bluuebunny/crossref_metadata_2025 huggingface dataset:
A Progression of Static Equilibrium Laboratory Exercises
Authors: Kutzner Mickey , Kutzner Andrew
Published: September 2013

Although simple architectural structures like bridges, catwalks, cantilevers, and Stonehenge have been integral in human societies for millennia, as have levers and other simple tools, modern students of introductory physics continue to grapple with Newton's conditions for static equilibrium. As formulated in typical introductory physics textbooks,1–4 these two conditions appear as ΣF=0(1) and Στ=0,(2) where each torque τ is defined as the cross product between the lever arm vector r and the corresponding applied force F, τ=r×F,(3) having magnitude, τ=Frsinθ.(4) The angle θ here is between the two vectors F and r. In Eq. (1), upward (downward) forces are considered positive (negative). In Eq. (2), counterclockwise (clockwise) torques are considered positive (negative). Equation (1) holds that the vector sum of the external forces acting on an object must be zero to prevent linear accelerations; Eq. (2) states that the vector sum of torques due to external forces about any axis must be zero to prevent angular accelerations. In our view these conditions can be problematic for students because a) the equations contain the unfamiliar summation notation Σ, b) students are uncertain of the role of torques in causing rotations, and c) it is not clear why the sum of torques is zero regardless of the choice of axis. Gianino5 describes an experiment using MBL and a force sensor to convey the meaning of torque as applied to a rigid-body lever system without exploring quantitative aspects of the conditions for static equilibrium.
A Cancer-Associated Mutation in Atypical Protein Kinase Cι Occurs in a Substrate-Specific Recruitment Motif
Authors: Linch Mark , Sanz-Garcia Marta , Soriano Erika , Zhang Yixiao , Riou Philippe , Rosse Carine , Cameron Angus , Knowles Phillip , Purkiss Andrew , Kjaer Svend , McDonald Neil Q. , Parker Peter J.
Published: September 2013

A cancer-associated mutation in protein kinase Cι selectively disrupts epithelial polarity by inhibiting the binding of specific substrates.
Science Signaling
Podcast: 17 September 2013
Authors: Parker Peter J. , Linch Mark , McDonald Neil Q. , VanHook Annalisa M.
Published: September 2013

A cancer-associated mutation in PKCι maps to a motif that mediates interactions between PKCι and substrates involved in cell polarity.
Characterization of Potential Drug Targets Farnesyl Diphosphate Synthase and Geranylgeranyl Diphosphate Synthase in Schistosoma mansoni
Authors: Ziniel Peter D. , Desai Janish , Cass Cynthia L. , Gatto Craig , Oldfield Eric , Williams David L.
Published: September 2013

Schistosomiasis affects over 200 million people worldwide, with over 200,000 deaths annually. Currently, praziquantel is the only drug available against schistosomiasis. We report here that
Schistosoma mansoni
farnesyl diphosphate synthase (
Sm
FPPS) and geranylgeranyl diphosphate synthase (
Sm
GGPPS) are potential drug targets for the treatment of schistosomiasis. We expressed active, recombinant
Sm
FPPS and
Sm
GGPPS for subsequent kinetic characterization and testing against a variety of bisphosphonate inhibitors. Recombinant
Sm
FPPS was found to be a soluble 44.2-kDa protein, while
Sm
GGPPS was a soluble 38.3-kDa protein. Characterization of the substrate utilization of the two enzymes indicates that they have overlapping substrate specificities. Against
Sm
FPPS, several bisphosphonates had 50% inhibitory concentrations (IC
50
s) in the low micromolar to nanomolar range; these inhibitors had significantly less activity against
Sm
GGPPS. Several lipophilic bisphosphonates were active against
ex vivo
adult worms, with worm death occurring over 4 to 6 days. These results indicate that FPPS and GGPPS could be of interest in the context of the emerging resistance to praziquantel in schistosomiasis therapy.
An FtsZ-Targeting Prodrug with Oral Antistaphylococcal Efficacy
In Vivo
Authors: Kaul Malvika , Mark Lilly , Zhang Yongzheng , Parhi Ajit K. , LaVoie Edmond J. , Pilch Daniel S.
Published: September 2013

The bacterial cell division protein FtsZ represents a novel antibiotic target that has yet to be exploited clinically. The benzamide PC190723 was among the first FtsZ-targeting compounds to exhibit
in vivo
efficacy in a murine infection model system. Despite its initial promise, the poor formulation properties of the compound have limited its potential for clinical development. We describe here the development of an
N
-Mannich base derivative of PC190723 with enhanced drug-like properties and oral
in vivo
efficacy. The
N
-Mannich base derivative (TXY436) is ∼100-fold more soluble than PC190723 in an acidic aqueous vehicle (10 mM citrate, pH 2.6) suitable for oral
in vivo
administration. At physiological pH (7.4), TXY436 acts as a prodrug, converting to PC190723 with a conversion half-life of 18.2 ± 1.6 min. Pharmacokinetic analysis following intravenous administration of TXY436 into mice yielded elimination half-lives of 0.26 and 0.96 h for the TXY436 prodrug and its PC190723 product, respectively. In addition, TXY436 was found to be orally bioavailable and associated with significant extravascular distribution. Using a mouse model of systemic infection with methicillin-sensitive
Staphylococcus aureus
or methicillin-resistant
S. aureus
, we show that TXY436 is efficacious
in vivo
upon oral administration. In contrast, the oral administration of PC190723 was not efficacious. Mammalian cytotoxicity studies of TXY436 using Vero cells revealed an absence of toxicity up to compound concentrations at least 64 times greater than those associated with antistaphylococcal activity. These collective properties make TXY436 a worthy candidate for further investigation as a clinically useful agent for the treatment of staphylococcal infections.
Optimizing Empiric Antibiotic Therapy in Patients with Severe β-Lactam Allergy
Authors: Koliscak Lindsey P. , Johnson James W. , Beardsley James R. , Miller David P. , Williamson John C. , Luther Vera P. , Ohl Christopher A.
Published: September 2013

Antibiotic selection is challenging in patients with severe β-lactam allergy due to declining reliability of alternate antibiotics. Organisms isolated from these patients may exhibit unique resistance phenotypes. The objective of this study was to determine which alternate antibiotics or combinations provide adequate empirical therapy for patients with β-lactam allergy who develop Gram-negative infections at our institution. We further sought to determine the effects of risk factors for drug resistance on empirical adequacy. A retrospective analysis was conducted for adult patients hospitalized from September 2009 to May 2010 who had a severe β-lactam allergy and a urine, blood, or respiratory culture positive for a Gram-negative organism and who met predefined criteria for infection. Patient characteristics, culture and susceptibility data, and predefined risk factors for antibiotic resistance were collected. Adequacies of β-lactam and alternate antibiotics were compared for all infections and selected subsets. The primary outcome was adequacy of each alternate antibiotic or combination for all infections. One hundred sixteen infections (40 pneumonias, 67 urinary tract infections, and 9 bacteremias) were identified. Single alternate agents were adequate less frequently than β-lactams and combination regimens. Only in cases without risk factors for resistance did single-agent regimens demonstrate acceptable adequacy rates; each factor conferred a doubling of risk for resistance. Resistance risk factors should be considered in selecting empirical antibiotics for Gram-negative pathogens in patients unable to take β-lactams due to severe allergy.
Protective Humoral Immunity Elicited by a Needle-Free Malaria Vaccine Comprised of a Chimeric Plasmodium falciparum Circumsporozoite Protein and a Toll-Like Receptor 5 Agonist, Flagellin
Authors: Carapau Daniel , Mitchell Robert , Nacer Adéla , Shaw Alan , Othoro Caroline , Frevert Ute , Nardin Elizabeth
Published: September 2013

Immunization withPlasmodiumsporozoites can elicit high levels of sterile immunity, and neutralizing antibodies from protected hosts are known to target the repeat region of the circumsporozoite (CS) protein on the parasite surface. CS-based subunit vaccines have been hampered by suboptimal immunogenicity and the requirement for strong adjuvants to elicit effective humoral immunity. Pathogen-associated molecular patterns (PAMPs) that signal through Toll-like receptors (TLRs) can function as potent adjuvants for innate and adaptive immunity. We examined the immunogenicity of recombinant proteins containing a TLR5 agonist, flagellin, and either full-length or selected epitopes of thePlasmodium falciparumCS protein. Mice immunized with either of the flagellin-modified CS constructs, administered intranasally (i.n.) or subcutaneously (s.c.), developed similar levels of malaria-specific IgG1 antibody and interleukin-5 (IL-5)-producing T cells. Importantly, immunization via the i.n. but not the s.c. route elicited sporozoite neutralizing antibodies capable of inhibiting >90% of sporozoite invasionin vitroandin vivo, as measured using a transgenic rodent parasite expressingP. falciparumCS repeats. These findings demonstrate that functional sporozoite neutralizing antibody can be elicited by i.n. immunization with a flagellin-modifiedP. falciparumCS protein and raise the potential of a scalable, safe, needle-free vaccine for the 40% of the world's population at risk of malaria.
Toll-Like Receptor 7 Mediates Early Innate Immune Responses to Malaria
Authors: Baccarella Alyssa , Fontana Mary F. , Chen Eunice C. , Kim Charles C.
Published: September 2013

Innate immune recognition of malaria parasites is the critical first step in the development of the host response. At present, Toll-like receptor 9 (TLR9) is thought to play a central role in sensing malaria infection. However, we and others have observed thatTlr9−/−mice, in contrast to mice deficient in the downstream adaptor, Myeloid differentiation primary response gene 88 (MYD88), exhibit few deficiencies in immune function during early infection with the malaria parasitePlasmodium chabaudi, implying that another MYD88-dependent receptor also contributes to the antimalarial response. Here we use candidate-based screening to identify TLR7 as a key sensor of earlyP. chabaudiinfection. We show that TLR7 mediates a rapid systemic response to infection through induction of cytokines such as type I interferons (IFN-I), interleukin 12, and gamma interferon. TLR7 is also required for induction of IFN-I by other species and strains ofPlasmodium, including an etiological agent of human disease,P. falciparum, suggesting that malaria parasites harbor a common pathogen-associated molecular pattern (PAMP) recognized by TLR7. In contrast to the nonredundant requirement for TLR7 in early immune activation, sensing through both TLR7 and TLR9 was required for proinflammatory cytokine production and immune cell activation during the peak of parasitemia. Our findings indicate that TLR7 plays a central role in early immune activation during malaria infection, whereas TLR7 and TLR9 contribute combinatorially to immune responses as infection progresses.
Desmoplastic ameloblastoma of mandible
Authors: Nair Preeti P , Bhat Guruprasad R , Neelakantan Shiba , Chatterjee Rhiti
Published: September 2013

Desmoplastic ameloblastoma is one of the six histopathological subtypes of ameloblastoma. The age and gender groups affected by desmoplastic are similar to those affected by the conventional ameloblastoma. It usually presents as a painless enlargement of the jaw. Owing to its deceptive radiological appearance as a mixed radiopaque–radiolucent lesion, it is often mistaken as a fibro-osseous lesion. Histologically, desmoplastic ameloblastoma has a densely collagenised and hypocellular stroma, where the epithelium tends to proliferate in the form of cords and nests instead of cellular islands. Most desmoplastic ameloblastomas display occasional classic islands of follicular ameloblastoma among the predominant strands and cords. Studies have shown that desmoplastic ameloblastoma shows a tendency to recur. We present a rare case of a tumour occurring in the anterior mandibular region in a 60-year-old man over a period of 11/2 months.
Knowledge about sports-related concussion: is the message getting through to coaches and trainers?
Authors: White Peta E , Newton Joshua D , Makdissi Michael , Sullivan S John , Davis Gavin , McCrory Paul , Donaldson Alex , Ewing Michael T , Finch Caroline F
Published: September 2013

Aim

The need for accurate diagnosis and appropriate return-to-play decisions following a concussion in sports has prompted the dissemination of guidelines to assist managing this condition. This study aimed to assess whether key messages within these guidelines are reflected in the knowledge of coaches and sports trainers involved in community sport.

Methods

An online knowledge survey was widely promoted across Australia in May–August 2012 targeting community Australian Football (AF) and Rugby League (RL) coaches and sports trainers. 260 AF coaches, 161 AF sports trainers, 267 RL coaches and 228 RL sports trainers completed the survey. Knowledge scores were constructed from Likert scales and compared across football codes and respondent groups.

Results

General concussion knowledge did not differ across codes but sports trainers had higher levels than did coaches. There were no significant differences in either concussion symptoms or concussion management knowledge across codes or team roles. Over 90% of respondents correctly identified five of the eight key signs or symptoms of concussion. Fewer than 50% recognised the increased risk of another concussion following an initial concussion. Most incorrectly believed or were uncertain that scans typically show damage to the brain after a concussion occurs. Fewer than 25% recognised, and >40% were uncertain that younger players typically take longer to recover from concussion than adults.

Conclusions

The key messages from published concussion management guidelines have not reached community sports coaches and sports trainers. This needs to be redressed to maximise the safety of all of those involved in community sport.
Do general practitioners follow treatment recommendations from guidelines in their decisions on heart failure management? A cross-sectional study
Authors: Swennen Maartje H J , Rutten Frans H , Kalkman Cor J , van der Graaf Yolanda , Sachs Alfred P E , van der Heijden Geert J M G
Published: September 2013

Objective

To investigate whether general practitioners (GPs) follow treatment recommendations from clinical practice guidelines in their decisions on the management of heart failure patients, and assess whether doctors’ characteristics are related to their decisions.

Design

Cross-sectional vignette study.

Setting

Continuing Medical Education meeting.

Participants

451 Dutch GPs.

Main outcome measures

Answers to four multiple-choice treatment decisions in clinical vignettes of a patient with heart failure and a reduced ejection fraction. With univariable and multivariable regression analyses, respondent characteristics were related to optimal treatment decisions.

Results

Of the 451 GPs, none took four optimal decisions: 7% considered stopping statin treatment, 36% initiated β-blocker treatment at a low-dose and 4% doubled the β-blocker in the up-titration phase. Finally, for our vignette patient now also suffering from chronic obstructive pulmonary disease, 45% of the GPs continued β-blocker therapy even when they considered prescribing a long-acting β2-agonist. While the relation between respondent characteristics and each decision was very different, none was independently associated with all four decisions. Giving priority to evidence-based medicine was independently related to stopping statin treatment and doubling the β-blocker in the up-titration phase.

Conclusions

GPs seem not to follow treatment recommendations from clinical practice guidelines in their decisions on the management of heart failure patients. The recommendations from guidelines may appear counterintuitive when statin treatment needs to be stopped when a patient feels comfortable, or when a β-blocker should be up-titrated in patients who experience more symptoms. Giving priority to evidence-based medicine is possibly positively related to difficult treatment decisions.
Recyclable ionic liquid tagged Co(salen) catalysts for the oxidation of lignin model compounds
Authors: Ambrose Kenson , Hurisso Bitu B. , Singer Robert D.
Published: September 2013

Ionic liquid tagged salen ligands containing two proximal 1,3-disubstituted imidazolium ionic liquid cores form cobalt(III) complexes capable of selectively oxidizing veratryl alcohol, a lignin model compound, to veratraldehyde using air or pure oxygen as the source of oxygen. Entrainment of these catalysts in either 1-butyl-3-methylimidazolium hexafluorophosphate, [bmim][PF6], or 1-butyl-3-methylimidazolium bistriflimide, [bmim][NTf2], hydrophobic ionic liquid solvents, results in biphasic reactions when water is used as the second solvent allowing the catalyst/ionic liquid phase to be recycled.
Data assimilation in stand-level forest inventories
Authors: Ehlers Sarah , Grafström Anton , Nyström Kenneth , Olsson Håkan , Ståhl Göran
Published: September 2013

The development of remote sensing methods through research and large-scale application nowadays makes it possible to obtain stand-level estimates of forest variables at short intervals and at low cost. This offers substantial possibilities to forestry practitioners, but it also poses challenges regarding how cost-efficient data acquisition strategies should be developed. For example, should cheap but low-quality data be acquired and discarded whenever new data become available or should investments be made in high-quality data that are continuously updated to last over a longer period of time? We suggest that the solution could be to establish data assimilation (DA) procedures linked to forest inventories to make appropriate use of data from several sources. With DA, old information is updated through growth forecasts and when new information becomes available it is assimilated with the old information; the different sources of information are made use of to the extent motivated by their accuracy. In this study we made a general assessment of the usefulness of DA in connection with stand-level forest inventories and we compared two different methodological approaches, the extended Kalman filter and the Bayesian method. Not surprisingly, the relative advantage of DA was found to be largest for cases where low-precision estimates of growing stock volume were obtained at short intervals and forecasts were made with accurate growth prediction models. The methodological comparison revealed a tendency of the extended Kalman filter to underestimate the variance of the estimates.
Precision of inventory using different edge overlap methods
Authors: West P.W.
Published: September 2013

Bias due to the sampling procedure may occur in estimates from forest inventory when sampled trees are close to the forest edge. The “mirage,” “walkthrough,” and “walk through and fro” methods are three practical measurement methods developed to avoid this problem. However, as an increasing proportion of the sample requires use of these methods, the precision of the population estimates made from the sample is likely to decline. Simulation studies were undertaken of forest inventory, using point sampling, to estimate mean stand basal area and stocking density in both an even-aged, monoculture radiata pine (Pinus radiata D. Don) plantation forest and an uneven-aged, multispecies, complex primary rainforest. In both forest types, bias arising from use of any of the three methods appeared to be negligible. As well, precision of estimates from the inventory was reduced only slightly, even when a high proportion of the samples required use of any one of the three methods. None of the methods appeared appreciably superior in this respect to any of the others. It was concluded that use of any of the three methods was unlikely to have any substantial effect on the overall precision of estimates made from forest inventory.
VELOCITY CORRELATIONS IN THE NAGEL–SCHRECKENBERG MODEL
Authors: LAKOUARI N. , JETTO K. , EZ-ZAHRAOUY H. , BENYOUSSEF A.
Published: September 2013

The correlation between the velocity of two successive vehicles as a function of time headway is studied in the one-dimensional cellular automata (CA) NaSch model within parallel dynamic update. It is found that a strong correlation occurs in short time headway. The behavior of the correlation velocity as a function of the car density in different traffic states is also investigated. Moreover, our study is also extended to a more complicated situation where the two vehicles are separated by a number n of other vehicles. It is shown that the velocity correlation coefficient depends strongly on the number n of vehicles in between and on their positions.
A LARGE FAMILY OF INDECOMPOSABLE PROJECTIVE MODULES FOR THE KHOVANOV–KUPERBERG ALGEBRAS OF sl3-WEBS
Authors: ROBERT LOUIS-HADRIEN
Published: September 2013

In this paper, we recall the construction from Mackaay–Pan–Tubbenhauer of the algebras Kϵ which allow to understand the sl3 homology for links in a local way (i.e. for tangles). Then, by studying the combinatorics of the Kuperberg bracket, we give a large family of non-elliptic webs whose associated projective modules are indecomposable over these algebras.
MODELING AND ANALYSIS OF AN SEIR MODEL WITH DIFFERENT TYPES OF NONLINEAR TREATMENT RATES
Authors: DUBEY B. , PATRA ATASI , SRIVASTAVA P. K. , DUBEY UMA S.
Published: September 2013

In this study, an SEIR epidemic model is proposed for treatment of infectives considering the development of acquired immunity in recovered individuals. We employed two different types of treatment functions. Stability analysis for disease-free as well as endemic equilibria is performed. It is observed that the existence of unique endemic equilibrium depends on the basic reproductive number R0as well as on treatment rate. Numerical simulations are performed on the proposed models to support and analyze theoretical findings.
The inauguration of the International Center for Interdisciplinary Science and Education in Quy Nhon, Vietnam, 12th August
Authors: Tran Thanh Van Jean
Published: September 2013

Almost 20 years ago, the Association "Rencontres du Vietnam" embarked on an unprecedented venture in the scientific community. Via a closely-knit and worldwide network of active scientists, the Association has organized high level international conferences in Vietnam, these conferences constitute a forum in which scientists from the developed and emerging nations can meet, present their work and discuss problems of mutual interest. These conferences have attracted not only leading scientists, including Nobel laureates from the developed world but also young Asian students, who can thereby benefit from contact with the creators of contemporary science.
An evaluation of the TRIPS computer system
Authors: Gebhart Mark , Maher Bertrand A. , Coons Katherine E. , Diamond Jeff , Gratz Paul , Marino Mario , Ranganathan Nitya , Robatmili Behnam , Smith Aaron , Burrill James , Keckler Stephen W. , Burger Doug , McKinley Kathryn S.
Published: September 2013

The TRIPS system employs a new instruction set architecture (ISA) called Explicit Data Graph Execution (EDGE) that renegotiates the boundary between hardware and software to expose and exploit concurrency. EDGE ISAs use a block-atomic execution model in which blocks are composed of dataflow instructions. The goal of the TRIPS design is to mine concurrency for high performance while tolerating emerging technology scaling challenges, such as increasing wire delays and power consumption. This paper evaluates how well TRIPS meets this goal through a detailed ISA and performance analysis. We compare performance, using cycles counts, to commercial processors. On SPEC CPU2000, the Intel Core 2 outperforms compiled TRIPS code in most cases, although TRIPS matches a Pentium 4. On simple benchmarks, compiled TRIPS code outperforms the Core 2 by 10% and hand-optimized TRIPS code outperforms it by factor of 3. Compared to conventional ISAs, the block-atomic model provides a larger instruction window, increases concurrency at a cost of more instructions executed, and replaces register and memory accesses with more efficient direct instruction-to-instruction communication. Our analysis suggests ISA, microarchitecture, and compiler enhancements for addressing weaknesses in TRIPS and indicates that EDGE architectures have the potential to exploit greater concurrency in future technologies.
Architectural implications of nanoscale integrated sensing and computing
Authors: Pistol Constantin , Chongchitmate Wutichai , Dwyer Christopher , Lebeck Alvin R.
Published: September 2013

This paper explores the architectural implications of integrating computation and molecular probes to form nanoscale sensor processors (nSP). We show how nSPs may enable new computing domains and automate tasks that currently require expert scientific training and costly equipment. This new application domain severely constrains nSP size, which significantly impacts the architectural design space. In this context, we explore nSP architectures and present an nSP design that includes a simple accumulator-based ISA, sensors, limited memory and communication transceivers. To reduce the application memory footprint, we introduce the concept of instruction-fused sensing. We use simulation and analytical models to evaluate nSP designs executing a representative set of target applications. Furthermore, we propose a candidate nSP technology based on optical Resonance Energy Transfer (RET) logic that enables the small size required by the application domain; our smallest design is about the size of the largest known virus. We also show laboratory results that demonstrate initial steps towards a prototype.
CTrigger
Authors: Park Soyeon , Lu Shan , Zhou Yuanyuan
Published: September 2013

Multicore hardware is making concurrent programs pervasive. Unfortunately, concurrent programs are prone to bugs. Among different types of concurrency bugs, atomicity violation bugs are common and important. Existing techniques to detect atomicity violation bugs suffer from one limitation: requiring bugs to manifest during monitored runs, which is an open problem in concurrent program testing.

This paper makes two contributions. First, it studies the interleaving characteristics of the common practice in concurrent program testing (i.e., running a program over and over) to understand why atomicity violation bugs are hard to expose. Second, it proposes CTrigger to effectively and efficiently expose atomicity violation bugs in large programs. CTrigger focuses on a special type of interleavings (i.e., unserializable interleavings) that are inherently correlated to atomicity violation bugs, and uses trace analysis to systematically identify (likely) feasible unserializable interleavings with low occurrence-probability. CTrigger then uses minimum execution perturbation to exercise low-probability interleavings and expose difficult-to-catch atomicity violation.

We evaluate CTrigger with real-world atomicity violation bugs from four sever/desktop applications (Apache, MySQL, Mozilla, and PBZIP2) and three SPLASH2 applications on 8-core machines. CTrigger efficiently exposes the tested bugs within 1--235 seconds, two to four orders of magnitude faster than stress testing. Without CTrigger, some of these bugs do not manifest even after 7 full days of stress testing. In addition, without deterministic replay support, once a bug is exposed, CTrigger can help programmers reliably reproduce it for diagnosis. Our tested bugs are reproduced by CTrigger mostly within 5 seconds, 300 to over 60000 times faster than stress testing.
Kendo
Authors: Olszewski Marek , Ansel Jason , Amarasinghe Saman
Published: September 2013

Although chip-multiprocessors have become the industry standard, developing parallel applications that target them remains a daunting task. Non-determinism, inherent in threaded applications, causes significant challenges for parallel programmers by hindering their ability to create parallel applications with repeatable results. As a consequence, parallel applications are significantly harder to debug, test, and maintain than sequential programs.

This paper introduces Kendo: a new software-only system that provides deterministic multithreading of parallel applications. Kendo enforces a deterministic interleaving of lock acquisitions and specially declared non-protected reads through a novel dynamically load-balanced deterministic scheduling algorithm. The algorithm tracks the progress of each thread using performance counters to construct a deterministic logical time that is used to compute an interleaving of shared data accesses that is both deterministic and provides good load balancing. Kendo can run on today's commodity hardware while incurring only a modest performance cost. Experimental results on the SPLASH-2 applications yield a geometric mean overhead of only 16% when running on 4 processors. This low overhead makes it possible to benefit from Kendo even after an application is deployed. Programmers can start using Kendo today to program parallel applications that are easier to develop, debug, and test.
Per-thread cycle accounting in SMT processors
Authors: Eyerman Stijn , Eeckhout Lieven
Published: September 2013

This paper proposes a cycle accounting architecture for Simultaneous Multithreading (SMT) processors that estimates the execution times for each of the threads had they been executed alone, while they are running simultaneously on the SMT processor. This is done by accounting each cycle to either a base, miss event or waiting cycle component during multi-threaded execution. Single-threaded alone execution time is then estimated as the sum of the base and miss event components; the waiting cycle component represents the lost cycle count due to SMT execution. The cycle accounting architecture incurs reasonable hardware cost (around 1KB of storage) and estimates single-threaded performance with average prediction errors around 7.2% for two-program workloads and 11.7% for four-program workloads.

The cycle accounting architecture has several important applications to system software and its interaction with SMT hardware. For one, the estimated single-thread alone execution time provides an accurate picture to system software of the actually consumed processor cycles per thread. The alone execution time instead of the total execution time (timeslice) may make system software scheduling policies more effective. Second, a new class of thread-progress aware SMT fetch policies based on per-thread progress indicators enable system software level priorities to be enforced at the hardware level.
Efficient online validation with delta execution
Authors: Tucek Joseph , Xiong Weiwei , Zhou Yuanyuan
Published: September 2013

Software systems are constantly changing. Patches to fix bugs and patches to add features are all too common. Every change risks breaking a previously working system. Hence administrators loathe change, and are willing to delay even critical security patches until after fully validating their correctness. Compared to off-line validation, on-line validation has clear advantages since it tests against real life workloads. Yet unfortunately it imposes restrictive overheads as it requires running the old and new versions side-by-side. Moreover, due to spurious differences (e.g. event timing, random number generation, and thread interleavings), it is difficult to compare the two for validation.

To allow more effective on-line patch validation, we propose a new mechanism, called delta execution, that is based on the observation that most patches are small. Delta execution merges the two side-by-side executions for most of the time and splits only when necessary, such as when they access different data or execute different code. This allows us to perform on-line validation not only with lower overhead but also with greatly reduced spurious differences, allowing us to effectively validate changes.

We first validate the feasibility of our idea by studying the characteristics of 240 patches from 4 server programs; our examination shows that 77% of the changes should not be expected to cause large changes and are thereby feasible for Delta execution. We then implemented Delta execution using dynamic instrumentation. Using real world patches from 7 server applications and 3 other programs, we compared our implementation of Delta execution against a traditional side-by-side on-line validation. Delta execution outperformed traditional validation by up to 128%; further, for 3 of the changes, spurious differences caused the traditional validation to fail completely while Delta execution succeeded. This demonstrates that Delta execution can allow administrators to use on-line validation to confidently ensure the correctness of the changes they apply.
Leak pruning
Authors: Bond Michael D. , McKinley Kathryn S.
Published: September 2013

Managed languages improve programmer productivity with type safety and garbage collection, which eliminate memory errors such as dangling pointers, double frees, and buffer overflows. However, because garbage collection uses reachability to over-approximate live objects, programs may still leak memory if programmers forget to eliminate the last reference to an object that will not be used again. Leaks slow programs by increasing collector workload and frequency. Growing leaks eventually crash programs.

This paper introduces leak pruning, which keeps programs running by predicting and reclaiming leaked objects at run time. It predicts dead objects and reclaims them based on observing data structure usage patterns. Leak pruning preserves semantics because it waits for heap exhaustion before reclaiming objects and poisons references to objects it reclaims. If the program later tries to access a poisoned reference, the virtual machine (VM) throws an error. We show leak pruning has low overhead in a Java VM and evaluate it on 10 leaking programs. Leak pruning does not help two programs, executes five substantial programs 1.6-81X longer, and executes three programs, including a leak in Eclipse, for at least 24 hours. In the worst case, leak pruning defers fatal errors. In the best case, it keeps leaky programs running with preserved semantics and consistent throughput.
TwinDrivers
Authors: Menon Aravind , Schubert Simon , Zwaenepoel Willy
Published: September 2013

In a virtualized environment, device drivers are often run inside a virtual machine (VM) rather than in the hypervisor, for reasons of safety and reduction in software engineering effort. Unfortunately, this approach results in poor performance for I/O-intensive devices such as network cards. The alternative approach of running device drivers directly in the hypervisor yields better performance, but results in the loss of safety guarantees for the hypervisor and incurs additional software engineering costs.

In this paper we present TwinDrivers, a framework which allows us to semi-automatically create safe and efficient hypervisor drivers from guest OS drivers. The hypervisor driver runs directly in the hypervisor, but its data resides completely in the driver VM address space. A Software Virtual Memory mechanism allows the driver to access its VM data efficiently from the hypervisor running in any guest context, and also protects the hypervisor from invalid memory accesses from the driver. An upcall mechanism allows the hypervisor to largely reuse the driver support infrastructure present in the VM. The TwinDriver system thus combines most of the performance benefits of hypervisor-based driver approaches with the safety and software engineering benefits of VM-based driver approaches.

Using the TwinDrivers hypervisor driver, we are able to improve the guest domain networking throughput in Xen by a factor of 2.4 for transmit workloads, and 2.1 for receive workloads, both in CPU-scaled units, and achieve close to 64-67 of native Linux throughput.
Architectural support for SWAR text processing with parallel bit streams
Authors: Cameron Robert D. , Lin Dan
Published: September 2013

Parallel bit stream algorithms exploit the SWAR (SIMD within a register) capabilities of commodity processors in high-performance text processing applications such as UTF-8 to UTF-16 transcoding, XML parsing, string search and regular expression matching. Direct architectural support for these algorithms in future SWAR instruction sets could further increase performance as well as simplifying the programming task. A set of simple SWAR instruction set extensions are proposed for this purpose based on the principle of systematic support for inductive doubling as an algorithmic technique. These extensions are shown to significantly reduce instruction count in core parallel bit stream algorithms, often providing a 3X or better improvement. The extensions are also shown to be useful for SWAR programming in other application areas, including providing a systematic treatment for horizontal operations. An implementation model for these extensions involves relatively simple circuitry added to the operand fetch components in a pipelined processor.
Caveolin-1 scaffolding domain promotes leukocyte adhesion by reduced basal endothelial nitric oxide-mediated ICAM-1 phosphorylation in rat mesenteric venules
Authors: Xu Sulei , Zhou Xueping , Yuan Dong , Xu Yanchun , He Pingnian
Published: September 2013

Exogenously applied caveolin-1 scaffolding domain (CAV) has been shown to inhibit inflammatory mediator-induced nitric oxide (NO) production and NO-mediated increases in microvessel permeability. However, the effect of CAV on endothelial basal NO that prevents leukocyte adhesion remains unknown. This study aims to investigate the roles of exogenously applied CAV in endothelial basal NO production, leukocyte adhesion, and adhesion-induced changes in microvessel permeability. Experiments were conducted in individually perfused rat mesenteric venules. Microvessel permeability was determined by measuring hydraulic conductivity (Lp). NO was quantified with fluorescence imaging in DAF-2-loaded vessels. Perfusing venules with CAV inhibited basal NO production without affecting basal Lp. Resuming blood flow in CAV-perfused vessels significantly increased leukocyte adhesion. The firmly adherent leukocytes altered neither basal Lp nor adherens junction integrity. Increases in Lp occurred only upon formyl-Met-Leu-Phe application that induces release of reactive oxygen species from the adherent leukocytes. The application of NO synthase inhibitor showed similar results to CAV, and NO donor abolished CAV-mediated leukocyte adhesion. Immunofluorescence staining showed increases in binding of ICAM-1 to an adhesion-blocking antibody concurrent with a Src-dependent ICAM-1 phosphorylation following CAV perfusion. Pre-perfusing vessels with anti-ICAM-1 blocking antibody or a Src kinase inhibitor attenuated CAV-induced leukocyte adhesion. These results indicate that the application of CAV, in addition to preventing excessive NO-mediated permeability increases, also causes reduction of basal NO and promotes ICAM-1-mediated leukocyte adhesion through Src activation-mediated ICAM-1 phosphorylation. CAV-induced leukocyte adhesion was uncoupled from leukocyte oxidative burst and microvessel barrier function, unless in the presence of a secondary stimulation.
Three-dimensional printing physiology laboratory technology
Authors: Sulkin Matthew S. , Widder Emily , Shao Connie , Holzem Katherine M. , Gloschat Christopher , Gutbrod Sarah R. , Efimov Igor R.
Published: September 2013

Since its inception in 19th-century Germany, the physiology laboratory has been a complex and expensive research enterprise involving experts in various fields of science and engineering. Physiology research has been critically dependent on cutting-edge technological support of mechanical, electrical, optical, and more recently computer engineers. Evolution of modern experimental equipment is constrained by lack of direct communication between the physiological community and industry producing this equipment. Fortunately, recent advances in open source technologies, including three-dimensional printing, open source hardware and software, present an exciting opportunity to bring the design and development of research instrumentation to the end user, i.e., life scientists. Here we provide an overview on how to develop customized, cost-effective experimental equipment for physiology laboratories.
Schwannoma in the Upper Limbs
Authors: Yuk Kwan Tang Chris , Fung Boris , Fok Margaret , Zhu Janet
Published: September 2013

Schwannomas are the commonest tumours of peripheral nerves. Despite the classical description that schwannomas are well encapsulated and can be completely enucleated during excision, a portion of them have fascicular involvement and could not be completely shelled out. A retrospective review for 8 patients was carried out over 10 years. 75% of schwannoma occurred over the distal region of upper limb (at elbow or distal to it). It occurs more in the mixed nerve instead of pure sensory or motor nerve. 50% of patients had mixed nerve involvement. Fascicular involvement was very common in schwannoma (75% of patients). Removal of the tumour with fascicles can cause functional deficit. At present, there is no method (including preoperative MRI) which can predict the occurrence of fascicular involvement; the authors therefore proposed a new system to stratify patients who may benefit from interfascicular nerve grafts. In this group of patients, the authors strongly recommend that the possibility and option of nerve graft should be discussed with patients prior to schwannoma excision, so that nerve grafting could be directly proceeded with patient consent in case there is fascicular involvement of tumour found intraoperatively.
Urethral Mucosa Prolapse in an 18-Year-Old Adolescent
Authors: Olumide Akadiri , Kayode Olusegun Ajenifuja , Babatola Bakare
Published: September 2013

Urethra mucosa prolapse is a benign condition in which there is a circular protrusion of the distal urethra through the external urethra meatus. It is more commonly seen in prepubertal black girls and postmenopausal white women. It is rare in the reproductive age group. This case describes the presentation and management of an 18-year-old adolescent with urethra mucosa prolapse.
In-VivoEffect of Andrographolide on Alveolar Bone Resorption Induced byPorphyromonas gingivalisand Its Relation with Antioxidant Enzymes
Authors: Al Batran Rami , Al-Bayaty Fouad H. , Al-Obaidi Mazen M. Jamil
Published: September 2013

Alveolar bone resorption is one of the most important facts in denture construction.Porphyromonas gingivalis(Pg) causes alveolar bone resorption, and morphologic measurements are the most frequent methods to identify bone resorption in periodontal studies. This study has aimed at evaluating the effect of Andrographolide (AND) on alveolar bone resorption in rats induced byPg. 24 healthy maleSprague Dawleyrats were divided into four groups as follows: normal control group and three experimental groups challenged orally withPgATCC 33277 five times a week supplemented with 20 mg/kg and 10 mg/kg of AND for twelve weeks. Alveolar bones of the left and right sides of the mandible were assessed by a morphometric method. The bone level, that is, the distance from the alveolar bone crest to cementumenamel junction (CEJ), was measured using 6.1 : 1 zoom stereomicroscope and software. AND reduced the effect ofPgon alveolar bone resorption and decreased the serum levels of Hexanoyl-Lysine (HEL); furthermore the reduced glutathione/oxidised glutathione (GSH/GSSG) ratio in AND treated groups (10 and 20 mg/kg) significantly increased when compared with thePggroup(P<0.05). We can conclude that AND suppresses alveolar bone resorption caused byPgin rats.
Effects of Thyroid Hormone Analogue and a Leukotrienes Pathway-Blocker on Reperfusion Injury Attenuation after Heart Transplantation
Authors: Al-Amran Fadhil G. , Hadi Najah R. , Al-Qassam Haider S. H.
Published: September 2013

Background. Global myocardial ischemia reperfusion injury after heart transplantation is believed to impair graft function and aggravate both acute and chronic rejection episodes.Objectives. To assess the possible protective potential of MK-886 and 3,5-diiodothyropropionic acid DITPA against global myocardial ischemia reperfusion injury after heart transplantation.Materials and Methods. Adult albino rats were randomized into 6 groups as follows: group I sham group; group II, control group; groups III and IV, control vehicles (1,2); group V, MK-886 treated group. Donor rats received MK-886 30 min before transplantation, and the same dose was repeated for recipients upon reperfusion; in group VI, DITPA treated group, donors and recipients rats were pretreated with DITPA for 7 days before transplantation.Results. Both MK-886 and DITPA significantly counteract the increase in the levels of cardiac TNF-α, IL-1β, and ICAM-1 and plasma level of cTnI (). Morphologic analysis showed that both MK-886 and DITPA markedly improved () the severity of cardiac injury in the heterotopically transplanted rats.Conclusions. The results of our study reveal that both MK-886 and DITPA may ameliorate global myocardial ischemia reperfusion injury after heart transplantation via interfering with inflammatory pathway.
Androgen Signaling Disruption during Fetal and Postnatal Development Affects Androgen Receptor and Connexin 43 Expression and Distribution in Adult Boar Prostate
Authors: Hejmej Anna , Górowska Ewelina , Kotula-Balak Małgorzata , Chojnacka Katarzyna , Zarzycka Marta , Zając Justyna , Bilińska Barbara
Published: September 2013

To date, limited knowledge exists regarding the role of the androgen signaling during specific periods of development in the regulation of androgen receptor (AR) and connexin 43 (Cx43) in adult prostate. Therefore, in this study we examined mRNA and protein expression, and tissue distribution of AR and Cx43 in adult boar prostates following fetal (GD20), neonatal (PD2), and prepubertal (PD90) exposure to an antiandrogen flutamide (50 mg/kg bw). In GD20 and PD2 males we found the reduction of the luminal compartment, inflammatory changes, decreased AR and increased Cx43 expression, and altered localization of both proteins. Moreover, enhanced apoptosis and reduced proliferation were detected in the prostates of these animals. In PD90 males the alterations were less evident, except that Cx43 expression was markedly upregulated. The results presented herein indicate that in boar androgen action during early fetal and neonatal periods plays a key role in the maintenance of normal phenotype and functions of prostatic cells at adulthood. Furthermore, we demonstrated that modulation of Cx43 expression in the prostate could serve as a sensitive marker of hormonal disruption during different developmental stages.