Non-Preemptive Shunting in M/M/1 and Dynamic Service Queueing Systems

We provide a study of two queueing systems, namely, an M/M/1 queueing system in which an incoming customer shunts, or skips line, and a dynamic server in an infinite capacity system moving among service nodes. In the former, we explore various aspects of the system, including waiting time, and the relationships between shunting and position in queue and rate of service. Through use of global balance equations, we find the probability that an arriving non-priority customer, finding customers waiting in the system, will shunt to a position other than behind the queue. In the latter, we explore a system in which a server with infinite capacity moves among indexed linear service nodes, receives customers at various nodes, and transports the customers to other indexed nodes in the hierarchy. We determine the expected waiting times at the nodes, expected service times, expected number of customers at a given node, expected number in the system, and expected number in service. The probabilities that an arrival finds n customers at a particular node, and in the entire system are obtained

Charakterizace faktorů podílejících se na regulaci intracelulární dynamiky vybraných auxinových přenašečů

Souhrn U rostlin je známo že mají schopnost nasměrovat svoje části, jak prýt, tak kořeny, pro zabezpečení maximálního zisku energie a příjmu živin, ale taky pro možnost vyhnout se toxickým podmínkám pro svůj růst. Regulace směru růstu, který zabezpečuje přežití rostliny, závisí na schopnosti rostlinných orgánů růst asymetricky. Asymetrický růst je regulován na buněčné úrovni na základě exogenních i interních signálů. Již v roce 1880 Darwin popsal tropismy a směrový růst na makroskopické úrovni; v současnosti je nevyhnutelné pochopit molekulární mechanismy, které zajišťují efektivní regulaci směrového růstu rostlin. V rámci svého studia jsem se zaměřil na mechanismy regulace směru růstu u rostlin. Kořen je komplexní trojrozměrný objekt, který stále upravuje svůj tvar a směr růstu. Vzhledem k tomu, že kořen potřebuje zvětšovat svůj povrch, aby byl schopen zajistit přísun živin a vody, je důležité pochopit, jak je kořen schopen adaptaci na konstantně se měnící růstové podmínky způsobené prorůstáním dál do půdy zvládnout. Pokud kořen není schopen prorůstat půdou efektivně kvůli silnému mechanickému odporu nebo nedostatku živin, pak je ovlivněn i růst prýtu. Optimální růst kořene je komplexní proces, na kterém se podílí rozmanitá spleť signálních drah, které jsou ovlivněny rostlinnými hormony, cukry, flavonoidy...Plants are known to adjust the orientation of their organs, shoot and root, to ensure maximal energy generation and nutrient uptake, but also to avoid toxic growth conditions. Directional growth regulation depends on asymmetric plant organ growth and it is crucial to ensure plant survival. It is orchestrated on cellular level in concert with exogenous and intrinsic signals. Even though tropistic growth responses of plants were described by Darwin on macroscopic level already in 1880, now it is necessary to understand molecular mechanisms that underpin efficient modulation of directional plant growth. During my studies I focused on factors that modulate directional root growth regulation. The root is a complex, three-dimensional object, which continuously modifies its shape and growth path. Since the root needs to expand its surface to supply the plant with nutrients and water, it is important to understand how roots cope with changing growth conditions while exploring the soil. If the root cannot manage to grow through soil efficiently, mechanical impedance and lack of resources will also restrict shoot growth as well. Manifold signaling pathways coordinate the complex processes that underpin efficient root growth, including those modulated by phytohormones, sugars, flavonoids and other...Katedra experimentální biologie rostlinDepartment of Experimental Plant BiologyPřírodovědecká fakultaFaculty of Scienc

Radar Sensor for Active Cruise Control

Cieľom práce bolo navrhnúť implementáciu adaptívneho tempomatu s pomocou radaru ako senzoru okolia pred vozidlom. V riešení bola použitá aplikácia VCDS-Lite na zisťovanie aktuálnej rýchlosti vozidla, a demo od spoločnosti Texas Instruments, na zachytávanie okolia pred vozidlom radarom AWR1843. Za použitia týchto dvoch aplikácií bolo vyhodnotené okolie pred vozidlom, z ktorého vychádzala inštrukcia pre vodiča. Výsledkom práce je aplikácia zobrazujúca aktuálnu rýchlosť vozidla spolu s aktuálnou inštrukciou adaptívneho tempomatu. Okrem nastavenia rýchlosti, aplikácia poskytuje aj možnosť nastavenia časového rozostupu od vozidla, ktoré nasleduje.The aim of the work was to design the implementation of adaptive cruise control with the help of radar as a sensor to evaluate the surroundings in front of the vehicle. The solution used the VCDS-Lite application to determine the current vehicle speed and the Medium Range Radar demo, from Texas Instruments, to capture the surroundings in front of the vehicle with AWR1843 radar. Using these two applications was evaluated the environment in front of the vehicle from which the instruction for a driver was derived. The result of the work is an application that displays the current vehicle speed along with the current adaptive cruise control instruction. In addition to setting the speed, the application also provides a setting of the time interval from the vehicle that follows.

Automated Blind Control

The objective of this project would be to design and prototype an automated, light and temperature sensing window blinds system. The device would detect temperature, both inside and outside, and incoming sunlight to determine proper window blind position for maximum energy savings. The user would also have the ability to change the settings of the blind from a remote device to a setting that they desire at any given tim

Rocket Telemetry System

The goal of this research project is to design a system for the Akronauts Rocket Design Team which will transmit flight data in real-time to a ground station. The data will be collected from various sensors (altitude, acceleration, GPS, etc). This data will be transmitted wirelessly and in real-time to a receiving station. Calculations and visualizations will be taken from the data, which will help the team improve their rocket designs. Additionally, GPS data will be useful to locate the rocket post-flight. Challenges will include the need for the system to transmit over the range of the rocket’s flight and to operate for the duration of the flight without needed recharged. Additionally, the rocket team desires a solution that can be operated without a license, limiting the frequencies that can be utilized

Monoclonal anti-envelope antibody AP33 protects humanized mice against a patient-derived hepatitis C virus challenge

End-stage liver disease caused by hepatitis C virus (HCV) infection is a major indication for liver transplantation. However, immediately after transplantation the liver graft of viremic patients universally becomes infected by circulating virus, resulting in accelerated liver disease progression. Currently available direct-acting antiviral therapies have reduced efficacy in patients with end-stage liver disease and prophylactic strategies to prevent HCV recurrence are still highly needed. In this study we compared the ability of two broadly reactive monoclonal antibodies (mAbs), designated 3/11 and AP33, recognizing a distinct but overlapping epitope in the viral E2 glycoprotein to protect humanized mice from a patient-derived HCV challenge. Their neutralizing activity was assessed using the HCVpp and HCVcc systems expressing multiple patient-derived envelopes and a human-liver chimeric mouse model. HCV RNA was readily detected in all control mice challenged with a patient-derived HCV genotype 1b isolate, while three out of four AP33-treated mice were completely protected. In contrast, only one out of four 3/11-treated mice remained HCV RNA negative throughout the observation period, while the other three had a viral load that was indistinguishable from that in the control group. The increased in vivo efficacy of AP33 was in line with its higher affinity and neutralizing capacity observed in vitro. Conclusion: Although mAbs AP33 and 3/11 target the same region in E2, only mAb AP33 can efficiently protect from challenge with a heterologous HCV population in vivo. Since mAb AP33 efficiently neutralizes viral variants that escaped the humoral immune response and re-infected the liver graft of transplant patients, it may be a valuable candidate to prevent HCV recurrence. In addition our data is valuable for the design of a prophylactic vaccine

Evolutionary conserved cysteines function as cis-acting regulators of Arabidopsis PIN-FORMED 2 distribution

Coordination of plant development requires modulation of growth responses that are under control of the phytohormone auxin. PIN-FORMED plasma membrane proteins, involved in intercellular transport of the growth regulator, are key to the transmission of such auxin signals and subject to multilevel surveillance mechanisms, including reversible post-translational modifications. Apart from well-studied PIN protein modifications, namely phosphorylation and ubiquitylation, no further post-translational modifications have been described so far. Here, we focused on root-specific Arabidopsis PIN2 and explored functional implications of two evolutionary conserved cysteines, by a combination of in silico and molecular approaches. PIN2 sequence alignments and modeling predictions indicated that both cysteines are facing the cytoplasm and therefore would be accessible to redox status-controlled modifications. Notably, mutant pin2C−A alleles retained functionality, demonstrated by their ability to almost completely rescue defects of a pin2 null allele, whereas high resolution analysis of pin2C−A localization revealed increased intracellular accumulation, and altered protein distribution within plasma membrane micro-domains. The observed effects of cysteine replacements on root growth and PIN2 localization are consistent with a model in which redox status-dependent cysteine modifications participate in the regulation of PIN2 mobility, thereby fine-tuning polar auxin transport

Tropism and neutralisation studies on bat influenza H17N10

The diversity of subtypes within Influenza A recently expanded with identification of H17N10 and H18N11 from bats. To study the tropism and zoonotic potential of these viruses, we successfully produced lentiviral pseudotypes bearing haemagglutinin H17 and neuraminidase N10. We investigated a range of cell lines from different species for their susceptibility to infection by these pseudotypes and show that a number of human haematopoietic cancer cell lines and the canine kidney MDCK II (but not MDCK I) cells are susceptible. Using microarrays and qRT-PCR we show that the dog leukocyte antigen DLA-DRA mRNA is over expressed in late passaged parental MDCK and commercial MDCK II cells, compared to early passaged parental MDCK and MDCK I cells, respectively. The human orthologue HLA-DRA encodes the alpha subunit of the MHC class II HLA-DR antigen-binding heterodimer. Small interfering RNA- or neutralizing antibody-targeting HLA-DRA, drastically reduced the susceptibility of Raji B cells to H17-PV. Conversely, over expression of HLA-DRA and its paralogue HLA-DRB1 on the surface of unsusceptible HEK293T/17 cells conferred susceptibility to H17-PV. The identification of HLA-DR as an H17N10 entry mediator will contribute to understanding the tropism of the virus and help to elucidate its zoonotic transmission. We also show that H17 pseudotypes can be efficiently neutralised by the broadly-neutralizing HA2 stalk monoclonal antibodies CR9114 and FI6. The lentiviral pseudotype system is a useful research tool, amenable for investigation of bat influenza tropism, restriction and pandemic preparedness, without safety issues of producing a replication-competent virus, to which the human population is naïve

Dramatic potentiation of the antiviral activity of HIV antibodies by cholesterol conjugation

The broadly neutralizing antibodies HIV 2F5 and 4E10, which bind to overlapping epitopes in the membrane- proximal external region (MPER) of the fusion protein gp41, have been proposed to use a two-step mechanism for neutralization: first, they bind and pre-concentrate at the viral membrane through their long, hydrophobic CDRH3 loops and second, they form a high-affinity complex with the protein epitope. Accordingly, mutagenesis of the CDRH3 can abolish their neutralizing activity, with no change in the affinity for the peptide epitope. We show here that we can mimic this mechanism by conjugating a cholesterol group outside of the paratope of an antibody. Cholesterol- conjugated antibodies bind to lipid-raft domains on the membrane and because of this enrichment, they show increased antiviral potency. In particular we find that cholesterol conjugation: (i) rescues the antiviral activity of CDRH3- mutated 2F5, (ii) increases the antiviral activity of WT 2F5, (iii) potentiates the non-membrane binding HIV antibody D5 10-100 fold (depending on the virus strain), and (iv) increases synergy between 2F5 and D5. Conjugation can be made at several positions, including variable and constant domains. Cholesterol conjugation therefore appears a general strategy to boost potency of antiviral antibodies and, since membrane affinity is engineered outside of the antibody paratope, it can complement affinity maturation strategies

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified