Ten-year immune persistence and safety of the HPV-16/18 AS04-adjuvanted vaccine in females vaccinated at 15–55 years of age

Women remain at risk of human papillomavirus (HPV) infection for most of their lives. The duration of protection against HPV-16/18 from prophylactic vaccination remains unknown. We investigated the 10-year immune response and long-term safety profile of the HPV-16/18 AS04-adjuvanted vaccine (AS04-HPV-16/18 vaccine) in females aged between 15 and 55 years at first vaccination. Females who received primary vaccination with three doses of AS04-HPV-16/18 vaccine in the primary phase-III study (NCT00196937) were invited to attend annual evaluations for long-term immunogenicity and safety. Anti-HPV-16/18 antibodies in serum and cervico-vaginal secretions (CVS) were measured using enzyme-linked immunosorbent assay (ELISA). Serious adverse events (SAEs) were recorded throughout the follow-up period. Seropositivity rates for anti-HPV-16 remained high (≥96.3%) in all age groups 10 years after first vaccination. It was found that 99.2% of 15–25-year olds remained seropositive for anti-HPV-18 compared to 93.7% and 83.8% of 26–45-year olds and 45–55-year olds, respectively. Geometric mean titers (GMT) remained above natural infection levels in all age groups. Anti-HPV-16 and anti-HPV-18 titers were at least 5.3-fold and 3.1-fold higher than titers observed after natural infection, respectively, and were predicted to persist above natural infection levels for ≥30 years in all age groups. At Year 10, anti-HPV-16/18 antibody titers in subjects aged 15–25 years remained above plateau levels observed in previous studies. Correlation coefficients for antibody titers in serum and CVS were 0.64 (anti-HPV-16) and 0.38 (anti-HPV-18). This study concluded that vaccinated females aged 15–55 years elicited sustained immunogenicity with an acceptable safety profile up to 10 years after primary vaccination, suggesting long-term protection against HPV

An overview of technical considerations for Western blotting applications to physiological research

The applications of Western/immuno-blotting (WB) techniques have reached multiple layers of the scientific community and are now considered routine procedures in the field of physiology. This is none more so than in relation to skeletal muscle physiology (i.e. resolving the mechanisms underpinning adaptations to exercise). Indeed, the inclusion of WB data is now considered an essential aspect of many such physiological publications to provide mechanistic insight into regulatory processes. Despite this popularity, and due to the ubiquitous and relatively inexpensive availability of WB equipment, the quality of WB in publications and subsequent analysis and interpretation of the data can be variable, perhaps resulting in spurious conclusions. This may be due to poor laboratory technique and/or lack of comprehension of the critical steps involved in WB and what quality control procedures should be in place to ensure robust data generation. The present review aims to provide a detailed description and critique of WB procedures and technicalities, from sample collection through preparation, blotting and detection to analysis of the data collected. We aim to provide the reader with improved expertise to critically conduct, evaluate and troubleshoot the WB process, to produce reproducible and reliable blots

The Apoptosome: Emerging Insights and New Potential Targets for Drug Design

Apoptosis plays a crucial role in tissue homeostasis, development and many diseases. The relevance of Apaf1, the molecular core of apoptosome, has been underlined in mitochondria-dependent apoptosis, which according to a growing body of evidence, is involved in various pathologies where the equilibrium of life-and-death is dysregulated, such as heart attack, stroke, liver failure, cancer and autoimmune diseases. Consequently, great interest has emerged in devising therapeutic strategies for regulating the key molecules involved in the life-and-death decision. Here we review recent progress in apoptosis-based pharmacological therapies and, in particular, we point out a possible role of the apoptosome as an emerging and promising pharmacological target

Enabling standardized cryptography on ultra-constrained 4-bit microcontrollers

4-bit microcontrollers (MCUs) are among the simplest, cheapest and most abundant computing devices that, thanks to their low power consumption, may be deployed even in passive RFID tags. Besides, 4-bit MCUs are embedded in a wide variety of daily-life objects that, when connected to a network, could become a substantial part of the Internet of Things. Despite the fact that quite a number of applications are security sensitive, no implementation of standardized cryptography has been available yet. In this work we present the first implementation of the Advanced Encryption Standard (AES) on a 4-bit MCU and thus, by closing this gap, enable security functionalities on myriads of legacy devices. Besides, we describe the first software implementation of PRINTcipher, a recently proposed block cipher optimized for printed electronics. We describe and apply various optimization techniques to develop time and code-size efficient implementations on the MARC4. As a result our AES implementation is not only the first on a 4-bit MCU, but also the most efficient among all cryptographic algorithms

Electric stimulation of the medial forebrain bundle influences sensorimotor gaiting in humans

BACKGROUND: Prepulse inhibition (PPI) of the acoustic startle response, a measurement of sensorimotor gaiting, is modulated by monoaminergic, presumably dopaminergic neurotransmission. Disturbances of the dopaminergic system can cause deficient PPI as found in neuropsychiatric diseases. A target specific influence of deep brain stimulation (DBS) on PPI has been shown in animal models of neuropsychiatric disorders. In the present study, three patients with early dementia of Alzheimer type underwent DBS of the median forebrain bundle (MFB) in a compassionate use program to maintain cognitive abilities. This provided us the unique possibility to investigate the effects of different stimulation conditions of DBS of the MFB on PPI in humans. RESULTS: Separate analysis of each patient consistently showed a frequency dependent pattern with a DBS-induced increase of PPI at 60 Hz and unchanged PPI at 20 or 130 Hz, as compared to sham stimulation. CONCLUSIONS: Our data demonstrate that electrical stimulation of the MFB modulates PPI in a frequency-dependent manner. PPI measurement could serve as a potential marker for optimization of DBS settings independent of the patient or the examiner

Diagnosis of Current Flow Patterns Inside Fault-Simulated Li-Ion Batteries via Non-Invasive, In Operando Magnetic Field Imaging

With the growing popularity of Li-ion batteries in large-scale applications, building a safer battery has become a common goal of the battery community. Although the small errors inside the cells trigger catastrophic failures, tracing them and distinguishing cell failure modes without knowledge of cell anatomy can be challenging using conventional methods. In this study, a real-time, non-invasive magnetic field imaging (MFI) analysis that can signal the battery current-induced magnetic field and visualize the current flow within Li-ion cells is developed. A high-speed, spatially resolved MFI scan is used to derive the current distribution pattern from cells with different tab positions at a current load. Current maps are collected to determine possible cell failures using fault-simulated batteries that intentionally possess manufacturing faults such as lead-tab connection failures, electrode misalignment, and stacking faults (electrode folding). A modified MFI analysis exploiting the magnetic field interference with the countercurrent-carrying plate enables the direct identification of defect spots where abnormal current flow occurs within the pouch cells. © 2023 Wiley-VCH GmbH.FALS

Traffic perception and hazard avoidance - Foundations and possibilities for implementation in novice driver preparation

Der vorliegende Innovationsbericht beschreibt die Forschungs- und Entwicklungsschwerpunkte der TÜV | DEKRA arge tp 21 im Hinblick auf das Fahrerlaubnisprüfungssystem für den Zeitraum 2011 - 2014. Diese lagen (1) in der Aufbereitung wissenschaftlicher Grundlagen zur Vermittlung und Erfassung von Kompetenzen im Bereich der Verkehrswahrnehmung und Gefahrenvermeidung bei Fahranfängern, (2) in der Evaluation und Weiterentwicklung der Theoretischen Fahrerlaubnisprüfung und (3) in Forschungs- und Entwicklungsarbeiten zur Optimierung der Praktischen Fahrerlaubnisprüfung sowie (4) in der Beschreibung des fahrzeugtechnischen Wandels und seiner Bedeutung für die Fahrausbildung und Fahrerlaubnisprüfung. Zu (1): Kompetenzdefizite von Fahranfängern gegenüber erfahrenen Fahrern in der Verkehrswahrnehmung und Gefahrenvermeidung sind durch eine Vielzahl empirischer Studien belegt. Die systematische Vermittlung und Aneignung entsprechender Fähigkeiten im Vorfeld der selbständigen Verkehrsteilnahme erscheint deshalb vielversprechend für die Verringerung fahranfängertypischer Unfallrisiken. Der Entwicklung diesbezüglicher Ausbildungs- und Prüfungskonzepte muss jedoch zunächst eine Beschreibung der zugrunde liegenden psychologischen Konstrukte vorausgehen. Im Berichtszeitraum wurden dazu die relevanten wahrnehmungs- und verkehrspsychologischen Grundlagen aufgearbeitet. Weiterhin wurden die international im Fahrerlaubniswesen bereits praktizierten innovativen PC-basierten Prüfungsansätze wie auch experimentelle Untersuchungen aus der "Hazard Perception"-Forschung analysiert. Schließlich wurden Lehr-Lernangebote für Fahranfänger recherchiert. Mit den im Bericht vorgelegten Ergebnissen wurde der theoretische Grundstein für die künftige Verankerung der Verkehrswahrnehmung und Gefahrenvermeidung in der Fahranfängervorbereitung gelegt. Hieran wird nun die Erarbeitung innovativer Lernangebote und Prüfungsaufgaben für Fahranfänger anschließen. Zu (2): Die Arbeiten zur Theoretischen Fahrerlaubnisprüfung umfassten die Evaluation von Prüfungsaufgaben und Paralleltests sowie auch weiterführende empirische Untersuchungen zur Bearbeitung anlassbezogener Fragestellungen (u. a. Modellrechnungen zur Erarbeitung von empirisch gestützten Empfehlungen für eine optimierte Prüfungsbewertung). Weiterhin wurden 2014, d. h. zum Ende des Berichtszeitraums, erstmals Aufgaben mit dynamischen Situationsdarstellungen eingesetzt. Die vorbereitenden Forschungs- und Entwicklungsarbeiten werden im Bericht überblicksartig dargestellt. Nicht zuletzt werden erste Ergebnisse der empirischen Erprobung innovativer Aufgabenformate diskutiert, bei denen neuartige Formen der Antworteingabe (Tastendruck, Pedal) und der Leistungsbewertung (Reaktionszeit) verwendet wurden. Die skizzierten Forschungsarbeiten lassen erkennen, dass seit einigen Jahren die Vorteile des Prüfmediums "Computer" erfolgreich genutzt werden. Sie zeigen jedoch auch, dass die PC-gestützte Prüfung weitere Potentiale " insbesondere im Bereich der Aufgabenentwicklung und Testkonstruktion " birgt, die es zukünftig auszuschöpfen gilt. Zu (3): Die Arbeiten zur Praktischen Fahrerlaubnisprüfung waren im Wesentlichen durch drei verbundene Projekte gekennzeichnet: Das BASt-Projekt "Optimierung der Praktischen Fahrerlaubnisprüfung" diente der Erarbeitung methodischer Grundlagen (es begann 2008 und endete im ersten Jahr des Berichtszeitraumes). Als zweites folgte eine von der TÜV | DEKRA arge tp 21 durchgeführte Machbarkeitsstudie (2011 bis 2012) zur Untersuchung der Praktikabilität einer elektronischen Prüfungsdokumentation ("e-Prüfprotokoll"). Das BASt-Projekt "Revision zu einer optimierten Praktischen Fahrerlaubnisprüfung" stellt schließlich das dritte Projekt dar (es begann im Jahr 2013 und wird über den Berichtszeitraum hinaus bis 2015 fortgeführt). Es dient dazu, die Inhalte, Verfahren und Abläufe der Prüfung (einschließlich Verfahrensweisen zu einer kontinuierlichen Evaluation) bis hin zur Einsatzreife weiterzuentwickeln und in ausgewählten Modellregionen zu erproben. Mit einer bundesweiten Implementierung der erarbeiteten Standards würde gewährleistet, dass die Entscheidung über die Zulassung zum motorisierten Straßenverkehr künftig auf einer differenzierten Fahrkompetenzeinschätzung basiert und festgestellte Kompetenzdefizite systematisch erfasst und zurückgemeldet werden " dies lässt eine verbesserte Sicherheitswirksamkeit der Praktischen Fahrerlaubnisprüfung erwarten. Zu (4): Fahrzeugtechnische Innovationen " seien es Fahrerassistenzsysteme, Antriebskonzepte ("e-Mobilität") oder das (teil-)automatisierte Fahren " kommen in immer kürzeren Abständen auf den Markt. Diese Entwicklungen sind mit veränderten Anforderungen an das Fahren verbunden und haben daher maßgeblichen Einfluss auf den Erwerb, die Überpruefung und den Erhalt von Fahrkompetenz. Im Bericht werden die daraus resultierenden zukünftigen Aufgabenstellungen für die Technischen Prüfstellen skizziert.The present innovation report describes key topics addressed in the relevant research and development activities of the TÜV | DEKRA arge tp 21 working group during the report period from 2011 to 2014. Such essential aspects were (1) presentation of the scientific foundations for development and assessment of novice driver competence relating to traffic perception and hazard avoidance, (2) evaluation and further development of the theoretical driving test, (3) research and development work aimed at optimisation of the practical driving test, and (4) description of the continuing advances in vehicle engineering and their significance for both driver training and testing. Re (1): Numerous empirical studies point to the competence deficits displayed by novice drivers compared to more experienced drivers in respect of traffic perception and hazard avoidance. The systematic development and acquisition of corresponding skills in advance of their solo participation in road traffic thus appears promising as a means to reduce novice-typical accident risks. The development of training and test concepts addressing traffic perception and hazard avoidance, however, requires prior description of the underlying psychological constructs. During the report period, the relevant perceptual and traffic psychology foundations were analysed alongside innovative, computer-based approaches which have already been implemented in international driving licence testing and experimental studies from the field of hazard perception research. A further study was conducted to survey teaching and learning offers for novice drivers. The results presented in the report provide a theoretical basis for the future anchoring of traffic perception and hazard avoidance in the system of novice driver preparation. This work must now be continued with the elaboration of innovative learning offers and corresponding assessment tasks for novice drivers. Re (2): The work on the theoretical driving test referred to the evaluation of individual test items and their assignment to parallel tests, as well as further empirical studies to answer specifically arising questions (e.g. model calculations to enable the elaboration of empirically founded recommendations on optimisation of the test assessment). In 2014, i.e. at the end of the current report period, furthermore, test items based on dynamic situation presentations were used for the first time. The report provides an overview of the preparatory research and development work. Last but not least, initial results from the empirical testing of innovative task formats implementing new forms of response input (keyboard, foot pedal) and performance assessment (reaction time) are discussed. The research and development work outlined in the report illustrates how benefits of the new test medium "computer" have been utilised successfully for a number of years. It is equally evident, however, that significant further potential is embodied in computer-based testing " especially in respect of task development and test design; the objective for the future must be to exploit this potential. Re (3): The research work on development of the practical driving test was essentially dominated by three projects: The BASt project "Optimisation of the Practical Driving Test" served to elaborate methodical foundations (it began in 2008 and was brought to conclusion during the first year of the report period). The second project was a feasibility study to investigate the practicability of an electronic test report, which was conducted by the TÜV | DEKRA arge tp 21 working group (2011 to 2012). The BASt project "Revision Project on an Optimised Practical Driving Test", finally, was commenced in 2013 and is scheduled to continue beyond the current report period into 2015. Its purpose is to continue development of the corresponding contents, methods and procedures (including methods which will enable continuous evaluation). Once ready for actual use, the results are to be tested in selected model regions. Subsequent nationwide implementation of the elaborated standards would ensure that decisions on the eligibility to participate in motorised road traffic are based on a differentiated assessment of driving competence. At the same time, observed competence deficits could be recorded systematically and communicated to the driving license applicant. This can be expected to strengthen the safety-enhancing impact of the practical driving test. Re (4): Technical innovations in vehicle engineering " whether driver assistance systems, new drive concepts ("e-mobility") or solutions for (partially) automated vehicle control " are entering the market at ever shorter intervals. Such developments bring changes in the demands placed on drivers and thus exert a decisive influence on the acquisition, assessment and upholding of driving competence. The report outlines the tasks resulting for the Technical Examination Centres in the future