Approximate methods for step function response of undamped non-linear spring mass systems with arbitrary hardening type spring characteristic

The possibility of applying two approximate methods for determining the salient features of response of undamped non-linear spring mass systems subjected to a step input, is examined. The results obtained on the basis of these approximate methods are compared with the exact results that are available for some particular types of spring characteristics. The extension of the approximate methods for non-linear systems with general polynomial restoring force characteristics is indicated.

Myotonic dystrophy type 2 (DM2) : Diagnostic methods and molecular pathology

Myotonic dystrophies type 1 (DM1) and type 2 (DM2) are the most common forms of muscular dystrophy affecting adults. They are autosomal dominant diseases caused by microsatellite tri- or tetranucleotide repeat expansion mutations in transcribed but not translated gene regions. The mutant RNA accumulates in nuclei disturbing the expression of several genes. The more recently identified DM2 disease is less well known, yet more than 300 patients have been confirmed in Finland thus far, and the true number is believed to be much higher. DM1 and DM2 share some features in general clinical presentation and molecular pathology, yet they show distinctive differences, including disease severity and differential muscle and fiber type involvement. However, the molecular differences underlying DM1 and DM2 muscle pathology are not well understood. Although the primary tissue affected is muscle, both DMs show a multisystemic phenotype due to wide expression of the mutation-carrying genes. DM2 is particularly intriguing, as it shows an incredibly wide spectrum of clinical manifestations. For this reason, it constitutes a real diagnostic challenge. The core symptoms in DM2 include proximal muscle weakness, muscle pain, myotonia, cataracts, cardiac conduction defects and endocrinological disturbations; however, none of these is mandatory for the disease. Myalgic pains may be the most disabling symptom for decades, sometimes leading to incapacity for work. In addition, DM2 may cause major socio-economical consequences for the patient, if not diagnosed, due to misunderstanding and false stigmatization. In this thesis work, we have (I) improved DM2 differential diagnostics based on muscle biopsy, and (II) described abnormalities in mRNA and protein expression in DM1 and DM2 patient skeletal muscles, showing partial differences between the two diseases, which may contribute to muscle pathology in these diseases. This is the first description of histopathological differences between DM1 and DM2, which can be used in differential diagnostics. Two novel high-resolution applications of in situ -hybridization have been described, which can be used for direct visualization of the DM2 mutation in muscle biopsy sections, or mutation size determination on extended DNA-fibers. By measuring protein and mRNA expression in the samples, differential changes in expression patterns affecting contractile proteins, other structural proteins and calcium handling proteins in DM2 compared to DM1 were found. The dysregulation at mRNA level was caused by altered transciption and abnormal splicing. The findings reported here indicate that the extent of aberrant splicing is higher in DM2 compared to DM1. In addition, the described abnormalities to some extent correlate to the differences in fiber type involvement in the two disorders.

Novel Functions of (p)ppGpp and Cyclic di-GMP in Mycobacterial Physiology Revealed by Phenotype Microarray Analysis of Wild-Type and Isogenic Strains of Mycobacterium smegmatis

The bacterial second messengers (p)ppGpp and bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) regulate important functions, such as transcription, virulence, biofilm formation, and quorum sensing. In mycobacteria, they regulate long-term survival during starvation, pathogenicity, and dormancy. Recently, a Pseudomonas aeruginosa strain lacking (p) ppGpp was shown to be sensitive to multiple classes of antibiotics and defective in biofilm formation. We were interested to find out whether Mycobacterium smegmatis strains lacking the gene for either (p)ppGpp synthesis (Delta rel(Msm)) or c-di-GMP synthesis (Delta dcpA) would display similar phenotypes. We used phenotype microarray technology to compare the growth of the wild-type and the knockout strains in the presence of several antibiotics. Surprisingly, the Delta rel(Msm) and Delta dcpA strains showed enhanced survival in the presence of many antibiotics, but they were defective in biofilm formation. These strains also displayed altered surface properties, like impaired sliding motility, rough colony morphology, and increased aggregation in liquid cultures. Biofilm formation and surface properties are associated with the presence of glycopeptidolipids (GPLs) in the cell walls of M. smegmatis. Thin-layer chromatography analysis of various cell wall fractions revealed that the levels of GPLs and polar lipids were reduced in the knockout strains. As a result, the cell walls of the knockout strains were significantly more hydrophobic than those of the wild type and the complemented strains. We hypothesize that reduced levels of GPLs and polar lipids may contribute to the antibiotic resistance shown by the knockout strains. Altogether, our data suggest that (p)ppGpp and c-di-GMP may be involved in the metabolism of glycopeptidolipids and polar lipids in M. smegmatis.

Arithmetic of cyclotomic fields and Fermat-type equations

Let l be any odd prime, and ζ a primitive l-th root of unity. Let C_l be the l-Sylow subgroup of the ideal class group of Q(ζ). The Teichmüller character w : Z_l → Z^*_l is given by w(x) = x (mod l), where w(x) is a p-1-st root of unity, and x ∈ Z_l. Under the action of this character, C_l decomposes as a direct sum of C^((i))_l, where C^((i))_l is the eigenspace corresponding to w^i. Let the order of C^((3))_l be l^h_3). The main result of this thesis is the following: For every n ≥ max( 1, h_3 ), the equation x^(ln) + y^(ln) + z^(ln) = 0 has no integral solutions (x,y,z) with l ≠ xyz. The same result is also proven with n ≥ max(1,h_5), under the assumption that C_l^((5)) is a cyclic group of order l^h_5. Applications of the methods used to prove the above results to the second case of Fermat's last theorem and to a Fermat-like equation in four variables are given.

The proof uses a series of ideas of H.S. Vandiver ([Vl],[V2]) along with a theorem of M. Kurihara [Ku] and some consequences of the proof of lwasawa's main conjecture for cyclotomic fields by B. Mazur and A. Wiles [MW]. In [V1] Vandiver claimed that the first case of Fermat's Last Theorem held for l if l did not divide the class number h^+ of the maximal real subfield of Q(e^(2πi/i)). The crucial gap in Vandiver's attempted proof that has been known to experts is explained, and complete proofs of all the results used from his papers are given.

Diagonal forms, linear algebraic methods and Ramsey-type problems

This thesis focuses mainly on linear algebraic aspects of combinatorics. Let N_t(H) be an incidence matrix with edges versus all subhypergraphs of a complete hypergraph that are isomorphic to H. Richard M. Wilson and the author find the general formula for the Smith normal form or diagonal form of N_t(H) for all simple graphs H and for a very general class of t-uniform hypergraphs H.

As a continuation, the author determines the formula for diagonal forms of integer matrices obtained from other combinatorial structures, including incidence matrices for subgraphs of a complete bipartite graph and inclusion matrices for multisets.

One major application of diagonal forms is in zero-sum Ramsey theory. For instance, Caro's results in zero-sum Ramsey numbers for graphs and Caro and Yuster's results in zero-sum bipartite Ramsey numbers can be reproduced. These results are further generalized to t-uniform hypergraphs. Other applications include signed bipartite graph designs.

Research results on some other problems are also included in this thesis, such as a Ramsey-type problem on equipartitions, Hartman's conjecture on large sets of designs and a matroid theory problem proposed by Welsh.

Assembly of multilayer films containing iron(III)- substituted Dawson-type heteropolyanions and its electrocatalytic properties: cyclic voltammetry, electrochemical impedance spectroscopy and UV-Vis spectrometry

Ultrathin multilayer films have been prepared by means of alternate adsorption of iron(Ill)-substituted heteropolytungstate anions and a cationic redox polymer on the 4-aminobenzoic acid modified glassy carbon electrode surface based on electrostatic layer-by-layer assembly. Cyclic voltammetry, electrochemical impedance spectroscopy and UV-Vis absorption spectrometry have been used to easily monitor the uniformity of thus-formed multilayer films. Especially, the electrochemical impedance spectroscopy is successfully used to monitor the multilayer deposition processes and is a very useful technique in the characterization of multilayer films because it provides valuable information about the interfacial impedance features. All these results reveal regular film growth with each layer adsorption. The resulting multilayer films can effectively catalyze the reduction of H2O2,NO2- and BrO3-.

STAR 3 randomized controlled trial to compare sensor-augmented insulin pump therapy with multiple daily injections in the treatment of type 1 diabetes: research design, methods, and baseline characteristics of enrolled subjects.

BACKGROUND: Sensor-augmented pump therapy (SAPT) integrates real-time continuous glucose monitoring (RT-CGM) with continuous subcutaneous insulin infusion (CSII) and offers an alternative to multiple daily injections (MDI). Previous studies provide evidence that SAPT may improve clinical outcomes among people with type 1 diabetes. Sensor-Augmented Pump Therapy for A1c Reduction (STAR) 3 is a multicenter randomized controlled trial comparing the efficacy of SAPT to that of MDI in subjects with type 1 diabetes. METHODS: Subjects were randomized to either continue with MDI or transition to SAPT for 1 year. Subjects in the MDI cohort were allowed to transition to SAPT for 6 months after completion of the study. SAPT subjects who completed the study were also allowed to continue for 6 months. The primary end point was the difference between treatment groups in change in hemoglobin A1c (HbA1c) percentage from baseline to 1 year of treatment. Secondary end points included percentage of subjects with HbA1c < or =7% and without severe hypoglycemia, as well as area under the curve of time spent in normal glycemic ranges. Tertiary end points include percentage of subjects with HbA1c < or =7%, key safety end points, user satisfaction, and responses on standardized assessments. RESULTS: A total of 495 subjects were enrolled, and the baseline characteristics similar between the SAPT and MDI groups. Study completion is anticipated in June 2010. CONCLUSIONS: Results of this randomized controlled trial should help establish whether an integrated RT-CGM and CSII system benefits patients with type 1 diabetes more than MDI.

The Effects of Several Paper Characteristics and Application Methods on the Sublimation Rate of Cyclododecane

Cyclododecane (CDD) is a waxy, solid cyclic hydrocarbon (C12H24) that sublimes at room temperature and possesses strong hydrophobicity. In paper conservation CDD is used principally as a temporary fixative of water-soluble media during aqueous treatments. Hydrophobicity, ease of reversibility, low toxicity, and absence of residues are reasons often cited for its use over alternative materials although the latter two claims continue to be debated in the literature. The sublimation rate has important implications for treatment planning as well as health and safety considerations given the dearth of reliable information on its toxicity and exposure limits. This study examined how the rate of sublimation is affected by fiber type, sizing, and surface finish as well as delivery in the molten phase and as a saturated solution in low boiling petroleum ether. The effect of warming the paper prior to application was also evaluated. Sublimation was monitored using gravimetric analysis after which samples were tested for residues with gas chromatography-flame ionization detection (GC-FID) to confirm complete sublimation. Water absorbency tests were conducted to determine whether this property is fully reestablished. Results suggested that the sublimation rate of CDD is affected minimally by all of the paper characteristics and application methods examined in this study. The main factors influencing the rate appear to be the thickness and mass of the CDD over a given surface area as well as temperature and ventilation. The GC-FID results showed that most of the CDD sublimed within several days of its disappearance from the paper surface regardless of the application method. Minimal changes occurred in the water absorbency of the samples following complete sublimation.

Regioselectivity and stereoselectivity of dioxygenase catalysed cis-dihydroxylation of mono- and tri-cyclic azaarene substrates

cis-Dihydrodiol metabolites were obtained from dioxygenase-catalysed asymmetric dihydroxylations of. five monocyclic (azabiphenyl) and four tricyclic (azaphenanthrene) azaarene substrates. Enantiopurity values and absolute configuration assignments were determined using a combination of stereochemical correlation, X-ray crystallography and spectroscopy methods. The degree of regioselectivity found during cis-dihydroxylation of monocyclic azaarenes (2,3 bond >> 3,4 bond) and of tricyclic azaarenes (bay region > non-bay region bonds) was dependent on the type of dioxygenase used. The cis-dihydrodiol metabolite from an azaarene (3-phenylpyridine) was utilised in the chemoenzymatic synthesis of the corresponding trans-dihydrodiol.

Monte Carlo radiation hydrodynamics:Methods, tests and application to Type Ia supernova ejecta

In astrophysical systems, radiation-matter interactions are important in transferring energy and momentum between the radiation field and the surrounding material. This coupling often makes it necessary to consider the role of radiation when modelling the dynamics of astrophysical fluids. During the last few years, there have been rapid developments in the use of Monte Carlo methods for numerical radiative transfer simulations. Here, we present an approach to radiation hydrodynamics that is based on coupling Monte Carlo radiative transfer techniques with finite-volume hydrodynamical methods in an operator-split manner. In particular, we adopt an indivisible packet formalism to discretize the radiation field into an ensemble of Monte Carlo packets and employ volume-based estimators to reconstruct the radiation field characteristics. In this paper the numerical tools of this method are presented and their accuracy is verified in a series of test calculations. Finally, as a practical example, we use our approach to study the influence of the radiation-matter coupling on the homologous expansion phase and the bolometric light curve of Type Ia supernova explosions. © 2012 The Authors Monthly Notices of the Royal Astronomical Society © 2012 RAS.

Intermittent chemotherapy plus either intermittent or continuous cetuximab for first-line treatment of patients with KRAS wild-type advanced colorectal cancer (COIN-B): a randomised phase 2 trial

Background: Advanced colorectal cancer is treated with a combination of cytotoxic drugs and targeted treatments. However, how best to minimise the time spent taking cytotoxic drugs and whether molecular selection can refine this further is unknown. The primary aim of this study was to establish how cetuximab might be safely and effectively added to intermittent chemotherapy.

Methods: COIN-B was an open-label, multicentre, randomised, exploratory phase 2 trial done at 30 hospitals in the UK and one in Cyprus. We enrolled patients with advanced colorectal cancer who had received no previous chemotherapy for metastases. Randomisation was done centrally (by telephone) by the Medical Research Council Clinical Trials Unit using minimisation with a random element. Treatment allocation was not masked. Patients were assigned (1:1) to intermittent chemotherapy plus intermittent cetuximab or to intermittent chemotherapy plus continuous cetuximab. Chemotherapy was FOLFOX (folinic acid and oxaliplatin followed by bolus and infused fluorouracil). Patients in both groups received FOLFOX and weekly cetuximab for 12 weeks, then either had a planned interruption (those taking intermittent cetuximab) or planned maintenance by continuing on weekly cetuximab (continuous cetuximab). On RECIST progression, FOLFOX plus cetuximab or FOLFOX was recommenced for 12 weeks followed by further interruption or maintenance cetuximab, respectively. The primary outcome was failure-free survival at 10 months. The primary analysis population consisted of patients who completed 12 weeks of treatment without progression, death, or leaving the trial. We tested BRAF and NRAS status retrospectively. The trial was registered, ISRCTN38375681.

Findings: We registered 401 patients, 226 of whom were enrolled. Results for 169 with KRAS wild-type are reported here, 78 (46%) assigned to intermittent cetuximab and 91 (54%) to continuous cetuximab. 64 patients assigned to intermittent cetuximab and 66 of those assigned to continuous cetuximab were included in the primary analysis. 10-month failure-free survival was 50% (lower bound of 95% CI 39) in the intermittent group versus 52% (lower bound of 95% CI 41) in the continuous group; median failure-free survival was 12·2 months (95% CI 8·8–15·6) and 14·3 months (10·7–20·4), respectively. The most common grade 3–4 adverse events were skin rash (21 [27%] of 77 patients vs 20 [22%] of 92 patients), neutropenia (22 [29%] vs 30 [33%]), diarrhoea (14 [18%] vs 23 [25%]), and lethargy (20 [26%] vs 19 [21%]).

Interpretation: Cetuximab was safely incorporated in two first-line intermittent chemotherapy strategies. Maintenance of biological monotherapy, with less cytotoxic chemotherapy within the first 6 months, in molecularly selected patients is promising and should be validated in phase 3 trials.

Prediction of integral type failures in semiconductor manufacturing through classification methods

Smart management of maintenances has become fundamental in manufacturing environments in order to decrease downtime and costs associated with failures. Predictive Maintenance (PdM) systems based on Machine Learning (ML) techniques have the possibility with low added costs of drastically decrease failures-related expenses; given the increase of availability of data and capabilities of ML tools, PdM systems are becoming really popular, especially in semiconductor manufacturing. A PdM module based on Classification methods is presented here for the prediction of integral type faults that are related to machine usage and stress of equipment parts. The module has been applied to an important class of semiconductor processes, ion-implantation, for the prediction of ion-source tungsten filament breaks. The PdM has been tested on a real production dataset. © 2013 IEEE.

Comparison of Two Pollen Counting Methods of Slides from a Hirst Type Volumetric Trap.

Two of the most frequently used methods of pollen counting on slides from Hirst type traps are evaluated in this paper: the transverse traverse method and the longitudinal traverse method. The study was carried out during June–July 1996 and 1997 on slides from a trap at Worcester, UK. Three pollen types were selected for this purpose: Poaceae, Urticaceae and Quercus. The statistical results show that the daily concentrations followed similar trends (p < 0.01, R-values between 0.78–0.96) with both methods during the two years, although the counts were slightly higher using the longitudinal traverses method. Significant differences were observed, however, when the distribution of the concentrations during 24 hour sampling periods was considered. For more detailed analysis, the daily counts obtained with both methods were correlated with the total number of pollen grains for the taxon over the whole slide, in two different situations: high and low concentrations of pollen in the atmosphere. In the case of high concentrations, the counts for all three taxa with both methods are significantly correlated with the total pollen count. In the samples with low concentrations, the Poaceae and Urticaceae counts with both methods are significantly correlated with the total counts, but none of Quercus counts are. Consideration of the results indicates that both methods give a reasonable approximation to the count derived from the slide as a whole. More studies need be done to explore the comparability of counting methods in order to work towards a Universal Methodology in Aeropalynology.