Synthesis and biological evaluation of a novel MUC1 glycopeptide conjugate vaccine candidate comprising a 4'-deoxy-4'-fluoro-Thomsen-Friedenreich epitope

The development of selective anticancer vaccines that provide enhanced protection against tumor recurrence and metastasis has been the subject of intense research in the scientific community. The tumor-associated glycoprotein MUC1 represents a well-established target for cancer immunotherapy and has been used for the construction of various synthetic vaccine candidates. However, many of these vaccine prototypes suffer from an inherent low immunogenicity and are susceptible to rapid in vivo degradation. To overcome these drawbacks, novel fluorinated MUC1 glycopeptide-BSA/TTox conjugate vaccines have been prepared. Immunization of mice with the 4' F-TF-MUC1-TTox conjugate resulted in strong immune responses overriding the natural tolerance against MUC1 and producing selective IgG antibodies that are cross-reactive with native MUC1 epitopes on MCF-7 human cancer cells

Bandwidth selection for kernel density estimation: a review of fully automatic selectors

On the one hand, kernel density estimation has become a common tool for empirical studies in any research area. This goes hand in hand with the fact that this kind of estimator is now provided by many software packages. On the other hand, since about three decades the discussion on bandwidth selection has been going on. Although a good part of the discussion is about nonparametric regression, this parameter choice is by no means less problematic for density estimation. This becomes obvious when reading empirical studies in which practitioners have made use of kernel densities. New contributions typically provide simulations only to show that the own selector outperforms some of the existing methods. We review existing methods and compare them on a set of designs that exhibit few bumps and exponentially falling tails. We concentrate on small and moderate sample sizes because for large ones the differences between consistent methods are often negligible, at least for practitioners. As a byproduct we find that a mixture of simple plug-in and cross-validation methods produces bandwidths with a quite stable performanc

Implementing miscanthus into farming systems:A review of agronomic practices, capital and labour demand

Miscanthus is a promising bioeconomy crop with several biomass utilisation pathways. However, its current cultivation area in Europe is relatively low. This is most likely due to a lack of knowledge about the imple- mentation of miscanthus into farming systems. This study reviews current best practices and suitable land areas for miscanthus cultivation. Biomass production costs and labour requirements were evaluated over the whole 20- year cultivation cycle of four utilisation pathways: combustion, animal bedding, and both conventional and organic biogas production. The assessment was performed for two field sizes (1 and 10 ha), two average annual yield levels (15 and 25 t dry matter ha 1), and both green and brown harvest regimes. The maximum attainable annual gross margins are 1657 € ha 1 for combustion, 13,920 € ha 1 for animal bedding, 2066 € ha 1 for conventional and 2088 € ha 1 for organic biogas production. The combustion pathway has the lowest labour demand (141.5 h ha 1), and animal bedding the highest (317.6 h ha 1) due to additional baling during harvest. Suitable cultivation areas include depleted soils, erosion-prone slopes, heavy clay soils and ecological focus areas such as riparian buffer zones and groundwater protection areas. On such sites, miscanthus would (i) improve soil and water quality, and (ii) enable viable agricultural land utilisation even on scattered patches and strips. Due to its low demands and perennial nature, miscanthus is suitable for sustainable intensification of indus- trial crop cultivation in a growing bioeconomy, benefiting soil and water quality, while providing large amounts of biomass for several utilisation pathways

Prosodic prominence in parkinsonian speech : a dynamical approach

In the present study, we investigate dynamic changes in prosodic highlighting strategies in PD patients and compare them to the productions of neurotypical speakers. Therefore, we compare the production of target words in divergent focus structure, contrastive focus and background. We recorded 40 German speakers: 20 patients with idiopathic Parkinson in medication ON condition, 14 males and 6 females, aged between 54 - 80 and 20 healthy aged and gender matched controls. All speakers were classified in terms of duration of the disorder, severity of the disorder, motoric activity level (UPDRS III, [6]), level of cognition and speech problems in terms of dysarthria. As speech material, we used a question-answer scenario presented on a computer screen to manipulate focal structure by means of contextualizing contexts. Nine target words were placed in either contrastive focus or background position in sentences such as (“The fly has touched the green nose.”) related to pictures on a computer screen [cf. fig.1]. Target words were always disyllabic (CV.CV structure), containing one of the three long vowels /i:/, /a:/ or /o:/, in the stressed syllable, such as /na:z@/. In total, we recorded 1440 tokens (9 target words x 40 speakers x 2 focus structures x 2 adjectives). For acoustic measurements, we analyzed the voice range, syllable duration, formant means and contours, the mean intensity and the F0 contours in terms of pitch height and tonal onglide [7]. For the upcoming conference, the results of all intonational and articulatory variables will be presented. We will discuss how much variation is tolerated in a dynamical system of prosodic prominence before the expression of prosodic functions is getting instable

Coarse‐Grained Refractory Composite Castables Based on Alumina and Niobium

Niobium-alumina composite aggregates with 60 vol% metal content and with particle sizes up to 3150 μm are produced using castable technology followed by sintering, and a crushing and sieving process. X-Ray diffraction (XRD) analysis reveals phase separation during crushing as the niobium:corundum volume ratios is between 37:57 and 64:31 among the 4 produced aggregate classes 0–45, 45–500, 500–1000, and 1000–3150 μm. The synthesized aggregates are used to produce coarse-grained refractory composites in a second casting and sintering step. The fine- and coarse-grained material shows porosities between 32% and 36% with a determined cold modulus of rupture of 20 and 12 MPa, and E-moduli of 37 and 46 GPa, respectively. The synthesized fine-grained composites reached true strain values between 0.08 at 1100 °C and 0.18 at 1500 °C and the coarse-grained ones values between 0.02 and 0.09. The electrical conductivity for the fine-grained and the coarse-grained material is 448±66 and 111±25  S cm$^{−1}$, respectively

Effect of a multinutrient intervention after ischemic stroke in female C57Bl/6 mice.

Stroke can affect females very differently from males, and therefore preclinical research on underlying mechanisms and the effects of interventions should not be restricted to male subjects, and treatment strategies for stroke should be tailored to benefit both sexes. Previously, we demonstrated that a multinutrient intervention (Fortasyn) improved impairments after ischemic stroke induction in male C57Bl/6 mice, but the therapeutic potential of this dietary treatment remained to be investigated in females. We now induced a transient middle cerebral artery occlusion (tMCAo) in C57Bl/6 female mice and immediately after surgery switched to either Fortasyn or an isocaloric Control diet. The stroke females performed several behavioral and motor tasks before and after tMCAo and were scanned in an 11.7 Tesla MRI scanner to assess brain perfusion, integrity and functional connectivity. To assess brain plasticity, inflammation and vascular integrity, immunohistochemistry was performed after sacrifice of the mice. We found that the multinutrient intervention had diverse effects on the stroke-induced impairments in females. Similar to previous observations in male stroke mice, brain integrity, sensorimotor integration and neurogenesis benefitted from Fortasyn, but impairments in activity and motor skills were not improved in female stroke mice. Overall, Fortasyn effects in the stroked females seem more modest in comparison to previously investigated stroked male mice. We suggest that with further optimization of treatment protocols more information on the efficacy of specific interventions in stroked females can be gathered. This in turn will help with the development of (gender-specific) treatment regimens for cerebrovascular diseases such as stroke

Short-term mechanical support with the Impella 5.x for mitral valve surgery in advanced heart failure—protected cardiac surgery

IntroductionSurgical treatment of patients with mitral valve regurgitation and advanced heart failure remains challenging. In order to avoid peri-operative low cardiac output, Impella 5.0 or 5.5 (5.x), implanted electively in a one-stage procedure, may serve as a peri-operative short-term mechanical circulatory support system (st-MCS) in patients undergoing mitral valve surgery.MethodsBetween July 2017 and April 2022, 11 consecutive patients underwent high-risk mitral valve surgery for mitral regurgitation supported with an Impella 5.x system (Abiomed, Inc. Danvers, MA). All patients were discussed in the heart team and were either not eligible for transcatheter edge-to-edge repair (TEER) or surgery was considered favorable. In all cases, the indication for Impella 5.x implantation was made during the preoperative planning phase.ResultsThe mean age at the time of surgery was 61.6 ± 7.7 years. All patients presented with mitral regurgitation due to either ischemic (n = 5) or dilatative (n = 6) cardiomyopathy with a mean ejection fraction of 21 ± 4% (EuroScore II 6.1 ± 2.5). Uneventful mitral valve repair (n = 8) or replacement (n = 3) was performed via median sternotomy (n = 8) or right lateral mini thoracotomy (n = 3). In six patients, concomitant procedures, either tricuspid valve repair, aortic valve replacement or CABG were necessary. The mean duration on Impella support was 8 ± 5 days. All, but one patient, were successfully weaned from st-MCS, with no Impella-related complications. 30-day survival was 90.9%.ConclusionProtected cardiac surgery with st-MCS using the Impella 5.x is safe and feasible when applied in high-risk mitral valve surgery without st-MCS-related complications, resulting in excellent outcomes. This strategy might offer an alternative and comprehensive approach for the treatment of patients with mitral regurgitation in advanced heart failure, deemed ineligible for TEER or with need of concomitant surgery