High-efficiency high voltage hybrid charge pump design with an improved chip area

A hybrid charge pump was developed in a 0.13- $\mu \text{m}$ Bipolar-CMOS-DMOS (BCD) process which utilised high drain-source voltage MOS devices and low-voltage integrated metal-insulator-metal (MIM) capacitors. The design consisted of a zero-reversion loss cross-coupled stage and a new self-biased serial-parallel charge pump design. The latter has been shown to have an area reduction of 60% in comparison to a Schottky diode-based Dickson charge pump operating at the same frequency. Post-layout simulations were carried out which demonstrated a peak efficiency of 38% at the output voltage of 18.5 V; the maximum specified output voltage of 27 V was also achieved. A standalone serial-parallel charge pump was shown to have a better transient response and a flatter efficiency curve; these are preferable for time-sensitive applications with a requirement of a broader range of output currents. These findings have significant implications for reducing the total area of implantable high-voltage devices without sacrificing charge pump efficiency or maximum output voltage

Development of electronics for microultrasound capsule endoscopy

Development of intracorporeal devices has surged in the last decade due to advancements in the semiconductor industry, energy storage and low-power sensing systems. This work aims to present a thorough systematic overview and exploration of the microultrasound (µUS) capsule endoscopy (CE) field as the development of electronic components will be key to a successful applicable µUSCE device. The research focused on investigating and designing high-voltage (HV, < 36 V) generating and driving circuits as well as a low-noise amplifier (LNA) for battery-powered and volume-limited systems. In implantable applications, HV generation with maximum efficiency is required to improve the operational lifetime whilst reducing the cost of the device. A fully integrated hybrid (H) charge pump (CP) comprising a serial-parallel (SP) stage was designed and manufactured for > 20 V and 0 - 100 µA output capabilities. The results were compared to a Dickson (DKCP) occupying the same chip area; further improvements in the SPCP topology were explored and a new switching scheme for SPCPs was introduced. A second regulated CP version was excogitated and manufactured to use with an integrated µUS pulse generator. The CP was manufactured and tested at different output currents and capacitive loads; its operation with an US pulser was evaluated and a novel self-oscillating CP mechanism to eliminate the need of an auxiliary clock generator with a minimum area overhead was devised. A single-output universal US pulser was designed, manufactured and tested with 1.5 MHz, 3 MHz, and 28 MHz arrays to achieve a means of fully-integrated, low-power transducer driving. The circuit was evaluated for power consumption and pulse generation capabilities with different loads. Pulse-echo measurements were carried out and compared with those from a commercial US research system to characterise and understand the quality of the generated pulse. A second pulser version for a 28 MHz array was derived to allow control of individual elements. The work involved its optimisation methodology and design of a novel HV feedback-based level-shifter. A low-noise amplifier (LNA) was designed for a wide bandwidth µUS array with a centre frequency of 28 MHz. The LNA was based on an energy-efficient inverter architecture. The circuit encompassed a full power-down functionality and was investigated for a self-biased operation to achieve lower chip area. The explored concepts enable realisation of low power and high performance LNAs for µUS frequencies

Retrospective Analysis utlilization of Lipid Modifying Agents

Univerzita Karlova v Praze, Farmaceutická fakulta v Hradci Králové Katedra Sociální a klinické farmacie Kandidát PharmDr. Robert Bartas, MBA Školitel Doc. RNDr. Jozef Kolář, CSc. Název disertační práce Retrospektivní analýza spotřeby hypolipidemik Léčiva snižující hladinu lipidů (hypolipidemika) jsou opakovaně cílem studií analyzujících mimo jiné jejich spotřebu a náklady. Údaje o spotřebách jednotlivých hypolipidemik v letech 2002 - 2009 byly získány z databáze Státního ústavu pro kontrolu léčiv a Všeobecné zdravotní pojišťovny v okrese Karviná. Spotřeby jednotlivých skupin hypolipidemik byly uvedeny v definovaných denních dávkách (DDD) podle anatomicko- terapeuticko-chemického (ATC) systému, náklady v Kč. Hodnoty DDD jsou podle metodiky WHO z roku 2009. Údaje o spotřebách jsou uvedeny v relativním ukazateli - počtu DDD na 1 000 obyvatel a den (DID). Ve sledovaném období se spotřeba fibrátů mírně snížila, ve skupině statinů došlo k nárůstu z 13,55 DID (2002) na 60,10 DID (2009). Celková spotřeba hypolipidemik v DID nadále roste (32,34 DID v roce 2002, 76,30 DID v roce 2009). Hypolipidemika jsou v České republice (ČR) na 5. místě z hlediska nákladů na jednotlivé lékové skupiny dle ATC. Účinná látka atorvastatin je již od roku 2007 na 1. místě. V porovnávaných údajích z okresu Karviná byla zjištěna...Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Social and Clinical Pharmacy Candidate PharmDr. Robert Bartas, MBA Supervisor Doc. RNDr. Jozef Kolář, CSc. Title of Doctoral Thesis Retrospective analysis utilization of lipid modifying agents Lipid lowering agents have been repeatedly the objective of studies analysing their utilization and costs. The objective of this study was to evaluate the structure and development of consumption of hypolipidemic agents. Material and methods. Data concerning utilization of individual hypolipidemic drugs from 2002 to 2009 were obtained from the State Institute for Drug Control database and General Health Insurance Company - Karvina district database. Utilization of hypolipidemic drugs were stated in DDDs in correspondence with the ATC Classification, and the costs in CZK. Information on utilization is expressed in the number of DDD per 1,000 inhabitants per 1 day (DID). Results. The utilization of fibrates slightly decreased, while statins an increase from 13.55 DID (2002) to 60.10 DID (2009) was observed. The total utilization of hypolipidemic drugs in DID has been continuously increasing (32.34 DID in 2002, 76.30 DID in 2009). Hypolipidemic drugs take the 5th place in the Czech Republic from the standpoint of expenses....Katedra sociální a klinické farmacieDepartment of Social and Clinical PharmacyFaculty of Pharmacy in Hradec KrálovéFarmaceutická fakulta v Hradci Králov

Variations on Keeler's Theorem

The 2010 Futurama episode The Prisoner of Benda features a mind swapping machine that swaps the minds of two people at a time with the restriction that the same pair of people cannot use the machine more than once. We show that if a machine swaps $n$ people cyclically with the condition that the same group of people cannot use the machine again, we can find a way to get everyone back. We prove our solution is optimal for when $n =3$. We also introduce an infinite variant of the mind swapping machine

Dopad finanční krize na kolektivní investování v České republice

V této diplomové práci jsme zkoumali dopady světové finanční krize ze září roku 2008 na trh investičních fondů v ČR. Porovnali jsme dopad této krize na světový, evropský a Český trh kolektivního investování. Pomocí lineární regrese (metody nejmenších čtverců) se zavedenými umělými proměnnými jsme potvrdili, že krize zasáhla nejen celkový objem investovaných finančních prostředků do fondů, ale i zastoupení jednotlivých typů fondů. Prokázali jsme také, že tato finanční krize se na světovém a evropském trhu projevila mezi 3. čtvrtletím roku 2007 a 1. čtvrtletím roku 2009, zatímco na Českém trhu mezi 3. čtvrtletím roku 2008 a 2. čtvrtletím roku 2009. V práci jsou také testované tyto hypotézy: 1) vliv burzovního indexu na cenu akciových fondů, 2) vliv krátkodobé úrokové míry na cenu fondů peněžního trhu, 3) vliv dlouhodobé úrokové míry na cenu dluhopisových fondů v podmínkách Českého trhu s kolektivním investováním.In this thesis we examined the implications of the financial crisis from the September 2008 for investments into mutual funds in the Czech Republic. We compared this implication for worldwide, European and Czech mutual funds market. Using the linear regression (ordinary least squares) with dummy variables we proved that crisis had implication not just for the whole level of invested financial resources but for the structure of mutual funds market as well. We showed that the crisis occurred at the world and European markets between 3rd quarter of 2007 and 1st quarter of 2009 meanwhile between 3rd quarter of 2008 and 2nd quarter of 2009 at the Czech mutual funds market. We tested these hypotheses as well: 1) influence of stock share index on the price of equity funds, 2) influence of the short interest rate on the price of money market funds, 3) influence of the long term interest rate on the price of bond funds under the conditions of the Czech mutual funds market.Institute of Economic StudiesInstitut ekonomických studiíFaculty of Social SciencesFakulta sociálních vě

Searching for New Z-DNA/Z-RNA Binding Proteins Based on Structural Similarity to Experimentally Validated Zα Domain.

Z-DNA and Z-RNA are functionally important left-handed structures of nucleic acids, which play a significant role in several molecular and biological processes including DNA replication, gene expression regulation and viral nucleic acid sensing. Most proteins that have been proven to interact with Z-DNA/Z-RNA contain the so-called Zα domain, which is structurally well conserved. To date, only eight proteins with Zα domain have been described within a few organisms (including human, mouse, Danio rerio, Trypanosoma brucei and some viruses). Therefore, this paper aimed to search for new Z-DNA/Z-RNA binding proteins in the complete PDB structures database and from the AlphaFold2 protein models. A structure-based similarity search found 14 proteins with highly similar Zα domain structure in experimentally-defined proteins and 185 proteins with a putative Zα domain using the AlphaFold2 models. Structure-based alignment and molecular docking confirmed high functional conservation of amino acids involved in Z-DNA/Z-RNA, suggesting that Z-DNA/Z-RNA recognition may play an important role in a variety of cellular processes

Power Consumption Considerations for Ultrasound Capsule Endoscopy

Ultrasound capsule endoscopy (USCE) promises to combine the usefulness of the traditional endoscope with the increased comfort, reduced risks, and wider reach of a capsule for diagnosis of gastrointestinal tract (GIT) diseases. Equipped with a microultrasound (µUS) array operating at frequencies higher than 20 MHz, the USCE device can benefit from increased axial resolution, while the use of an array can provide a wider field of view via electronic beam-steering. However, reduced available power and limited physical dimensions are obstacles presently hindering the development of such medical devices. This paper proposes and evaluates US array driving techniques to reduce power consumption, discusses the limitations of receiving electronics and considers achievable B-mode imaging frame rates. Two array drivers were used in this study: a custom-made CMOS pulser, with details published previously, and a commercial research array controller (Vantage HF 128, Verasonics, WA, USA). Peak (i peak ) and average (i avg ) supply current measurements performed for a variable number of elements transmitting (Tx) simultaneously in a 28 MHz µUS array (Vermon, France) show that Tx apertures comprising &lt;7 active elements are most suitable. Furthermore, because of the high i peak supplied to the array, charge storage on board the USCE device is required for any Tx configuration

Unheeded SARS-CoV-2 proteins? A deep look into negative-sense RNA.

SARS-CoV-2 is a novel positive-sense single-stranded RNA virus from the Coronaviridae family (genus Betacoronavirus), which has been established as causing the COVID-19 pandemic. The genome of SARS-CoV-2 is one of the largest among known RNA viruses, comprising of at least 26 known protein-coding loci. Studies thus far have outlined the coding capacity of the positive-sense strand of the SARS-CoV-2 genome, which can be used directly for protein translation. However, it has been recently shown that transcribed negative-sense viral RNA intermediates that arise during viral genome replication from positive-sense viruses can also code for proteins. No studies have yet explored the potential for negative-sense SARS-CoV-2 RNA intermediates to contain protein-coding loci. Thus, using sequence and structure-based bioinformatics methodologies, we have investigated the presence and validity of putative negative-sense ORFs (nsORFs) in the SARS-CoV-2 genome. Nine nsORFs were discovered to contain strong eukaryotic translation initiation signals and high codon adaptability scores, and several of the nsORFs were predicted to interact with RNA-binding proteins. Evolutionary conservation analyses indicated that some of the nsORFs are deeply conserved among related coronaviruses. Three-dimensional protein modeling revealed the presence of higher order folding among all putative SARS-CoV-2 nsORFs, and subsequent structural mimicry analyses suggest similarity of the nsORFs to DNA/RNA-binding proteins and proteins involved in immune signaling pathways. Altogether, these results suggest the potential existence of still undescribed SARS-CoV-2 proteins, which may play an important role in the viral lifecycle and COVID-19 pathogenesis

Are There Hidden Genes in DNA/RNA Vaccines?

Due to the fast global spreading of the Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2), prevention and treatment options are direly needed in order to control infection-related morbidity, mortality, and economic losses. Although drug and inactivated and attenuated virus vaccine development can require significant amounts of time and resources, DNA and RNA vaccines offer a quick, simple, and cheap treatment alternative, even when produced on a large scale. The spike protein, which has been shown as the most antigenic SARS-CoV-2 protein, has been widely selected as the target of choice for DNA/RNA vaccines. Vaccination campaigns have reported high vaccination rates and protection, but numerous unintended effects, ranging from muscle pain to death, have led to concerns about the safety of RNA/DNA vaccines. In parallel to these studies, several open reading frames (ORFs) have been found to be overlapping SARS-CoV-2 accessory genes, two of which, ORF2b and ORF-Sh, overlap the spike protein sequence. Thus, the presence of these, and potentially other ORFs on SARS-CoV-2 DNA/RNA vaccines, could lead to the translation of undesired proteins during vaccination. Herein, we discuss the translation of overlapping genes in connection with DNA/RNA vaccines. Two mRNA vaccine spike protein sequences, which have been made publicly-available, were compared to the wild-type sequence in order to uncover possible differences in putative overlapping ORFs. Notably, the Moderna mRNA-1273 vaccine sequence is predicted to contain no frameshifted ORFs on the positive sense strand, which highlights the utility of codon optimization in DNA/RNA vaccine design to remove undesired overlapping ORFs. Since little information is available on ORF2b or ORF-Sh, we use structural bioinformatics techniques to investigate the structure-function relationship of these proteins. The presence of putative ORFs on DNA/RNA vaccine candidates implies that overlapping genes may contribute to the translation of smaller peptides, potentially leading to unintended clinical outcomes, and that the protein-coding potential of DNA/RNA vaccines should be rigorously examined prior to administration

The languages of peace during the French religious wars

The desirability of peace was a common topos in sixteenth-century political rhetoric, and the duty of the king to uphold the peace for the benefit of his subjects was also a long-established tradition. However, the peculiar circumstances of the French religious wars, and the preferred royal policy of pacification, galvanized impassioned debate among both those who supported and those who opposed confessional coexistence. This article looks at the diverse ways in which peace was viewed during the religious wars through an exploration of language and context. It draws not only on the pronouncements of the crown and its officials, and of poets and jurists, but also on those of local communities and confessional groups. Opinion was not just divided along religious lines; political imperatives, philosophical positions and local conditions all came into play in the arguments deployed. The variegated languages of peace provide a social and cultural dimension for the contested nature of sixteenth-century French politics. However, they could not restore harmony to a war-torn and divided kingdom