The Intersection of Function-as-a-Service and Stream Computing

With recent advancements in the field of computing including the emergence of cloud computing, the consumption and accessibility of computational resources have increased drastically. Although there have been significant movements towards more sustainable computing, there are many more steps to be taken to decrease the amount of energy consumed and greenhouse gases released from the computing sector. Historically, the switch from on-premises computing to cloud computing has led to less energy consumption through the design of efficient data centers. By releasing direct control of the hardware that their software is run on, an organization can also increase efficiency and reduce costs. A new development in cloud computing has been serverless computing. Even though the term "serverless" is a misnomer because all applications are still executed on servers, serverless lets an organization resign another level of control, managing instances of virtual machines, to their cloud provider in order to reduce their cost. The cloud provider then provisions resources on-demand enabling less idle time. This reduction of idle time is a direct reduction of computing resources used, therefore resulting in a decrease in energy consumption. One form of serverless computing, Function-as-a-Service (FaaS), may have a promising future replacing some stream computing applications in order to increase efficiency and reduce waste. To explore these possibilities, the development of a stream processing application using traditional methods through Kafka Streams and FaaS through AWS Lambda was completed in order to demonstrate that FaaS can be used for stateless stream processing

Generation of Inhomogeneous Acoustic Waves Using an Array of Loudspeakers

In previous studies it has been shown that pressure fields created by inhomogeneous sound waves (waves which decay in a direction perpendicular to their propagation direction) are able to transmit energy into objects more effectively than ones created by conventional sound waves. This behavior may be useful in the detection of hidden explosive threats. To explore this, a device capable of constructing inhomogeneous waves is being developed. The proposed device is an acoustic array consisting of several high-frequency speakers. The speakers are independently driven to construct a desired inhomogeneous pressure field on a target surface. Inhomogeneous pressure fields were reconstructed across a span of decay parameters and standoff distances. Results show low root-mean-square errors at realistic levels of power consumption. These results imply that the device can recreate desired inhomogeneous pressure fields with high enough accuracy and low enough power consumption to test the energy transmission properties of inhomogeneous waves on mock explosives, which may be useful in applications related to improvised explosive device detection and defeat

Array-based Inhomogeneous Soundwave Generation to Enhance Sound Transmission into Solids

The acoustic excitation of energetic materials has been demonstrated to be useful in detection and defeat applications, but its efficacy is hindered by the inability to transmit a high percentage of incident acoustic energy across the air/energetic material interface. While large acoustical impedance differences usually prevent energy transmission from air into a solid, inhomogeneous incident waves have been found to transmit a significant percentage of their energy into the target material. Thus, inhomogeneous waves, whose amplitudes decay spatially in a direction different from the propagation direction, are an optimal choice for this application; however, it is difficult to create such a waveform by using a simple source. The objective of the present work is to demonstrate that by tuning the strengths and phases of sound sources in a linear array, an interference pattern can be generated such that an inhomogeneous wave forms on a surface of interest. Furthermore, it is demonstrated that by adjusting the level of inhomogeneity of the wave and its incidence angle, one can target the parameters associated with optimal sound transmission, and that these waves can be generated even in the presence of small errors in the powers and phases of the sources

Universal IMF vs dark halo response in early-type galaxies: breaking the degeneracy with the fundamental plane

We use the relations between aperture stellar velocity dispersion (\sigma_ap), stellar mass (M_sps), and galaxy size (R_e) for a sample of \sim 150,000 early-type galaxies from SDSS/DR7 to place constraints on the stellar initial mass function (IMF) and dark halo response to galaxy formation. We build LCDM based mass models that reproduce, by construction, the relations between galaxy size, light concentration and stellar mass, and use the spherical Jeans equations to predict \sigma_ap. Given our model assumptions (including those in the stellar population synthesis models), we find that reproducing the median \sigma_ap vs M_sps relation is not possible with {\it both} a universal IMF and a universal dark halo response. Significant departures from a universal IMF and/or dark halo response are required, but there is a degeneracy between these two solutions. We show that this degeneracy can be broken using the strength of the correlation between residuals of the velocity-mass (\Delta log \sigma_ap) and size-mass (\Delta log R_e) relations. The slope of this correlation, d_vr \equiv \Delta log \sigma_ap/\Delta log R_e, varies systematically with galaxy mass from d_vr \simeq -0.45 at M_sps \sim 10^{10}M_sun, to d_vr \simeq -0.15 at M_sps \sim 10^{11.6} M_sun. The virial fundamental plane (FP) has d_vr=-1/2, and thus we find the tilt of the observed FP is mass dependent. Reproducing this tilt requires {\it both} a non-universal IMF and a non-universal halo response. Our best model has mass-follows-light at low masses (Msps < 10^{11.2}M_sun) and unmodified NFW haloes at M_sps \sim 10^{11.5} M_sun. The stellar masses imply a mass dependent IMF which is "lighter" than Salpeter at low masses and "heavier" than Salpeter at high masses.Comment: 19 pages, 16 figures, accepted to MNRAS. More extensive discussion, 4 new figures, conclusions unchange

IGG3 Subclass Antibodies Recognize Antigenically Drifted Influenza Viruses and SARS-CoV-2 Variants Through Efficient Bivalent Binding

The constant domains of antibodies are important for effector functions, but less is known about how they can affect binding and neutralization of viruses. Here, we evaluated a panel of human influenza virus monoclonal antibodies (mAbs) expressed as IgG1, IgG2, or IgG3. We found that many influenza virus-specific mAbs have altered binding and neutralization capacity depending on the IgG subclass encoded and that these differences result from unique bivalency capacities of the subclasses. Importantly, subclass differences in antibody binding and neutralization were greatest when the affinity for the target antigen was reduced through antigenic mismatch. We found that antibodies expressed as IgG3 bound and neutralized antigenically drifted influenza viruses more effectively. We obtained similar results using a panel of SARS-CoV-2-specific mAbs and the antigenically advanced B.1.351 and BA.1 strains of SARS-CoV-2. We found that a licensed therapeutic mAb retained neutralization breadth against SARS-CoV-2 variants when expressed as IgG3, but not IgG1. These data highlight that IgG subclasses are not only important for fine-tuning effector functionality but also for binding and neutralization of antigenically drifted viruses

The association of depression and all-cause and cause-specific mortality: an umbrella review of systematic reviews and meta-analyses

Background: Depression is a prevalent and disabling mental disorder that frequently co-occurs with a wide range of chronic conditions. Evidence has suggested that depression could be associated with excess all-cause mortality across different settings and populations, although the causality of these associations remains unclear. Methods: We conducted an umbrella review of systematic reviews and meta-analyses of observational studies. PubMed, PsycINFO, and Embase electronic databases were searched through January 20, 2018. Systematic reviews and meta-analyses that investigated associations of depression and all-cause and cause-specific mortality were selected for the review. The evidence was graded as convincing, highly suggestive, suggestive, or weak based on quantitative criteria that included an assessment of heterogeneity, 95% prediction intervals, small-study effects, and excess significance bias. Results: A total of 26 references providing 2 systematic reviews and data for 17 meta-analytic estimates met inclusion criteria (19 of them on all-cause mortality); data from 246 unique studies (N = 3,825,380) were synthesized. All 17 associations had P < 0.05 per random effects summary effects, but none of them met criteria for convincing evidence. Associations of depression and all-cause mortality in patients after acute myocardial infarction, in individuals with heart failure, in cancer patients as well as in samples from mixed settings met criteria for highly suggestive evidence. However, none of the associations remained supported by highly suggestive evidence in sensitivity analyses that considered studies employing structured diagnostic interviews. In addition, associations of depression and all-cause mortality in cancer and post-acute myocardial infarction samples were supported only by suggestive evidence when studies that tried to adjust for potential confounders were considered. Conclusions: Even though associations between depression and mortality have nominally significant results in all assessed settings and populations, the evidence becomes weaker when focusing on studies that used structured interviews and those that tried to adjust for potential confounders. A causal effect of depression on all-cause and cause-specific mortality remains unproven, and thus interventions targeting depression are not expected to result in lower mortality rates at least based on current evidence from observational studies

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

Comprehensive Cancer-Predisposition Gene Testing in an Adult Multiple Primary Tumor Series Shows a Broad Range of Deleterious Variants and Atypical Tumor Phenotypes.

Multiple primary tumors (MPTs) affect a substantial proportion of cancer survivors and can result from various causes, including inherited predisposition. Currently, germline genetic testing of MPT-affected individuals for variants in cancer-predisposition genes (CPGs) is mostly targeted by tumor type. We ascertained pre-assessed MPT individuals (with at least two primary tumors by age 60 years or at least three by 70 years) from genetics centers and performed whole-genome sequencing (WGS) on 460 individuals from 440 families. Despite previous negative genetic assessment and molecular investigations, pathogenic variants in moderate- and high-risk CPGs were detected in 67/440 (15.2%) probands. WGS detected variants that would not be (or were not) detected by targeted resequencing strategies, including low-frequency structural variants (6/440 [1.4%] probands). In most individuals with a germline variant assessed as pathogenic or likely pathogenic (P/LP), at least one of their tumor types was characteristic of variants in the relevant CPG. However, in 29 probands (42.2% of those with a P/LP variant), the tumor phenotype appeared discordant. The frequency of individuals with truncating or splice-site CPG variants and at least one discordant tumor type was significantly higher than in a control population (χ2 = 43.642; p ≤ 0.0001). 2/67 (3%) probands with P/LP variants had evidence of multiple inherited neoplasia allele syndrome (MINAS) with deleterious variants in two CPGs. Together with variant detection rates from a previous series of similarly ascertained MPT-affected individuals, the present results suggest that first-line comprehensive CPG analysis in an MPT cohort referred to clinical genetics services would detect a deleterious variant in about a third of individuals.JW is supported by a Cancer Research UK Cambridge Cancer Centre Clinical Research Training Fellowship. Funding for the NIHR BioResource – Rare diseases project was provided by the National Institute for Health Research (NIHR, grant number RG65966). ERM acknowledges support from the European Research Council (Advanced Researcher Award), NIHR (Senior Investigator Award and Cambridge NIHR Biomedical Research Centre), Cancer Research UK Cambridge Cancer Centre and Medical Research Council Infrastructure Award. The University of Cambridge has received salary support in respect of EM from the NHS in the East of England through the Clinical Academic Reserve. The views expressed are those of the authors and not necessarily those of the NHS or Department of Health. DGE is an NIHR Senior Investigator and is supported by the all Manchester NIHR Biomedical Research Centre

Long-baseline neutrino oscillation physics potential of the DUNE experiment

The sensitivity of the Deep Underground Neutrino Experiment (DUNE) to neutrino oscillation is determined, based on a full simulation, reconstruction, and event selection of the far detector and a full simulation and parameterized analysis of the near detector. Detailed uncertainties due to the flux prediction, neutrino interaction model, and detector effects are included. DUNE will resolve the neutrino mass ordering to a precision of 5σ, for all ΑCP values, after 2 years of running with the nominal detector design and beam configuration. It has the potential to observe charge-parity violation in the neutrino sector to a precision of 3σ (5σ) after an exposure of 5 (10) years, for 50% of all ΑCP values. It will also make precise measurements of other parameters governing long-baseline neutrino oscillation, and after an exposure of 15 years will achieve a similar sensitivity to sin22θ13 to current reactor experiments