118 research outputs found

    Novi aktivni leap-frog filtar trećeg reda

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    This paper presents the realization of third-order low-pass active-RC filters using a new Leap-Frog (LF) topology. New structure is a simplified LF structure with the elements calculated directly from the transfer function coefficients. Several versions of the circuits are presented and compared. The comparison to other common thirdorder filter sections is done, as well. The new LF filter has the reduced number of components, reduced complexity and straightforward design procedure compared to classical filters. As an illustration of the efficiency of the proposed new LF filter, the sensitivity analysis using Schoeffler sensitivity measure as well as output thermal noise analysis was performed on examples with Butterworth and Chebyshev 0.5dB pass-band ripple transfer functions. Using PSpice with a TL081 opamp model, the filter performance is simulated and the results compared and verified by measurements on a discrete-component breadboard filter. All equations needed for the step-by-step design are given.U radu je predstavljena realizacija nisko-propusnog aktivnog-RC filtra trećeg reda koji upotrebljava novu "leap-frog" (LF) topologiju. Nova struktura je pojednostavljena LF struktura s elementima koji se računaju direktno iz koeficijenata prijenosne funkcije. Nekoliko inačica krugova je prikazano i obavljena je usporedba. Napravljena je usporedba tako.er i s drugim uobičajenim filtarskim sekcijama trećeg reda. Novi LF filtar ima smanjeni broj komponenata, smanjenu kompleksnost i jednostavniji postupak projektiranja u usporedbi s klasičnim filtrima. Za ilustraciju učinkovitosti predstavljenog novog LF filtra, provedena je analiza osjetljivosti pomoću Schoefflerove mjere osjetljivosti i analiza termičkog šuma na izlazu na primjerima s prijenosnim funkcijama po Butterworthu i Chebyshevu s valovitošću u području propuštanja od 0.5 dB. Pomoću PSpice-a s modelom pojačala TL081, filtarska svojstva su simulirana, uspore.ena i potvr.ena mjerenjima na filtrima realiziranim pomoću diskretnih elemenata na štampanoj pločici. U radu su dane sve potrebne jednadžbe u postupku projektiranja korak po korak

    The envelope protein of Usutu virus attenuates West Nile virus virulence in immunocompetent mice

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    West Nile virus (WNV) and Usutu virus (USUV) are the two most widespread mosquito-borne flaviviruses in Europe causing severe neuroinvasive disease in humans. Here, following standardization of the murine model with wild type (wt) viruses, we engineered WNV and USUV genome by reverse genetics. A recombinant virus carrying the 5′ UTR of WNV within the USUV genome backbone (r-USUV5′-UTR WNV) was rescued; when administered to mice this virus did not cause signs or disease as wt USUV suggesting that 5′ UTR of a marked neurotropic parental WNV was not per se a virulence factor. Interestingly, a chimeric virus carrying the envelope (E) protein of USUV in the WNV genome backbone (r-WNVE-USUV) showed an attenuated profile in mice compared to wt WNV but significantly more virulent than wt USUV. Moreover, except when tested against serum samples originating from a live WNV infection, r-WNVE-USUV showed an identical antigenic profile to wt USUV confirming that E is also the major immunodominant protein of USUV

    CNS distribution, signalling properties and central effects of G-protein coupled receptor 4

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    This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordInformation on the distribution and biology of the G-protein coupled receptor 4 (GPR4) in the brain is limited. It is currently thought that GPR4 couples to Gs proteins and may mediate central respiratory sensitivity to CO2. Using a knock-in mouse model, abundant GPR4 expression was detected in the cerebrovascular endothelium and neurones of dorsal raphe, retro-trapezoidal nucleus locus coeruleus and lateral septum. A similar distribution was confirmed using RNAscope in situ hybridisation. In HEK293 cells, overexpressing GPR4, it was highly constitutively active at neutral pH with little further increase in cAMP towards acidic pH. The GPR4 antagonist NE 52-QQ57 effectively blocked GPR4-mediated cAMP accumulation (IC50 26.8 nM in HEK293 cells). In HUVEC which natively express GPR4, physiological acidification (pH 7.4-7.0) resulted in a cAMP increase by ∼55% which was completely prevented by 1 μM NE 52-QQ57. The main extracellular organic acid, l-lactic acid (LL; 1-10 mM), suppressed pH dependent activation of GPR4 in HEK293 and HUVEC cells, suggesting allosteric negative modulation. In unanaesthetised mice and rats, NE 52-QQ57 (20 mg kg-1) reduced ventilatory response to 5 and 10% CO2. In anaesthetised rats, systemic administration of NE 52-QQ57 (up to 20 mg kg-1) had no effect on hemodynamics, cerebral blood flow and blood oxygen level dependent responses. Central administration of NE 52-QQ57 (1 mM) in vagotomised anaesthetised rats did not affect CO2-induced respiratory responses. Our results indicate that GPR4 is expressed by multiple neuronal populations and endothelium and that its pH sensitivity is affected by level of expression and LL. NE 52-QQ57 blunts hypercapnic response to CO2 but this effect is absent under anaesthesia, possibly due to the inhibitory effect of LL on GPR4.Biotechnology and Biological Sciences Research Council (BBSRC)Medical Research Council (MRC)Wellcome Trus

    Multiple detection and spread of novel strains of the SARS-CoV-2 B.1.177 (B.1.177.75) lineage that test negative by a commercially available nucleocapsid gene real-time RT-PCR

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    Several lineages of SARS-CoV-2 are currently circulating worldwide. During SARS-CoV-2 diagnostic activities performed in Abruzzo region (central Italy) several strains belonging to the B.1.177.75 lineage tested negative for the N gene but positive for the ORF1ab and S genes (+/+/- pattern) by the TaqPath COVID-19 CE-IVD RT-PCR Kit manufactured by Thermofisher. By sequencing, a unique mutation, synonymous 28948C > T, was found in the N-negative B.1.177.75 strains. Although we do not have any knowledge upon the nucleotide sequences of the primers and probe adopted by this kit, it is likely that N gene dropout only occurs when 28948C > T is coupled with 28932C > T, this latter present, in turn, in all B.1.177.75 sequences available on public databases. Furthermore, epidemiological analysis was also performed. The majority of the N-negative B.1.177.75 cases belonged to two clusters apparently unrelated to each other and both clusters involved young people. However, the phylogeny for sequences containing the +/+/- pattern strongly supports a genetic connection and one common source for both clusters. Though, genetic comparison suggests a connection rather than indicating the independent emergence of the same mutation in two apparently unrelated clusters. This study highlights once more the importance of sharing genomic data to link apparently unrelated epidemiological clusters and to, remarkably, update molecular tests

    CNS distribution, signalling properties and central effects of G-protein coupled receptor 4

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    This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordInformation on the distribution and biology of the G-protein coupled receptor 4 (GPR4) in the brain is limited. It is currently thought that GPR4 couples to Gs proteins and may mediate central respiratory sensitivity to CO2. Using a knock-in mouse model, abundant GPR4 expression was detected in the cerebrovascular endothelium and neurones of dorsal raphe, retro-trapezoidal nucleus locus coeruleus and lateral septum. A similar distribution was confirmed using RNAscope in situ hybridisation. In HEK293 cells, overexpressing GPR4, it was highly constitutively active at neutral pH with little further increase in cAMP towards acidic pH. The GPR4 antagonist NE 52-QQ57 effectively blocked GPR4-mediated cAMP accumulation (IC50 26.8 nM in HEK293 cells). In HUVEC which natively express GPR4, physiological acidification (pH 7.4-7.0) resulted in a cAMP increase by ∼55% which was completely prevented by 1 μM NE 52-QQ57. The main extracellular organic acid, l-lactic acid (LL; 1-10 mM), suppressed pH dependent activation of GPR4 in HEK293 and HUVEC cells, suggesting allosteric negative modulation. In unanaesthetised mice and rats, NE 52-QQ57 (20 mg kg-1) reduced ventilatory response to 5 and 10% CO2. In anaesthetised rats, systemic administration of NE 52-QQ57 (up to 20 mg kg-1) had no effect on hemodynamics, cerebral blood flow and blood oxygen level dependent responses. Central administration of NE 52-QQ57 (1 mM) in vagotomised anaesthetised rats did not affect CO2-induced respiratory responses. Our results indicate that GPR4 is expressed by multiple neuronal populations and endothelium and that its pH sensitivity is affected by level of expression and LL. NE 52-QQ57 blunts hypercapnic response to CO2 but this effect is absent under anaesthesia, possibly due to the inhibitory effect of LL on GPR4.Biotechnology and Biological Sciences Research Council (BBSRC)Medical Research Council (MRC)Wellcome Trus

    Adenocarcinoma of the third and fourth portion of the duodenum: a case report and review of the literature

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    A 65-year-old woman presented with abdominal pain, weight loss, fatigue, and microcytic anemia. Esophagogastroduodenoscopy, until the second part of duodenum, was normal. Ultrasound and computed tomography demonstrated a solid mass in the distal duodenum. A repeat endoscopy confirmed an ulcerative, intraluminar mass in the third and fourth part of the duodenum. Segmental resection of the third and fourth portion of the duodenum was performed. Histology revealed an adenocarcinoma. On the 4th postoperative day, the patient developed severe acute pancreatitis leading to multiple organ failure and died on the 30th postoperative day

    The impact of generation Y’s customer experience on emotions: online banking sector

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    Recently, banking sector focused on attracting Generation Y (individuals born between 1980 and 2000) because they have emerged as a huge force with growing spending power which will unavoidably rival with Baby Boomers’ market dominance. They try to attract them through a unique customer experience, especially the ability of differentiation. Using the Mehrabian & Russell’s model of stimulus (S) - organism (O) - response (R), this study developed the Generation Y customer experience framework that intends to explain their consumer emotional responses toward customer experience attributes in a bank through three aspects: pleasure, dominance, and arousal toward online banks. Empirical evidence, based on data from a survey suggests that the overall customer experience attributes in the bank had a positive relation with emotional responses in different ways. “Value for money”, “Getting things right the first time” and “Put the consumer first” emerged as the most important attributes for Generation Y in experiencing a bank.info:eu-repo/semantics/acceptedVersio

    CNS distribution, signalling properties and central effects of G-protein coupled receptor 4

    Get PDF
    Information on the distribution and biology of the G-protein coupled receptor 4 (GPR4) in the brain is limited. It is currently thought that GPR4 couples to Gs proteins and may mediate central respiratory sensitivity to CO2. Using a knock-in mouse model, abundant GPR4 expression was detected in the cerebrovascular endothelium and neurones of dorsal raphe, retro-trapezoidal nucleus locus coeruleus and lateral septum. A similar distribution was confirmed using RNAscope in situ hybridisation. In HEK293 cells, overexpressing GPR4, it was highly constitutively active at neutral pH with little further increase in cAMP towards acidic pH. The GPR4 antagonist NE 52-QQ57 effectively blocked GPR4-mediated cAMP accumulation (IC50 26.8 nM in HEK293 cells). In HUVEC which natively express GPR4, physiological acidification (pH 7.4-7.0) resulted in a cAMP increase by ∼55% which was completely prevented by 1 μM NE 52-QQ57. The main extracellular organic acid, L-lactic acid (LL; 1-10 mM), suppressed pH dependent activation of GPR4 in HEK293 and HUVEC cells, suggesting allosteric negative modulation. In unanaesthetised mice and rats, NE 52-QQ57 (20 mg kg-1) reduced ventilatory response to 5 and 10% CO2. In anaesthetised rats, systemic administration of NE 52-QQ57 (up to 20 mg kg-1) had no effect on hemodynamics, cerebral blood flow and blood oxygen level dependent responses. Central administration of NE 52-QQ57 (1 mM) in vagotomised anaesthetised rats did not affect CO2-induced respiratory responses. Our results indicate that GPR4 is expressed by multiple neuronal populations and endothelium and that its pH sensitivity is affected by level of expression and LL. NE 52-QQ57 blunts hypercapnic response to CO2 but this effect is absent under anaesthesia, possibly due to the inhibitory effect of LL on GPR4
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