosporium
(teleomorph
Pseudallescheria
) are
Pseudallescheria boydii
,
Scedosporium aurantiacum
,
Scedosporium apiospermum
, and
Scedosporium prolificans
, while
Pseudallescheria minutispora
,
Petriellopsis desertorum
, and
Scedosporium dehoogii
are exceptional agents of disease. Three molecular methods targeting the partial β-tubulin gene were developed and evaluated to identify six closely related species of the
S. apiospermum
complex using quantitative real-time PCR (qPCR), PCR-based reverse line blot (PCR-RLB), and loop-mediated isothermal amplification (LAMP). qPCR was not specific enough for the identification of all species but had the highest sensitivity. The PCR-RLB assay was efficient for the identification of five species. LAMP distinguished all six species unambiguously. The analytical sensitivities of qPCR, PCR-RLB, and LAMP combined with MagNAPure, CTAB (cetyltrimethylammonium bromide), and FTA filter (Whatman) extraction were 50, 5 × 10
3
, and 5 × 10
2
cells/μl, respectively. When LAMP was combined with a simplified DNA extraction method using an FTA filter, identification to the species level was achieved within 2 h, including DNA extraction. The FTA-LAMP assay is therefore recommended as a cost-effective, simple, and rapid method for the identification of
Scedosporium
species.
Overestimation of Incidence of Hepatitis B Virus Mixed-Genotype Infections by Use of the New Line Probe INNO-LiPA Genotyping Assay
Authors: Mercier Mélanie , Laperche Syria , Girault Annie , Sureau Camille , Servant-Delmas Annabelle
Published: December 2010

The new version of the INNO-LiPA HBV genotyping assay (Innogenetics) developed to identify all hepatitis B virus (HBV) genotypes, A to H, has been evaluated in comparison with sequencing of PCR-amplified HBV DNA from 200 samples before or after cloning. The genotyping data obtained with INNO-LiPA were in agreement with those from direct sequencing in the 179 samples characterized by the two methods. INNO-LiPA revealed 28 mixed infections. However, sequencing after molecular cloning confirmed only 15 of them and did not identify any that were of genotype H (
n
= 9). Our study demonstrates that INNO-LiPA overestimates mixed infections as a result of erroneous genotype H detection.