Application of machine learning to predict monomer retention of therapeutic proteins after long term storage.

An important aspect of initial developability assessments as well formulation development and selection of therapeutic proteins is the evaluation of data obtained under accelerated stress condition, i.e. at elevated temperatures.

Catch-up-ESUS - follow-up in embolic stroke of undetermined source (ESUS) in a prospective, open-label, observational study: study protocol and initial baseline data.

Introduction: So far there is no uniform, commonly accepted diagnostic and therapeutic algorithm for patients with embolic stroke of undetermined source (ESUS). Recent clinical trials on secondary stroke prevention in ESUS did not support the use of oral anticoagulation. As ESUS comprises heterogeneous subgroups including a wide age-range, concomitant patent foramen ovale (PFO), and variable probability for atrial fibrillation (AF), an individualised approach is urgently needed.

Maximum tensile stress and strain of skin of the domestic pig-differences concerning pigs from organic and non-organic farming.

The purpose of this work has been to determine differences in biomechanical properties of porcine skin from organic and non-organic farming as porcine skin is widely used as a model for human skin. A test apparatus was used, using gravity to stretch and finally tear a dumbbell-shaped specimen of prepared abdominal skin with a testing surface area of 25 × 4 mm. A total of 32 specimens were taken from seven individual pigs, three from organic and four from non-organic farming, in different orientations with respect to the Langer's lines.

Advancing Therapeutic Protein Discovery and Development through Comprehensive Computational and Biophysical Characterization.

Therapeutic protein candidates should exhibit favorable properties that render them suitable to become drugs. Nevertheless, there are no well-established guidelines for the efficient selection of proteinaceous molecules with desired features during early stage development. Such guidelines can emerge only from a large body of published research that employs orthogonal techniques to characterize therapeutic proteins in different formulations.

Enhancement of de novo sequencing, assembly and annotation of the Mongolian gerbil genome with transcriptome sequencing and assembly from several different tissues.

Background: The Mongolian gerbil (Meriones unguiculatus) has historically been used as a model organism for the auditory and visual systems, stroke/ischemia, epilepsy and aging related research since 1935 when laboratory gerbils were separated from their wild counterparts. In this study we report genome sequencing, assembly, and annotation further supported by transcriptome sequencing and assembly from 27 different tissues samples.

Results: The genome was sequenced using Illumina HiSeq 2000 and after assembly resulted in a final genome size of 2.

Molecule-Induced Radical Formation (MIRF) Reactions-A Reappraisal.

Radical chain reactions are commonly initiated through the thermal or photochemical activation of purpose-built initiators, through photochemical activation of substrates, or through well-designed redox processes. Where radicals come from in the absence of these initiation strategies is much less obvious and are often assumed to derive from unknown impurities. In this situation, molecule-induced radical formation (MIRF) reactions should be considered as well-defined alternative initiation modes.

Diagnosis of Feline Infectious Peritonitis: A Review of the Current Literature.

Feline infectious peritonitis (FIP) is a fatal disease that poses several challenges for veterinarians: clinical signs and laboratory changes are non-specific, and there are two pathotypes of the etiologic agent feline coronavirus (FCoV), sometimes referred to as feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV) that vary fundamentally in their virulence, but are indistinguishable by a number of diagnostic methods. This review focuses on all important steps every veterinary practitioner has to deal with and new diagnostic tests that can be considered when encountering a cat with suspected FIP with the aim to establish a definitive diagnosis. It gives an overview on all available direct and indirect diagnostic tests and their sensitivity and specificity reported in the literature in different sample material.

Feasibility study of a safe sled environment for reclined frontal deceleration tests with human volunteers.

The goal of the study was to assess the feasibility of a safe crash environment for volunteer tests in reclined seating positions. An iterative multimodal approach was chosen, consisting of full-body human body model (HBM) simulations, anthropomorphic test device (ATD) physical testing, and volunteer testing. To estimate a noninjurious deceleration pulse, the iterative inclination of the seat was supported through HBM simulations and physical ATD testing.

Comparing consequences of using two different definitions for body regions for the improvement of personal protective equipment for powered two-wheelers.

Various definitions and uses of the term can be found in the literature. A definition of body regions using the Abbreviated Injury Scale (AIS) codes not strictly aligned with AIS chapters was developed for use in the European Commission-funded PIONEERS project (Protective Innovations of New Equipment for Enhanced Rider Safety). This work aims to examine the consequences of differently defined body regions on injury priority ranking using the percentage of patients showing at least moderate injury severity (AIS 2+) per regarded body region.

Coupling Multi-Angle Light Scattering to Reverse-Phase Ultra-High-Pressure Chromatography (RP-UPLC-MALS) for the characterization monoclonal antibodies.

Multi-angle light scattering coupled with size-exclusion chromatography (SEC-MALS) is a standard approach for protein characterization. Recently MALS detection has been coupled with ion-exchange chromatography (IEX) which demonstrated the feasibility and high value of MALS in combination with non-sized-based fractionation methods. In this study we coupled reverse-phase ultra-high pressure liquid chromatography (RP-UPLC) with a low-dispersion MALS detector for the characterization of intact monoclonal antibody (mAbs) and their fragments.

Axonal Computations.

Axons functionally link the somato-dendritic compartment to synaptic terminals. Structurally and functionally diverse, they accomplish a central role in determining the delays and reliability with which neuronal ensembles communicate. By combining their active and passive biophysical properties, they ensure a plethora of physiological computations.

Favorable prognosis in pediatric brainstem low-grade glioma: Report from the German SIOP-LGG 2004 cohort.

Reports on pediatric low-grade glioma (LGG) of the caudal brainstem are retrospective with heterogeneous cohorts, variable treatments and inconsistent outcome data. We analyzed their natural history and asked whether brainstem location proved unfavorable for survival within the framework of the comprehensive SIOP-LGG 2004 management strategy. Within the prospectively registered, population-based German SIOP-LGG 2004 cohort 116 patients (age 0.

Characterization of Native Reversible Self-Association of a Monoclonal Antibody Mediated by Fab-Fab Interaction.

The native reversible self-association of monoclonal antibodies has been associated with high viscosity, liquid-liquid, and liquid-solid phase separation. We investigated the native reversible self-association of an IgG1, which exerts this association even at low protein concentrations, in detail to gain further understanding of this phenomenon by extensive characterization of the association as a function of multiple factors, namely pH, temperature, salt concentration, and protein concentration. The nature of the self-association of the full-length IgG1 as well as the corresponding Fab and Fc fragment was studied by viz.

Retinal inner nuclear layer volume reflects inflammatory disease activity in multiple sclerosis; a longitudinal OCT study.

Background: The association of peripapillary retinal nerve fibre layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness with neurodegeneration in multiple sclerosis (MS) is well established. The relationship of the adjoining inner nuclear layer (INL) with inflammatory disease activity is less well understood.

Objective: The objective of this paper is to investigate the relationship of INL volume changes with inflammatory disease activity in MS.

Inducing Different Neuronal Subtypes from Astrocytes in the Injured Mouse Cerebral Cortex.

Astrocytes are particularly promising candidates for reprogramming into neurons, as they maintain some of the original patterning information from their radial glial ancestors. However, to which extent the position of astrocytes influences the fate of reprogrammed neurons remains unknown. To elucidate this, we performed stab wound injury covering an entire neocortical column, including the gray matter (GM) and white matter (WM), and targeted local reactive astrocytes via injecting FLEx switch (Cre-On) adeno-associated viral (AAV) vectors into mGFAP-Cre mice.

Dual chamber cartridges in a continuous pharmaceutical freeze-drying concept: Determination of the optimal dynamic infrared heater temperature during primary drying.

The applicability of DCCs in a continuous freeze-drying concept based on spin freezing and infrared heating was evaluated. Maximum applicable filling volume was evaluated. Secondly the mechanistic model for the determination of the optimal dynamic infrared heater temperature during primary drying of regular vials during continuous freeze-drying was adapted and validated for DCCs.

Trends in the use of hematopoietic stem cell transplantation for adults with acute lymphoblastic leukemia in Europe: a report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT).

Hematopoietic stem cell transplantation (HSCT) is considered an effective way to prevent relapse in adults with acute lymphoblastic leukemia (ALL). This study aimed to assess general trends in the use of various types of HSCTs performed between 2001 and 2015 in Europe, based on data reported to the European Society for Blood and Marrow Transplantation registry. We also evaluated HSCT rates with respect to ALL incidence in selected countries.

Cooperative population coding facilitates efficient sound-source separability by adaptation to input statistics.

Our sensory environment changes constantly. Accordingly, neural systems continually adapt to the concurrent stimulus statistics to remain sensitive over a wide range of conditions. Such dynamic range adaptation (DRA) is assumed to increase both the effectiveness of the neuronal code and perceptual sensitivity.

The neuropathology of fatal encephalomyelitis in human Borna virus infection.

After many years of controversy, there is now recent and solid evidence that classical Borna disease virus 1 (BoDV-1) can infect humans. On the basis of six brain autopsies, we provide the first systematic overview on BoDV-1 tissue distribution and the lesion pattern in fatal BoDV-1-induced encephalitis. All brains revealed a non-purulent, lymphocytic sclerosing panencephalomyelitis with detection of BoDV-1-typical eosinophilic, spherical intranuclear Joest-Degen inclusion bodies.

Choroid plexus-derived miR-204 regulates the number of quiescent neural stem cells in the adult brain.

Regulation of adult neural stem cell (NSC) number is critical for lifelong neurogenesis. Here, we identified a post-transcriptional control mechanism, centered around the microRNA 204 (miR-204), to control the maintenance of quiescent (q)NSCs. miR-204 regulates a spectrum of transcripts involved in cell cycle regulation, neuronal migration, and differentiation in qNSCs.

Nanoscopic analysis of 53BP1, BRCA1 and Rad51 reveals new insights in temporal progression of DNA-repair and pathway choice.

The accumulation and spatial distribution of 53BP1, BRCA1 and Rad51, key proteins in DNA double-strand break (DSB) repair, was investigated with high temporal resolution over a time span of 24 h, using STED nanoscopy. DNA lesions were induced by irradiation with high-LET (linear energy transfer) α-particles. We show that 53BP1 IRIF formation occurs quickly in almost all cells and after about 6 h the fraction of 53BP1 IRIF positive cells slowly declines.

Association Between Occupational Exposure to Disinfectants and Asthma in Young Adults Working in Cleaning or Health Services: Results From a Cross-Sectional Analysis in Germany.

Objective: To analyze the association of occupational disinfectants use with asthma and wheezing in young professionals.

Methods: Three hundred sixty-five participants from the German Study on Occupational Allergy Risks II aged 20 to 24 years and working in cleaning or health services answered a questionnaire on respiratory health, occupational exposure to disinfectants, and potential confounders. By logistic regression, we calculated the association between duration of occupational disinfectants exposure and doctor-diagnosed asthma, current asthma, and current wheezing.

Which Reimbursement System Fits Inpatient Palliative Care? A Qualitative Interview Study on Clinicians' and Financing Experts' Experiences and Views.

Internationally, a variety of reimbursement systems exists for palliative care (PC). In Germany, PC units (PCUs) may choose between per-diem rates and diagnosis-related groups (DRGs). Both systems are controversially discussed.

Small Fluorescein Arsenical Hairpin-Based Förster Resonance Energy Transfer Analysis Reveals Changes in Amino- to Carboxyl-Terminal Interactions upon OAG Activation of Classical Transient Receptor Potential 6.

Although the overall structure of many classical transient receptor potential proteins (TRPC), including human and murine TRPC6, were recently resolved by cryoelectron microscopy analysis, structural changes during channel activation by 1-oleoyl-1-acetyl-sn-glycerol (OAG), the membrane-permeable analog of diacylglycerol, were not defined. Moreover, data on carboxyl- and amino-terminal interactions were not provided, as the amino-terminal regions of murine and human TRPC6 were not resolved. Therefore, we employed a Förster resonance energy transfer (FRET) approach using a small fluorescein arsenical hairpin (FlAsH) targeted to a short tetracysteine sequence at the unresolved amino-terminus and cerulean, a cyan fluorescent protein, as a tag at the carboxyl-terminus of the murine TRPC6 protein.