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The emergence and spread of antibiotic resistance represent a growing threat to public health. Of particular concern is the appearance of β-lactamases, which are capable to hydrolyze and inactivate the most important class of antibiotics, the β-lactams. Effective β-lactamase inhibitors and mechanistic insights into their action are central in overcoming this type of resistance, and in this context boronate-based β-lactamase inhibitors were just recently approved to treat multidrug-resistant bacteria. Using boric acid as a simplified inhibitor model, time-resolved serial crystallography was employed to obtain mechanistic insights into binding to the active site serine of β-lactamase CTX-M-14, identifying a reaction time frame of 80–100 ms. In a next step, the subsequent 1,2-diol boric ester formation with glycerol in the active site was monitored proceeding in a time frame of 100–150 ms. Furthermore, the displacement of the crucial anion in the active site of the β-lactamase was verified as an essential part of the binding mechanism of substrates and inhibitors. In total, 22 datasets of β-lactamase intermediate complexes with high spatial resolution of 1.40–2.04 Å and high temporal resolution range of 50–10,000 ms were obtained, allowing a detailed analysis of the studied processes. Mechanistic details captured here contribute to the understanding of molecular processes and their time frames in enzymatic reactions. Moreover, we could demonstrate that time-resolved crystallography can serve as an additional tool for identifying and investigating enzymatic reactions. Boronate-based ß-lactamase inhibitors play an important role in treating multidrug-resistant bacteria infection, however, the molecular mechanism of inhibition remains unclear. Here, the authors use time-resolved serial crystallography to investigate the binding process by using boric acid as a model against β-lactamase CTX-M-14, revealing the binding to the active site serine within 80–100 ms, a subsequent 1,2-diol boric ester formation with glycerol within 100–150 ms, as well as the displacement of the sulfate anion in the active site. [ABSTRACT FROM AUTHOR]

This paper presents a study on the temperature dependent photo-elastic coefficient in single-crystal silicon with (100) and (110) orientations at a wavelength of 1550 nm. The measurement of the photo-elastic coefficient was performed using a polarimetric scheme across a wide temperature range from 5 to 300 K. The experimental setup employed high-sensitivity techniques and incorporated automatic beam path correction, ensuring precise and accurate determination of the coefficient's values. The results show excellent agreement with previous measurements at room temperature, specifically yielding a value of d n / d σ = - 2.463 × 10 - 11 1/Pa for the (100) orientation. Interestingly, there is a significant difference in photo-elasticity between the different crystal orientations of approximately 50 % . The photo-elastic coefficient's absolute value increases by approximately 40% with decreasing temperature down to 5 K. These findings provide valuable insights into the photo-elastic properties of silicon and its behavior under varying mechanical stress, particularly relevant for optomechanical precision experiments like cryogenic gravitational wave detectors and microscale optomechanical quantum sensors. [ABSTRACT FROM AUTHOR]

The most precise measurement tools of humankind are equipped with ultra-stable lasers. State-of-the-art laser stabilization techniques are based on external cavities, that are limited by noise originated in the coatings of the cavity mirrors. Microstructured mirror coatings (so-called meta-mirrors) are a promising technology to overcome the limitations of coating noise and therewith pave the way towards next-generation ultra-stable lasers. We present experimental realization of a 12,000-finesse optical cavity based on one low-noise meta-mirror. The use of the mirrors studied here in cryogenic silicon cavities represents an order of magnitude reduction in the current limiting mirror noise, such that the stability limit due to fundamental noise can be reduced to 5 × 10−18. Meta-mirrors may help realize ultra-stable lasers for high-precision metrology, for applications like gravitational wave detection and quantum optics. The authors experimentally realize a new type of microstructured meta-mirror and use it to form a Fabry-Perot cavity with low thermal noise and a high finesse of 12,000. [ABSTRACT FROM AUTHOR]

This paper offers a systematic literature review of real-time detection and classification of Power Quality Disturbances (PQDs). A particular focus is given to voltage sags and notches, as voltage sags cause huge economic losses while research on voltage notches is still very incipient. A systematic method based on scientometrics, text similarity and the analytic hierarchy process is proposed to structure the review and select the most relevant literature. A bibliometric analysis is then performed on the bibliographic data of the literature to identify relevant statistics such as the evolution of publications over time, top publishing countries, and the distribution by relevant topics. A set of articles is subsequently selected to be critically analyzed. The critical review is structured in steps for real-time detection and classification of PQDs, namely, input data preparation, preprocessing, transformation, feature extraction, feature selection, detection, classification, and characterization. Aspects associated with the type of disturbance(s) addressed in the literature are also explored throughout the review, including the perspectives of those studies aimed at multiple PQDs, or specifically focused on voltage sags or voltage notches. The real-time performance of the reviewed tools is also examined. Finally, unsolved issues are discussed, and prospects are highlighted. [ABSTRACT FROM AUTHOR]

Purpose: Metastatic breast cancer is the second leading cause of cancer-related death in women. The 5-year survival rate for metastatic breast cancer has remained near 26.9 % for over a decade. The recruitment of hematopoietic stem cells with high expression of the vascular endothelial growth factor receptor 1 (VEGFR-1) has been implicated in early stages of metastasis formation. We propose the use of an 18F-labeled single-chain version of VEGF121, re-engineered to be selective for VEGFR-1 (scVR1), as a positron emission tomography (PET) imaging agent to non-invasively image early-stage metastases.Procedures: scVR1 was 18F-labeled via a biorthogonal click reaction between site-specifically trans-cyclooctene functionalized scVR1 and an Al18F labeled tetrazine-NODA (1,4,7-triazacyclononane-1,4-diiacetic acid). The [18F]AlF-NODA-scVR1 was purified using a PD10 column and subsequently analyzed on HPLC to determine radiochemical purity. Animal experiments were performed in 6-8-week-old female BALB/c mice bearing orthotopic primary 4T1 breast tumors or 4T1 metastatic lesions. The [18F]AlF-NODA-scVR1 tracer was administered via tail vein injection; PET imaging and ex vivo analysis was performed 2 h post-injection.Results: The [18F]AlF-NODA-scVR1 was prepared with a 98.2 ± 1.5 % radiochemical purity and an apparent molar activity of 7.5 ± 1.2 GBq/μmol. The specific binding of scVR1 to VEGFR-1 was confirmed via bead-based assay. The ex vivo biodistribution showed tumor uptake of 3.5 ± 0.5 % ID/g and was readily observable in PET images. Metastasis formation was detected with [18F]AlF-NODA-scVR1 tracer showing colocalization with bioluminescent imaging as well as ex vivo autoradiography and immunofluorescent staining of VEGFR-1.Conclusions: The diagnostic capabilities of the [18F]AlF-NODA-scVR1 PET tracer was confirmed in both orthotopic and metastatic murine cancer models. These results support the potential use of [18F]AlF-NODA-scVR1 as a PET tracer that could image metastases, providing clinicians with an additional tool to assess a patient's need for adjuvant therapies. [ABSTRACT FROM AUTHOR]

This educational study aimed to explore the feasibility and acceptance of a literacy exercise adopted from the realworld of scientific publishing in a cell and tissue biology course. For that purpose, a tertiary-level multimodality science course, which integrated a blended learning faculty and student lectures, journal club, and wet laboratory sessions including a research project as well as examinations, was complemented by essaywriting of a review and peerreviewing of five manuscripts. All tasks contributed to the final course mark. Special emphasis was laid on the usability of different E-Learning applications for scientific writing and teacher- and peerassessment procedures. Further, potential influences of student characteristics on their peer- and self-assessments as well as their acceptance of the feedback from their peers were evaluated. Seventy-five undergraduate students from different Bachelor programs were included in the study. Plagiarism check and double-blind assessments of the essays were performed using "Turnitin.com." Students self-assessed their paper and received feedback from five peers and the teacher. Peer assessment was more severe than the teacher- or self-assessment, and the peer mark correlated best with the final course mark. Students with better marks assessed more generously, and there had moderate tendencies for influences of gender and background on peer feedback behavior. The students perceived the writing and assessment exercises, especially being peer-assessed, as demanding, but rewarding and a great learning experience. The additional tasks were feasible using E-Learning technology, which should foster future biomedical courses to train writing skills and the ability to cope with different roles in the scientific community. [ABSTRACT FROM AUTHOR]

Despite growing applications of social and healthcare marketing to enhance public well-being through anti-stigma campaigns, little research investigates how public stigma surrounding health conditions might limit the outcomes of these campaigns. By drawing on the theory of implicit worldviews, this study identifies reasons for public stigma as well as associated message frames to address these reasons. Study 1a provides evidence that implicit worldviews are relevant to campaign results. Study 1b and Study 2 demonstrate that fitting consumers' implicit worldview with suitable (i.e., biomedical or biopsychosocial) health frames reduces stigma endorsement. Study 3 identifies the perceived severity of a mental illness as a boundary condition; marketing communications have the greatest impact when they refer to an illness with lower perceived severity. Finally, Study 4 expands understanding of the phenomenon by extending the findings to physical health conditions (i.e., obesity). The article concludes by discussing the implications of these findings for policy and future applications. [ABSTRACT FROM AUTHOR]

Studies of biological systems typically require the application of several complementary methods able to yield statistically-relevant results at a unique level of sensitivity. Combined X-ray fluorescence and ptychography offer excellent elemental and structural imaging contrasts at the nanoscale. They enable a robust correlation of elemental distributions with respect to the cellular morphology. Here we extend the applicability of the two modalities to higher X-ray excitation energies, permitting iron mapping. Using a long-range scanning setup, we applied the method to two vital biomedical cases. We quantified the iron distributions in a population of macrophages treated with Mycobacterium-tuberculosis-targeting iron-oxide nanocontainers. Our work allowed to visualize the internalization of the nanocontainer agglomerates in the cytosol. From the iron areal mass maps, we obtained a distribution of antibiotic load per agglomerate and an average areal concentration of nanocontainers in the agglomerates. In the second application we mapped the calcium content in a human bone matrix in close proximity to osteocyte lacunae (perilacunar matrix). A concurrently acquired ptychographic image was used to remove the mass-thickness effect from the raw calcium map. The resulting ptychography-enhanced calcium distribution allowed then to observe a locally lower degree of mineralization of the perilacunar matrix. [ABSTRACT FROM AUTHOR]

While Moore's law states that the number of transistors is approximately doubled every 2 years, powering these transistors simultaneously is only possible as long as Dennard scaling continues. Unfortunately, voltage scaling has slowed down in recent years, and microprocessor designers have hit what is known as the 'utilization wall' or the 'dark silicon' effect. Vectorization, parallelization, specialization and heterogeneity are the key approaches to deal with this utilization wall. However, how software developers can maximize energy efficiency of these architectures remains an open question. This paper presents an energy evaluation of parallelization using both physical and logical cores (i.e., SMT/Hyper-Threading), vectorization (SSE, Advanced Vector Extensions and NEON) and dynamic core reconfiguration [ $$\hbox {Intel}^{\circledR }$$ 's Turbo Boost Technology (TBT)]. The evaluation spans microprocessors for embedded, laptop, desktop and server markets, since there is a convergence among them towards energy efficiency. The analyzed processors include Intel's Core $$^\mathrm{TM}$$ i5 and i7 family and ARM $$^{\circledR }$$ 's Cortex $$^\mathrm{TM}$$ A9 and A15. Results show that software developers should prioritize vectorization over thread parallelism when possible, as it yields better energy efficiency, especially on the Intel platforms. Application scalability can be reduced drastically when using vectorization and threading simultaneously since vectorization increases pressure on the memory subsystem. Intel's TBT further improves energy efficiency by an additional 10-20 % depending on the number of active threads. [ABSTRACT FROM AUTHOR]

Smooth spherical micro glass particles are the reference particle system to demonstrate the correlation between single contacts and the particle packing properties. To investigate the influence of the van der Waals attraction force, the particles will be functionalized to obtain hydrophilic and hydrophobic surfaces. To remove the impurities and hydrophilize the particle surfaces a very strong oxidizing agent is used-the peroxymonosulfuric acid. In order to generate a hydrophobic glass surface, the process of silanization is applied. The comprehensive force displacement model of elastic-plastic and adhesive contacts are discussed. Therefore the model 'stiff particles with soft contacts' is used to quantify and compare the elastic-plastic contact properties. In this work, the particle contacts are experimentally investigated by means of atomic force microscopy (AFM), nanoindentation and shear tests. While the AFM and nanoindenter measurements are aimed to analyse single particle contacts, shear tests are used for particle packing studies. The fundamental challenge and question is addressed and answered: How do the micro mechanical material properties change when the glass surfaces are functionalized? Do we obtain the same behavior for the used micro glass particles when we compare the different methods? [ABSTRACT FROM AUTHOR]

The contact mechanics of individual, very small particles with other particles and walls is studied using a nanoindenter setup that allows normal and lateral displacement control and measurement of the respective forces. The sliding, rolling and torsional forces and torques are tested with borosilicate microspheres, featuring radii of about $$10\,\upmu \hbox {m}$$ . The contacts are with flat silicon substrates of different roughness for pure sliding and rolling and with silicon based, ion-beam crafted rail systems for combined rolling and torsion. The experimental results are discussed and compared to various analytical predictions and contact models, allowing for two concurrent interpretations of the effects of surface roughness, plasticity and adhesion. This enables us to determine both rolling and torsion friction coefficients together with their associated length scales. Interestingly, even though normal contacts behave elastically (Hertzian), all other modes of motion display effects due to surface roughness and consequent plastic deformation. The influence of adhesion is interpreted in the framework of different models and is very different for different degrees of freedom, being largest for rolling. [ABSTRACT FROM AUTHOR]

Background and aims: Soil amendment with silicon (Si) can significantly increase resistance of susceptible sugarcane cultivars grown in pots to stalk borer Eldana saccharina (Lepidoptera: Pyralidae). This study tested the hypothesis that a single application of silicate can increase resistance to E. saccharina and increase yield in field-grown sugarcane. Methods: Two Si materials (Calmasil® and Slagment® at 4 and 8 t/ha) were applied at planting to a field trial extending over three successive crops and incorporating three sugarcane cultivars varying in borer susceptibility. Results: Both materials, especially Slagment, significantly increased soil, leaf and stalk Si content, but leaf Si levels seldom exceeded 0.5 %. Silicon treatment significantly reduced percent stalks bored in all three crops and stalk length bored in the second ratoon crop, but did not affect borer numbers per 100 stalks (E/100) or increase cane or sucrose yield. Borer damage and E/100 were significantly and consistently reduced in the resistant cultivar. Conclusions: We argue that if leaf Si% in field sugarcane can be elevated to or exceed 0.8 %, using materials that release Si slowly, substantial reductions in stalk damage and sucrose loss could be achieved in susceptible cultivars in low-Si soils. [ABSTRACT FROM AUTHOR]

The Threshold Capability Integrated Theoretical Framework (TCITF) is presented as a framework for the design of university curricula, aimed at developing graduates' capability to deal with previously unseen situations in their professional, social, and personal lives. The TCITF is a new theoretical framework derived from, and heavily dependent upon, the ideas of the Threshold Concepts Framework (Meyer and Land ; Land et al. ) and Capability Theory (Bowden and Marton ; Bowden et al. ; Bowden ). Capability theory is firmly based in phenomenography and variation theory, is concerned with the development of knowledge capability, but has had limited application in practice. The threshold concepts framework has enjoyed greater acceptance by a large range of academics in many fields. This acceptance has initially focussed on analytic studies of what constitutes a threshold concept-and the location and distribution of such concepts-in a given domain. In many instances subsequent attention has focussed on issues of pedagogy and assessment, including the design of curricula. We propose a merging of capability theory and the threshold concepts framework and argue that capability and variation theories provide the ideal mechanism for developing a strong pedagogical approach based on newly emerging knowledge of the critical features of threshold concepts within different domains. [ABSTRACT FROM AUTHOR]

The present study aims to analyse the complex relationships between the relevant constructs of students' demographic background, perceptions, learning patterns and (proxy measures of) learning outcomes in order to delineate the possible direct, indirect, or spurious effects among them. The analytical methodology is substantively framed against the studies of Richardson (British Journal of Educational Psychology 76:867-893, , Higher Education 54:385-416, ) that utilised a regression-based methodology to infer the possible causal relationships among the relevant learning constructs. A composite research instrument, written in Chinese and derived from the Inventory of Learning Styles (ILS) and the Course Experience Questionnaire (CEQ), was used to collect students' feedback on their perceptions of the learning environment and their learning patterns. Valid responses were obtained from 1,572 students studying at six institutions in the post-secondary education sector in Hong Kong, a new response-context for both the CEQ and the ILS. In adapting the research instruments to a new Chinese response-context, the findings are generally consistent with those reported in other published works (e.g. no relationship between students' demographic background and their satisfaction with the programme, and a significant relationship between students' exhibition of undirected learning patterns and low expected performance), but there are also some noteworthy discrepancies. The findings therefore buttress the confidence with which an ILS-based General Theoretical Model of student learning, adapted from Richardson (British Journal of Educational Psychology 76:867-893, , Higher Education 54:385-416, ), may be used to conceptualise and interpret the dynamics of variation across different cultural response-contexts. While the CEQ provides some valuable complementary insights, it is an instrument that requires further development in the response-context of the present study. [ABSTRACT FROM AUTHOR]

The present study builds on earlier work by Meyer and Land (2003) which introduced the generative notion ofthreshold conceptswithin (and across) disciplines, in the sense of transforming the internal view of subject matter or part thereof. In this earlier work such concepts were further linked to forms of knowledge that are ‘troublesome’, after the work of Perkins (1999). It was argued that these twinned sets of ideas may define critical moments of irreversible conceptual transformation in the educational experiences of learners, and their teachers. The present study aims (a) to examine the extent to which such phenomena can be located within personal understandings of discipline-specific epistemological discourses, (b) to develop more extensively notions ofliminalitywithin learning that were raised in the first paper, and (c) to propose a conceptual framework within which teachers may advance their own reflective practice. [ABSTRACT FROM AUTHOR]

Introduction: Changes in somatosensory evoked potentials (SEPs) were used to identify cerebral ischemia and to predict neurological outcome during the application of temporary clips in aneurysm surgery.Methods: SEPs were recorded intra-operatively in 76 patients with 79 aneurysms (8 in the posterior fossa). Twenty aneurysms ruptured during surgery, and 37 temporary clips were applied over an average of 8.1 minutes (range: 2-25 minutes).Results: Of 17 cases with complete loss of potential, 14 were associated with temporary clips. Two losses were persistent with postoperative neurological deficit after 10 minutes of clipping. Six showed incomplete recovery after a mean loss of 19.2 minutes following clipping of 9.3 minutes, resulting in a new deficit in four patients. Despite complete recovery of potential in six patients after a 1 loss over 18.8 minutes following clipping of 10.7 minutes, four patients developed neurological deficits. The sensitivity of SEPs in determining permanent neurological deficits was 57%, and the was specificity 88%. The duration of temporary clipping was significantly shorter in patients without resulting new neurological deficit (Mann-Whitney Test; p < 0.01). The risk of a new deficit was 30.7% in cases where less than 8 minutes of clipping was performed, and the risk was 80.9% when clipping exceeded 8 minutes. The extent of recovery of potentials and the duration of SEP changes was strongly associated with the postoperative deficits (Kolmogorov-Smirnov Test, p = 0.009; p = 0.001, Mann-Whitney Test). Pathological p(ti)O2 measurements were obtained in 6 of 12 patients. In four patients, temporary occlusion was followed by a parallel alteration of SEPs and p(ti)O2 below 10 mmHg.Conclusion: There is no genuinely safe permissible occlusion time. Despite complete recovery of SEPs after a loss of potential, the patient may develop new deficits. [ABSTRACT FROM AUTHOR]

The field trialling of inventory scales reflecting variation in students' mathematics study and learning processes is described. These scales predict learning outcomes (final marks), but with differentiated patterns of relationship to those outcomes. In combination, the scales also detect cohorts of students at risk of study failure. The work reported is in the broader context of developing an individual-differences-based model of student learning. Although this model is sited specifically within mathematics learning, the methodology of its development is transferable to other discipline contexts. The trialled scales complement others already developed that reflect affective variation in students' mathematics study. [ABSTRACT FROM AUTHOR]

Focuses on interpretive meanings associated with concepts of price in phenomenographic terminology within second order perspectives of students. Qualitative variation in student conception of price; Distinction between price associated with intrinsic property of commodity and resultant outcome of market forces; Interpretive limitations.

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An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Rolling resistance ranks among the top ten automobile megatrends, because it is directly linked to fuel efficiency and emissions reduction. The mechanisms controlling this phenomenon are hidden deeply inside the complexity of tire tread materials and do elude direct experimental observation. Here we use atomistic molecular modelling to identify a novel nano-mechanical mechanism for dissipative loss in silica filled elastomers when the latter are subjected to dynamic strain. The force-vs-particle separation curve of a single silica particle-to-silica particle contact, embedded inside a polyisoprene rubber matrix, is obtained, while the contact is opened and closed by a cyclic force. We confirm the occurrence of spontaneous relative displacements ('jolts') of the filler particles. These jolts give rise to energy dissipation in addition to the usual viscous loss in the polymer matrix. As the temperature is increased the new loss mechanism becomes dominant. This has important technical implications for the control and reduction of tire rolling resistance as well as for many other elastomer composite applications involving dynamic loading. [ABSTRACT FROM AUTHOR]