Publikationen

Hematopoietic stem cell (HSC) transplantation is successfully applied since the late 1950s. However, its efficacy can be impaired by insufficient numbers of donor HSCs. A promising strategy to overcome this hurdle is the use of an advanced ex vivo culture system that supports the proliferation and, at the same time, maintains the pluripotency of HSCs. Therefore, we have developed artificial 3D bone marrow-like scaffolds made of polydimethylsiloxane (PDMS) that model the natural HSC niche in vitro. These 3D PDMS scaffolds in combination with an optimized HSC culture medium allow the amplification of high numbers of undifferentiated HSCs. After 14 days in vitro cell culture, we performed transcriptome and proteome analysis. Ingenuity pathway analysis indicated that the 3D PDMS cell culture scaffolds altered PI3K/AKT/mTOR pathways and activated SREBP, HIF1α and FOXO signaling, leading to metabolic adaptations, as judged by ELISA, Western blot and metabolic flux analysis. These molecular signaling pathways can promote the expansion of HSCs and are involved in the maintenance of their pluripotency. Thus, we have shown that the 3D PDMS scaffolds activate key molecular signaling pathways to amplify the numbers of undifferentiated HSCs ex vivo effectively.

In this work we consider extensions of a conjecture due to Alspach, Mason, and Pullman from 1976. This conjecture concerns edge decompositions of tournaments into as few paths as possible. There is a natural lower bound for the number paths needed in an edge decomposition of a directed graph in terms of its degree sequence; the conjecture in question states that this bound is correct for tournaments of even order. The conjecture was recently resolved for large tournaments, and here we investigate to what extent the conjecture holds for directed graphs in general. In particular, we prove that the conjecture holds with high probability for the random directed graph Dn,pDn,pD_{n,p} for a large range of p.

Low-cost mechanical ventilators have been developed in order to deal with the shortage of traditional ventilators whose quantity is not sufficient in an emergency context in Perú. Protofy, a company from Spain, designed one of the first low-cost mechanical ventilation systems OxyGEN which was approved by a medicine agency in its country in special context of COVID 19. Therefore, as main of this article, a redesign of this system named OxygenIP.PE was carried out according to local requirements and available technology, but maintaining its working concept based on compression mechanism by cams. Sensors were added and a control algorithm of the respiratory rate was developed. Ventilation curves monitoring over time was implemented; in this sense, a mathematical model of the whole system was developed. OxygenIP.PE was redesigned, fabricated, and tested measuring its ventilation curves over time. Results indicate that this redesign provides a sturdy equipment able to work during a longer lifetime than the original. The replicability of the ventilation curves behavior is ensured, while the mechanism dimensions are adapted for a particular airbag resuscitator. The mathematical model of the whole system can satisfactorily determine the ventilation curves over time and is used to show the air pressure, volume, and flow as a function of the compression arm's angular position and differential pressure through the breathing circuit measurement, furthermore the algorithms designed as a consequence of the mathematical model were implemented for Raspberry and ARDUINO microcontrollers. There were obtained parameters of pressure 10-65 cmH2O, airflow 50-65 l/m, volume 0-0.5 l, at two values of beat per minute (BPM) 15 and 25.

Heparin-induced thrombocytopenia (HIT) antibodies (Abs) can mediate and activate blood cells, forming blood clots. To detect HIT Abs, immunological assays with high sensitivity (≥95%) and fast response are widely used, but only about 50% of these tests are accurate as non-HIT Abs also bind to the same antigens. We aim to develop biosensor-based electrical detection to better differentiate HIT-like from non-HIT-like Abs. As a proof of principle, we tested with two types of commercially available monoclonal Abs including KKO (inducing HIT) and RTO (noninducing HIT). Platelet factor 4/Heparin antigens were immobilized on gold electrodes, and binding of antibodies on the chips was detected based on the change in the charge transfer resistance (Rct). Binding of KKO on sensors yielded a significantly lower charge transfer resistance than that of RTO. Bound antibodies and their binding characteristics on the sensors were confirmed and characterized by complementary techniques. Analysis of thermal kinetics showed that RTO bonds are more stable than those of KKO, whereas KKO exhibited a higher negative ζ potential than RTO. These different characteristics made it possible to electrically differentiate these two types of antibodies. Our study opens a new avenue for the development of sensors for better detection of pathogenic Abs in HIT patients.

It is common knowledge that molecular energy level offsets of a type II heterojunction formed at the donor-acceptor interface are considered to be the driving force for photoinduced charge transfer in organic solar cells. Usually, these offsets - present between molecular energy levels of the donor and acceptor - are obtained via cyclic voltammetry (CV) measurements of organic semiconductors cast in a film or dissolved in solution. Simply transferring such determined energy levels from solution or film of single materials to blend films may be obviously limited and not be possible in full generality. Herein, we report various cases of material combinations in which novel non-fullerene acceptors did not yield successful charge transfer, although energy levels obtained by CV on constituting single materials indicate a type II heterojunction. Whilst the integer charge transfer (ICT) model provides one explanation for a relative rise of molecular energy levels of acceptors, further details and other cases have not been studied so far in great detail. By applying energy-resolved electrochemical impedance spectroscopy (ER-EIS) on several donor-acceptor combinations, a Fano-like resonance feature associated with a distinctive molecular energy level of the acceptor as well as various relative molecular energy level shifts of different kinds could be observed. By analyzing ER-EIS and absorption spectra, not only the exciton binding energy within single materials could be determined, but also the commonly unknown binding energy of the CT state with regard to the joint density of states (jDOS) of the effective semiconductor. The latter is defined by transitions between the highest occupied molecular orbitals (HOMO) of the donor and the lowest unoccupied molecular orbitals (LUMO) of the acceptor. Using this technique among others, we identified cases in which charge generation may occur either via uphill or by downhill processes between the charge transfer exciton and the electronic gap of the effective semiconductor. Exceptionally high CT-exciton binding energies and thus low charge generation yields were obtained for a case in which the donor and acceptor yielded a too intimate blend morphology, indicating π-π stacking as a potential cause for unfavorable molecular energy level alignment.