Age Replacement and Service Rate Control of Stochastically Degrading Queues

This thesis considers the problem of optimally selecting a periodic replacement time for a multiserver queueing system in which each server is subject to degradation as a function of the mean service rate and a stochastic and dynamic environment. Also considered is the problem of optimal service rate selection for such a system. In both cases, the performance metric is the long-run average cost rate. Analytical expressions are obtained, in terms of Laplace transforms, for the nonlinear objective functions, necessitating the use of numerical Laplace transform inversion to evaluate candidate solutions in conjunction with standard numerical algorithms. Due to the convexity of the objective function, the optimal replacement time is computed using a hybrid bisection-secant method which yields globally optimal solutions. The optimal service rates are obtained via gradient search methods but are only guaranteed to provide locally optimal solutions. The analytical results are implemented on three notional examples that demonstrate the benefits of dynamically adjusting service rates under the described maintenance policy

Hydrogel microparticles from lithographic processes: Novel materials for fundamental and applied colloid science

In recent years, there has been a surge in methods to synthesize geometrically and chemically complex microparticles. Analogous to atoms, the concept of a “periodic table” of particles has emerged and continues to be expanded upon. Complementing the natural intellectual curiosity that drives the creation of increasingly intricate particles is the pull from applications that take advantage of such high-value materials. Complex particles are now being used in fields ranging from diagnostics and catalysis, to self-assembly and rheology, where material composition and microstructure are closely linked with particle function. This is especially true of polymer hydrogels, which offer an attractive and broad class of base materials for synthesis. Lithography affords the ability to engineer particle properties a priori and leads to the production of homogenous ensembles of particles. This review summarizes recent advances in synthesizing hydrogel microparticles using lithographic processes and highlights a number of emerging applications. We discuss advantages and limitations of current strategies, and conclude with an outlook on future trends in the field.National Science Foundation (U.S.) (Grant DMR-1006147)Novartis-MIT Center for Continuous ManufacturingNational Institute for Biomedical Imaging and Bioengineering (U.S.) (Grant R21EB008814

Encoded Hydrogel Microparticles for Sensitive and Multiplex microRNA Detection Directly from Raw Cell Lysates

In recent years, microRNAs (miRNAs) have emerged as promising diagnostic markers because of their unique dysregulation patterns under various disease conditions and high stability in biological fluids. However, current methods of analyzing miRNA levels typically require RNA isolation, which is cumbersome and time-consuming. To achieve high-throughput and accurate miRNA profiling, this study eliminates the need for purification steps by detecting miRNA directly from raw cellular lysate using nonfouling polyethylene glycol microparticles. In contrast to recent studies on direct miRNA measurements from cell lysate, our hydrogel-based system provides high-confidence quantification with robust performance. The lysis buffer for the assay was optimized to maximize reaction and labeling efficiency, and this assay has a low limit of detection (<1000 cells) without target amplification. Additionally, the capability for multiplexing was demonstrated through analyzing the levels of three endogenous miRNAs in 3T3 cell lysate. This versatile platform holds great potential for rapid and reliable direct miRNA quantification in complex media, and can be further extended to single-cell analysis by exploiting the flexibility and scalability of our system.National Cancer Institute (U.S.) (Grant 5R21CA177393-02

Observation of Scaling Violations in Scaled Momentum Distributions at HERA

Charged particle production has been measured in deep inelastic scattering (DIS) events over a large range of $x$ and $Q^2$ using the ZEUS detector. The evolution of the scaled momentum, $x_p$, with $Q^2,$ in the range 10 to 1280 $GeV^2$, has been investigated in the current fragmentation region of the Breit frame. The results show clear evidence, in a single experiment, for scaling violations in scaled momenta as a function of $Q^2$.Comment: 21 pages including 4 figures, to be published in Physics Letters B. Two references adde

Implications of Storing Urinary DNA from Different Populations for Molecular Analyses

Molecular diagnosis using urine is established for many sexually transmitted diseases and is increasingly used to diagnose tumours and other infectious diseases. Storage of urine prior to analysis, whether due to home collection or bio-banking, is increasingly advocated yet no best practice has emerged. Here, we examined the stability of DNA in stored urine in two populations over 28 days.Urine from 40 (20 male) healthy volunteers from two populations, Italy and Zambia, was stored at four different temperatures (RT, 4 degrees C, -20 degrees C & -80 degrees C) with and without EDTA preservative solution. Urines were extracted at days 0, 1, 3, 7 and 28 after storage. Human DNA content was measured using multi-copy (ALU J) and single copy (TLR2) targets by quantitative real-time PCR. Zambian and Italian samples contained comparable DNA quantity at time zero. Generally, two trends were observed during storage; no degradation, or rapid degradation from days 0 to 7 followed by little further degradation to 28 days. The biphasic degradation was always observed in Zambia regardless of storage conditions, but only twice in Italy.Site-specific differences in urine composition significantly affect the stability of DNA during storage. Assessing the quality of stored urine for molecular analysis, by using the type of strategy described here, is paramount before these samples are used for molecular prognostic monitoring, genetic analyses and disease diagnosis

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

The Properties of Planck Galactic Cold Clumps in the L1495 Dark Cloud

Planck Galactic Cold Clumps (PGCCs) possibly represent the early stages of star formation. To understand better the properties of PGCCs, we studied 16 PGCCs in the L1495 cloud with molecular lines and continuum data from Herschel, JCMT/SCUBA-2, and the PMO 13.7 m telescope. Thirty dense cores were identified in 16 PGCCs from 2D Gaussian fitting. The dense cores have dust temperatures of T d = 11–14 K, and H2 column densities of ${N}_{{{\rm{H}}}_{2}}$ = (0.36–2.5) × 1022 cm−2. We found that not all PGCCs contain prestellar objects. In general, the dense cores in PGCCs are usually at their earliest evolutionary stages. All the dense cores have non-thermal velocity dispersions larger than the thermal velocity dispersions from molecular line data, suggesting that the dense cores may be turbulence-dominated. We have calculated the virial parameter α and found that 14 of the dense cores have α 2. This suggests that some of the dense cores are not bound in the absence of external pressure and magnetic fields. The column density profiles of dense cores were fitted. The sizes of the flat regions and core radii decrease with the evolution of dense cores. CO depletion was found to occur in all the dense cores, but is more significant in prestellar core candidates than in protostellar or starless cores. The protostellar cores inside the PGCCs are still at a very early evolutionary stage, sharing similar physical and chemical properties with the prestellar core candidates