Consider a manufacturing line that produces parts of several types. Each part must be processed by at most one machine in each of several banks of machines. This paper presents an algorithm that ...schedules the loading of parts into such a line. The objective is primarily to minimize the makespan and secondarily to minimize queueing. The problem is decomposed into three subproblems and each of these is solved using a fast heuristic. The most challenging subproblem is that of finding a good loading sequence, and this is addressed using workload concepts and an approximation to dynamic programming. We make several extensions to the algorithm in order to handle limited storage capacity, expediting, and reactions to system dynamics. The algorithm was tested by computing schedules for a real production line, and the results are discussed.
The thymidine kinase (tk) mutagenesis assay is often utilized to determine the frequency of herpes simplex virus (HSV) replication-mediated mutations. Using this assay, clinical and laboratory HSV-2 ...isolates were shown to have a 10- to 80-fold higher frequency of spontaneous mutations compared to HSV-1.
A panel of HSV-1 and HSV-2, along with polymerase-recombinant viruses expressing type 2 polymerase (Pol) within a type 1 genome, were evaluated using the tk and non-HSV DNA mutagenesis assays to measure HSV replication-dependent errors and determine whether the higher mutation frequency of HSV-2 is a distinct property of type 2 polymerases.
Although HSV-2 have mutation frequencies higher than HSV-1 in the tk assay, these errors are assay-specific. In fact, wild type HSV-1 and the antimutator HSV-1 PAAr5 exhibited a 2-4 fold higher frequency than HSV-2 in the non-HSV DNA mutatagenesis assay. Furthermore, regardless of assay, HSV-1 recombinants expressing HSV-2 Pol had error rates similar to HSV-1, whereas the high mutator virus, HSV-2 6757, consistently showed significant errors. Additionally, plasmid DNA containing the HSV-2 tk gene, but not type 1 tk or LacZ DNA, was shown to form an anisomorphic DNA structure.
This study suggests that the Pol is not solely responsible for the virus-type specific differences in mutation frequency. Accordingly, it is possible that (a) mutations may be modulated by other viral polypeptides cooperating with Pol, and (b) the localized secondary structure of the viral genome may partially account for the apparently enhanced error frequency of HSV-2.
We report the discovery and characterization of the transiting extrasolar planet TOI-1710 b. It was first identified as a promising candidate by the Transiting Exoplanet Survey Satellite. Its ...planetary nature was then established with SOPHIE and HARPS-N spectroscopic observations via the radial-velocity method. The stellar parameters for the host star are derived from the spectra and a joint Markov chain Monte-Carlo adjustment of the spectral energy distribution and evolutionary tracks of TOI-1710. A joint MCMC analysis of the TESS light curve and the radial-velocity evolution allows us to determine the planetary system properties. From our analysis, TOI-1710 b is found to be a massive warm super-Neptune (
M
p
= 28.3 ± 4.7
M
⊕
and
R
p
= 5.34 ± 0.11
R
⊕
) orbiting a G5V dwarf star (
T
eff
= 5665 ± 55 K) on a nearly circular 24.3-day orbit (
e
= 0.16 ± 0.08). The orbital period of this planet is close to the estimated rotation period of its host star
P
rot
= 22.5 ± 2.0 days and it has a low Keplerian semi-amplitude
K
= 6.4 ± 1.0 m s
−1
; we thus performed additional analyses to show the robustness of the retrieved planetary parameters. With a low bulk density of 1.03 ± 0.23 g cm
−3
and orbiting a bright host star (
J
= 8.3,
V
= 9.6), TOI-1710 b is one of the best targets in this mass-radius range (near the Neptunian desert) for atmospheric characterization via transmission spectroscopy, a key measurement in constraining planet formation and evolutionary models of sub-Jovian planets.
Abstract
We report the discovery of one super-Earth- (TOI-1749b) and two sub-Neptune-sized planets (TOI-1749c and TOI-1749d) transiting an early M dwarf at a distance of 100 pc, which were first ...identified as planetary candidates using data from the TESS photometric survey. We have followed up this system from the ground by means of multiband transit photometry, adaptive optics imaging, and low-resolution spectroscopy, from which we have validated the planetary nature of the candidates. We find that TOI-1749b, c, and d have orbital periods of 2.39, 4.49, and 9.05 days, and radii of 1.4, 2.1, and 2.5
R
⊕
, respectively. We also place 95% confidence upper limits on the masses of 57, 14, and 15
M
⊕
for TOI-1749b, c, and d, respectively, from transit timing variations. The periods, sizes, and tentative masses of these planets are in line with a scenario in which all three planets initially had a hydrogen envelope on top of a rocky core, and only the envelope of the innermost planet has been stripped away by photoevaporation and/or core-powered mass-loss mechanisms. These planets are similar to other planetary trios found around M dwarfs, such as TOI-175b,c,d and TOI-270b,c,d, in the sense that the outer pair has a period ratio within 1% of 2. Such a characteristic orbital configuration, in which an additional planet is located interior to a near 2:1 period-ratio pair, is relatively rare around FGK dwarfs.
In vitro susceptibility assays of herpes simplex virus (HSV) do not necessarily correlate with treatment outcome. An HSV type 1 (HSV-1) isolate, N4, recovered from a patient who presented with herpes ...keratitis with localized immunosuppression, was characterized for susceptibility. Although the 50% inhibitory concentration (IC50) for this isolate was less than the accepted breakpoint for defining resistance to acyclovir (>2.0 µg/mL), the following lines of evidence suggest that the isolate was acyclovir resistant: (1) the clinical history confirmed that the infection was nonresponsive to acyclovir; (2) the in vitro susceptibility was similar to that of a thymidine kinase (TK)-negative, acyclovir-resistant virus SLU360; (3) the IC50 of acyclovir was more than 10 times the IC50 for an acyclovir-susceptible control strain; (4) plaque-purified clonal isolates were resistant to acyclovir (IC50s, >2.0 µg/mL); and (5) biochemical studies indicated that the HSV-1 N4 TK was partially impaired for acyclovir phosphorylation. Although residue changes were found in both the viral tk and pol coding regions of HSV-1 N4, characterization of a recombinant virus expressing the HSV-1 N4 polymerase suggested that the TK and Pol together conferred the acyclovir-resistance phenotype.
Background: A number of in vitro assays are used to determine susceptibility of HSV to antiviral agents, but results from these in vitro assays do not necessarily correlate with treatment outcome.
...Objectives: A method with improved capability for identifying an isolate as acyclovir (ACV) or penciclovir (PCV) resistant when resistance is borderline could greatly improve the management of HSV disease.
Study design: A comparative evaluation of four in vitro assays, plaque reduction (PRA), DNA hybridization, plating efficiency (PEA) and plaque autoradiography (PAR) was performed to accurately identify and measure resistance of a TK-altered clinical HSV isolate (HSV-1 N4) from a patient who was non-responsive to ACV treatment. Two established criteria for the prediction of antiviral resistance, IC
50≥2.0 μg/ml or an IC
50 greater than 10× above a sensitive virus IC
50, as well as testing in human (MRC-5) and nonhuman (Vero and CV-1 monkey kidney) cell lines were evaluated.
Results: The PRA and DNA hybridization assays accurately identified HSV-1 N4 as ACV
r in human cells when using the 10× above sensitive virus IC
50 resistance criterion. Moreover, the PEA and PAR assays failed to classify HSV-1 N4 as drug resistant and indicate that these technologies alone are inadequate for identifying resistant virus.
Conclusions: The data presented herein indicate that the PRA and DNA hybridization assays most accurately identified an otherwise borderline-resistant isolate as drug resistant: (i) when a sensitive virus is used within each individual assay as a control, (ii) when ACV and PCV susceptibility is evaluated in human cells, and (iii) when the 10× above sensitive IC
50 criterion is used to classify a virus as drug-resistant. Testing of additional clinical samples is warranted to further confirm these findings.
Acyclovir (ACV) resistant herpes simplex virus (HSV) isolates can be readily selected in animal infection models receiving suboptimal ACV treatment, however no comparative studies of the emergence of ...resistance following suboptimal treatment with valacyclovir (VCV) or famciclovir (FCV), the prodrugs of acyclovir and penciclovir, respectively, have been reported.
Mice (n = 30) were infected with HSV type 1 or 2 in the ear pinnae and administered oral prodrugs at one fifth a dose previously shown to be effective. To select and amplify drug-resistant HSV, a total of seven consecutive in vivo passages with suboptimal treatment were performed for each virus sample and progeny virus from each passage was characterized by the plaque reduction (PRA) and plating efficiency assays (PEA).
No drug-resistant HSV-2 and only a single drug-resistant HSV-1 variant were identified. Virus recovered from the first three sequential passages of this HSV-1 sample was susceptible by PRA, although the proportion of resistant virus recovered gradually increased upon passage. The resistant HSV-1 phenotype was confirmed by PRA after four sequential passages in mice. Unexpectedly, this in vivo-selected drug-resistant HSV-1 failed to yield an infection completely refractory to treatment in subsequent passages.
Sub-optimal therapy of immunocompetent mice with either VCV or FCV did not readily select for HSV-mutants resistant to either ACV or PCV, suggesting that selection of resistance with either prodrug remains difficult using this system. Futhermore, this study suggests that the PEA may represent a useful adjunct to the PRA for monitoring alterations in the proportion of drug-resistant virus even when no change in IC50 is apparent.
Gender Prespecified Sampling for Cost Control Trung Le, K.; Diop, A.; Wittrock, J. ...
International journal of public opinion research,
12/2014, Letnik:
26, Številka:
4
Journal Article
Recenzirano
Nationally representative surveys administered in the Middle East and North Africa typically are conducted using methodological techniques developed from outside the region. Sometimes these best ...practices require modification for local contexts, and one common -- but costly -- adaptation is to use teams of male and female interviewers for face-to-face surveys. We address the trade-off between costs and quality by testing a sampling method based on gender matching of interviewers and respondents. The benefits are twofold: (1) a reduction in survey costs and (2) simplified within-household selection. We find a notable reduction in field costs when field-tested in Qatar. Such a sampling method could be exported to other countries where societal conditions make teams of interviewers necessary for face-to-face surveys.
In neuroblastoma, amplification of the protooncogene N-myc is the most important molecular characteristic predicting a bad outcome for the patients. Despite the importance of the N-myc gene, little ...is known about the mechanisms regulating its expression. We found evidence that insulin-like growth factor II stimulates the growth of neuroblastoma in a paracrine fashion. Two neuroblastoma cell lines predominantly expressed IGF-II whereas two other cell lines expressed the IGF-receptor. In a receptor-positive cell line, N-myc expression was enhanced by stimulation with IGF-II. As the growth-stimulating signals of the IGF receptor are transmitted via Ras proteins, inactivation of Ras is one promising tool to prevent the induction of N-myc expression by IGF-II. Treatment of neuroblastoma cells with an inhibitor of the farnesyl-protein-transferase (FPTase) inactivated H-ras protein completely and N-ras protein by more than 50 %. Cell growth of neuroblastoma cells in serum containing medium was clearly diminished by inhibition of FPTase. The growth-promoting effect of IGF-II was reduced to exactly half the amount observed in non-inhibited cells.
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