This brief paper describes CoronaZ, a project for the Distributed Systems course at the University of Helsinki. All the code of the project is publicly available on GitHub repository. This project ...simulates a contact tracing application where each node represents a person (or a unique device attached to someone) that send signals to each other when in range and communicate the data collected to a server using the publish-subscribe pattern. The server, called broker, can then be polled by a node called consumer that will send the data to a database. A front-end application then requests this data and displays the movement and the latest updates via the browser. The idea came from simulating this kind of movements with Arduino boards capable of communicating between themselves using the nrf24l01 and to the broker with esp8266. Unfortunately this was not possible given the relatively strict amount of time that each of the students involved could dedicate to the project and the waiting time to get the necessary hardware.
Abstract Sexually transmitted HIV-1 strains utilize the chemokine receptor CCR5 for viral entry and inhibitors targeting this coreceptor offer great promise for antiretroviral therapy. They also ...raise the question, however, whether viral variants exhibiting altered coreceptor interactions and resistance against these antiviral agents might still be pathogenic. In the present study, we analyzed a SIVmac239 envelope (Env) mutant (239DL) containing two mutations in the V3 loop which reduced viral entry via CCR5 by 10- to 20-fold, disrupted utilization of common alternative SIV coreceptors and changed the way Env engaged CCR5. To evaluate its replicative capacity and pathogenic potential in vivo we infected six rhesus macaques with 239DL. We found that 239DL replication was only slightly attenuated early during infection. Thereafter, a D324V change, which restored efficient CCR5 usage and coincided with 239wt-like levels of viral replication, emerged in two animals. In contrast, the viral geno- and phenotype remained stable in the other four rhesus macaques. Although these animals had about 100-fold reduced viral RNA loads relative to 239wt-infected macaques, they showed pronounced CD4 T-cell depletion in the intestinal lamina propria, and one developed opportunistic infections and died with simian AIDS. Thus, changes in the V3 loop that diminished CCR5 usage and altered Env interactions with CCR5 reduced the pathogenic potential of SIVmac in rhesus macaques but did not abolish it entirely.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Stromal interaction molecule 1 (STIM1)
4
deficiency is a rare genetic disorder of store-operated Calcium entry (SOCE), associated with a complex syndrome including immunodeficiency and immune ...dysregulation. The link from the molecular defect to these clinical manifestations is incompletely understood. We report 2 patients with a homozygous R429C point mutation in
STIM1
completely abolishing SOCE in T cells. Immunological analysis of one patient revealed that despite the expected defect of T cell proliferation and cytokine production
in vitro
, significant antiviral T cell populations were generated
in vivo
. These T cells proliferated in response to viral antigens and showed normal antiviral cytotoxicity. However, antiviral immunity was insufficient to prevent chronic CMV and EBV infections with a possible contribution of impaired NK cell function and a lack of NKT cells. Furthermore, autoimmune cytopenia, eczema and intermittent diarrhea suggested impaired immune regulation. Forkhead box protein 3 (FOXP3) positive regulatory T cells (Treg) were present but showed an abnormal phenotype. The suppressive function of STIM1 deficient Treg cells
in vitro,
however, was normal. Given these partial defects in cytotoxic and regulatory T cell function, impairment of other immune cell populations probably contributes more to the pathogenesis of immunodeficiency and autoimmunity in STIM1 deficiency than previously appreciated.
Background
We compared dose–response curves of the hypnotic effects of desflurane, sevoflurane and isoflurane. In addition, we analyzed the k
e0
values of the different anesthetics. The EEG ...parameters Bispectral index (BIS, Aspect Medical Systems, Natick, MA, version XP) and Narcotrend index (MonitorTechnik, Bad Bramstedt, Germany, version 4.0) were used as measures of the pharmacodynamic effect.
Methods
With IRB approval and informed consent we analyzed the data of three studies including 61 adult patients scheduled for radical prostatectomies. At least 45 min after induction of general anesthesia, end-tidal concentrations of desflurane, sevoflurane or isoflurane were varied between 0.5 and 2 MAC. We transferred the end-tidal concentrations into age-related MAC values. The relationship between MAC effect compartment concentrations and EEG was modeled with a variation of the classical fractional sigmoid E
max
model with two linked sigmoidal curves. All parameters were calculated as a population fit by NONMEM V (GloboMax, Hanover, USA) by minimizing log likelihood.
Results
The k
e0
values of the population fit derived from BIS data were 0.54 min
−1
for desflurane, 0.24 min
−1
for sevoflurane and 0.16 min
−1
for isoflurane, from the Narcotrend index 0.43 min
−1
for desflurane, 0.26 min
−1
for sevoflurane and 0.18 min
−1
for isoflurane. The change between the first and the second sigmoidal curve was positioned at nearly the same Narcotrend- and BIS index values between 41 and 44.
Conclusions
The first order rate constant (k
e0
value) determining the equilibration between age-related MAC values and MAC effect site concentration is substantially higher for desflurane than for sevoflurane or isoflurane.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Induction of heme oxygenase (HO)-1 may confer hepatocellular protection, e.g., in reperfusion injury. Previous reports suggest that intracellular cAMP up-regulates HO-1. The aim of the present study ...was to assess the role of adrenoceptor agonists as a means to induce HO-1 and to assess molecular mechanisms of HO-1 gene expression by adrenoceptor agonists. Induction of HO-1 in primary cultures of hepatocytes and in rat liver in vivo was assessed by Northern blot, Western blot, and immunohistochemistry. The beta-receptor agonists (+/-)isoproterenol and (-)isoproterenol induced HO-1 in primary cultures of hepatocytes but not the inactive enantiomer (+)isoproterenol. No induction of HO-1 was observed after alpha1, alpha2, beta2, or beta 3 agonists. beta1-Receptor agonists dobutamine and xamoterol induced HO-1 dose dependently, whereas the beta1-receptor antagonist metoprolol attenuated HO-1 induction by beta1-receptor agonists. Furthermore, 8 Br-cAMP and forskolin induced HO-1. Inhibition of protein kinase A (PKA) abolished induction by dobutamine and 8 Br-cAMP. Parallel changes were observed for the transcription factor AP-1. In vivo infusion of dobutamine for 6 h induced HO-1 in rat livers. Immunohistochemical detection of HO-1 revealed a pericentral expression pattern of HO-1 in hepatocytes, i.e., the area at risk for ischemia/reperfusion injury. These results suggest induction of HO-1 by beta1-adrenoceptor agonists via the PKA pathway in hepatocytes, reflecting a potential means for "pharmacological preconditioning."
Bullous pemphigoid (BP) is an autoimmune blistering skin disease characterized by autoantibodies to hemidesmosomal proteins. The initiation and regulation of the autoimmune response are poorly ...understood. We analysed cell subsets with immunoregulatory functions in untreated BP patients. While the numbers of circulating NKT and NK cells were normal, gammadelta T cells were reduced in BP patients. gammadelta T cells were rarely detected in lesional skin, arguing against their sequestration in the skin. In most patients, clinical remission and reduction of autoantibody titres after immunosuppressive therapy was not accompanied by an increase of circulating gammadelta T cells. V gammadelta gene usage was not altered in BP patients and the gammadelta T cells of BP patients were functional as they proliferated in response to isopentenyl pyrophosphate. Our data provide a basis for further investigations on the role of gammadelta T cells in the immunopathogenesis of BP.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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