bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of Prosthetic Foot Stiffness to Reduce Metabolic Cost and Intact Knee Loading During Below-Knee Amputee Walking: A Theoretical Study
Authors: Fey Nicholas P. , Klute Glenn K. , Neptune Richard R.
Published: October 2012

Unilateral below-knee amputees develop abnormal gait characteristics that include bilateral asymmetries and an elevated metabolic cost relative to non-amputees. In addition, long-term prosthesis use has been linked to an increased prevalence of joint pain and osteoarthritis in the intact leg knee. To improve amputee mobility, prosthetic feet that utilize elastic energy storage and return (ESAR) have been designed, which perform important biomechanical functions such as providing body support and forward propulsion. However, the prescription of appropriate design characteristics (e.g., stiffness) is not well-defined since its influence on foot function and important in vivo biomechanical quantities such as metabolic cost and joint loading remain unclear. The design of feet that improve these quantities could provide considerable advancements in amputee care. Therefore, the purpose of this study was to couple design optimization with dynamic simulations of amputee walking to identify the optimal foot stiffness that minimizes metabolic cost and intact knee joint loading. A musculoskeletal model and distributed stiffness ESAR prosthetic foot model were developed to generate muscle-actuated forward dynamics simulations of amputee walking. Dynamic optimization was used to solve for the optimal muscle excitation patterns and foot stiffness profile that produced simulations that tracked experimental amputee walking data while minimizing metabolic cost and intact leg internal knee contact forces. Muscle and foot function were evaluated by calculating their contributions to the important walking subtasks of body support, forward propulsion and leg swing. The analyses showed that altering a nominal prosthetic foot stiffness distribution by stiffening the toe and mid-foot while making the ankle and heel less stiff improved ESAR foot performance by offloading the intact knee during early to mid-stance of the intact leg and reducing metabolic cost. The optimal design also provided moderate braking and body support during the first half of residual leg stance, while increasing the prosthesis contributions to forward propulsion and body support during the second half of residual leg stance. Future work will be directed at experimentally validating these results, which have important implications for future designs of prosthetic feet that could significantly improve amputee care.
Bubbles that Change the Speed of Sound
Authors: Planinšič Gorazd , Etkina Eugenia
Published: October 2012

The influence of bubbles on sound has long attracted the attention of physicists. In his 1920 book1 Sir William Bragg described sound absorption caused by foam in a glass of beer tapped by a spoon. Frank S. Crawford described and analyzed the change in the pitch of sound in a similar experiment and named the phenomenon the “hot chocolate effect.”2 In this paper we describe a simple and robust experiment that allows an easy audio and visual demonstration of the same effect (unfortunately without the chocolate) and offers several possibilities for student investigations. In addition to the demonstration of the above effect, the experiments described below provide an excellent opportunity for students to devise and test explanations with simple equipment.
Preference by Association: How Memory Mechanisms in the Hippocampus Bias Decisions
Authors: Wimmer G. Elliott , Shohamy Daphna
Published: October 2012

The Right Choice?

So-called irrational decisions made by humans are popular fodder for “believe it or not” stories. But what's actually happening when we make choices that do not seem to be justifiable on purely economic or logical grounds? Presumably, we are not simply making errors; instead, our choices may reflect an internal bias that we are not aware of.
Wimmer and Shohamy
(p.
270
) show how the hippocampus can instill an unconscious bias in valuations, whereby an object that is not highly valued on its own, increases in value when it becomes implicitly associated with a truly high-value object. As a consequence, we then end up preferring the associated object over a neutral object of equal objective value while not really knowing why.
Developmental Pattern Formation: Insights from Physics and Biology
Authors: Kicheva Anna , Cohen Michael , Briscoe James
Published: October 2012

The spatial organization of cell fates during development involves the interpretation of morphogen gradients by cellular signaling cascades and transcriptional networks. Recent studies use biophysical models, genetics, and quantitative imaging to unravel how tissue-level morphogen behavior arises from subcellular events. Moreover, data from several systems show that morphogen gradients, downstream signaling, and the activity of cell-intrinsic transcriptional networks change dynamically during pattern formation. Studies from
Drosophila
and now also vertebrates suggest that transcriptional network dynamics are central to the generation of gene expression patterns. Together, this leads to the view that pattern formation is an emergent behavior that results from the coordination of events occurring across molecular, cellular, and tissue scales. The development of novel approaches to study this complex process remains a challenge.
Comment on “Climatic Niche Shifts Are Rare Among Terrestrial Plant Invaders”
Authors: Webber Bruce L. , Le Maitre David C. , Kriticos Darren J.
Published: October 2012

Petitpierre
et al
. (Reports, 16 March 2012, p. 1344) conclude that niche shifts are rare for terrestrial plant invaders and that this justifies the use of correlative modeling to project species geographic ranges for biological invasions and climate change. We draw attention to the limitations of their conceptual assumptions and the importance of niche shifts excluded from their analyses.
Immunotherapy Against HPV16/18 Generates Potent T
H
1 and Cytotoxic Cellular Immune Responses
Authors: Bagarazzi Mark L. , Yan Jian , Morrow Matthew P. , Shen Xuefei , Parker R. Lamar , Lee Jessica C. , Giffear Mary , Pankhong Panyupa , Khan Amir S. , Broderick Kate E. , Knott Christine , Lin Feng , Boyer Jean D. , Draghia-Akli Ruxandra , White C. Jo , Kim J. Joseph , Weiner David B. , Sardesai Niranjan Y.
Published: October 2012

CD8
+
T cells with cytolytic activity are induced after therapeutic human papillomavirus vaccination in humans.
From “Cheers” to Fears
Authors: Mashour George A.
Published: October 2012

Alcohol-related changes in the prefrontal cortex may pave the way for posttraumatic stress disorder.
Detection of Legionella bozemanae, a New Cause of Septic Arthritis, by PCR Followed by Specific Culture
Authors: Just Søren Andreas , Knudsen John Bonde , Uldum Søren Anker , Holt Hanne Marie
Published: October 2012

Legionella bozemanae
is a rare isolate in clinical specimens. We describe a case of joint infection due to
L. bozemanae
in an immunocompromised patient with dermatomyositis. Without the use of PCR screening or culture on specialized medium, the organism would not have been detected.
Diversity of Bipolaris Species in Clinical Samples in the United States and Their Antifungal Susceptibility Profiles
Authors: da Cunha K. C. , Sutton D. A. , Fothergill A. W. , Cano J. , Gené J. , Madrid H. , De Hoog S. , Crous P. W. , Guarro J.
Published: October 2012

A set of 104 isolates from human clinical samples from the United States, morphologically compatible withBipolaris, were morphologically and molecularly identified through the sequence analysis of the internal transcribed space (ITS) region of the nuclear ribosomal DNA (rDNA). The predominant species wasBipolaris spicifera(67.3%), followed byB. hawaiiensis(18.2%),B. cynodontis(8.6%),B. micropus(2.9%),B. australiensis(2%), andB. setariae(1%).Bipolaris cynodontis,B. micropus, andB. setariaerepresent new records from clinical samples. The most common anatomical sites where isolates were recovered were the nasal region (30.7%), skin (19.2%), lungs (14.4%), and eyes (12.5%). The antifungal susceptibilities of 5 species ofBipolaristo 9 drugs are provided. With the exception of fluconazole and flucytosine, the antifungals tested showed good activity.
Evaluation of Clostridium difficile Fecal Load and Limit of Detection during a Prospective Comparison of Two Molecular Tests, the illumigene C. difficile and Xpert C. difficile/Epi Tests
Authors: Gyorke Clare E. , Wang Susan , Leslie Jhansi L. , Cohen Stuart H. , Solnick Jay V. , Polage Christopher R.
Published: October 2012

In a large prospective comparison, the illumigene test detected
Clostridium difficile
in 98% of toxin-positive and 58% of toxin-negative samples confirmed positive by other methods. The Xpert was uniformly sensitive. Most samples with discrepant results had
C. difficile
concentrations below the illumigene limit of detection. The significance of low-level
C. difficile
detection needs investigation.
Association of Relapse of Clostridium difficile Disease with BI/NAP1/027
Authors: Marsh Jane W. , Arora Rangolee , Schlackman Jessica L. , Shutt Kathleen A. , Curry Scott R. , Harrison Lee H.
Published: October 2012

Recurrent
Clostridium difficile
infection (CDI) occurs in up to 35% of patients. Recurrences can be due to either relapse with the same strain or reinfection with another strain. In this study, multilocus variable-number tandem-repeat analysis (MLVA) was performed on
C. difficile
isolates from patients with recurrent CDI to distinguish relapse from reinfection. In addition, univariate and multivariate analyses were performed to identify risk factors associated with relapse. Among patients with a single recurrence, relapse due to the original infecting strain was more prevalent than reinfection and the interval between episodes was shorter than among patients who had reinfections. Among patients with >1 recurrence, equal distributions of relapse and reinfection or a combination of the two episode types were observed. Initial infection with the BI/NAP1/027 epidemic clone was found to be a significant risk factor for relapse. This finding may have important implications for patient therapy. Classification of recurrent CDI episodes by MLVA can be utilized to make informed patient care decisions and to accurately define new CDI cases for infection control and reimbursement purposes.
Point-Counterpoint: Is the Era of Viral Culture Over in the Clinical Microbiology Laboratory?
Authors: Hodinka Richard L. , Kaiser Laurent , Hodinka Richard L. , Kaiser Laurent
Published: October 2012

Conventional tube culture systems have long been the mainstay in clinical virology for the growth and identification of viruses from clinical specimens. Innovations such as centrifugation-enhanced shell vial and multiwell plate cultures and the use of genetically engineered and mixed cell lines, coupled with faster detection of viral replication, have allowed for reasonable turnaround times for even some of the most slowly growing clinically important human viruses. However, molecular methods, in particular, the PCR, have usurped the role of viral culture in many laboratories, limiting the use of this traditional method of virus detection or replacing it altogether. Advances and improvements in molecular technology over time have also resulted in newer generations of more rapid and accurate molecular assays for the detection, quantification, and genetic characterization of viruses. For this point-counterpoint, we have asked two individuals, Richard L. Hodinka of the Children's Hospital of Philadelphia, a clinical virologist whose laboratory has completely eliminated viral culture in favor of molecular methods, and Laurent Kaiser, head of the Virology Laboratory at the University of Geneva Hospital, who continues to be a strong advocate of viral culture, to discuss the relevance of viral culture in the molecular age.
Differences between Two Clinical Staphylococcus capitis Subspecies as Revealed by Biofilm, Antibiotic Resistance, and Pulsed-Field Gel Electrophoresis Profiling
Authors: Cui Bintao , Smooker Peter M. , Rouch Duncan A. , Daley Andrew J. , Deighton Margaret A.
Published: October 2012

Coagulase-negative staphylococci have been identified as major causes of late-onset neonatal bacteremia in neonatal intensive care units. Sixty isolates of
Staphylococcus capitis
obtained from blood cultures of neonates between 2000 and 2005 were examined in this study. Biochemical analysis confirmed that 52 of these isolates belonged to the subsp.
urealyticus
, and the remaining 8 belonged to the subsp.
capitis.
Isolates of the predominant subsp.
urealyticus
clones were characterized by their resistance to penicillin, erythromycin, and oxacillin and their biofilm formation ability, whereas subsp.
capitis
isolates were generally antibiotic susceptible and biofilm negative. Pulsed-field gel electrophoresis (PFGE) after SacII digestion separated the 60 isolates into five major clusters. Sequence analysis showed that, in
S. capitis
, the
ica
operon plus the negative regulator
icaR
was 4,160 bp in length. PCRs demonstrated the presence of the
ica
operon in all isolates. Further analysis of five isolates (two biofilm-positive subsp.
urealyticus
, one biofilm-negative subsp.
urealyticus
, and two biofilm-negative subsp.
capitis
) revealed that the
ica
operons were identical in all of the biofilm-positive subsp.
urealyticus
strains; however, the biofilm-negative isolates showed variations. The distinctive phenotypic and genotypic characteristics revealed by this study may affect the epidemiology of the two subspecies of
S. capitis
in the clinical setting. These results may provide a better understanding of the contribution of these two species to bloodstream infections in neonates.
Structure and Function of AvtR, a Novel Transcriptional Regulator from a Hyperthermophilic Archaeal Lipothrixvirus
Authors: Peixeiro N. , Keller J. , Collinet B. , Leulliot N. , Campanacci V. , Cortez D. , Cambillau C. , Nitta K. R. , Vincentelli R. , Forterre P. , Prangishvili D. , Sezonov G. , van Tilbeurgh H.
Published: October 2012

The structural and functional analysis of the protein AvtR encoded by
Acidianus
filamentous virus 6 (AFV6), which infects the archaeal genus
Acidianus
, revealed its unusual structure and involvement in transcriptional regulation of several viral genes. The crystal structure of AvtR (100 amino acids) at 2.6-Å resolution shows that it is constituted of a repeated ribbon-helix-helix (RHH) motif, which is found in a large family of bacterial transcriptional regulators. The known RHH proteins form dimers that interact with DNA using their ribbon to create a central β-sheet. The repeated RHH motifs of AvtR superpose well on such dimers, but its central sheet contains an extra strand, suggesting either conformational changes or a different mode of DNA binding. Systematic evolution of ligands by exponential enrichment (SELEX) experiments combined with systematic mutational and computational analysis of the predicted site revealed 8 potential AvtR targets in the AFV6 genome. Two of these targets were studied in detail, and the complex role of AvtR in the transcriptional regulation of viral genes was established. Repressing transcription from its own gene,
gp29
, AvtR can also act as an activator of another gene,
gp30
. Its binding sites are distant from both genes' TATA boxes, and the mechanism of AvtR-dependent regulation appears to include protein oligomerization starting from the protein's initial binding sites. Many RHH transcriptional regulators of archaeal viruses could share this regulatory mechanism.
Long-Distance RNA-RNA Interactions in the Coronavirus Genome Form High-Order Structures Promoting Discontinuous RNA Synthesis during Transcription
Authors: Mateos-Gomez Pedro A. , Morales Lucia , Zuñiga Sonia , Enjuanes Luis , Sola Isabel
Published: October 2012

Coronavirus (CoV) transcription requires a high-frequency recombination process that links newly synthesized minus-strand subgenomic RNA copies to the leader region, which is present only once, at the 5′ end of the genome. This discontinuous RNA synthesis step is based on the complementarity between the transcription-regulating sequences (TRSs) at the leader region and those preceding each gene in the nascent minus-strand RNA. Furthermore, the template switch requires the physical proximity of RNA genome domains located between 20,000 and 30,000 nucleotides apart. In this report, it is shown that the efficacy of this recombination step is promoted by novel additional long-distance RNA-RNA interactions between RNA motifs located close to the TRSs controlling the expression of each gene and their complementary sequences mapping close to the 5′ end of the genome. These interactions would bring together the motifs involved in the recombination process. This finding indicates that the formation of high-order RNA structures in the CoV genome is necessary to control the expression of at least the viral N gene. The requirement of these long-distance interactions for transcription was shown by the engineering of CoV replicons in which the complementarity between the newly identified sequences was disrupted. Furthermore, disruption of complementarity in mutant viruses led to mutations that restored complementarity, wild-type transcription levels, and viral titers by passage in cell cultures. The relevance of these high-order structures for virus transcription is reinforced by the phylogenetic conservation of the involved RNA motifs in CoVs.
The N-Terminal Region of IFITM3 Modulates Its Antiviral Activity by Regulating IFITM3 Cellular Localization
Authors: Jia Rui , Pan Qinghua , Ding Shilei , Rong Liwei , Liu Shan-Lu , Geng Yunqi , Qiao Wentao , Liang Chen
Published: October 2012

Interferon-inducible transmembrane (IFITM) protein family members IFITM1, -2, and -3 restrict the infection of multiple enveloped viruses. Significant enrichment of a minor IFITM3 allele was recently reported for patients who were hospitalized for seasonal and 2009 H1N1 pandemic flu. This IFITM3 allele lacks the region corresponding to the first amino-terminal 21 amino acids and is unable to inhibit influenza A virus. In this study, we found that deleting this 21-amino-acid region relocates IFITM3 from the endosomal compartments to the cell periphery. This finding likely underlies the lost inhibition of influenza A virus that completes its entry exclusively within endosomes at low pH. Yet, wild-type IFITM3 and the mutant with the 21-amino-acid deletion inhibit HIV-1 replication equally well. Given the pH-independent nature of HIV-1 entry, our results suggest that IFITM3 can inhibit viruses that enter cells via different routes and that its N-terminal region is specifically required for controlling pH-dependent viruses.
RNA Interference as a Cellular Defense Mechanism against the DNA Virus Baculovirus
Authors: Jayachandran Balachandran , Hussain Mazhar , Asgari Sassan
Published: October 2012

In insects, the RNA interference (RNAi) pathway plays a major role in antiviral responses, as shown against many RNA viruses. The response includes the cleavage of double-stranded RNA genome or intermediates, produced during replication, into viral short interfering RNAs (v-siRNAs). Using deep sequencing, we found that a large number of small reads of ∼20 nucleotides from
Helicoverpa armigera
larvae infected with
Helicoverpa armigera
single nucleopolyhedrovirus (HaSNPV) were mapped to certain open reading frames in the viral genome (hot spots) that are mostly structural and auxiliary late genes. After excluding the possibility of these small RNAs being microRNAs, it was determined that Dicer-2, the main enzyme implicated in the RNAi response in insects, is involved in the generation of v-siRNAs. In
Dicer-2
- but not
Dicer-1
-silenced cells, higher transcript levels of the hot spot genes were detected, and as a consequence the virus replicated more efficiently. The results suggest that the viral transcripts are degraded by the RNAi response of the host. This may, however, be to the advantage of the virus by preventing overreplication of the virus, which may otherwise lead to the premature death of the host cells.
Endovascular approach and technique for treatment of transverse-sigmoid dural arteriovenous fistula with cortical reflux: the importance of venous sinus sacrifice
Authors: Carlson Andrew Phillip , Alaraj Ali , Amin-Hanjani Sepideh , Charbel Fady T , Aletich Victor
Published: October 2012

Background

Treatment of dural arteriovenous fistula involving the transverse-sigmoid region with cortical reflux is complex and treatment options may require sacrifice of the fistulous segment of the sinus.

Objective

To review our results in this subset of patients and describe current endovascular decision-making and approaches.

Methods

We reviewed cases of endovascular sinus sacrifice for dural fistulas at our institution from 2007 to 2012. Demographic, decision-making, technical and outcome data were collected.

Results

Seven patients were identified who underwent endovascular sinus sacrifice for treatment of dural fistula during this 4-year period. Determination of the fistulous sinus segment was based on the pattern of cortical drainage. Endovascular access to the sinus was achieved by transarterial, transvenous or via open surgery in one case. Complete cure of the target fistula was obtained in all cases. One patient had transient post-procedure headache. There were no hemorrhages, new neurological deficits or signs of increased intracranial pressure. Six of the seven patients had angiographic follow-up at least 6 months after treatment with no recurrence.

Conclusions

Fistulas of the transverse-sigmoid sinuses with cortical reflux may require sacrifice of the parent sinus for cure. Defining the fistulous segment and occluding this segment deliberately, completely and precisely is essential for cure. Several modalities and approaches can be used to achieve this. For properly selected patients, cure of the lesions can be achieved with this method with low risk of morbidity.
FUNDAMENTAL PHYSICS EXPLORED WITH HIGH INTENSITY LASER
Authors: TAJIMA T. , HOMMA K.
Published: October 2012

Over the last century the method of particle acceleration to high energies has become the prime approach to explore the fundamental nature of matter in laboratory. It appears that the latest search of the contemporary accelerator based on the colliders shows a sign of saturation (or at least a slow-down) in increasing its energy and other necessary parameters to extend this frontier. We suggest two pronged approach enabled by the recent progress in high intensity lasers. First we envision the laser-driven plasma accelerator may be able to extend the reach of the collider. For this approach to bear fruit, we need to develop the technology of high averaged power laser in addition to the high intensity. For this we mention that the latest research effort of ICAN is an encouraging sign. In addition to this, we now introduce the concept of the noncollider paradigm in exploring fundamental physics with high intensity (and large energy) lasers. One of the examples we mention is the laser wakefield acceleration (LWFA) far beyond TeV without large luminosity. If we relax or do not require the large luminosity necessary for colliders, but solely in ultrahigh energy frontier, we are still capable of exploring such a fundamental issue. Given such a high energetic particle source and high-intensity laser fields simultaneously, we expect to be able to access new aspects on the matter and the vacuum structure from fundamental physical point of views. LWFA naturally exploits the nonlinear optical effects in the plasma when it becomes of relativistic intensity. Normally nonlinear optical effects are discussed based upon polarization susceptibility of matter to external fields. We suggest application of this concept even to the vacuum structure as a new kind of order parameter to discuss vacuum-originating phenomena at semimacroscopic scales. This viewpoint unifies the following observables with the unprecedented experimental environment we envision; the dispersion relation of photons at extremely short wavelengths in vacuum (a test of the Lorentz invariance), the dispersion relation of the vacuum under high-intensity laser fields (nonperturbative QED and possibly QCD effects), and wave-mixing processes possibly caused by exchanges of low-mass and weakly coupling fields relevant to cosmology with the coherent nature of high-flux photons (search for light dark matter and dark energy). These observables based on polarization susceptibility of vacuum would add novel insights to phenomena discovered in cosmology and particle physics where order parameters such as curvature and particle masses are conventionally discussed. In other words the introduction of high intensity laser and its methodology enriches the approach of fundamental and particle physics in entirely new dimensions.
CROSSOVER BETWEEN MAGNETIC REVERSAL MODES IN ORDERED Ni AND Co NANOTUBE ARRAYS
Authors: PROENCA MARIANA P. , SOUSA CELIA T. , VENTURA JOAO , ARAUJO JOAO P. , ESCRIG JUAN , VAZQUEZ MANUEL
Published: October 2012

Ordered arrays of Ni and Co nanowires and nanotubes, with diameters between 30 nm and 60 nm, were prepared by electrodeposition into nanoporous alumina templates. The study of the corresponding magnetization reversal processes was performed by analyzing the angular dependence of coercivity (Hc) and using a simple analytical model. The agreement between experimental and theoretical data shows that magnetization in nanowire arrays reverses by means of nucleation and propagation of a transverse domain wall, independently of the diameter. However, a critical diameter of ~ 50 nm was found in the case of nanotubes, above which a nonmonotonic angular dependent Hc was observed, evidencing a transition between vortex and transverse reversal modes.
How to achieve (some) balance in anti-circumvention laws
Authors: Samuelson Pamela , Reichman Jerome H. , Dinwoodie Graeme
Published: October 2012

Should users of technically protected content be able to give notice and require content owners to take down the technical measure to enable fair uses?
Are people biased in their use of search engines?
Authors: Keane Mark T. , O'Brien Maeve , Smyth Barry
Published: October 2012

Assessing user search behavior when deciding which links to follow in rank-ordered results lists.
Translation caching
Authors: Barr Thomas W. , Cox Alan L. , Rixner Scott
Published: October 2012

This paper explores the design space of MMU caches that accelerate virtual-to-physical address translation in processor architectures, such as x86-64, that use a radix tree page table. In particular, these caches accelerate the page table walk that occurs after a miss in the Translation Lookaside Buffer. This paper shows that the most effective MMU caches are translation caches, which store partial translations and allow the page walk hardware to skip one or more levels of the page table.

In recent years, both AMD and Intel processors have implemented MMU caches. However, their implementations are quite different and represent distinct points in the design space. This paper introduces three new MMU cache structures that round out the design space and directly compares the effectiveness of all five organizations. This comparison shows that two of the newly introduced structures, both of which are translation cache variants, are better than existing structures in many situations.

Finally, this paper contributes to the age-old discourse concerning the relative effectiveness of different page table organizations. Generally speaking, earlier studies concluded that organizations based on hashing, such as the inverted page table, outperformed organizations based upon radix trees for supporting large virtual address spaces. However, these studies did not take into account the possibility of caching page table entries from the higher levels of the radix tree. This paper shows that any of the five MMU cache structures will reduce radix tree page table DRAM accesses far below an inverted page table.
An intra-chip free-space optical interconnect
Authors: Xue Jing , Garg Alok , Ciftcioglu Berkehan , Hu Jianyun , Wang Shang , Savidis Ioannis , Jain Manish , Berman Rebecca , Liu Peng , Huang Michael , Wu Hui , Friedman Eby , Wicks Gary , Moore Duncan
Published: October 2012

Continued device scaling enables microprocessors and other systems-on-chip (SoCs) to increase their performance, functionality, and hence, complexity. Simultaneously, relentless scaling, if uncompensated, degrades the performance and signal integrity of on-chip metal interconnects. These systems have therefore become increasingly communications-limited. The communications-centric nature of future high performance computing devices demands a fundamental change in intra- and inter-chip interconnect technologies.

Optical interconnect is a promising long term solution. However, while significant progress in optical
signaling
has been made in recent years,
networking
issues for on-chip optical interconnect still require much investigation. Taking the underlying optical signaling systems as a drop-in replacement for conventional electrical signaling while maintaining conventional packet-switching architectures is unlikely to realize the full potential of optical interconnects. In this paper, we propose and study the design of a fully distributed interconnect architecture based on free-space optics. The architecture leverages a suite of newly-developed or emerging devices, circuits, and optics technologies. The interconnect avoids packet relay altogether, offers an ultra-low transmission latency and scalable bandwidth, and provides fresh opportunities for coherency substrate designs and optimizations.
SieveStore
Authors: Pritchett Timothy , Thottethodi Mithuna
Published: October 2012

Emerging solid-state storage media can significantly improve storage performance and energy. However, the high cost-per-byte of solid-state media has hindered wide-spread adoption in servers. This paper proposes a new, cost-effective architecture - SieveStore - which enables the use of solid-state media to significantly filter access to storage ensembles. Our paper makes three key contributions. First, we make a case for highly-selective, storage-ensemble-level disk-block caching based on the highly-skewed block popularity distribution and based on the dynamic nature of the popular block set. Second, we identify the problem of
allocation-writes
and show that selective cache allocation to reduce allocation-writes -
sieving
- is fundamental to enable efficient ensemble-level disk-caching. Third, we propose two practical variants of SieveStore. Based on week-long block access traces from a storage ensemble of 13 servers, we find that the two components (sieving and ensemble-level caching) each contribute to SieveStore's cost-effectiveness. Compared to unsieved, ensemble-level disk-caches, SieveStore achieves significantly higher hit ratios (35%-50% more, on average) while using only 1/7
th
the number of SSD drives. Further, ensemble-level caching is strictly better in cost-performance compared to per-server caching.
LReplay
Authors: Chen Yunji , Hu Weiwu , Chen Tianshi , Wu Ruiyang
Published: October 2012

Debugging parallel program is a well-known difficult problem. A promising method to facilitate debugging parallel program is using hardware support to achieve deterministic replay. A hardware-assisted deterministic replay scheme should have a small log size, as well as low design cost, to be feasible for adopting by industrial processors. To achieve the goals, we propose a novel and succinct hardware-assisted deterministic replay scheme named LReplay. The key innovation of LReplay is that instead of recording the logical time orders between instructions or instruction blocks as previous investigations, LReplay is built upon recording the pending period information [6]. According to the experimental results on Godson-3, the overall log size of LReplay is about 0.55B/K-Inst (byte per k-instruction) for sequential consistency, and 0.85B/K-Inst for Godson-3 consistency. The log size is smaller in an order of magnitude than state-of-art deterministic replay schemes incuring no performance loss. Furthermore, LReplay only consumes about $1.3%$ area of Godson-3, since it requires only trivial modifications to the existing components of Godson-3. The above features of LReplay demonstrate the potential of integrating hardware-assisted deterministic replay into future industrial processors.
Timetraveler
Authors: Voskuilen Gwendolyn , Ahmad Faraz , Vijaykumar T. N.
Published: October 2012

As chip multiprocessors emerge as the prevalent microprocessor architecture, support for debugging shared-memory parallel programs becomes important. A key difficulty is the programs' nondeterministic semantics due to which replay runs of a buggy program may not reproduce the bug. The non-determinism stems from memory races where accesses from two threads, at least one of which is a write, go to the same memory location. Previous hardware schemes for memory race recording log the predecessor-successor thread ordering at memory races and enforce the same orderings in the replay run to achieve deterministic replay. To reduce the log size, the schemes exploit transitivity in the orderings to avoid recording redundant orderings. To reduce the log size further while requiring minimal hardware, we propose
Timetraveler
which for the first time exploits acyclicity of races based on the key observation that an acyclic race need not be recorded even if the race is not covered already by transitivity. Timetraveler employs a novel and elegant mechanism called
post-dating
which both ensures that acyclic races, including those through the L2, are eventually ordered correctly, and identifies cyclic races. To address false cycles through the L2, Timetraveler employs another novel mechanism called
time-delay buffer
which delays the advancement of the L2 banks' timestamps and thereby reduces the false cycles. Using simulations, we show that Timetraveler reduces the log size for commercial workloads by 88% over the best previous approach while using only a 696-byte time-delay buffer.
Shared caches in multicores
Authors: Irwin Mary Jane
Published: October 2012

As we transition from clock-frequency performance scaling to performance scaling with multicores, the pressure on the memory hierarchy is increasing dramatically. Many different on-chip cache topologies have been proposed/implemented; effective management of these shared caches is crucial to multicore performance.

This talk will begin with a description of a cache miss classification scheme for multicores (compulsory, inter-core misses, intra-core misses) that gives insight into the interactions between memory transactions of the different cores on a chip sharing a cache. Ways to improve the on-chip cache performance with architectural enhancements, compiler enhancements, and runtime system enhancements will then be discussed. If the application thread mapping and the on-chip topology is static (i.e., does not change during runtime), then compiler enhancements that support cache topology aware code optimization can be used to significantly improve an application's performance. Results from such an augmented compiler, where the topology is exposed to the compiler and where the compiler also does thread-to-core mapping assignments, will be presented. If the application thread mapping or the on-chip topology is dynamic, then other alternatives exist. For example, a thread scheduler, or allocator, can make decisions about moving threads to different cores during runtime in the hopes of improving overall cache performance. Initial experiments with the REEact system being developed by researchers at Penn State-UPittsburgh-UVirginia that "reacts" to hardware conditions (such as cache miss rates, hot-spots, etc.) by reallocating threads at runtime will be outlined. Finally, if the on-chip cache topology itself is dynamic (i.e., is designed to be reconfigurable at runtime), large performance benefits might be obtained. However, both hardware and software design challenges to realizing such a dynamic system abound. Some of these challenges will be briefly discussed.
A case for FAME
Authors: Tan Zhangxi , Waterman Andrew , Cook Henry , Bird Sarah , Asanović Krste , Patterson David
Published: October 2012

Given the multicore microprocessor revolution, we argue that the architecture research community needs a dramatic increase in simulation capacity. We believe FPGA Architecture Model Execution (FAME) simulators can increase the number of useful architecture research experiments per day by two orders of magnitude over Software Architecture Model Execution (SAME) simulators. To clear up misconceptions about FPGA-based simulation methodologies, we propose a FAME taxonomy to distinguish the costperformance of variations on these ideas. We demonstrate our simulation speedup claim with a case study wherein we employ a prototype FAME simulator, RAMP Gold, to research the interaction between hardware partitioning mechanisms and operating system scheduling policy. The study demonstrates FAME's capabilities: we run a modern parallel benchmark suite on a research operating system, simulate 64-core target architectures with multi-level memory hierarchy timing models, and add experimental hardware mechanisms to the target machine. The simulation speedup achieved by our adoption of FAME-250×-enables experiments with more realistic time scales and data set sizes thanare possible with SAME.
Security refresh
Authors: Seong Nak Hee , Woo Dong Hyuk , Lee Hsien-Hsin S.
Published: October 2012

Phase change memory (PCM) is an emerging memory technology for future computing systems. Compared to other non-volatile memory alternatives, PCM is more matured to production, and has a faster read latency and potentially higher storage density. The main roadblock precluding PCM from being used, in particular, in the main memory hierarchy, is its limited write endurance. To address this issue, recent studies proposed to either reduce PCM's write frequency or use wear-leveling to evenly distribute writes. Although these techniques can extend the lifetime of PCM, most of them will not prevent deliberately designed malicious codes from wearing it out quickly. Furthermore, all the prior techniques did not consider the circumstances of a compromised OS and its security implication to the overall PCM design. A compromised OS will allow adversaries to manipulate processes and exploit side channels to accelerate wear-out.

In this paper, we argue that a PCM design not only has to consider normal wear-out under normal application behavior, most importantly, it must take the worst-case scenario into account with the presence of malicious exploits and a compromised OS to address the durability and security issues simultaneously. In this paper, we propose a novel, low-cost hardware mechanism called Security Refresh to avoid information leak by constantly migrating their physical locations inside the PCM, obfuscating the actual data placement from users and system software. It uses a dynamic randomized address mapping scheme that swaps data using random keys upon each refresh due. The hardware overhead is tiny without using any table. The best lifetime we can achieve under the worst-case malicious attack is more than six years. Also, our scheme incurs around 1% performance degradation for normal program operations.
Sentry
Authors: Shriraman Arrvindh , Dwarkadas Sandhya
Published: October 2012

Light-weight, flexible access control, which allows software to regulate reads and writes to any granularity of memory region, can help improve the reliability of today's multi-module multi-programmer applications, as well as the efficiency of software debugging tools. Unfortunately, access control in today's processors is tied to support for virtual memory, making its use both heavy weight and coarse grain. In this paper, we propose Sentry, an auxiliary level of virtual memory tagging that is entirely subordinate to existing virtual memory-based protection mechanisms and can be manipulated at the user level. We implement these tags in a complexity-effective manner using an M-cache (metadata cache) structure that only intervenes on L1 misses, thereby minimizing changes to the processor core. Existing cache coherence states are repurposed to implicitly validate permissions for L1 hits. Sentry achieves its goal of flexible and light-weight access control without disrupting existing inter-application protection, sidestepping the challenges associated with adding a new protection framework to an existing operating system.

We illustrate the benefits of our design point using 1) an Apache-based web server that uses the M-cache to enforce protection boundaries among its modules and 2) a watchpoint-based tool to demonstrate low-overhead debugging. Protection is achieved with very few changes to the source code, no changes to the programming model, minimal modifications to the operating system, and with low overhead incurred only when accessing memory regions for which the additional level of access control is enabled.
Debunking the 100X GPU vs. CPU myth
Authors: Lee Victor W. , Kim Changkyu , Chhugani Jatin , Deisher Michael , Kim Daehyun , Nguyen Anthony D. , Satish Nadathur , Smelyanskiy Mikhail , Chennupaty Srinivas , Hammarlund Per , Singhal Ronak , Dubey Pradeep
Published: October 2012

Recent advances in computing have led to an explosion in the amount of data being generated. Processing the ever-growing data in a timely manner has made throughput computing an important aspect for emerging applications. Our analysis of a set of important throughput computing kernels shows that there is an ample amount of parallelism in these kernels which makes them suitable for today's multi-core CPUs and GPUs. In the past few years there have been many studies claiming GPUs deliver substantial speedups (between 10X and 1000X) over multi-core CPUs on these kernels. To understand where such large performance difference comes from, we perform a rigorous performance analysis and find that after applying optimizations appropriate for both CPUs and GPUs the performance gap between an Nvidia GTX280 processor and the Intel Core i7-960 processor narrows to only 2.5x on average. In this paper, we discuss optimization techniques for both CPU and GPU, analyze what architecture features contributed to performance differences between the two architectures, and recommend a set of architectural features which provide significant improvement in architectural efficiency for throughput kernels.
Auto-generation of communication benchmark traces
Authors: Deshpande Vivek , Wu Xing , Mueller Frank
Published: October 2012

Benchmarks are essential for evaluating HPC hardware and software for petascale machines and beyond. But benchmark creation is a tedious manual process. As a result, benchmarks tend to lag behind the development of complex scientific codes. Our work automates the creation of communication benchmarks. Given an MPI application, we utilize ScalaTrace, a lossless and scalable framework to trace communication operations and execution time while abstracting away the computations. A single trace file that reflects the behavior of all nodes is subsequently expanded to C source code by a novel code generator. This resulting benchmark code is compact, portable, human-readable, and accurately reflects the original application's communication characteristics and performance. Experimental results demonstrate that generated source code of benchmarks preserves both the communication patterns and the run-time behavior of the original application. Such automatically generated benchmarks not only shorten the transition from application development to benchmark extraction but also facilitate code obfuscation, which is essential for benchmark extraction from commercial and restricted applications.
APC
Authors: Sun Xian-He , Wang Dawei
Published: October 2012

Due to the infamous "memory wall" problem and a drastic increase in the number of data intensive applications, memory rather than processor has become the leading performance bottleneck of modern computing systems. Evaluating and understanding memory system performance is increasingly becoming the core of high-end computing. Conventional memory metrics, such as miss ratio, average miss latency, average memory access time, etc., are designed to measure a given memory performance parameter, and do not reflect the overall performance of a memory system. On the other hand, widely used system measurement metrics, such as IPC and Flops are designed to measure CPU performance, and do not directly reflect memory performance. In this paper, we proposed a novel memory metric, Access Per Cycle (APC), to measure overall memory performance with consideration of the complexity of modern memory systems. A unique contribution of APC is its separation of memory evaluation from CPU evaluation; therefore, it provides a quantitative measurement of the "data-intensiveness" of an application. The concept of APC is introduced; a constructive investigation counting the number of data accesses and access cycles at differing levels of the memory hierarchy is conducted; finally some important usages of APC are presented. Simulation results show that APC is significantly more appropriate than the existing memory metrics in evaluating modern memory systems.
Paths Less Traveled: Evo-Devo Approaches to Investigating Animal Morphological Evolution
Authors: Mallarino Ricardo , Abzhanov Arhat
Published: October 2012

One of the chief aims of modern biology is to understand the causes and mechanisms of morphological evolution. Multicellular animals display a stunning diversity of shapes and sizes of their bodies and individual suborganismal structures, much of it important to their survival. What is the most efficient way to study the evolution of morphological diversity? The old-new field of evolutionary developmental biology (evo-devo) can be particularly useful for understanding the origins of animal forms, as it aims to consolidate advances from disparate fields such as phylogenetics, genomics, morphometrics, cell biology, and developmental biology. We analyze the structure of some of the most successful recent evo-devo studies, which we see as having three distinct but highly interdependent components: (a) morphometrics, (b) identification of candidate mechanisms, and (c) functional experiments. Our case studies illustrate how multifarious evo-devo approaches taken within the three-winged evo-devo research program explain developmental mechanisms for morphological evolution across different phylogenetic scales.
Functional Diversity of Laminins
Authors: Domogatskaya Anna , Rodin Sergey , Tryggvason Karl
Published: October 2012

Laminins are a large family of conserved, multidomain trimeric basement membrane proteins that contribute to the structure of extracellular matrix and influence the behavior of associated cells, such as adhesion, differentiation, migration, phenotype stability, and resistance to anoikis. In lower organisms such as Hydra there is only one isoform of laminin, but higher organisms have at least 16 trimeric isoforms with varying degrees of cell/tissue specificity. In vitro protein and cell culture studies, gene manipulation in animals, and laminin gene mutations in human diseases have provided insight into the specific functions of some laminins, but the biological roles of many isoforms are still largely unexplored, mainly owing to difficulties in isolating them in pure form from tissues or cells. In this review, we elucidate the evolution of laminins, describe their molecular complexity, and explore the current knowledge of their diversity and functional aspects, including laminin-mediated signaling via membrane receptors, in vitro cell biology, and involvement in various tissues gained from animal model and human disease studies. The potential use of laminins in cell biology research and biotechnology is discussed.