Antibody-directed enzyme prodrug therapy: pharmacokinetics and plasma levels of prodrug and drug in a phase I clinical trial

OBJECTIVE: The objective of the study was to determine the major factors that underlie auditory/audiological performance measures in an elderly population, with particular emphasis on finding those factors responsible for speech understanding under specific conditions of interference. DESIGN: Audiological status and auditory performance of a group of elderly (60- to 81-yr-old) and normal-hearing young (18- to 30-yr-old) individuals was determined through a test battery. When present, the hearing loss of elderly subjects was symmetrical in the two ears and, at most, moderate. The battery included tests of speech intelligibility on the word and sentence levels, with and without the presence of interfering speech. In addition to pure-tone and speech reception thresholds, perception of spectrally or temporally distorted speech as well as auditory resolution of frequency, time, and space were tested. Two tests received special consideration: the Speech Perception In Noise Test and the Modified Rhyme Reverberation Test. Taking the overall results as well as various subsets of the results, principal component analyses were conducted to identify major factors underlying auditory performance. RESULTS: The factors extracted by the principal component analyses present a portrayal of the auditory performance profile in which effects of interference, high-frequency hearing, and basic auditory function play a major role. Interference factors include general susceptibility to noise as well as segregation of concurrent speech sounds on the basis of temporal dissimilarities and spatial separation. Comparison of factors extracted from various subsets of tests indicate that factors underlying the decline of the "cocktail party effect" in the elderly are addressed mostly by tests specifically designed to assess speech understanding in spatially distributed babble or in a reverberant environment. CONCLUSIONS: Factor analysis of test measures obtained from a group of elderly individuals with normal hearing or mild-to-moderate hearing loss led to two main findings. First, it portrayed hearing loss as a component of different factors rather than as a factor on its own. Second, the independence of measures of speech understanding in babble or reverberation from other measures suggests that such tests should become an integral part of audiological test batteries designed to assess auditory functions in aging.     

Where is the teacher? Digital analytics for classroom proxemics

The term Classroom Proxemics refers to how teachers and students use classroom space, and the impact of this and the spatial design on learning and teaching. This study addresses the divide between, on the one hand, substantial work on proxemics based on classroom observations and, on the other hand, emerging work to design automated feedback that helps teachers identify salient patterns in their use of the classroom space. This study documents how digital analytics were designed in service of a senior teacher's practice-based inquiry into classroom proxemics. Indoor positioning data from four teachers were analysed, visualized and used as evidence to compare three distinct learning designs enacted in a physics classroom. This study demonstrates how teachers can make effective use of such visualizations, to gain insight into their classroom practice. This is evidenced by (a) documenting teachers' reflections on visualizations of positioning data, both their own and that of peers and (b) identifying the types of indicator (operationalized as analytical metrics) that foreground the most useful information for teachers to gain insight into their practice.     

Beyond equidistant sampling for performance and cost: A loop‐shaping approach applied to a motion system

Nonequidistant sampling potentially enhances the performance/cost trade‐off that is present in traditional equidistant sampling schemes. The aim of this paper is to develop a systematic feedback control design approach for systems that go beyond equidistant sampling. A loop‐shaping design framework for such nonequidistantly sampled systems is developed that addresses both stability and performance. The framework only requires frequency response function measurements of the LTI system, whereas it appropriately addresses the linear periodically time‐varying behavior introduced by the nonequidistant sampling. Experimental validation on a motion system demonstrates the superiority of the design framework for nonequidistantly sampled systems compared to traditional designs that rely on equidistant sampling.     

Stable inversion of LPTV systems with application in position-dependent and non-equidistantly sampled systems

Many control applications, including feedforward and learning control, involve the inverse of a dynamical system. For nonminimum-phase systems, the response of the inverse system is unbounded. For linear time-invariant (LTI), nonminimum-phase systems, a bounded, noncausal inverse response can be obtained through an exponential dichotomy. For generic linear time-varying (LTV) systems, such a dichotomy does not exist in general. The aim of this paper is to develop an inversion approach for an important class of LTV systems, namely linear periodically time-varying (LPTV) systems, which occur in, e.g. position-dependent systems with periodic tasks and non-equidistantly sampled systems. The proposed methodology exploits the periodicity to determine a bounded inverse for general LPTV systems. Conditions for existence are provided. The method is successfully demonstrated in several application cases, including position-dependent and non-equidistantly sampled systems.     

Digitized neutron imaging with high spatial resolution at a low power research reactor: Applications to steel and rock samples

Improved spatial detector resolution is exploited for engineering and geology, e.g., for the investigation of boron distribution in steel, consolidated aspects of building materials, and grain analysis in feldspar. The strengths and limitations of the upgraded instrument are evaluated in the context of these projects. First promising results have been obtained and will extend the range of applications for the neutron imaging beam-line at the Atomic Institute in Vienna.     

In718合金锤击锻造过程中的本构方程

采用对复杂的多道次变形的应力－应变曲线进行简化的新思路,建立了能反映Ｉｎ７１８合金高应变速率锤击锻造过程中的应变、变形速率、变形温度、变形道次与间隙时间等参数间综合影响的本构方程。借助有限元计算方法实现了工业涡轮盘高应变速率锤击锻造过程的数值模拟。     

Integrin‐Targeting Fluorescent Proteins: Exploration of RGD Insertion Sites

The potential of the fluorescent protein scaffold to control peptide sequence functionality is illustrated by an exploration of fluorescent proteins as novel probes for targeting integrins. A library of fluorescent mCitrine proteins with RGD motifs incorporated at several positions in loops within the protein main chain was generated and characterized. Amino acid mutations to RGD as well as RGD insertions were evaluated: both led to constructs with typical mCitrine fluorescent properties. Screening experiments against four human integrin receptors revealed two strong‐binding constructs and two selective integrin binders. The effect of the site of RGD incorporation illustrates the importance of the protein scaffold on RGD sequence functionality, leading to fluorescent protein constructs with the potential for selective integrin targeting.     

α‐Ketoheterocycles as Inhibitors of Leishmania mexicana Cysteine Protease CPB

Cysteine proteases of the papain superfamily are present in nearly all eukaryotes and also play pivotal roles in the biology of parasites. Inhibition of cysteine proteases is emerging as an important strategy to combat parasitic diseases such as sleeping sickness, Chagas disease, and leishmaniasis. Inspired by the in vivo antiparasitic activity of the vinylsulfone‐based cysteine protease inhibitors, a series of α‐ketoheterocycles were developed as reversible inhibitors of a recombinant L. mexicana cysteine protease, CPB2.8. Three isoxazoles and especially one oxadiazole compound are potent reversible inhibitors of CPB2.8; however, in vitro whole‐organism screening against a panel of protozoan parasites did not fully correlate with the observed inhibition of the cysteine protease.     

Prediction of Martensite Start Temperature for Lightweight Fe-Mn-Al-C Steels

A tailor-made thermodynamic database of the Fe-Mn-Al-C system was developed using the CALPHAD approach. The database enables predicting phase equilibria and thereby assessing the resulting microstructures of Fe-Mn-Al-C alloys. Available information on the martensite start (M_s) temperature was reviewed. By employing the M_s property model in the Thermo-Calc software together with the new thermodynamic database and experimental M_s temperatures, a set of model parameters for the Fe-Mn-Al-C system in the M_s model was optimised. Employing the newly evaluated parameters, the calculated M_s temperatures of the alloys in the Fe-Mn-Al-C system were compared with the available measured M_s temperatures. Predictions of M_s temperatures were performed for the alloys, Fe-10, 15 and 20 wt.% Mn-xAl-yC. The predictability of the M_s model can be further validated when new experimental M_s temperatures of the Fe-Mn-Al-C system are available.