Reconstructions and phase transitions of the Ge(001) surface

The authors have calculated the energy differences between the four members of the 2*1 family (b(2*1), c(4*2), p(2*2) and p(4*1)) of the Ge (001) surface by taking only electrostatic interactions between the dimers into account. They have found that p(2*2) is the lowest-energy reconstruction at zero temperature. The phase transitions from ordered p(2*2) to disordered (2*1) and ordered c(4*2) to disordered (2*1) are discussed using the authors' energy calculations, the mean-field approximation, the Ising model and Onsagers' exact solution. A second-order phase transition is found at about 200-250 K from an ordered p(2*2) (c(4*2)) dimer reconstruction to a disordered (2*1) dimer reconstruction assuming a charge transfer of 0.08e between the up atom and the down atom of the asymmetric dimer

Conference Reflection: On Blindness, the Nature of Elephants, and Educational Research

Adapted from ‘The Blind Men and the Elephant’John Godfrey Saxe (1816-1887) Once there were some scholars, to learning much inclined,Who went to see the Elephant (all of them were blind)So each by observation, might satisfy their mind.The first approached the elephant, and, happening to fall,Against a broad and sturdy side, at once began to bawl:‘The elephant, it seems, is nothing but a wall!’Another, feeling a tusk, cried: ‘What have we here?(To me it is both reliable and clear)This wonder of an elephant is very like a spear!’A third approached the animal (now wily and awake)Then happening (by grounded chance) to take,Trunk in hand, cried ‘the elephant is a snake!’Then a fourth reached for, and felt about the knee(Having paid a substantial entrance fee)Then proudly declared that the elephant was a tree.A fifth, now touching an ear (weathered and tan),States ‘what this resembles is clear to the blindest of man,The marvel of the elephant is very much like a fan!’The sixth no sooner had begun about the beast to grope,Then seizing the tail, that fell within his scope,Said finally, ‘the elephant is a rope!’And so the scholars, inquired loud and long,Each with opinion exceeding and strong,Though each was in the right, still all were in the wrong!An Invitation to Meet the ElephantThe Eastern Cape of South Africa has much to offer. It has popular activities, married with opportunities to interact with people and wildlife of many persuasions. So, when the invitation to participate in the 8th International Invitational Research and Development Seminar on Environmental and Health Education came, it was quite impossible to refuse. Port Elizabeth, said the website: ‘beckons with an attractive atmosphere of year-round holiday fun against a backdrop of urban activity … leisure options encompass a wide range’. Of course, this is only a small and distorted picture of what the Eastern Cape represents to the local inhabitants. So, I had to acknowledge that for now (as some kind of Canadian snowbird) I was going to be coming in‘blind’ and I hoped that there would be some reliable guides on hand when I arrived. The tourist website went on to describe parks, botanical gardens, nature reserves and an abundance of wildlife. It notes that in Port Elizabeth, the ‘1820 Settlers’ were introduced to their new land, and there they built some of the graceful homes that still enhance the city’s landscape; it is also related that the settlers’ trail eventually extended north from here and travelled through Grahamstown (our eventual destination). Of great interest (and also nearbyto Port Elizabeth) is the Addo Elephant National Park which is said to support about 350 elephants, in addition to Cape buffalo, black rhino, kudu and over 180 bird species. Keenly, I was anticipating the possibility of a chance meeting with some elephants during this, my second visit to the Eastern Cape

Local probing of coupled interfaces between two-dimensional electron and hole gases in oxide heterostructures by variable-temperature scanning tunneling spectroscopy

The electronic structure of an epitaxial oxide heterostructure containing two spatially separated two-dimensional conducting sheets, one electronlike (2DEG) and the other holelike (2DHG), has been investigated using variable temperature scanning tunneling spectroscopy. Heterostructures of LaAlO3/SrTiO3 bilayers on (001)-oriented SrTiO3 (STO) substrates provide the unique possibility to study the coupling between subnanometer spaced conducting interfaces. The band gap increases dramatically at low temperatures due to a blocking of the transition from the conduction band of the STO substrate to the top of the valence band of the STO capping layer. This prevents the replenishment of the depleted electrons in the capping layer from the underlying 2DEG and enables charging of the 2DHG by applying a negative sample bias voltage within the band gap region. At low temperatures the 2DHG can be probed separately with the proposed experimental geometry, although the 2DEG is located less than 1 nm belo

Parallel electron-hole bilayer conductivity from electronic interface reconstruction

The perovskite SrTiO$_3$-LaAlO$_3$ structure has advanced to a model system to investigate the rich electronic phenomena arising at polar interfaces. Using first principles calculations and transport measurements we demonstrate that an additional SrTiO$_3$ capping layer prevents structural and chemical reconstruction at the LaAlO$_3$ surface and triggers the electronic reconstruction at a significantly lower LaAlO$_3$ film thickness than for the uncapped systems. Combined theoretical and experimental evidence (from magnetotransport and ultraviolet photoelectron spectroscopy) suggests two spatially separated sheets with electron and hole carriers, that are as close as 1 nm.Comment: Phys. Rev. Lett., in pres

Two-stage model-based design of cancer phase I dose escalation trials: evaluation using the phase I program of barasertib (AZD1152)

Introduction Modeling and simulation of pharmacokinetics and pharmacodynamics has previously been shown to be potentially useful in designing Phase I programs of novel anti-cancer agents that show hematological toxicity. In this analysis, a two-stage model-based trial design was evaluated retrospectively using data from the Phase I program with the aurora kinase inhibitor barasertib. Methods Data from two Phase I trials and four regimens were used (n = 79). Using barasertib-hydroxy QPA plasma concentrations and neutrophil count data from only study 1A, a PKPD model was developed and subsequently used to predict the MTD and a safe starting dose for the other trials. Results The PKPD model based on data from the first study adequately described the time course of neutrophil count fluctuation. The two-stage model-based design provided safe starting doses for subsequent phase I trials for barasertib. Predicted safe starting dose levels were higher than those used in two subsequent trials, but lower than used in the other trial. Discussion The two-stage approach could have been applied safely to define starting doses for alternative dosing strategies with barasertib. The limited improvement in efficiency for the phase I program of barasertib may have been due to the fact that starting doses for the studied phase I trials were already nearly optimal. Conclusion Application of the two-stage model-based trial design in Phase I programs with novel anti-cancer drugs that cause haematological toxicity is feasible, safe, and may lead to a reduction in the number of patient treated at sub-therapeutic dose-levels

Two-stage model-based clinical trial design to optimize phase I development of novel anticancer agents

Background The phase I program of anticancer agents usually consists of multiple dose escalation studies to select a safe dose for various administration schedules. We hypothesized that pharmacokinetic and pharmacodynamic (PK–PD) modeling of an initial phase I study (stage 1) can be used for selection of an optimal starting dose for subsequent studies (stage 2) and that a post-hoc PK–PD analysis enhances the selection of a recommended dose for phase II evaluation. The aim of this analysis was to demonstrate that this two-stage model-based design, which does not interfere in the conduct of trials, is safe, efficient and effective. Methods PK and PD data of dose escalation studies were simulated for nine compounds and for five administration regimens (stage 1) for drugs with neutropenia as dose-limiting toxicity. PK–PD models were developed for each simulated study and were used to determine a starting dose for additional phase I studies (stage 2). The model-based design was compared to a conventional study design regarding safety (number of dose-limiting toxicities (DLTs)), efficiency (number of patients treated with a dose below the recommended dose) and effectiveness (precision of dose selection). Retrospective data of the investigational anticancer drug indisulam were used to show the applicability of the model-based design. Results The model-based design was as safe as the conventional design (median number of DLTs = 3) and resulted in a reduction of the number of patients who were treated with a dose below the recommended dose (−27%, power 89%). A post-hoc model-based determination of the recommended dose for future phase II studies was more precise than the conventional selection of the recommended dose (root mean squared error 8.3% versus 30%). Conclusions A two-stage model-based phase I design is safe for anticancer agents with dose-limiting myelosuppression and may enhance the efficiency of dose escalation studies by reducing the number of patients treated with a dose below the recommended dose and by increasing the precision of dose selection for phase II evaluation