Quantifying single gene copy number by measuring fluorescent probe lengths on combed genomic DNA

An approach was developed for the quantification of subtle gains and losses of genomic DNA. The approach relies on a process called molecular combing. Molecular combing consists of the extension and alignment of purified molecules of genomic DNA on a glass coverslip. It has the advantage that a large number of genomes can be combed per coverslip, which allows for a statistically adequate number of measurements to be made on the combed DNA. Consequently, a high-resolution approach to mapping and quantifying genomic alterations is possible. The approach consists of applying fluorescence hybridization to the combed DNA by using probes to identify the amplified region. Measurements then are made on the linear hybridization signals to ascertain the region's exact size. The reliability of the approach first was tested for low copy number amplifications by determining the copy number of chromosome 21 in a normal and trisomy 21 cell line. It then was tested for high copy number amplifications by quantifying the copy number of an oncogene amplified in the tumor cell line GTL-16. These results demonstrate that a wide range of amplifications can be accurately and reliably quantified. The sensitivity and resolution of the approach likewise was assessed by determining the copy number of a single allele (160 kb) alteration.

Size-Dependent and Step-Modulated Supramolecular Electrochemical Properties of Catechol-Derived Adlayers at Pt(hkl) Surfaces

The electrochemical reactivity of catechol-derived adlayers is reported at platinum (Pt) single-crystal electrodes. Pt(111) and stepped vicinal surfaces are used as model surfaces possessing well-ordered nanometer-sized Pt(111) terraces ranging from 0.4 to 12 nm. The electrochemical experiments were designed to probe how the control of monatomic step-density and of atomic-level step structure can be used to modulate molecule–molecule interactions during self-assembly of aromatic-derived organic monolayers at metallic single-crystal electrode surfaces. A hard sphere model of surfaces and a simplified band formation model are used as a theoretical framework for interpretation of experimental results. The experimental results reveal (i) that supramolecular electrochemical effects may be confined, propagated, or modulated by the choice of atomic level crystallographic features (i.e.monatomic steps), deliberately introduced at metallic substrate surfaces, suggesting (ii) that substrate-defect engineering may be used to tune the macroscopic electronic properties of aromatic molecular adlayers and of smaller molecular aggregates.

An international cohort comparison of size effects on job growth

The contribution of different-sized businesses to job creation continues to attract policymakers’ attention; however, it has recently been recognised that conclusions about size were confounded with the effect of age. We probe the role of size, controlling for age, by comparing the cohorts of firms born in 1998 over their first decade of life, using variation across half a dozen northern European countries Austria, Finland, Germany, Norway, Sweden and the UK to pin down size effects. We find that a very small proportion of the smallest firms play a crucial role in accounting for cross-country differences in job growth. A closer analysis reveals that the initial size distribution and survival rates do not seem to explain job growth differences between countries, rather it is a small number of rapidly growing firms that are driving this result.

A heuristic algorithm to generate test program sequences for moving probe electronic test equipment

The electronics industry, is experiencing two trends one of which is the drive towards miniaturization of electronic products. The in-circuit testing predominantly used for continuity testing of printed circuit boards (PCB) can no longer meet the demands of smaller size circuits. This has lead to the development of moving probe testing equipment. Moving Probe Test opens up the opportunity to test PCBs where the test points are on a small pitch (distance between points). However, since the test uses probes that move sequentially to perform the test, the total test time is much greater than traditional in-circuit test. While significant effort has concentrated on the equipment design and development, little work has examined algorithms for efficient test sequencing. The test sequence has the greatest impact on total test time, which will determine the production cycle time of the product. Minimizing total test time is a NP-hard problem similar to the traveling salesman problem, except with two traveling salesmen that must coordinate their movements. The main goal of this thesis was to develop a heuristic algorithm to minimize the Flying Probe test time and evaluate the algorithm against a "Nearest Neighbor" algorithm. The algorithm was implemented with Visual Basic and MS Access database. The algorithm was evaluated with actual PCB test data taken from Industry. A statistical analysis with 95% C.C. was performed to test the hypothesis that the proposed algorithm finds a sequence which has a total test time less than the total test time found by the "Nearest Neighbor" approach. Findings demonstrated that the proposed heuristic algorithm reduces the total test time of the test and, therefore, production cycle time can be reduced through proper sequencing.

Single non-normalized data of electron probe analyses of all glass shard samples from the Seward Peninsula and the Lipari obsidian reference standard

Permafrost degradation influences the morphology, biogeochemical cycling and hydrology of Arctic landscapes over a range of time scales. To reconstruct temporal patterns of early to late Holocene permafrost and thermokarst dynamics, site-specific palaeo-records are needed. Here we present a multi-proxy study of a 350-cm-long permafrost core from a drained lake basin on the northern Seward Peninsula, Alaska, revealing Lateglacial to Holocene thermokarst lake dynamics in a central location of Beringia. Use of radiocarbon dating, micropalaeontology (ostracods and testaceans), sedimentology (grain-size analyses, magnetic susceptibility, tephra analyses), geochemistry (total nitrogen and carbon, total organic carbon, d13Corg) and stable water isotopes (d18O, dD, d excess) of ground ice allowed the reconstruction of several distinct thermokarst lake phases. These include a pre-lacustrine environment at the base of the core characterized by the Devil Mountain Maar tephra (22 800±280 cal. a BP, Unit A), which has vertically subsided in places due to subsequent development of a deep thermokarst lake that initiated around 11 800 cal. a BP (Unit B). At about 9000 cal. a BP this lake transitioned from a stable depositional environment to a very dynamic lake system (Unit C) characterized by fluctuating lake levels, potentially intermediate wetland development, and expansion and erosion of shore deposits. Complete drainage of this lake occurred at 1060 cal. a BP, including post-drainage sediment freezing from the top down to 154 cm and gradual accumulation of terrestrial peat (Unit D), as well as uniform upward talik refreezing. This core-based reconstruction of multiple thermokarst lake generations since 11 800 cal. a BP improves our understanding of the temporal scales of thermokarst lake development from initiation to drainage, demonstrates complex landscape evolution in the ice-rich permafrost regions of Central Beringia during the Lateglacial and Holocene, and enhances our understanding of biogeochemical cycles in thermokarst-affected regions of the Arctic.

The 100th anniversary of the four-point probe technique: the role of probe geometries in isotropic and anisotropic systems

The electrical conductivity of solid-state matter is a fundamental physical property and can be precisely derived from the resistance measured via the four-point probe technique excluding contributions from parasitic contact resistances. Over time, this method has become an interdisciplinary characterization tool in materials science, semiconductor industries, geology, physics, etc, and is employed for both fundamental and application-driven research. However, the correct derivation of the conductivity is a demanding task which faces several difficulties, e.g. the homogeneity of the sample or the isotropy of the phases. In addition, these sample-specific characteristics are intimately related to technical constraints such as the probe geometry and size of the sample. In particular, the latter is of importance for nanostructures which can now be probed technically on very small length scales. On the occasion of the 100th anniversary of the four-point probe technique, introduced by Frank Wenner, in this review we revisit and discuss various correction factors which are mandatory for an accurate derivation of the resistivity from the measured resistance. Among others, sample thickness, dimensionality, anisotropy, and the relative size and geometry of the sample with respect to the contact assembly are considered. We are also able to derive the correction factors for 2D anisotropic systems on circular finite areas with variable probe spacings. All these aspects are illustrated by state-of-the-art experiments carried out using a four-tip STM/SEM system. We are aware that this review article can only cover some of the most important topics. Regarding further aspects, e.g. technical realizations, the influence of inhomogeneities or different transport regimes, etc, we refer to other review articles in this field.

Pore size distributions derived from adsorption isotherms, immersion calorimetry, and isosteric heats: A comparative study

We compare the pore size distribution of a well-characterized activated carbon derived from model-dependent, adsorption integral equation (AIE) methods with those from model-independent, immersion calorimetry and isosteric heat analyses. The AIE approach applied to nitrogen gave a mean pore width of 0.57 nm; the CO2 distribution exhibited wider dispersion. Spherical model application to CO2 and diffusion limitations for nitrogen and argon were proposed as primary reasons for inconsistency. Immersion enthalpy revealed a sharp decrease in available area equivalent to a cut-off due to molecular exclusion when the accessible surface was assessed against probe kinetic diameter. Mean pore width was identified as 0.58 ± 0.02 nm, endorsing the underlying assumptions for the nitrogen-based AIE approach. A comparison of the zero-coverage isosteric heat of adsorption for various non-polar adsorptives by the porous test sample was compared with the same adsorptives in contact with a non-porous reference adsorbent, leading to an energy ratio or adsorption enhancement factor. A linear relationship between the energy ratio and probe kinetic diameter indicated a primary pore size at 0.59 nm. The advantage of this enthalpy, model-independent methods over AIE were due to no assumptions regarding probe molecular shape, and no assumptions for pore shape and/or connectivity.

Tracking people in 3D using position, size and shape

This paper presents a prototype tracking system for tracking people in enclosed indoor environments where there is a high rate of occlusions. The system uses a stereo camera for acquisition, and is capable of disambiguating occlusions using a combination of depth map analysis, a two step ellipse fitting people detection process, the use of motion models and Kalman filters and a novel fit metric, based on computationally simple object statistics. Testing shows that our fit metric outperforms commonly used position based metrics and histogram based metrics, resulting in more accurate tracking of people.

ERP success: Does organisation size matter?

Organisations invest enormous sums of money in acquiring Enterprise Resource Planning (ERP) systems, presumably expecting positive impacts to the organisation and its functions. Despite the optimistic motives some ERP projects have reported nil or detrimental impacts. This paper studies the proposition that the size of an organisation (e.g. small, large) may have contributed to the differences in receiving benefits reported in prior studies in this domain. The alleged differences in organisational performance are empirically measured using a prior validated model, using five constructs and fortytwo sub-constructs. Information is gathered from three hundred and ten respondents representing twenty-seven public sector organisations. Results suggests that (1) larger organisations have received more benefits compared to small organisations, (2) small organisations demonstrated higher reliance on their ERP systems, (3) employment cohorts demonstrate significant differences in perceived benefits in small and large organisations.