123 research outputs found
Work-to-family enrichment and gender inequalities in eight European countries
All social roles have positive and rewarding as well as negative/problematic aspects. Research on the workâfamily interface has predominantly focused on conflicting roles. In contrast, this paper extends research on workâfamily enrichment (WFE), a positive aspect of work and gender differences in WFE in a cross-national context. Drawing upon social role theory and the culture sensitive theory on workâfamily enrichment, we examined gender differences in experiences of developmental WFE in a sample of service sector employees in eight European countries. In line with traditional gender roles, women reported more WFE than men. The relationship was moderated by both an objective and subjective measure of gender egalitarianism but in the opposite direction as hypothesized. The gender gap in WFE was larger in more gender-egalitarian countries, where women may be better able to transfer resources from the work domain to benefit their family role than in low egalitarian societies. National differences in labour market factors, family models and the public discourse on workâlife balance mainly explain the unanticipated findings
Fn3 Proteins Engineered to Recognize Tumor Biomarker Mesothelin Internalize Upon Binding
Mesothelin is a cell surface protein that is overexpressed in numerous cancers, including breast, ovarian, lung, liver, and pancreatic tumors. Aberrant expression of mesothelin has been shown to promote tumor progression and metastasis through interaction with established tumor biomarker CA125. Therefore, molecules that specifically bind to mesothelin have potential therapeutic and diagnostic applications. However, no mesothelin-targeting molecules are currently approved for routine clinical use. While antibodies that target mesothelin are in development, some clinical applications may require a targeting molecule with an alternative protein fold. For example, non-antibody proteins are more suitable for molecular imaging and may facilitate diverse chemical conjugation strategies to create drug delivery complexes. In this work, we engineered variants of the fibronectin type III domain (Fn3) non-antibody protein scaffold to bind to mesothelin with high affinity, using directed evolution and yeast surface display. Lead engineered Fn3 variants were solubly produced and purified from bacterial culture at high yield. Upon specific binding to mesothelin on human cancer cell lines, the engineered Fn3 proteins internalized and co-localized to early endosomes. To our knowledge, this is the first report of non-antibody proteins engineered to bind mesothelin. The results validate that non-antibody proteins can be engineered to bind to tumor biomarker mesothelin, and encourage the continued development of engineered variants for applications such as targeted diagnostics and therapeutics
Fn3 Proteins Engineered to Recognize Tumor Biomarker Mesothelin Internalize Upon Binding
Mesothelin is a cell surface protein that is overexpressed in numerous cancers, including breast, ovarian, lung, liver, and pancreatic tumors. Aberrant expression of mesothelin has been shown to promote tumor progression and metastasis through interaction with established tumor biomarker CA125. Therefore, molecules that specifically bind to mesothelin have potential therapeutic and diagnostic applications. However, no mesothelin-targeting molecules are currently approved for routine clinical use. While antibodies that target mesothelin are in development, some clinical applications may require a targeting molecule with an alternative protein fold. For example, non-antibody proteins are more suitable for molecular imaging and may facilitate diverse chemical conjugation strategies to create drug delivery complexes. In this work, we engineered variants of the fibronectin type III domain (Fn3) non-antibody protein scaffold to bind to mesothelin with high affinity, using directed evolution and yeast surface display. Lead engineered Fn3 variants were solubly produced and purified from bacterial culture at high yield. Upon specific binding to mesothelin on human cancer cell lines, the engineered Fn3 proteins internalized and co-localized to early endosomes. To our knowledge, this is the first report of non-antibody proteins engineered to bind mesothelin. The results validate that non-antibody proteins can be engineered to bind to tumor biomarker mesothelin, and encourage the continued development of engineered variants for applications such as targeted diagnostics and therapeutics
Electrically controlled long-distance spin transport through an antiferromagnetic insulator
Spintronics uses spins, the intrinsic angular momentum of electrons, as an
alternative for the electron charge. Its long-term goal is in the development
of beyond-Moore low dissipation technology devices. Recent progress
demonstrated the long-distance transport of spin signals across ferromagnetic
insulators. Antiferromagnetically ordered materials are however the most common
class of magnetic materials with several crucial advantages over ferromagnetic
systems. In contrast to the latter, antiferromagnets exhibit no net magnetic
moment, which renders them stable and impervious to external fields. In
addition, they can be operated at THz frequencies. While fundamentally their
properties bode well for spin transport, previous indirect observations
indicate that spin transmission through antiferromagnets is limited to short
distances of a few nanometers. Here we demonstrate the long-distance, over tens
of micrometers, propagation of spin currents through hematite (\alpha-Fe2O3),
the most common antiferromagnetic iron oxide, exploiting the spin Hall effect
for spin injection. We control the spin current flow by the interfacial
spin-bias and by tuning the antiferromagnetic resonance frequency with an
external magnetic field. This simple antiferromagnetic insulator is shown to
convey spin information parallel to the compensated moment (N\'eel order) over
distances exceeding tens of micrometers. This newly-discovered mechanism
transports spin as efficiently as the net magnetic moments in the best-suited
complex ferromagnets. Our results pave the way to ultra-fast, low-power
antiferromagnet-insulator-based spin-logic devices that operate at room
temperature and in the absence of magnetic fields
Pest and disease management system for supporting winter oilseed rape decisions (PASSWORD) - vaildation phase (HGCA Project Report No. 390)
Pests and particularly diseases cause serious loss of yield and quality in winter oilseed rape estimated to exceed ÂŁ80 million/annum in some years. These losses have occurred despite an annual expenditure of about ÂŁ3.5 million for insecticides and ÂŁ12 million on fungicides. Decision-making is difficult because there is complex spatial and temporal variation in pest and disease problems and improved guidance is required. The main objective of this project was to test new disease models developed in the first phase of this project and deliver a decision support system for both pest and disease control in oilseed rape.
The regional light leaf spot forecast is well-established and reliable and indicates an increased risk of this disease in spring 2006. A new regional forecast for stem canker incidence preharvest has been developed and made available on the Internet. It was successful in 2004/05 and offers strategic guidance on risk provided weather factors are within the range used to develop the model. A four-stage crop-specific stem canker risk assessment method was developed that predicts the onset of phoma leaf spotting using post-harvest weather data and thermal time relationships for canker development and canker severity. Yield loss can then be calculated from canker severity and the economic impact of stem canker predicted.
There is some flexibility in the timing of fungicide sprays to control stem canker. Delays of 2 to 3 weeks beyond a 10-20% plants affected threshold did not adversely affect yield. Stem canker severity and yield of different cultivars showed large variation between years and sites and smaller, but significant, variation in responses to fungicide. When phoma leaf spot appears in late autumn, it is only when plants are small that stem canker is likely to cause yield loss. In commercial crops, there were consistent trends for higher yields to be associated with higher fungicide inputs. Light leaf spot was very difficult to control with fungicides in the Aberdeen area where use of resistant cultivars is essential. The most effective disease control was obtained using a combination of resistant cultivars and fungicides. In some years, responses to fungicides were not cost-effective and targeting their use to high-risk situations is necessary to give the best margins over input costs.
Close contact was maintained with potential users during the project and they influenced priorities and design features. The components of PASSWORD decision support system were tested and provide guidance for the management of invertebrate pests, phoma stem canker and light leaf spot. The system will be available to ArableDS for use in autumn 2006
Temporal and spectral fingerprint of ultrafast all-coherent spin switching
Future information technology demands ultimately fast, low-loss quantum control. Intense light fields have facilitated important milestones, such as inducing novel states of matter, accelerating electrons ballistically, or coherently flipping the valley pseudospin. These dynamics leave unique signatures, such as characteristic bandgaps or high-order harmonic radiation. The fastest and least dissipative way of switching the technologically most important quantum attribute â the spin â between two states separated by a potential barrier is to trigger an all-coherent precession. Pioneering experiments and theory with picosecond electric and magnetic fields have suggested this possibility, yet observing the actual dynamics has remained out of reach. Here, we show that terahertz (1 THz = 1012 Hz) electromagnetic pulses allow coherent navigation of spins over a potential barrier and we reveal the corresponding temporal and spectral fingerprints. This goal is achieved by coupling spins in antiferromagnetic TmFeO3 with the locally enhanced THz electric field of custom-tailored antennas. Within their duration of 1 ps, the intense THz pulses abruptly change the magnetic anisotropy and trigger a large-amplitude ballistic spin motion. A characteristic phase flip, an asymmetric splitting of the magnon resonance, and a long-lived offset of the Faraday signal are hallmarks of coherent spin switching into adjacent potential minima, in agreement with a numerical simulation. The switchable spin states can be selected by an external magnetic bias. The low dissipation and the antennaâs sub-wavelength spatial definition could facilitate scalable spin devices operaÂŹting at THz rates
Validierung und ReliabilitĂ€tsprĂŒfung des Nijmegen Cochlear Implant Questionnaire in deutscher Sprache
Hintergrund: Der Nijmegen Cochlear Implant Questionnaire (NCIQ) ist ein krankheitsspezifischer Fragebogen zur Erhebung der gesundheitsbezogenen LebensqualitĂ€t von Patienten vor und nach Cochleaimplantation. Ziel der Arbeit: Validierung und ReliabilitĂ€tsprĂŒfung der deutschen Ăbersetzung des NCIQ. Material und Methoden: Es wurde eine prospektive Studie an 100 postlingual ertaubten oder hochgradig schwerhörigen Patienten durchgefĂŒhrt, welche prĂ€operativ sowie 3 und 6 Monate nach einer Cochleaimplantation mittels NCIQ, Abbreviated Profile of Hearing Aid Benefit (APHAB) und Hearing Participation Scale (HPS) untersucht wurden. Als Kontrolle fungierte ein postlingual ertaubtes oder hochgradig schwerhöriges, unbehandeltes Patientenkollektiv (nâŻ=â54). Cronbachâα und Test-Retest-ReliabilitĂ€t dienten der ReliabilitĂ€tsĂŒberprĂŒfung. Es wurde auf Inhaltsâ, Ăbereinstimmungs- und auf diskriminative ValiditĂ€t getestet. Die KonstruktvaliditĂ€tsprĂŒfung basiert auf kĂŒrzlich veröffentlichen Daten. Als GĂŒtekriterien wurden die SensitivitĂ€t und eine ROC("Receiver Operating Characteristic")-Analyse, inklusive AUC("Area Under the ROC Curve")-Betrachtung, eingesetzt. Ergebnisse: Das Test-Retesting ergab nach 3 und 6 Monaten postoperativ stabile NCIQ-Werte. Die Cronbach-α-Werte wiesen auf eine gute interne Konsistenz hin. Der NCIQ diskriminierte valide zwischen behandelten und unbehandelten Patientengruppen. Es ergaben sich statistisch signifikante, wenn auch schwache, Korrelationen zwischen dem NCIQ und dem APHAB (râŻ=â-0,22; pâŻ=â0,04) und dem HPS (râŻ=â0,30; pâŻ=â0,01). SensitivitĂ€ts- und ROC-Analysen zeigten eine gute MessqualitĂ€t des deutschsprachigen NCIQ. Schlussfolgerung: Die deutsche Ăbersetzung des NCIQ misst zuverlĂ€ssig und valide die LebensqualitĂ€t vor und nach Cochleaimplantation und kann zur klinischen Erfolgskontrolle nach Cochleaimplantationen verwendet werden.Background: The Nijmegen Cochlear Implant Questionnaire (NCIQ) is a disease-speciïŹc
questionnaire to determine the health-related quality of life (HRQoL) of patients before
and after cochlear implantation. Objective: This study aimed to assess the validity and reliability of the German translation of the NCIQ. Materials and methods: A prospective study was performed in 100 postlingually deaf or severely hearing-impaired patients. HRQoL was assessed using the NCIQ, the Abbreviated ProïŹle of Hearing Aid BeneïŹt (APHAB), and the Hearing Participation Scale (HPS) before as well as 3 and 6 months after cochlear implantation. An untreated group of postlingually deaf or severely hearing-impaired patients (n = 54) served as a control. Cronbach's α and testâretest reliability were measured. The content, discrimination, and agreement validity were tested. The evaluation of construct validity was based on recently published data. Sensitivity and receiver operating curve (ROC) analysis,
including consideration of the area under the curve (AUC), were used as quality criteria. Results: The test-retest analysis showed stable NCIQ values 3 and 6 months postoperatively. The Cronbachâs α values indicated good internal consistency. The NCIQ validly discriminated between treated and untreated patient groups. There were statistically signiïŹcant albeit weak correlations between the NCIQ and the APHAB (r = -0.22; p = 0.04) and the HPS (r = 0.30; p = 0.01). Sensitivity and ROC analyses showed good measurement quality of the German-speaking NCIQ. Conclusion: The German translation of the NCIQ reliably and validly measures HRQoL before and after cochlear implantation and can be used for clinical monitoring after treatment with cochlear implants
Selenoprotein dio2 is a regulator of mitochondrial function, morphology and uprmt in human cardiomyocytes
Members of the fetal-gene-program may act as regulatory components to impede deleterious events occurring with cardiac remodeling, and constitute potential novel therapeutic heart failure (HF) targets. Mitochondrial energy derangements occur both during early fetal development and in patients with HF. Here we aim to elucidate the role of DIO2, a member of the fetal-gene-program, in pluripotent stem cell (PSC)-derived human cardiomyocytes and on mitochondrial dynamics and energetics, specifically. RNA sequencing and pathway enrichment analysis was performed on mouse cardiac tissue at different time points during development, adult age, and ischemia-induced HF. To determine the function of DIO2 in cardiomyocytes, a stable human hPSC-line with a DIO2 knockdown was made using a short harpin sequence. Firstly, we showed the selenoprotein, type II deiodinase (DIO2): the enzyme responsible for the tissue-specific conversion of inactive (T4) into active thyroid hormone (T3), to be a member of the fetal-gene-program. Secondly, silencing DIO2 resulted in an increased reactive oxygen species, impaired activation of the mitochondrial unfolded protein response, severely impaired mitochondrial respiration and reduced cellular viability. Microscopical 3D reconstruction of the mitochondrial network displayed substantial mitochondrial fragmentation. Summarizing, we identified DIO2 to be a member of the fetal-gene-program and as a key regulator of mitochondrial performance in human cardiomyocytes. Our results suggest a key position of human DIO2 as a regulator of mitochondrial function in human cardiomyocytes
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