bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacological and Patient-Specific Response Determinants in Patients with Hospital-Acquired Pneumonia Treated with Tigecycline
Authors: Bhavnani Sujata M. , Rubino Christopher M. , Hammel Jeffrey P. , Forrest Alan , Dartois Nathalie , Cooper C. Angel , Korth-Bradley Joan , Ambrose Paul G.
Published: December 2011

Pharmacokinetic and clinical data from tigecycline-treated patients with hospital-acquired pneumonia (HAP) who were enrolled in a phase 3 clinical trial were integrated in order to evaluate pharmacokinetic-pharmacodynamic (PK-PD) relationships for efficacy. Univariable and multivariable analyses were conducted to identify factors associated with clinical and microbiological responses, based on data from 61 evaluable HAP patients who received tigecycline intravenously as a 100-mg loading dose followed by 50 mg every 12 h for a minimum of 7 days and for whom there were adequate clinical, pharmacokinetic, and response data. The final multivariable logistic regression model for clinical response contained albumin and the ratio of the free-drug area under the concentration-time curve from 0 to 24 h (
f
AUC
0–24
) to the MIC (
f
AUC
0–24
:MIC ratio). The odds of clinical success were 13.0 times higher for every 1-g/dl increase in albumin (
P
< 0.001) and 8.42 times higher for patients with
f
AUC
0–24
:MIC ratios of ≥0.9 compared to patients with
f
AUC
0–24
:MIC ratios of <0.9 (
P
= 0.008). Average model-estimated probabilities of clinical success for the albumin/
f
AUC
0–24
:MIC ratio combinations of <2.6/<0.9, <2.6/≥0.9, ≥2.6/<0.9, and ≥2.6/≥0.9 were 0.21, 0.57, 0.64, and 0.93, respectively. For microbiological response, the final model contained albumin and ventilator-associated pneumonia (VAP) status. The odds of microbiological success were 21.0 times higher for every 1-g/dl increase in albumin (
P
< 0.001) and 8.59 times higher for patients without VAP compared to those with VAP (
P
= 0.003). Among the remaining variables evaluated, the MIC had the greatest statistical significance, an observation which was not surprising given the differences in MIC distributions between VAP and non-VAP patients (MIC
50
and MIC
90
values of 0.5 and 0.25 mg/liter versus 16 and 1 mg/liter for VAP versus non-VAP patients, respectively;
P
= 0.006). These findings demonstrated the impact of pharmacological and patient-specific factors on the clinical and microbiological responses.
Correlation of the Virological Response to Short-Term Maraviroc Monotherapy with Standard and Deep-Sequencing-Based Genotypic Tropism Prediction Methods
Authors: Gonzalez-Serna A. , McGovern R. A. , Harrigan P. R. , Vidal F. , Poon A. F. Y. , Ferrando-Martinez S. , Abad M. A. , Genebat M. , Leal M. , Ruiz-Mateos E.
Published: December 2011

Genotypic tropism testing methods are emerging as the first step before prescription of the CCR5 antagonist maraviroc (MVC) to HIV-infected patients in Europe. Studies validating genotypic tests have included other active drugs that could have potentially convoluted the effects of MVC. The maraviroc clinical test (MCT) is an
in vivo
drug sensitivity test based on the virological response to a short-term exposure to MVC monotherapy. Thus, our aim was to compare the results of genotypic tropism testing methods with the short-term virological response to MVC monotherapy. A virological response in the MCT was defined as a ≥1-log
10
decrease in HIV RNA or undetectability after 8 days of drug exposure. Seventy-three patients undergoing the MCT were included in this study. We used both standard genotypic methods (
n
= 73) and deep sequencing (
n
= 27) on MCT samples at baseline. For the standard methods, the most widely used genotypic algorithms for analyzing the V3 loop sequence, geno2pheno and PSSM, were used. For deep sequencing, the geno2pheno algorithm was used with a false-positive rate cutoff of 3.5. The discordance rates between the standard genotypic methods and the virological response were approximately 20% (including mostly patients without a virological response). Interestingly, these discordance rates were similar to that obtained from deep sequencing (18.5%). The discordance rates between the genotypic methods (tropism assays predictive of the use of the CCR5 coreceptor) and the MCT (
in vivo
MVC sensitivity assay) indicate that the algorithms used by genotypic methods are still not sufficiently optimized.
Lsr2 Peptides of Mycobacterium leprae Show Hierarchical Responses in Lymphoproliferative Assays, with Selective Recognition by Patients with Anergic Lepromatous Leprosy
Authors: Chaduvula Mehervani , Murtaza A. , Misra Namita , Narayan N. P. Shankar , Ramesh V. , Prasad H. K. , Rani Rajni , Chinnadurai R. K. , Nath Indira
Published: December 2011

Lsr2 protein ofMycobacterium lepraewas shown earlier to elicit B and T cell responses in leprosy patients (20, 28). Lymphoproliferation toM. lepraeand Lsr2 antigens was observed in >70% of tuberculoid (T) patients and in 16 and 34% of lepromatous (L) patients, respectively. We focused on theM. lepraenonresponders in the lepromatous group using 22 synthetic Lsr2 peptides (end-to-end peptides A to F and overlapping peptides p1 to p16) inin vitroT cell responses. A total of 125 leprosy and 13 tuberculosis patients and 19 healthy controls from the area of endemicity (here, healthy controls, or HC) were investigated. The highest responses were observed (67 to 100%) in HC for all peptides except p1 to p3, and the lowest was observed in tuberculosis patients. Significant differences in lymphoproliferation were observed in T, L, and HC groups (analysis of variance [ANOVA],P= 0.000 to 0.015) for all end-to-end peptides except B and for p5 and p7 to p10. Hierarchical recognition between lepromatous and tuberculoid leprosy was noted for p8 (P< 0.05) and between the HC and L groups for p7 to p10, p15, and p16 (P< 0.005 toP< 0.02). Significant lymphoproliferation was observed to peptides A to F and p1 to p9, p11, p12, p15, p16 (P= 0.000 to 0.001) with 40% responding to peptides C and p16 in L patients. Lepromatous patients also showed significantly higher levels of a gamma interferon (IFN-γ) response to peptide C than to other peptides (P< 0.05). Major histocompatibility complex (MHC) class II bias for peptide recognition was not observed. These studies indicate that Lsr2 has multiple T cell epitopes that inducein vitroT cell responses in the highly infective lepromatous leprosy patients.
Differential Gene Expression in Mice Infected with Distinct Toxoplasma Strains
Authors: Hill Rachel D. , Gouffon Julia S. , Saxton Arnold M. , Su Chunlei
Published: December 2011

Toxoplasma gondii
is the causative agent of toxoplasmosis in human and animals. In a mouse model,
T. gondii
strains can be divided into three groups, including the virulent, intermediately virulent, and nonvirulent. The clonal type I, II, and III
T. gondii
strains belong to these three groups, respectively. To better understand the basis of virulence phenotypes, we investigated mouse gene expression responses to the infection of different
T. gondii
strains at day 5 after intraperitoneal inoculation with 500 tachyzoites. The transcriptomes of mouse peritoneal cells showed that 1,927, 1,573, and 1,009 transcripts were altered more than 2-fold by type I, II, and III infections, respectively, and that the majority of altered transcripts were shared. Overall transcription patterns were similar in type I and type II infections, and both had greater changes than infection with type III. Quantification of parasite burden in mouse spleens showed that the burden with type I infection was 1,000 times higher than that of type II and that the type II burden was 20 times higher than that of type III. Fluorescence-activated cell sorting revealed that type I and II infections had comparable macrophage populations, and both were higher than the population with type III infection. In addition, type I infection had a higher percentage of neutrophils than type II and III infections. Taken together, these results suggested that there is a common gene expression response to
T. gondii
infection in mice. This response is further modified by parasite strain-specific factors that determine their distinct virulence phenotypes.
Roles of Interleukin-17 in an Experimental Legionella pneumophila Pneumonia Model
Authors: Kimizuka Yoshifumi , Kimura Soichiro , Saga Tomoo , Ishii Makoto , Hasegawa Naoki , Betsuyaku Tomoko , Iwakura Yoichiro , Tateda Kazuhiro , Yamaguchi Keizo
Published: December 2011

Interleukin-17 (IL-17) is a key factor in T helper type 17 (Th17) lineage host responses and plays critical roles in immunological control of a variety of infectious diseases. AlthoughLegionella pneumophila, an intracellular bacterium found widely in the environment, often causes a serious and life-threatening pneumonia in humans, the contribution of IL-17 to immune function duringLegionellapneumonia is unknown. In the present study, we used an experimentalLegionellapneumonia infection to clarify the role of IL-17 in the resulting immune response. We observed robust production of pulmonary IL-17A and IL-17F (IL-17A/F), peaking on day 1 and declining thereafter. Upregulated production of tumor necrosis factor alpha (TNF-α), IL-6, and IL-1β, but not monocyte chemotactic protein 1 (MCP-1), was observed inLegionella-infected bone marrow-derived macrophages from BALB/c mice that had been stimulated with IL-17A or IL-17F. A significant decrease in the production of proinflammatory cytokines IL-6 and TNF-α was observed in IL-17A/F-deficient mice (BALB/c background) infected withL. pneumophila. Moreover, we found impaired neutrophil migration and lower numbers of chemokines (KC, LIX, and MIP-2) in IL-17A/F-deficient mice. IL-17A/F-deficient mice also eliminatedL. pneumophilamore slowly and were less likely to survive a lethal challenge. These results demonstrate that IL-17A/F plays a critical role inL. pneumophilapneumonia, probably through induction of proinflammatory cytokines and accumulation of neutrophils at the infection site.
Critical Role of LuxS in the Virulence of Campylobacter jejuni in a Guinea Pig Model of Abortion
Authors: Plummer Paul , Sahin Orhan , Burrough Eric , Sippy Rachel , Mou Kathy , Rabenold Jessica , Yaeger Mike , Zhang Qijing
Published: December 2011

Previous studies on
Campylobacter jejuni
have demonstrated the role of LuxS in motility, cytolethal distending toxin production, agglutination, and intestinal colonization; however, its direct involvement in virulence has not been reported. In this study, we demonstrate a direct role of
luxS
in the virulence of
C. jejuni
in two different animal hosts. The IA3902 strain, a highly virulent sheep abortion strain recently described by our laboratory, along with its isogenic
luxS
mutant and
luxS
complement strains, was inoculated by the oral route into both a pregnant guinea pig virulence model and a chicken colonization model. In both cases, the IA3902
luxS
mutant demonstrated a complete loss of ability to colonize the intestinal tract. In the pregnant model, the mutant also failed to induce abortion, while the wild-type strain was highly abortifacient. Genetic complementation of the
luxS
gene fully restored the virulent phenotype in both models. Interestingly, when the organism was inoculated into guinea pigs by the intraperitoneal route, no difference in virulence (abortion induction) was observed between the
luxS
mutant and the wild-type strain, suggesting that the defect in virulence following oral inoculation is likely associated with a defect in colonization and/or translocation of the organism out of the intestine. These studies provide the first direct evidence that LuxS plays an important role in the virulence of
C. jejuni
using an
in vivo
model of natural disease.
Hamstring muscle injuries in professional football: the correlation of MRI findings with return to play
Authors: Ekstrand Jan , Healy Jeremiah C , Waldén Markus , Lee Justin C , English Bryan , Hägglund Martin
Published: December 2011

Background

Hamstring injury is the single most common injury in professional football. MRI is commonly used to confirm the diagnosis and provide a prognosis of lay-off time.

Objective

To evaluate the use of MRI as a prognostic tool for lay-off after hamstring injuries in professional football players and to study the association between MRI findings and injury circumstances.

Methods

Prospective cohort study where 23 European professional teams, were followed between 2007 and 2011. Team medical staffs recorded individual player exposure and time-loss injuries. Radiological grading was performed using a modified Peetrons classification into four grades where grades 2 and 3 represent fibre disruption.

Results

In total, 516 hamstring injuries occurred and 58% of these were examined by MRI. Thirteen per cent were grade 0 injuries, 57% grade 1, 27% of grade 2 and 3% of grade 3. Grade 0 and 1 injuries accounted for 56% (2141/3830 days) of the total lay-off. The lay-off time differed between all four radiological grades of injury (8±3, 17±10, 22±11 and 73±60 days, p<0.0001). Eighty-three per cent of injuries affected the biceps femoris while 11% and 5% occurred to the semimembranosus and semitendinosus, respectively. Re-injuries (N=34/207) constituted 16% of injuries. All re-injuries occurred to the biceps femoris.

Conclusion

MRI can be helpful in verifying the diagnosis of a hamstring injury and to prognosticate lay-off time. Radiological grading is associated with lay-off times after injury. Seventy per cent of hamstring injuries seen in professional football are of radiological grade 0 or 1, meaning no signs of fibre disruption on MRI, but still cause the majority of absence days.
Planning and implementing a nationwide football-based health-education programme
Authors: Dvorak Jiri , Fuller Colin W , Junge Astrid
Published: December 2011

Communicable and non-communicable diseases place enormous social and economic burdens on developed and developing countries. Health education leading to changes in people's attitudes and behaviours remains the best approach for reducing the problem of communicable diseases while there is evidence that programmes providing regular physical exercise and advocating a controlled diet can reduce the prevalence of many non-communicable diseases. Hence, the delivery of health education and physical activity within a single coherent programme offers great potential for simultaneously addressing both health issues. Since 2006, FIFA has developed and tested a novel football-based health-education programme for children entitled ‘11 for Health’, which is aimed at increasing children's levels of physical activity while also delivering 11 simple health messages. When new interventions of this type are published in the scientific literature, it is often not possible to describe important background information about the project that could assist other researchers in developing and implementing similar programmes. This paper attempts to bridge this gap by describing the aims and objectives, organisation, planning, implementation and monitoring requirements needed to deliver FIFA's ‘11 for Health’ programme, first as a pilot project and subsequently as a nationwide project, through a tripartite arrangement between FIFA, the national Football Association and the Government Ministries in Mauritius.
ON MAXIMAL IDEMPOTENT-CLOSED SUBRINGS OF Mn(𝔽)
Authors: CVETKO-VAH KARIN , LEECH JONATHAN
Published: December 2011

Rings of matrices whose idempotents are closed under multiplication are studied and those rings that are maximal subject to certain constraints are characterized.
FINITE IDEMPOTENT INVERSE MONOID PRESENTATIONS
Authors: SILVA PEDRO V.
Published: December 2011

Several decidability problems for finite idempotent presentations of inverse monoids are solved, giving also insight into their structure. Besides providing a new elementary solution for the problem, solutions are obtained for the following problems: computing the maximal subgroups, being combinatorial, being semisimple, being fundamental, having infinite [Formula: see text]-classes. The word problem for the least fundamental quotient is also solved, with an unexpected consequence.
A ŠVARC–MILNOR LEMMA FOR MONOIDS ACTING BY ISOMETRIC EMBEDDINGS
Authors: GRAY ROBERT , KAMBITES MARK
Published: December 2011

We continue our program of extending key techniques from geometric group theory to semigroup theory, by studying monoids acting by isometric embeddings on spaces equipped with asymmetric, partially defined distance functions. The canonical example of such an action is a cancellative monoid acting by translation on its Cayley graph. Our main result is an extension of the Švarc–Milnor lemma to this setting.
SUBHIERARCHIES OF THE SECOND LEVEL IN THE STRAUBING–THÉRIEN HIERARCHY
Authors: KLÍMA ONDŘEJ , POLÁK LIBOR
Published: December 2011

In a recent paper we assigned to each positive variety [Formula: see text] and each nonnegative integer k the class of all finite unions of finite intersections or Boolean combinations of the languages of the form L0a1L1a2…aℓLℓ, where ℓ ≤ k, a1,…,aℓ are letters and L0,…,Lℓ are in the variety [Formula: see text]. For these polynomial operators on a wide class of varieties we gave a certain algebraic counterpart in terms of identities satisfied by syntactic (ordered) monoids of languages considered. Here we apply our constructions to particular examples of varieties of languages obtaining four hierarchies of (positive) varieties. Two of them have the 3/2 level of the Straubing–Thérien hierarchy as their limits, and two others tend to the level two of this hierarchy. We concentrate here on the existence of finite bases of identities for corresponding pseudovarieties of (ordered) monoids and we are looking for inclusions among those varieties.
TIME VARIABLE COSMOLOGICAL CONSTANT OF HOLOGRAPHIC ORIGIN WITH INTERACTION IN BRANS–DICKE THEORY
Authors: LU JIANBO , MA LINA , LIU MOLIN , WU YABO
Published: December 2011

Time variable cosmological constant (TVCC) of holographic origin with interaction in Brans–Dicke theory is discussed in this paper. We investigate some characters for this model, and show the evolutions of deceleration parameter and equation of state (EOS) for dark energy. It is shown that in this scenario an accelerating universe can be obtained and the evolution of EOS for dark energy can cross over the boundary of phantom divide. In addition, a geometrical diagnostic method, jerk parameter, is applied to this model to distinguish it with cosmological constant.
3D JOINT MOMENTS IN TRANSFEMORAL AND TRANSTIBIAL AMPUTEES: WHEN IS THE "GROUND REACTION VECTOR TECHNIQUE" AN ALTERNATIVE TO INVERSE DYNAMICS?
Authors: FANTOZZI SILVIA , GAROFALO PIETRO , CUTTI ANDREA GIOVANNI , STAGNI RITA
Published: December 2011

The aim of the present study was to identify the phases of gait and the joints where the "ground reaction vector technique" (GRVT) can represent an acceptable alternative to the use of inverse dynamics (ID), when considering subjects with a lower-limb amputation. First, an analytical investigation of the ID of the three joints of the lower limb is given, distinguishing the gravitational, the inertial and the ground reaction contributions. The first two contributions require inertial parameters estimation; for this purpose, literature anthropometric data are typically used, both for the unimpaired and prosthetic limb, as accurate specific inertial parameters for the prosthetic limb are difficult to obtain from companies or require time consuming estimation. This assumption potentially leads to errors in the three-dimensional (3D) joint moment estimation. Second, the results of two case studies, a trans-femoral amputee with two different prostheses and a trans-tibial amputee, showed that the GRVT can explain the most part of the net joint moment for the ankle and the knee in the whole stance phase, and for the hip in the first part of the stance, leading to a similar clinical evaluation without any assumptions on inertial parameters.
FINITE ELEMENT ANALYSIS ON FLUID FILTRATION IN SYSTEM OF PERMEABLE CURVED CAPILLARY AND TISSUE
Authors: HE YING , HIMENO RYUTARO
Published: December 2011

Fluid filtration across a capillary wall, which is associated with many diseases, is noteworthy for its significant role in cancer treatment. In this study, the coupled fluid dynamic phenomenon within a capillary and its surrounding tissues has been numerically analyzed in order to investigate the effect of capillary geometry, filtration coefficient, and tissue pressure on capillary filtration. The computational domain is composed of a fluid capillary subdomain coupled with a porous tissue subdomain. The flows in the sub-domains are described by the Stokes and Darcy equations, respectively, which are solved in a coupled manner by applying a nodal replacement scheme at the capillary wall. Distributions of pressure and flow velocity are presented, which show that the interfacial pressure drop is strongly influenced by permeability, tissue boundary pressure, and capillary radii. These results provide useful information on the relationship between the interstitial flow pattern and oxygen transport.
Excessive thickening of the cortical layer in graptolites
Authors: Bates Denis , Kozłowska Anna , Chmielarz Dagmara , Lenz Alfred
Published: December 2011

A number of graptolites with thickened periderm, both dendroids and graptoloids, have been examined with the SEM. The thickening is by the deposition of layers of ectocortical tissue, clearly as bandages in the graptoloids. In
Colonograptus colonus
and some ‘diplograptids’, the thickening is most pronounced in the proximal regions of the rhabdosome, and can lead to the partial or complete occlusion of the aperture of the sicula and proximal thecae, as well as thickening the virgella. This thickening is interpreted as an adaptation connected with an extra gerontic production of cortex, which might have served as a reinforcement of the rhabdosome, or as an adaptation to modify or retain, the centre of gravity in the water column, or both. In
Amphigraptus
sp. the thickening appears to be common, and is concentrated on the dorsal side of the stipes. In
Dendrograptus
sp. thickening is also common: the main branches become excessively thickened, uniformly around the stipes, the side branches less thickened. In
Cyrtograptus
, thickening is rare, and appears to be gerontic, with the exception of a new form tentatively identified as
Cyrtograptus
in which thickening is uniform throughout the rhabdosome, and may have been formed initially. In
Colonograptus
and several ‘diplograptids’, the thickened proximal part shows it is much heavier than the distal part, suggesting a downwards vertical direction of the proximal end. In
Amphigraptus
the asymmetrical thickening suggests an orientation with the ventral side uppermost.
Biogeography and Mass Extinction: Extirpation and re-invasion of
Normalograptus
species (Graptolithina) in the Late Ordovician Palaeotropics
Authors: Goldman Daniel , Mitchell Charles E. , Melchin Michael J. , Fan Junxuan , Wu Shuang-Ye , Sheets H. David
Published: December 2011

Normalograptids constitute a distinctive but not easily identified group of derived axonophorans. A new study of
Normalograptus
morphology indicates that many Late Ordovician taxa previously identified as
Normalograptus
are actually referable to
Styracograptus
and related climacograptoids. These re-identifications have led to the recognition of a complex biogeographic history among normalograptids and their descendants, including an interesting pattern that had previously been overlooked – a late Katian disappearance of
Normalograptus
from the palaeotropics. Normalograptid palaeogeographic distribution in the Ordovician appears to comprise 5 main phases: (1) evolutionary origin probably in relatively high palaeolatitudes in the early to mid Darriwilian; (2) spread to global distribution in later Darriwilian time; (3) retreat from most low palaeolatitude regions during the early Katian, with perhaps a slightly delayed retreat from Laurentia; (4) a complete extirpation from the low palaeolatitudes by the mid Katian (Ea4); (5) reinvasion of the low palaeolatitudes that accompanies the remarkable ecological and evolutionary replacement of the Diplograptina by species of
Normalograptus
and their descendants during the latest Katian–early Hirnantian. We propose two sets of hypotheses to explain Late Ordovician
Normalograptus
distribution. First, given the low species diversity of
Normalograptus
, we suggest as a null hypothesis that the disappearance of normalograptids from low palaeolatitudes during the late Sandbian and early Katian as simply a stochastic outcome – a small clade simply went extinct by chance alone. The alternative is that the loss of
Normalograptus
species reflects some form of extinction for cause, either: (1) competitive exclusion; or (2) an inability to adapt to changing environmental conditions. In the case of the competitive exclusion hypothesis, the most likely competitors are species of the Diplograptina.
Phylogeny and Adaptive Radiation of the Neograptina (Graptoloida) During the Hirnantian Mass Extinction and Silurian Recovery
Authors: Melchin M. J. , Mitchell C. E. , Naczk-Cameron A. , Fan J. X. , Loxton J.
Published: December 2011

Cladistic analysis of some Hirnantian (latest Ordovician) and Rhuddanian–Aeronian (early Silurian) biserial graptolites and basal monograptids has been undertaken in order to test hypotheses of the relationships among the Neograptina (‘normalograptids’ and their descendents) and to provide a phylogenetic framework for understanding the early Silurian adaptive radiation of graptoloids. It is clear that Silurian graptolite faunas are dominated by two major clades, here named the superfamilies Retiolitoidea and Monograptoidea. Several other lineages whose basal relationships are unresolved, including
Normalograptus
and
Metaclimacograptus
, persisted through much of the Llandovery. The Retiolitoidea includes some taxa previously assigned to the Normalograptidae, as well as petalolithids and retiolitids. The Monograptoidea includes akidograptids, dimorphograptids, the uniserial monograptids, as well as stem taxa previously regarded as normalograptids. Both of these major clades had their origins in Late Ordovician time and began their diversification within the Hirnantian–early Rhuddanian, in step with the two main phases of the Hirnantian Mass Extinction. The Neograptina also exhibit an additional interval of accelerated turnover in the Rhuddanian during which the characteristic Silurian fauna largely replaced the Hirnantian Neograptina. One new family, Neodiplograptidae, and four new genera are described:
Avitograptus
,
Rickardsograptus
,
Korenograptus
and
Paramplexograptus
.
The systematic relationship of the monograptid species
acinaces
Törnquist, 1899 and
rheidolensis
Jones, 1909
Authors: Zalasiewicz Jan , Russell Catherine , Snelling Andrea , Williams Mark
Published: December 2011

The relationship between the early Silurian (Rhuddanian) monograptid species
rheidolensis
Jones, 1909 and
acinaces
Törnquist, 1899 has been contentious, with debate as regards both their possible synonymy and their generic assignation. We have re-examined the type and associated material of
rheidolensis
, and conclude that this taxon is almost certainly a junior synonym of
acinaces
. Lacking ventral apertural processes,
acinaces
does not belong within
Lagarograptus
, as previously thought, but may be placed within
Huttagraptus
, as proposed by Koren' & Bjerreskov (1997). The confusion between these two taxa arose because the material that Jones assigned to
rheidolensis
includes two taxa, one representing non-topotype (and probably mis-localized) specimens of an undoubted
Neolagarograptu
s. This is morphologically very similar to, and probably referable to, the late Aeronian species
Neolagarograptus tenuis
, the type material of which we show here to be tectonically distorted.
Computing the volume of a union of balls
Authors: Cazals Frederic , Kanhere Harshad , Loriot Sébastien
Published: December 2011

Balls and spheres are amongst the simplest 3
D
modeling primitives, and computing the volume of a union of balls is an elementary problem. Although a number of strategies addressing this problem have been investigated in several communities, we are not aware of any robust algorithm, and present the first such algorithm.

Our calculation relies on the decomposition of the volume of the union into convex regions, namely the restrictions of the balls to their regions in the power diagram. Theoretically, we establish a formula for the volume of a restriction, based on Gauss' divergence theorem. The proof being constructive, we develop the associated algorithm. On the implementation side, we carefully analyse the predicates and constructions involved in the volume calculation, and present a certified implementation relying on interval arithmetic. The result is certified in the sense that the exact volume belongs to the interval computed.

Experimental results are presented on hand-crafted models illustrating various difficulties, as well as on the 58,898 models found in the tenth of July 2009 release of the Protein Data Bank.
Book Review: 'Michael Allen's e-Learning Annual 2012'
Authors: Bean Cammy
Published: December 2011

eLearn magazine contributor, Cammy Bean reviews Dr. Michael Allen's e-Learning Annual for 2012, which includes a wide range of topics and authors with opposing viewpoints from a veritable who's who of names in the learning industry.
WiSec 2011 demo
Authors: Ortmann Steffen , Langendörfer Peter , Kornemann Stephan
Published: December 2011

This paper shortly introduces our real-time jamming detection approach which can be executed on standard wireless sensor nodes. The benefits are that no thresholds need to be defined since it detects jamming based on deviations of the Received Signal Strength Indication (RSSI) and the fact that for doing so it needs only 422 Bytes of memory including execution code and stored RSSI values. Our mock-up demonstrator visualises how various attacks of permanent, periodic and random jamming effect RSSI values and how the sensor nodes independently of the location of the jammer reliably indicate ongoing jamming.
WiSec 2011 poster
Authors: Schmidt Thomas C. , Wählisch Matthias , Jochheim Benjamin , Gröning Michael
Published: December 2011

New approaches for detecting attack traces in network traffic are needed for handheld devices that commonly own limited resources, but multiple, heterogeneous network interfaces. In this paper, we report on early results for statistical traffic analysis based on the Shannon Entropy. Unlike previous work, our time-frequency analysis extracts the non-stationary properties of entropy signals. From this context-adaptive technique, we obtain a clear signature of binary instructions and can also detect embedded shellcode.
SHERIFF
Authors: Liu Tongping , Berger Emery D.
Published: December 2011

False sharing is an insidious problem for multithreaded programs running on multicore processors, where it can silently degrade performance and scalability. Previous tools for detecting false sharing are severely limited: they cannot distinguish false sharing from true sharing, have high false positive rates, and provide limited assistance to help programmers locate and resolve false sharing.

This paper presents two tools that attack the problem of false sharing: Sheriff-Detect and Sheriff-Protect. Both tools leverage a framework we introduce here called Sheriff. Sheriff breaks out threads into separate processes, and exposes an API that allows programs to perform per-thread memory isolation and tracking on a per-page basis. We believe Sheriff is of independent interest.

Sheriff-Detect finds instances of false sharing by comparing updates within the same cache lines by different threads, and uses sampling to rank them by performance impact. Sheriff-Detect is precise (no false positives), runs with low overhead (on average, 20%), and is accurate, pinpointing the exact objects involved in false sharing. We present a case study demonstrating Sheriff-Detect's effectiveness at locating false sharing in a variety of benchmarks.

Rewriting a program to fix false sharing can be infeasible when source is unavailable, or undesirable when padding objects would unacceptably increase memory consumption or further worsen runtime performance. Sheriff-Protect mitigates false sharing by adaptively isolating shared updates from different threads into separate physical addresses, effectively eliminating most of the performance impact of false sharing. We show that Sheriff-Protect can improve performance for programs with catastrophic false sharing by up to 9×, without programmer intervention.
Accentuating the positive
Authors: Weeratunge Dasarath , Zhang Xiangyu , Jaganathan Suresh
Published: December 2011

Concurrency bugs are often due to inadequate synchronization that fail to prevent specific (undesirable) thread interleavings. Such errors, often referred to as Heisenbugs, are difficult to detect, prevent, and repair. In this paper, we present a new technique to increase program robustness against Heisenbugs. We profile correct executions from provided test suites to infer fine-grained atomicity properties. Additional deadlock-free locking is injected into the program to guarantee these properties hold on production runs. Notably, our technique does not rely on witnessing or analyzing erroneous executions. The end result is a scheme that only permits executions which are guaranteed to preserve the atomicity properties derived from the profile. Evaluation results on large, real-world, open-source programs show that our technique can effectively suppress subtle concurrency bugs, with small runtime overheads (typically less than 15%).
Kind analysis for MATLAB
Authors: Doherty Jesse , Hendren Laurie , Radpour Soroush
Published: December 2011

MATLAB is a popular dynamic programming language used for scientific and numerical programming. As a language, it has evolved from a small scripting language intended as an interactive interface to numerical libraries, to a very popular language supporting many language features and libraries. The overloaded syntax and dynamic nature of the language, plus the somewhat organic addition of language features over the years, makes static analysis of modern MATLAB quite challenging. A fundamental problem in MATLAB is determining the kind of an identifier. Does an identifier refer to a variable, a named function or a prefix? Although this is a trivial problem for most programming languages, it was not clear how to do this properly in MATLAB. Furthermore, there was no simple explanation of kind analysis suitable for MATLAB programmers, nor a publicly-available implementation suitable for compiler researchers.

This paper explains the required background of MATLAB, clarifies the kind assignment program, and proposes some general guidelines for developing good kind analyses. Based on these foundations we present our design and implementation of a variety of kind analyses, including an approach that matches the intended behaviour of modern MATLAB 7 and two potentially better alternatives.

We have implemented all the variations of the kind analysis in McLab, our extensible compiler framework, and we present an empirical evaluation of the various analyses on a large set of benchmark programs.
Integrated language definition testing
Authors: Kats Lennart C.L. , Vermaas Rob , Visser Eelco
Published: December 2011

The reliability of compilers, interpreters, and development environments for programming languages is essential for effective software development and maintenance. They are often tested only as an afterthought. Languages with a smaller scope, such as domain-specific languages, often remain untested. General-purpose testing techniques and test case generation methods fall short in providing a low-threshold solution for test-driven language development. In this paper we introduce the notion of a language-parametric testing language (LPTL) that provides a reusable, generic basis for declaratively specifying language definition tests. We integrate the syntax, semantics, and editor services of a language under test into the LPTL for writing test inputs. This paper describes the design of an LPTL and the tool support provided for it, shows use cases using examples, and describes our implementation in the form of the Spoofax testing language.
PREFAIL
Authors: Joshi Pallavi , Gunawi Haryadi S. , Sen Koushik
Published: December 2011

As hardware failures are no longer rare in the era of cloud computing, cloud software systems must "prevail" against multiple, diverse failures that are likely to occur. Testing software against multiple failures poses the problem of combinatorial explosion of multiple failures. To address this problem, we present PreFail, a programmable failure-injection tool that enables testers to write a wide range of policies to prune down the large space of multiple failures. We integrate PreFail to three cloud software systems (HDFS, Cassandra, and ZooKeeper), show a wide variety of useful pruning policies that we can write for them, and evaluate the speed-ups in testing time that we obtain by using the policies. In our experiments, our testing approach with appropriate policies found all the bugs that one can find using exhaustive testing while spending 10X--200X less time than exhaustive testing.
Automatic fine-grain locking using shape properties
Authors: Golan-Gueta Guy , Bronson Nathan , Aiken Alex , Ramalingam G. , Sagiv Mooly , Yahav Eran
Published: December 2011

We present a technique for automatically adding fine-grain locking to an abstract data type that is implemented using a dynamic forest -i.e., the data structures may be mutated, even to the point of violating forestness temporarily during the execution of a method of the ADT. Our automatic technique is based on Domination Locking, a novel locking protocol. Domination locking is designed specifically for software concurrency control, and in particular is designed for object-oriented software with destructive pointer updates. Domination locking is a strict generalization of existing locking protocols for dynamically changing graphs. We show our technique can successfully add fine-grain locking to libraries where manually performing locking is extremely challenging. We show that automatic fine-grain locking is more efficient than coarse-grain locking, and obtains similar performance to hand-crafted fine-grain locking.
Trustworthy numerical computation in Scala
Authors: Darulova Eva , Kuncak Viktor
Published: December 2011

Modern computing has adopted the floating point type as a default way to describe computations with real numbers. Thanks to dedicated hardware support, such computations are efficient on modern architectures, even in double precision. However, rigorous reasoning about the resulting programs remains difficult. This is in part due to a large gap between the finite floating point representation and the infinite-precision real-number semantics that serves as the developers' mental model. Because programming languages do not provide support for estimating errors, some computations in practice are performed more and some less precisely than needed.

We present a library solution for rigorous arithmetic computation. Our numerical data type library tracks a (double) floating point value, but also a guaranteed upper bound on the error between this value and the ideal value that would be computed in the real-value semantics. Our implementation involves a set of linear approximations based on an extension of affine arithmetic. The derived approximations cover most of the standard mathematical operations, including trigonometric functions, and are more comprehensive than any publicly available ones. Moreover, while interval arithmetic rapidly yields overly pessimistic estimates, our approach remains precise for several computational tasks of interest. We evaluate the library on a number of examples from numerical analysis and physical simulations. We found it to be a useful tool for gaining confidence in the correctness of the computation.
Hybrid partial evaluation
Authors: Shali Amin , Cook William R.
Published: December 2011

Hybrid partial evaluation (HPE) is a pragmatic approach to partial evaluation that borrows ideas from both online and offline partial evaluation. HPE performs offline-style specialization using an online approach without static binding time analysis. The goal of HPE is to provide a practical and predictable level of optimization for programmers, with an implementation strategy that fits well within existing compilers or interpreters. HPE requires the programmer to specify where partial evaluation should be applied. It provides no termination guarantee and reports errors in situations that violate simple binding time rules, or have incorrect use of side effects in compile-time code. We formalize HPE for a small imperative object-oriented language and describe Civet, a straightforward implementation of HPE as a relatively simple extension of a Java compiler. Code optimized by Civet performs as well as the output of a state-of-the-art offline partial evaluator.
A step towards transparent integration of input-consciousness into dynamic program optimizations
Authors: Tian Kai , Zhang Eddy , Shen Xipeng
Published: December 2011

Dynamic program optimizations are critical for the efficiency of applications in managed programming languages and scripting languages. Recent studies have shown that exploitation of program inputs may enhance the effectiveness of dynamic optimizations significantly. However, current solutions for enabling the exploitation require either programmers' annotations or intensive offline profiling, impairing the practical adoption of the techniques.

This current work examines the basic feasibility of transparent integration of input-consciousness into dynamic program optimizations, particularly in managed execution environments. It uses transparent learning across production runs as the basic vehicle, and investigates the implications of cross-run learning on each main component of input-conscious dynamic optimizations. It proposes several techniques to address some key challenges for the transparent integration, including randomized inspection-instrumentation for cross-user data collection, a sparsity-tolerant algorithm for input characterization, and selective prediction for efficiency protection. These techniques make it possible to automatically recognize the relations between the inputs to a program and the appropriate ways to optimize it. The whole process happens transparently across production runs; no need for offline profiling or programmer intervention. Experiments on a number of Java programs demonstrate the effectiveness of the techniques in enabling input-consciousness for dynamic optimizations, revealing the feasibility and potential benefits of the new optimization paradigm in some basic settings.
Kismet
Authors: Jeon Donghwan , Garcia Saturnino , Louie Chris , Taylor Michael Bedford
Published: December 2011

Software engineers now face the difficult task of refactoring serial programs for parallel execution on multicore processors. Currently, they are offered little guidance as to how much benefit may come from this task, or how close they are to the best possible parallelization. This paper presents Kismet, a tool that creates parallel speedup estimates for unparallelized serial programs. Kismet differs from previous approaches in that it does not require any manual analysis or modification of the program. This difference allows quick analysis of many programs, avoiding wasted engineering effort on those that are fundamentally limited. To accomplish this task, Kismet builds upon the hierarchical critical path analysis (HCPA) technique, a recently developed dynamic analysis that localizes parallelism to each of the potentially nested regions in the target program. It then uses a parallel execution time model to compute an approximate upper bound for performance, modeling constraints that stem from both hardware parameters and internal program structure.

Our evaluation applies Kismet to eight high-parallelism NAS Parallel Benchmarks running on a 32-core AMD multicore system, five low-parallelism SpecInt benchmarks, and six medium-parallelism benchmarks running on the finegrained MIT Raw processor. The results are compelling. Kismet is able to significantly improve the accuracy of parallel speedup estimates relative to prior work based on critical path analysis.
A theory of substructural types and control
Authors: Tov Jesse A. , Pucella Riccardo
Published: December 2011

Exceptions are invaluable for structured error handling in high-level languages, but they are at odds with linear types. More generally, control effects may delete or duplicate portions of the stack, which, if we are not careful, can invalidate all substructural usage guarantees for values on the stack. We have developed a type-and-effect system that tracks control effects and ensures that values on the stack are never wrongly duplicated or dropped. We present the system first with abstract control effects and prove its soundness. We then give examples of three instantiations with particular control effects, including exceptions and delimited continuations, and show that they meet the soundness criteria for specific control effects.
Automated construction of JavaScript benchmarks
Authors: Richards Gregor , Gal Andreas , Eich Brendan , Vitek Jan
Published: December 2011

JavaScript is a highly dynamic language for web-based applications. Innovative implementation techniques for improving its speed and responsiveness have been developed in recent years. Industry benchmarks such as WebKit SunSpider are often cited as a measure of the efficacy of these techniques. However, recent studies have shown that these benchmarks fail to accurately represent the dynamic nature of modern JavaScript applications, and so may be poor predictors of real-world performance. Worse, they may guide the development of optimizations which are unhelpful for real applications. Our goal is to develop a tool and techniques to automate the creation of realistic and representative benchmarks from existing web applications. We propose a record-and-replay approach to capture JavaScript sessions which has sufficient fidelity to accurately recreate key characteristics of the original application, and at the same time is sufficiently flexible that a recording produced on one platform can be replayed on a different one. We describe JSBench, a flexible tool for workload capture and benchmark generation, and demonstrate its use in creating eight benchmarks based on popular sites. Using a variety of runtime metrics collected with instrumented versions of Firefox, Internet Explorer, and Safari, we show that workloads created by JSBench match the behavior of the original web applications.
Declaratively programming the mobile web with Mobl
Authors: Hemel Zef , Visser Eelco
Published: December 2011

A new generation of mobile touch devices, such as the iPhone, iPad and Android devices, are equipped with powerful, modern browsers. However, regular websites are not optimized for the specific features and constraints of these devices, such as limited screen estate, unreliable Internet access, touch-based interaction patterns, and features such as GPS. While recent advances in web technology enable web developers to build web applications that take advantage of the unique properties of mobile devices, developing such applications exposes a number of problems, specifically: developers are required to use many loosely coupled languages with limited tool support and application code is often verbose and imperative. We introduce mobl, a new language designed to declaratively construct mobile web applications. Mobl integrates languages for user interface design, styling, data modeling, querying and application logic into a single, unified language that is flexible, expressive, enables early detection of errors, and has good IDE support.