In recent years, several studies and simulations have been made on changing the current Radio Access Network (RAN) architecture into a more centralized access network where the base band processing is done in a central oce (CO) instead of out by the antenna site. This new architecture is denoted as the mobile fronthaul and is planned to be in use for the coming 5G network. The studies that have been made so far suggest that the new architecture can reduce cost, power usage and latency which are important factors regarding environmental, economical and data transmission issues. Furthermore, the new architecture allows a smarter distribution of data for each sector covered by the antennas, reducing redundant data transmission and thus increases the data eciency. The disadvantage or challenge however is that some of the optical components will be transferred from the currently controlled environment in the CO to an uncontrolled outdoor environment at the antenna site, which may generate risks as these components may be sensitive to especially changes in temperature. In this master thesis, the optical performance of four di erent passive lter setups, using a thin lm lter (TFF), an arrayed waveguide grating (AWG) and an interleaver, has been studied and compared in order to nd the most suitable lter setup for the mobile fronthaul. These optical parameters include insertion loss, isolation, crosstalk, 3 dB passband, center wavelength drift and also bit error-rate (BER) which have all been measured over a temperature interval of -40-85oC. Moreover, the measurement results have been compared with results from simulations done with VPItransmissionmaker. From the measurement results, the TFF had a better optical performance and reliability compared to the AWG mainly due to a higher isolation and a lower BER penalty of 0.2 dB compared to 0.5-1.5 dB for the AWG. Considering data capacity and economical aspects for a more realistic mobile fronthaul scenario with 80 channels using dense wavelength division multiplexing (DWDM) however, the AWG connected to the interleaver is more benecial without risking negative a ects on trac performance. / Under senare år har flera studier och simulationer utförts med syfte att ändra arkitekturen på dagens radioaccess-nätverk till ett mer centraliserat nätverk där basbandsprocesseringen sker i en central nod istället för ute vid antennen och radiomasterna. Denna nya arkitektur kallas mobile fronthaul och planeras att realiseras till 5G-nätet. De studier som har gjorts hittills indikerar på att den nya arkitekturen kan minska ekonomiska kostnader, elanvändningen och latens vilka är viktiga faktorer som bland annat rör miljö-, ekonomi och kapacitetrelaterade områden. Dessutom kan data fördelas på ett smartare sätt över alla delområden som antennerna täcker vilket minskar redundant datatrafik och därmed ökar den effektiva mängden data som skickas ut. Problemet eller utmaningen är att vissa optiska komponenter behöver flyttas från en nuvarande kontrollerad miljö till en okontrollerad utemiljö vid radiomasterna vilket kan medföra risker då dessa komponenter främst kan vara väldigt temperaturkänsliga. Inom detta examensarbete har optisk prestanda studerats, analyserats och jämförts mellan fyra olika filterkonstellationer bestående av ett tunnfilmsfilter, ett AWG-filter och en interleaver med syfte att finna vilken konstellation som passar bäst för mobile fronthaularkitekturen. De optiska parametrarna består av insertionsförluster, isolation, överhörningsinterferens, 3 dB-passband, centervåglängdsdrift samt bitfelsgrad vilka alla har blivit undersökta över ett temperaturintervall på -40-85oC. Utöver detta så har mätresultaten jämförts med simulationer gjorda med VPItransmissionmaker. Utifrån mätresultaten kunde det konstateras att tunnfilmfiltret hade bättre optiska egenskaper och även högre trovärdighet jämfört med AWG-filtret främst på grund av en högre isolation och lägre bitfelsgradsstraff på 0.2 dB jämfört med 0.5-1.5 dB för AWG-filtret. Om en endast avväger datakapacitet och ekonomiska aspekter för ett mer realistiskt scenario för mobile fronthaul med 80 DWDM-kanaler så är AWG-filtret tillsammans med interleavern mer foördelaktig att välja utan att riskera några negativa påverkningar på trafikprestandan.

Recently, the portfolio of compounds approved for inhalation therapy has expanded rapidly for lung disease therapies. The rationale for this delivery approach includes a more targeted and localized delivery to the diseased site with reduced systemic exposure, potentially leading to decreased adverse side effects. We have proposed that brittle matrix powders prepared by thin film freezing (TFF) are a suitable platform for pulmonary drug delivery which can achieve high lung concentrations while limit the corresponding systemic levels associated with toxicity, and enhanced physicochemical and aerodynamic properties can be obtained by varying TFF processing parameters. In Chapter 2, the in vitro and in vivo performance of an amorphous formulation prepared by TFF and a crystalline micronized formulation produced by milling was compared for Tacrolimus (TAC). TFF processed matrix powders was capable of achieving deep lung delivery due to its low density, highly porous and brittle characteristics. When emitted from a Miat® monodose inhaler, TFF processed TAC formulations exhibited a fine particle fraction (FPF) of 83.3% and a mass median aerodynamic diameter (MMAD) of 2.26 µm. Single dose 24-h pharmacokinetic studies in rats demonstrated that the TAC formulation prepared by TFF exhibited higher pulmonary bioavailability with a prolonged retention time in the lung, possibly due to decreased clearance (e.g., macrophage phagocytosis), compared to the micronized TAC formulation. Additionally, TFF formulation generated a lower systemic TAC concentration with smaller variability than the micronized formulation following inhalation, potentially leading to reduced side effects related to the drug in systemic circulation. Chapter 3 investigated the impact of processing parameters in the TFF process on the physicochemical and aerodynamic properties of the resulting formulations. All of these enhanced powder properties resulted from higher freezing rate contributed to a better aerodynamic performance of the obtaining formulations. Moreover, a decreasing trend of FPF was observed for these TFF powders when the initial solid concentrations increased. The variation of the freezing rate and initial solid loading in the TFF process enabled the production of formulations with enhanced physicochemical properties and improved aerodynamic performance. / text

Perfusion operation mode is currently under fast expansion in mammalian cell based manufacturing of biopharmaceuticals, not only for labile drug protein but also for stable proteins such as monoclonal antibodies (mAbs). Perfusion mode can advantageously offer a stable cell environment, long-term production with high productivity and consistent product quality. Intensified high cell density culture (HCDC) is certainly one of the most attractive features of a perfusion process due to the high volumetric productivity in a small footprint that it can provide. Advancements in single-use technology have alleviated the intrinsic complexity of perfusion processes while the maturing in cell retention devices has improved process robustness. The knowledge for perfusion process has been gradually built and the “continuous” concept is getting more and more acceptance in the field. This thesis presents the development of robust perfusion process at very high cell densities in various culture systems. Four HCDC perfusion systems were developed with industrial collaborators with three different mAb producing Chinese Hamster Ovary (CHO) cell lines: 1-2) WAVE Bioreactor™ Cellbag prototype equipped with cell separation by hollow fiber filter utilizing Alternating Tangential Flow (ATF) and Tangential Flow Filtration (TFF) techniques; 3) Fiber matrix based CellTank™ prototype; 4) Glass stirred tank bioreactor equipped with ATF. In all the systems, extremely high viable cell densities above 130 million viable cells per milliliter (MVC/mL) up to 214 MVC/mL were achieved. Steady states were maintained and studied at 20-30 MVC/mL and 100-130 MVC/mL for process development. Perfusion rate selection based on cell specific perfusion rate (CSPR) was systematically investigated and exometabolome study was performed to explore the metabolic footprint of HCDC perfusion process. / <p>QC 20170523</p>

Cancers represent second the most common cause of death in the Czech Republic. The most common are breast and colorectal cancers. Identification of prognostic factors improving decision-making approaches for treatment optimization belongs to the key aims of clinical research in oncology. Carriers of mutation in cancer-susceptibility genes represent a small but clinically important group of high-risk patients. The implementation of NGS have accelerated predisposing genes analyses. The large extent of data about the presence of variants in predisposing genes is in striking contrast to only a very limited information available about clinico-pathological characteristics of mutation carriers. Determination of the risk of tumor development in carriers of rare mutations or variants of unclear significance in genes with incomplete penetrance represent substantial drawbacks of current NGS analyses. To address these issues, we have attempted i) to introduce a unified approach to NGS analysis in breast cancer patients, ii) to characterize importance of prognostic factors in BRCA1/BRCA2 mutation carriers, and iii) to identify the cancer risks in carriers of germline mutations in the CHEK2 gene. Colorectal cancer represents seemingly histologically homogeneous disease. However, at the molecular level it can be...

Mixed-signal processing systems especially data converters can be reliably tested at high frequencies using on-chip testing schemes based on memory. In this thesis, an on-chip testing strategy based on shift registers/memory (2 k bits) has been proposed for digital-to-analog converters (DACs) operating at 5 GHz. The proposed design uses word length of 8 bits in order to test DAC at high speed of 5 GHz. The proposed testing strategy has been designed in standard 65 nm CMOS technology with additional requirement of 1-V supply. This design has been implemented using Cadence IC design environment. The additional advantage of the proposed testing strategy is that it requires lower number of I/O pins and avoids the large number of high speed I/O pads. It therefore also solves the problem of the bandwidth limitation that is associated with I/O transmission paths. The design of the on-chip tester based on memory contains no analog block and is implemented entirely in digital domain. In the proposed design, low frequency of 1 MHz has been used outside the chip to load the data into the memory during the write mode. During the read mode, the frequency of 625 MHz is used to read the data from the memory. A multiplexing system is used to reuse the stored data during read mode to test the intended functionality and performance. In order to convert the parallel data into serial data at high frequency at the memory output, serializer has been used. By using the frequencies of 1.25 GHz and 2.5 GHz, the serializer speeds up the data from the lower frequency of 625 MHz to the highest frequency of 5 GHz in order to test DAC at 5 GHz.

To diagnose patients suffering from blood clotting disorders latex immununoassays (LIA) can be used. A time consuming manual tangential flow filtration (TFF) process suggests the implementation of an automatic TFF system to improve the efficiency, profitability, and expandability of the production facility of LIA at Nordic Biomarker. Tests were made of the automatic TFF system's ability to perform the desired steps of concentration, dilution and diafiltration, both with purified water and mimicked product. The mimicked product of micro particles (MP) mixed with monoclonal antibodies (mAb) was also used to further test the system's pressure control, safety alarms and stops, and to determine a permeate flux by a critical flux experiment. The results imply a functional TFF system able to automatically concentrate the process fluid and maintain a stable volume during diafiltration, although an additional permeate pump was ordered to be able to attain a fully functional performance of the automatic TFF process. The final part of the implementation was to initiate a validation draft including a risk assessment, OQ plan and PQ plan that resulted in a plan of the main tests to be performed. To conclude, the essential part of the implementation of a high quality and efficient automatic TFF process was conducted to facilitate future expansion of the production of LIA.

Background: The focus of this study was to investigate how producing human bone marrow (hBM) derived mesenchymal stromal cell (MSC) extracellular vehicles (EVs) in a high purity isolation system would affect their established characterization criteria and address the validity of these methods of EV production. Additionally, we set out to functionally characterize the hBM-MSC-EVs for their identified immunomodulatory ability while also assessing the presence of novel MSC-EV marker NRP1 identified by our group to further affirm its validity as a functional MSC-EV identity marker. Methods: Each hBM-MSC-EV donor was cultured in a hollow-fiber bioreactor system in non-stimulating serum/xeno-free conditions for 25 days to produce EVs persistently under quiescent conditions to characterize the hBM-MSC-EVs in their native form. EVs were isolated by traditional PEG-based precipitation for preliminary characterization to monitor bioreactor production wherein they were characterized using multimodal tangential flow filtration coupled with fast protein liquid chromatograph (FPLC) size exclusion/high-affinity purifications to obtain the final highly purified EV sample. Additionally, functional analysis of their immunomodulatory ability, EVs and MSCs were incubated with activated peripheral blood mononuclear cells (PBMCs) as an in-vitro model to evaluate their potency. Results: The hBM-MSC-EVs produced from the bioreactor system showed consistent characterization in accordance with the MISEV2018 establish criteria. We were also able to demonstrate their functional ability by observing statistically significantly immunomodulatory ability of activated PBMCs equivalent to native MSC ability. We were also able to validate the present of NRP1 on all hBM-MSC-EV samples produced confirming its validity as a MSC-EV marker. Conclusion: The significance of the results obtained from this study confirms the production of MSC-EV using a bioreactor and high purity isolation for obtaining consistent MSC-EVs for downstream investigation. Additionally, we were able to demonstrate the significance of MSC-EVs on MSC signaling for immunomodulation by showing equivalent functional potency when tested in-vitro. These results contribute to further understanding the biological attributes of MSC-EVs and contribute to the validation of currently established characterization guidelines.

No description available.