On the Impact of Low-Rate Attacks

Recent research have exposed new breeds of attacks that are capable of denying service or inflicting significant damage to TCP flows, without sustaining the attack traffic. Such attacks are often referred to as "low-rate" attacks and they stand in sharp contrast against traditional Denial of Service (DoS) attacks that can completely shut off TCP flows by flooding an Internet link. In this paper, we study the impact of these new breeds of attacks and the extent to which defense mechanisms are capable of mitigating the attack's impact. Through adopting a simple discrete-time model with a single TCP flow and a nonoblivious adversary, we were able to expose new variants of these low-rate attacks that could potentially have high attack potency per attack burst. Our analysis is focused towards worst-case scenarios, thus our results should be regarded as upper bounds on the impact of low-rate attacks rather than a real assessment under a specific attack scenario.

Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer: a European Organization for Research and Treatment of Cancer Randomized Study with cross-over.

PURPOSE: To compare the efficacy of paclitaxel versus doxorubicin given as single agents in first-line therapy of advanced breast cancer (primary end point, progression-free survival ¿PFS) and to explore the degree of cross-resistance between the two agents. PATIENTS AND METHODS: Three hundred thirty-one patients were randomized to receive either paclitaxel 200 mg/m(2), 3-hour infusion every 3 weeks, or doxorubicin 75 mg/m(2), intravenous bolus every 3 weeks. Seven courses were planned unless progression or unacceptable toxicity occurred before the seven courses were finished. Patients who progressed within the seven courses underwent early cross-over to the alternative drug, while a delayed cross-over was optional for the remainder of patients at the time of disease progression. RESULTS: Objective response in first-line therapy was significantly better (P =.003) for doxorubicin (response rate ¿RR, 41%) than for paclitaxel (RR, 25%), with doxorubicin achieving a longer median PFS (7.5 months for doxorubicin v 3.9 months for paclitaxel, P <.001). In second-line therapy, cross-over to doxorubicin (91 patients) and to paclitaxel (77 patients) gave response rates of 30% and 16%, respectively. The median survival durations of 18.3 months for doxorubicin and 15.6 months for paclitaxel were not significantly different (P =.38). The doxorubicin arm had greater toxicity, but this was counterbalanced by better symptom control. CONCLUSION: At the dosages and schedules used in the present study, doxorubicin achieves better disease and symptom control than paclitaxel in first-line treatment. Doxorubicin and paclitaxel are not totally cross-resistant, which supports further investigation of these drugs in combination or in sequence, both in advanced disease and in the adjuvant setting.

Transmission of single HIV-1 genomes and dynamics of early immune escape revealed by ultra-deep sequencing.

We used ultra-deep sequencing to obtain tens of thousands of HIV-1 sequences from regions targeted by CD8+ T lymphocytes from longitudinal samples from three acutely infected subjects, and modeled viral evolution during the critical first weeks of infection. Previous studies suggested that a single virus established productive infection, but these conclusions were tempered because of limited sampling; now, we have greatly increased our confidence in this observation through modeling the observed earliest sample diversity based on vastly more extensive sampling. Conventional sequencing of HIV-1 from acute/early infection has shown different patterns of escape at different epitopes; we investigated the earliest escapes in exquisite detail. Over 3-6 weeks, ultradeep sequencing revealed that the virus explored an extraordinary array of potential escape routes in the process of evading the earliest CD8 T-lymphocyte responses--using 454 sequencing, we identified over 50 variant forms of each targeted epitope during early immune escape, while only 2-7 variants were detected in the same samples via conventional sequencing. In contrast to the diversity seen within epitopes, non-epitope regions, including the Envelope V3 region, which was sequenced as a control in each subject, displayed very low levels of variation. In early infection, in the regions sequenced, the consensus forms did not have a fitness advantage large enough to trigger reversion to consensus amino acids in the absence of immune pressure. In one subject, a genetic bottleneck was observed, with extensive diversity at the second time point narrowing to two dominant escape forms by the third time point, all within two months of infection. Traces of immune escape were observed in the earliest samples, suggesting that immune pressure is present and effective earlier than previously reported; quantifying the loss rate of the founder virus suggests a direct role for CD8 T-lymphocyte responses in viral containment after peak viremia. Dramatic shifts in the frequencies of epitope variants during the first weeks of infection revealed a complex interplay between viral fitness and immune escape.

Measuring fast gene dynamics in single cells with time-lapse luminescence microscopy.

Time-lapse fluorescence microscopy is an important tool for measuring in vivo gene dynamics in single cells. However, fluorescent proteins are limited by slow chromophore maturation times and the cellular autofluorescence or phototoxicity that arises from light excitation. An alternative is luciferase, an enzyme that emits photons and is active upon folding. The photon flux per luciferase is significantly lower than that for fluorescent proteins. Thus time-lapse luminescence microscopy has been successfully used to track gene dynamics only in larger organisms and for slower processes, for which more total photons can be collected in one exposure. Here we tested green, yellow, and red beetle luciferases and optimized substrate conditions for in vivo luminescence. By combining time-lapse luminescence microscopy with a microfluidic device, we tracked the dynamics of cell cycle genes in single yeast with subminute exposure times over many generations. Our method was faster and in cells with much smaller volumes than previous work. Fluorescence of an optimized reporter (Venus) lagged luminescence by 15-20 min, which is consistent with its known rate of chromophore maturation in yeast. Our work demonstrates that luciferases are better than fluorescent proteins at faithfully tracking the underlying gene expression.

A two-dimensional numerical investigation of the oscillatory flow behaviour in rectangular fire compartments with a single horizontal ceiling vent

This paper presents a comparison of fire field model predictions with experiment for the case of a fire within a compartment which is vented (buoyancydriven) to the outside by a single horizontal ceiling vent. Unlike previous work, the mathematical model does not employ a mixing ratio to represent vent temperatures but allows the model to predict vent temperatures a priori. The experiment suggests that the flow through the vent produces oscillatory behaviour in vent temperatures with puffs of smoke emerging from the fire compartment. This type of flow is also predicted by the fire field model. While the numerical predictions are in good qualitative agreement with observations, they overpredict the amplitudes of the temperature oscillations within the vent and also the compartment temperatures. The discrepancies are thought to be due to three-dimensional effects not accounted for in this model as well as using standard ‘practices’ normally used by the community with regards to discretization and turbulence models. Furthermore, it is important to note that the use of the k–ε turbulence model in a transient mode, as is used here, may have a significant effect on the results. The numerical results also suggest that a linear relationship exists between the frequency of vent temperature oscillation (n) and the heat release rate (Q0) of the type n∝Q0.290, similar to that observed for compartments with two horizontal vents. This relationship is predicted to occur only for heat release rates below a critical value. Furthermore, the vent discharge coefficient is found to vary in an oscillatory fashion with a mean value of 0.58. Below the critical heat release rate the mean discharge coefficient is found to be insensitive to fire size.

Estimating the flow rate capacity of an overturned rail carriage end exit in the presence of smoke

While incidents requiring the rapid egress of passengers from trains are infrequent, perhaps the most challenging scenario for passengers involves the evacuation from an overturned carriage subjected to fire. In this paper we attempt to estimate the flow rate capacity of an overturned rail carriage end exit. This was achieved through two full-scale evacuation experiments, in one of which the participants were subjected to non-toxic smoke. The experiments were conducted as part of a pilot study into evacuation from rail carriages. In reviewing the experimental results, it should be noted that only a single run of each trial was undertaken with a limited — though varied — population. As a result it is not possible to test the statistical significance of the evacuation times quoted and so the results should be treated as indicative rather than definitive. The carriage used in the experiments was a standard class Mark IID which, while an old carriage design, shares many features with those carriages commonly found on the British rail network. In the evacuation involving smoke, the carriage end exit was found to achieve an average flow rate capacity of approximately 5.0 persons/min. The average flow rate capacity of the exit without smoke was found to be approximately 9.2 persons/min. It was noted that the presence of smoke tended to reduce significantly the exit flow rate. Due to the nature of the experimental conditions, these flow rates are considered optimistic. Finally, the authors make several recommendations for improving survivability in rail accidents. Copyright © 2000 John Wiley & Sons, Ltd.

Statistical Procedure For Estimating Grey Seal Pup Production From A Single Census

The variable start and duration of the Grey seal breeding season makes the estimation of total pup production from a single census very difficult. Classifying the count into morphological age classes enables the form and timing of the birth rate curve and estimates of pup mortality rates to be elucidated. A simulation technique is described which enables the duration of each morphological stage to be determined from a series of such classified counts taken over one season. A further statistical technique uses these estimates to calculate the mean timing and duration of the breeding season from a single classified count taken from similar populations in subsequent years. This information allows total pup production to be calculated for any appropriate breeding colony. Some guidance is given as to the optimal timing of that single census which would yield the best estimate of production, although the precise date is not critical to the success of the technique. Results from single census estimates obtained in this way are compared with known production data from more detailed surveys for a number of different colonies.

rbcL sequences indicate a single evolutionary origin of multinucleate cells in the red algal tribe Callithamnieae.

In the Ceramiaceae, one of the largest families of the red algae, there are from 1 to 4000 nuclei in each vegetative cell, but each tribe is homogeneous with respect to the uninucleate/multinucleate character state, except for the Callithamnieae. The goals of this study were to analyze rbcL gene sequences to clarify the evolution of taxa within the tribe Callithamnieae and to evaluate the potential evolutionary significance of the development of multinucleate cells in certain taxa. The genus Aglaothamnion, segregated from Callithamnion because it is uninucleate, was paraphyletic in all analyses. Callithamnion (including Aristothamnion) was monophyletic although not robustly so, apparently due to variations between taxa in rate of sequence evolution. Morphological synapomorphies were identified at different depths in the tree, supporting the molecular phylogenetic analysis. The uninucleate character state is ancestral in this tribe. The evolution of multinucleate cells has occurred once in the Callithamnieae. Multiple nuclei in each cell may combine the benefits of small C values (rapid cell cycle) with large cells (permitting morphological elaboration) while maintaining a constant ratio of nuclear volume: cytoplasmic volume.

Single-ionization of helium at Ti:sapphire wavelengths: rates and scaling laws

We present a numerical and theoretical study of intense-field single-electron ionization of helium at 390 nm and 780 nm. Accurate ionization rates (over an intensity range of (0.175-34) X10^14 W/ cm^2 at 390 nm, and (0.275 - 14.4) X 10^14 W /cm^2 at 780 nm) are obtained from full-dimensionality integrations of the time-dependent helium-laser Schroedinger equation. We show that the power law of lowest order perturbation theory, modified with a ponderomotive-shifted ionization potential, is capable of modelling the ionization rates over an intensity range that extends up to two orders of magnitude higher than that applicable to perturbation theory alone. Writing the modified perturbation theory in terms of scaled wavelength and intensity variables, we obtain to first approximation a single ionization law for both the 390 nm and 780 nm cases. To model the data in the high intensity limit as well as in the low, a new function is introduced for the rate. This function has, in part, a resemblance to that derived from tunnelling theory but, importantly, retains the correct frequency-dependence and scaling behaviour derived from the perturbative-like models at lower intensities. Comparison with the predictions of classical ADK tunnelling theory confirms that ADK performs poorly in the frequency and intensity domain treated here.

Analysis of multiple aspects of a repeated signal: power and rate of rapping during shell fights in hermit crabs

Repeated activities used by animals during contests are assumed to act as signals advertising the quality of the sender. However, their exact functions are not well understood and observations fit only a limited set of the predictions made by models of signaling systems. Experimental studies of contest behavior tend to focus on analysis of the rate of signaling, but individual performances may also vary in magnitude. Both of these features can vary between outcomes and within contests. We examined changes in the rate and power of shell rapping during shell fights in hermit crabs. We show that both rate and power decline during the course of the encounter and that the duration of pauses between bouts of shell rapping increases with an index of the total effort put into each bout. This supports the idea that the vigor of shell rapping is regulated by fatigue and could therefore act as a signal of stamina. By examining different interacting components of this complex activity, we gain greater insight into its function than would be achieved by investigating a single aspect in isolation.

Genetic association analyses of non-synonymous single nucleotide polymorphisms in diabetic nephropathy

Aims/hypothesis: Diabetic nephropathy, characterised by persistent proteinuria, hypertension and progressive kidney failure, affects a subset of susceptible individuals with diabetes. It is also a leading cause of end-stage renal disease (ESRD). Non-synonymous (ns) single nucleotide polymorphisms (SNPs) have been reported to contribute to genetic susceptibility in both monogenic disorders and common complex diseases. The objective of this study was to investigate whether nsSNPs are involved in susceptibility to diabetic nephropathy using a case-control design.

Methods: White type 1 diabetic patients with (cases) and without (controls) nephropathy from eight centres in the UK and Ireland were genotyped for a selected subset of nsSNPs using Illumina's GoldenGate BeadArray assay. A ? 2 test for trend, stratified by centre, was used to assess differences in genotype distribution between cases and controls. Genomic control was used to adjust for possible inflation of test statistics, and the False Discovery Rate method was used to account for multiple testing.

Results: We assessed 1,111 nsSNPs for association with diabetic nephropathy in 1,711 individuals with type 1 diabetes (894 cases, 817 controls). A number of SNPs demonstrated a significant difference in genotype distribution between groups before but not after correction for multiple testing. Furthermore, neither subgroup analysis (diabetic nephropathy with ESRD or diabetic nephropathy without ESRD) nor stratification by duration of diabetes revealed any significant differences between groups.

Conclusions/interpretation: The nsSNPs investigated in this study do not appear to contribute significantly to the development of diabetic nephropathy in patients with type 1 diabetes.

Unravelling the genetic basis of renal diseases; from single gene to multifactorial disorders

Chronic kidney disease is common with up to 5% of the adult population reported to have an estimated glomerular filtration rate of

Estimation of survival rate and extinction probability for stage-structured populations with overlapping life stages

The development of methods providing reliable estimates of demographic parameters (e. g., survival rates, fecundity) for wild populations is essential to better understand the ecology and conservation requirements of individual species. A number of methods exist for estimating the demographics of stage-structured populations, but inherent mathematical complexity often limits their uptake by conservation practitioners. Estimating survival rates for pond-breeding amphibians is further complicated by their complex migratory and reproductive behaviours, often resulting in nonobservable states and successive cohorts of eggs and tadpoles. Here we used comprehensive data on 11 distinct breeding toad populations (Bufo calamita) to clarify and assess the suitability of a relatively simple method [the Kiritani-Nakasuji-Manly (KNM) method] to estimate the survival rates of stage-structured populations with overlapping life stages. The study shows that the KNM method is robust and provides realistic estimates of amphibian egg and larval survival rates for species in which breeding can occur as a single pulse or over a period of several weeks. The study also provides estimates of fecundity for seven distinct toad populations and indicates that it is essential to use reliable estimates of fecundity to limit the risk of under- or overestimating the survival rates when using the KNM method. Survival and fecundity rates for B. calamita populations were then used to define population matrices and make a limited exploration of their growth and viability. The findings of the study recently led to the implementation of practical conservation measures at the sites where populations were most vulnerable to extinction. © 2010 The Society of Population Ecology and Springer.

Method for the in situ preparation of a single layer of zeolite Beta crystals on a molybdenum substrate for microreactor applications

A method for the hydrothermal synthesis of a single layer of zeolite Beta crystals on a molybdenum substrate for microreactor applications has been developed. Before the hydrothermal synthesis, the surface of the substrate was modified by an etching procedure that increases the roughness at the nanoscale level without completely eliminating the surface lay structure. Then, thin films of Al2O3 (170 nm) and TiO2 (50 nm) were successively deposited by atomic layer deposition (ALD) on the substrate. The internal Al2O3 film protects the Mo substrate from oxidation up to 550 degrees C in an oxidative environment. The high wettability of the external TiO2 film after UV irradiation increases zeolite nucleation on its surface. The role of the metal precursor (TiCl4 vs TiI4), deposition temperature (300 vs 500 degrees C), and film thickness (50 vs 100 nm) was investigated to obtain titania films with the slowest decay in the superhydrophilic behavior after UV irradiation. Zeolite Beta coatings with a Si/Al ratio of 23 were grown at 140 degrees C for 48 It. After ion exchange with a 10(-4) M cobalt acetate solution, the activity of the coatings was determined in the ammoxidation of ethylene to acetonitrile in a microstructured reactor. A maximum reaction rate of 220 mu mol C2H3N g(-1) s(-1) was obtained at 500 degrees C, with 42% carbon selectivity to acetonitrile. (C) 2007 Elsevier Inc. All rights reserved.

The preparation of highly ordered single layer ZSM-5 coating on prefabricated stainless steel microchannels

An elegant way to prepare catalytically active microreactors is by applying a coating of zeolite crystals onto a metal microchannel structure. In this study the hydrothermal formation of ZSM-5 zeolitic coatings on AISI 316 stainless steel plates with a microchannel structure has been investigated at different synthesis mixture compositions. The procedures of coating and thermal treatment have also been optimized. Obtaining a uniform thickness of the coating within 0.5 mm wide microchannels requires a careful control of various synthesis variables. The role of these factors and the problems in the synthesis of these zeolitic coatings are discussed. In general, the synthesis is most sensitive to the H2O/Si ratio as well as to the orientation of the plates with respect to the gravity vector. Ratios of H2O/Si=130 and Si/template=13 were found to be optimal for the formation of a zeolitic film with a thickness of one crystal at a temperature of 130 degreesC and a synthesis time of about 35 h. At such conditions, ZSM-5 crystals were formed with a typical size of 1.5 mu mx1.5 mu mx1.0 mum and a very narrow (within 0.2 mum) crystal size distribution. The prepared samples proved to be active in the selective catalytic reduction (SCR) of NO with ammonia. The activity tests have been carried out in a plate-type microreactor. The microreactor shows no mass transfer limitations and a larger SCR reaction rate is observed in comparison with pelletized Ce-ZSM-5 catalysts; (C) 2001 Elsevier Science B.V. All rights reserved.