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Copyright of Computer Measurement & Control is the property of Magazine Agency of Computer Measurement & Control and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Control strategies for variable-air-volume (VAV) air conditioning significantly affect both the air quality within buildings and the consumption of building energy. Current control techniques effectively regulate room temperature using feedback on temperature discrepancies, yet they also elevate the wear on terminal devices and boost the energy usage of the supply fan. In this paper, the hysteresis and inertia parameters of end air valves and supply fans under two seasonal conditions are derived from experimental data. Aiming at the problems of frequent switching of the end air valve, long total switching stroke, and high energy consumption of the air supply fan, a fuzzy PI regulation method is proposed based on the original pressure-independent series PI regulation, which effectively solves the above problems. Initially, data on how room temperature reacts to changes in air supply fan speed and the position of end air valves during winter and summer were gathered. Following model identification, parameters for various seasonal conditions were determined. Secondly, the roles of different components in the variable-air-volume regulation process were investigated. Investigations revealed that within pressure-independent variable-air-volume control, the supply fan and end air valve emerged as the primary subjects of the study. A double-closed-loop control with the speed control of the supply fan as the outer loop and the opening control of the end air valve as the inner loop was adopted. Compared with the traditional serial PI regulation, the room temperature error of this method was increased, but it reduced the total stroke of the valve by more than 43%, which greatly reduced the valve's loss and noise and saved more than 2.7% of the energy consumption of the air supply fan. [ABSTRACT FROM AUTHOR]

Rac GTPases are required for neutrophil adhesion and migration, and for the neutrophil effector responses that kill pathogens. These Rac-dependent functions are impaired when neutrophils lack the activators of Rac, Rac-GEFs from the Prex, Vav, and Dock families. In this study, we demonstrate that Tiam1 is also expressed in neutrophils, governing focal complexes, actin cytoskeletal dynamics, polarisation, and migration, in a manner depending on the integrin ligand to which the cells adhere. Tiam1 is dispensable for the generation of reactive oxygen species but mediates degranulation and NETs release in adherent neutrophils, as well as the killing of bacteria. In vivo, Tiam1 is required for neutrophil recruitment during aseptic peritonitis and for the clearance of Streptococcus pneumoniae during pulmonary infection. However, Tiam1 functions differently to other Rac-GEFs. Instead of promoting neutrophil adhesion to ICAM1 and stimulating b2 integrin activity as could be expected, Tiam1 restricts these processes. In accordance with these paradoxical inhibitory roles, Tiam1 limits the fMLP-stimulated activation of Rac1 and Rac2 in adherent neutrophils, rather than activating Rac as expected. Tiam1 promotes the expression of several regulators of small GTPases and cytoskeletal dynamics, including aPix, Psd4, Rasa3, and Tiam2. It also controls the association of Rasa3, and potentially aPix, Git2, Psd4, and 14-3-3z/d, with Rac. We propose these latter roles of Tiam1 underlie its effects on Rac and b2 integrin activity and on cell responses. Hence, Tiam1 is a novel regulator of Rac-dependent neutrophil responses that functions differently to other known neutrophil Rac-GEFs. [ABSTRACT FROM AUTHOR]

Berzah kavramı İslamî ilimler literatüründe yaygın olarak bilinen “kabir hayatı” anlamının yanında, İbnü’l-Arabî düşüncesinde iki şey/durum/mertebeyi birbirinden ayıran ve her ikisinden de bazı özellikleri kendinde taşıyan şeyler için kullanılır. İbnü’l-Arabî’nin bu kullanımı sınırlı değildir; hatta araştırmacılara göre ondaki bu birleştiren ve ayıran (câmî ve fâsıl) berzahları tespit etmek olanaksızdır çünkü bunlar oldukça fazladır. Berzah kavramının İbnü’l-Arabî’deki bu orijinal yapısı onun görüşlerini anlamamızı kolaylaştırmaktadır. Müellifin berzah olmakla nitelediği şeylerden biri de vâv harfidir. Onun vâv harfine berzahlık fonksiyonu yüklemesi iki sebebe dayanır: Birinci olarak bir harfin yalnızca literal düzlemde değil, ontolojik bir görev icra edecek biçimde berzah oluşu, müellifin harflere yüklediği ontolojik işlevlerle doğrudan ilgilidir. İkinci olarak ise bu harfin berzah olması onun fonetik, morfolojik ve sentaktik özelliklerinden kaynaklanmaktadır. Çalışmamızda öncelikle berzah kavramı ve İbnü’l-Arabî’nin genel hatlarıyla berzah düşüncesi ele alınmış; ardından harflerin ontolojik niteliğine, bu bağlamda vâv harfinin seslendiriliş, yazılış ve kelime ya da cümle içindeki konumuna, bu halleriyle berzahî nitelik taşıdığına ve bir berzah olarak İbnü’l-Arabî’nin düşünce sisteminde diğer hangi varlıklara denk geldiğine temas edilmiştir. Bu bağlamda vâvın, mümkünleri varlık sahasına getiren “kün!” kelimesinin ortasında bulunarak “kâf-ı kenziyye” olan kâf ile, Allah dışındakileri niteleyen nûnun arasında bulunduğu görülür. Kün kelimesinin son harfi olan nûnun arasında da bir vâv bulunur, bu da şehâdet ve gayb âlemlerinin arasının ayrıldığını gösterir. Âlem hem Allah’a perde olan hem de O’na işaret eden bir alem ise bunun yaratıldığı günlerin sayısı olan altının, vâvın ebced karşılığı olması da tesadüf değildir. Vâv pek çok açıdan insan-ı kâmili de simgeler, kâmil insan ise Allah ile diğer insanlar arasında bir berzahtır. Kimi araştırmacılara göre Fütûhât’ın altı ana bölüme ayrılması da yönlerin ve yaratılış günlerinin sayısının altı olması ya da vâvın insan-ı kâmili simgelemesi ile eserin kapsayıcılığı arasındaki benzerliktendir. Aynı şekilde hakîkat-ı Muhammediyye’nin de berzahî bir özelliği vardır ve bu açıdan vâv Muhammedî hakikati de niteler.

ABSTRACT Vav proteins are guanine exchange factors that activate Rac1/RhoA signaling to regulate many biological processes including inflammatory responses. Here, the expression and functional significance of Vav’s were investigated during dengue virus (DENV) infection. In primary monocyte-derived macrophages, Vav1, −2, and −3 mRNA levels demonstrate variable responses to DENV infection and correlate with DENV-induced host inflammatory (IL-6 and TNF-α), antiviral (viperin), or cell adhesion [intercellular cell adhesion molecule (ICAM-1)] mRNA induction. Strong positive correlations were seen in particular for Vav2 with TNF-α and Vav3 with IL-6 mRNA. In the retinal pigmented epithelial cell line, ARPE-19, Vav2 was the main Vav expressed and was not affected by DENV infection. Heterologous Vav1 expression in ARPE-19 cells induced an increase in basal IL-6 mRNA but did not enhance DENV-induced mRNA responses. DENV RNA and DENV-induced viperin and IL-6 mRNA responses were also unaffected by Vav2 siRNA knockdown. Treatment of DENV-infected ARPE-19 cells with EHop-016 to block Vav signaling did not affect DENV RNA levels but increased DENV-mediated induction of IL-6 mRNA. More detailed assessment of DENV-induced responses to azathioprine, a clinically used immunosuppressant that can also block Vav signaling and act as a nucleoside analog, similarly demonstrated no change in DENV RNA levels but resulted in inhibition of DENV-induced phospho-ERK and increased DENV-induced-IL-6 and viperin mRNA in ARPE-19 cells. Thus, levels of Vav are associated with DENV-induced inflammatory responses, and blocking Vav signaling pathways does not compromise control of viral replication but may influence DENV-induced host responses. IMPORTANCE Dengue disease is characterized by an inflammatory-mediated immunopathology, with elevated levels of circulating factors including TNF-α and IL-6. If the damaging inflammatory pathways could be blocked without loss of antiviral responses or exacerbating viral replication, then this would be of potential therapeutic benefit. The study here has investigated the Vav guanine exchange factors as a potential alternative signaling pathway that may drive dengue virus (DENV)-induced inflammatory responses, with a focus on Vav1 and 2. While Vav proteins were positively associated with mRNA for inflammatory cytokines, blocking Vav signaling didn’t affect DENV replication but prevented DENV-induction of p-ERK and enhanced IL-6 (inflammatory) and viperin (antiviral) mRNA. These initial data suggest that Vav proteins could be a target that does not compromise control of viral replication and should be investigated further for broader impact on host inflammatory responses, in settings such as antibody-dependent enhancement of infection and in different cell types.

Walter Cannon was a highly regarded American neurologist and physiologist with extremely broad interests. In the tradition of Cannon and his broad interests, we discuss our laboratory's multifaceted work in signal transduction over the past 40+ years. We show how our questioning of how growth hormone (GH) in the blood communicates with cells throughout the body to promote body growth and regulate body metabolism led to insight into not only body height but also important regulators of malignancy and body weight. Highlights include finding that 1) A critical initiating step in GH signal transduction is GH activating the GH receptor-associated tyrosine kinase JAK2; 2) GH activation of JAK2 leads to activation of a number of signaling proteins, including STAT transcription factors; 3) JAK2 is autophosphorylated on multiple tyrosines that regulate the activity of JAK2 and recruit signaling proteins to GH/GH receptor/JAK2 complexes; 4) Constitutively activated STAT proteins are associated with cancer; 5) GH activation of JAK2 recruits the adapter protein SH2B1 to GH/GH receptor/JAK2 complexes where it facilitates GH regulation of the actin cytoskeleton and motility; and 6) SH2B1 is recruited to other receptors in the brain, where it enhances satiety, most likely in part by regulating leptin action and neuronal connections of appetite-regulating neurons. These findings have led to increased understanding of how GH functions, as well as therapeutic interventions for certain cancer and obese individuals, thereby reinforcing the great importance of supporting basic research since one never knows ahead of time what important insight it can provide. [ABSTRACT FROM AUTHOR]

The concept of barzakhis usedforthingsthat distinguish betweentwo things/situations/levels in the thought of Ibn al-'Arabî and carry some characteristics of both, as well as the meaning of "life in the grave" which is widely known in the literature of Islamic sciences. This use of Ibn al-'Arabi is not limited, accordingto the scholars itis impossible to identifythe barzakhs that unite and separate (jâmî and fasıl) in his works because they are quite numerous. This original structure of the concept of barzakh in Ibn al-'Arabi makes it easier for us to understand his views. One of the thingsthatIbn al-'Arabi describes as barzakh is the letterwaw. Ibn al-'Arabi's attributing a barzakh function to the letter waw is based on two reasons: Firstly, the fact that a letter is barzakh not only in the literal context, but in such a way that performs an ontological task is directly related to the ontological functions that Ibn al-'Arabi ascribes to the letters. Secondly, the barzakh of this letter is due to its phonetic, morphological and syntactic features. In our study, first of all, the concept of barzakh and Ibn al-Arabi's thought of barzakh were discussed, then it is mentioned that the ontological character of the letters, the pronunciation of the letter waw, its position in the word or sentence, its function as a barzakh with these states and which other entities it corresponds to in Ibn al-'Arabi's metaphysical system. In this context, it is seen that the letter waw is in the middle of the word 'kun', which brings the possible beings into existence. There is also a waw between the last letter of the word kun, nun, which shows that there is a separation between the realms of visible and the unseen, ifthe universe is a sign that is both a veil for Allah and points to Him, it is not a coincidence that the number of days in which it was created, 6, is the abjad equivalent of waw. Waw also symbolizes the perfect human being in many respects and the perfect human being is a barzakh between Allah and other people. According to some scholars, the division of Futuhât into sixmain partsis due to the factthatthe number of directions and days of creation is six, or the similarity between the waw's symbolization of the perfect human being and the comprehensiveness of the work. Likewise, Haqiqat al-Muhammadiyya has an intermediate feature, and in this respect, it also characterizes the Muhammadan truth. [ABSTRACT FROM AUTHOR]

Control strategies for variable-air-volume (VAV) air conditioning significantly affect both the air quality within buildings and the consumption of building energy. Current control techniques effectively regulate room temperature using feedback on temperature discrepancies, yet they also elevate the wear on terminal devices and boost the energy usage of the supply fan. In this paper, the hysteresis and inertia parameters of end air valves and supply fans under two seasonal conditions are derived from experimental data. Aiming at the problems of frequent switching of the end air valve, long total switching stroke, and high energy consumption of the air supply fan, a fuzzy PI regulation method is proposed based on the original pressure-independent series PI regulation, which effectively solves the above problems. Initially, data on how room temperature reacts to changes in air supply fan speed and the position of end air valves during winter and summer were gathered. Following model identification, parameters for various seasonal conditions were determined. Secondly, the roles of different components in the variable-air-volume regulation process were investigated. Investigations revealed that within pressure-independent variable-air-volume control, the supply fan and end air valve emerged as the primary subjects of the study. A double-closed-loop control with the speed control of the supply fan as the outer loop and the opening control of the end air valve as the inner loop was adopted. Compared with the traditional serial PI regulation, the room temperature error of this method was increased, but it reduced the total stroke of the valve by more than 43%, which greatly reduced the valve’s loss and noise and saved more than 2.7% of the energy consumption of the air supply fan.

Introduction: Rac-GTPases and their Rac-GEF activators play important roles in neutrophil-mediated host defence. These proteins control the adhesion molecules and cytoskeletal dynamics required for neutrophil recruitment to inflamed and infected organs, and the neutrophil effector responses that kill pathogens. Methods: Here,we used live cell TIRF-FRET imaging in neutrophils fromRac-FRET reporter mice with deficiencies in the Rac-GEFs Dock2, Tiam1 or Prex1/Vav1 to evaluate if these proteins activate spatiotemporally distinct pools of Rac, and to correlate patterns of Rac activity with the neutrophil responses they control. Results: All the GEFs were required for neutrophil adhesion, and Prex1/Vav1 were important during spreading and for the velocity of migration during chemotaxis. However, Dock2 emerged as the prominent regulator of neutrophil responses, as this GEF was required for neutrophil polarisation and random migration, for migration velocity during chemokinesis, for the likelihood to migrate and for the speed of migration and of turning during chemotaxis, as well as for rapid particle engulfment during phagocytosis. We identified characteristic spatiotemporal patterns of Rac activity generated by Dock2 which correlate with the importance of the Rac-GEF in these neutrophil responses. We also demonstrate a requirement for Dock2 in neutrophil recruitment during aseptic peritonitis. Discussion: Collectively, our data provide a first direct comparison of the pools of Rac activity generated by different types of Rac-GEFs, and identify Dock2 as a key regulator of polarisation, migration and phagocytosis in primary neutrophils. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Engineering Sciences & Information Technology is the property of Arab Journal of Sciences & Research Publishing (AJSRP) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Since the COVID-19 outbreak, special attention has been paid to proper ventilation and building management systems. The indoor air CO2 concentration level is still used as an effective indicator to evaluate indoor air quality. Many different sensors have appeared on the market in the last two years. However, calibration procedures and guidance on proper installation have not been well described by manufacturers. The research method is based on a review of technical parameters. The practical measurements of CO2 concentration were taken using different sensors. For these purposes three different premises were selected. It was found that CO2 measurement failure happened in residential buildings without mechanical ventilation. Meanwhile, in well ventilated buildings all sensors have shown similar results and the difference between sensors located in different zones was minimal. [ABSTRACT FROM AUTHOR]

Btk and Vav proteins are all components of the signalosome that builds upon B cell receptor (BCR) activation. However, the role of Vav proteins within the signalosome is quite complex and not yet fully understood. Until now, studies of these have focused predominantly on a deficiency of Vav proteins alone or in combination with other Vav protein family members. Since a physical association of Btk with Vav was shown previously, we asked whether these molecules lie in the same or independent signaling pathways. By analyzing Vav1 and Vav3 single knock-out mice and generating double-knock-out animals deficient for either Vav1 or Vav3 and Btk, we observed, in line with previous publications, no severe B cell developmental defects when either Vav1 or Vav3 alone are not expressed. However, a simultaneous deficiency of Btk together with either Vav1 or Vav3 leads to a severe reduction of splenic B cells, which exhibit an immature phenotype. B cell developmental defects of Btk/Vav1-double deficient mice in the periphery were more severe than those observed in Btk-single-deficient animals. Additionally, morphological changes in splenic microarchitecture were observed in double- but also in single-knock-out mutants. These observations were accompanied by reduced BCR-induced Ca2+ mobilization, proliferation, germinal center formation and immunoglobulin secretion. Although deletion of Btk alone impaired Ca2+ mobilization upon BCR activation, the defect was even more severe when Vav1 or Vav3 were also mutated, indicating that Btk and the Vav proteins act in separate pathways that converge on Ca2+ signaling. In vitro ASC differentiation suggests that both B and T cells contribute to the observed phenotype of a Btk/Vav-double deficiency. Our results show that Vav proteins and Btk are both components of the BCR-activated signalosome but control separate signaling pathways important for B cell development.

Since the COVID-19 outbreak, special attention has been paid to proper ventilation and building management systems. The indoor air CO2 concentration level is still used as an effective indicator to evaluate indoor air quality. Many different sensors have appeared on the market in the last two years. However, calibration procedures and guidance on proper installation have not been well described by manufacturers. The research method is based on a review of technical parameters. The practical measurements of CO2 concentration were taken using different sensors. For these purposes three different premises were selected. It was found that CO2 measurement failure happened in residential buildings without mechanical ventilation. Meanwhile, in well ventilated buildings all sensors have shown similar results and the difference between sensors located in different zones was minimal.

Accurate indoor air temperature (IAT) predictions for heating, ventilation, and air conditioning (HVAC) systems are challenging, especially for multi-zone building and for different HVAC system types. Moreover, the nonlinearity of the buildings thermal dynamics makes the IAT prediction more difficult since it is affected by complex factors such as controlled and uncontrolled points, outside weather conditions and occupancy schedule. This paper presents a long short-term memory (LSTM) model to predict IAT for multi-zone building based on direct multi-step prediction with sequence-to-sequence approach. Two strategies, LSTM-MISO and LSTM-MIMO, are built for multi-input single-output and multi-input multi-output, respectively. The performance of these two strategies has been evaluated based on two case studies on real smart buildings using variable air volume (VAV) and constant air volume (CAV) systems. For both buildings, experimental results showed that the LSTM models outperform multilayer perceptron models by reducing the prediction error by 50%. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) infection during pregnancy can result in a significant impact on the brain and eye of the developing fetus, termed congenital zika syndrome (CZS). At a morphological level, the main serious presentations of CZS are microcephaly and retinal scarring. At a cellular level, many cell types of the brain may be involved, but primarily neuronal progenitor cells (NPC) and developing neurons. Vav proteins have guanine exchange activity in converting GDP to GTP on proteins such as Rac1, Cdc42 and RhoA to stimulate intracellular signaling pathways. These signaling pathways are known to play important roles in maintaining the polarity and self-renewal of NPC pools by coordinating the formation of adherens junctions with cytoskeletal rearrangements. In developing neurons, these same pathways are adopted to control the formation and growth of neurites and mediate axonal guidance and targeting in the brain and retina. This review describes the role of Vavs in these processes and highlights the points of potential ZIKV interaction, such as (i) the binding and entry of ZIKV in cells via TAM receptors, which may activate Vav/Rac/RhoA signaling; (ii) the functional convergence of ZIKV NS2A with Vav in modulating adherens junctions; (iii) ZIKV NS4A/4B protein effects on PI3K/AKT in a regulatory loop via PPI3 to influence Vav/Rac1 signaling in neurite outgrowth; and (iv) the induction of SOCS1 and USP9X following ZIKV infection to regulate Vav protein degradation or activation, respectively, and impact Vav/Rac/RhoA signaling in NPC and neurons. Experiments to define these interactions will further our understanding of the molecular basis of CZS and potentially other developmental disorders stemming from in utero infections. Additionally, Vav/Rac/RhoA signaling pathways may present tractable targets for therapeutic intervention or molecular rationale for disease severity in CZS.

Importance: Dengue disease is characterized by an inflammatory-mediated immunopathology, with elevated levels of circulating factors including TNF-α and IL-6. If the damaging inflammatory pathways could be blocked without loss of antiviral responses or exacerbating viral replication, then this would be of potential therapeutic benefit. The study here has investigated the Vav guanine exchange factors as a potential alternative signaling pathway that may drive dengue virus (DENV)-induced inflammatory responses, with a focus on Vav1 and 2. While Vav proteins were positively associated with mRNA for inflammatory cytokines, blocking Vav signaling didn't affect DENV replication but prevented DENV-induction of p-ERK and enhanced IL-6 (inflammatory) and viperin (antiviral) mRNA. These initial data suggest that Vav proteins could be a target that does not compromise control of viral replication and should be investigated further for broader impact on host inflammatory responses, in settings such as antibody-dependent enhancement of infection and in different cell types., Competing Interests: The authors declare no conflict of interest.

Vav1 works both as a catalytic Rho GTPase activator and an adaptor molecule. These functions, which are critical for T cell development and antigenic responses, are tyrosine phosphorylation-dependent. However, it is not known whether other posttranslational modifications can contribute to the regulation of the biological activity of this protein. Here, we show that Vav1 becomes acetylated on lysine residues in a stimulation- and SH2 domain-dependent manner. Using a collection of both acetylation- and deacetylation-mimicking mutants, we show that the acetylation of four lysine residues (Lys222, Lys252, Lys587, and Lys716) leads to the downmodulation of the adaptor function of Vav1 that triggers the stimulation of the nuclear factor of activated T cells (NFAT). These sites belong to two functional subclasses according to mechanistic criteria. We have also unveiled additional acetylation sites potentially involved in either the stimulation (Lys782) or the downmodulation (Lys335, Lys374) of specific Vav1-dependent downstream responses. Collectively, these results indicate that Nε-lysine acetylation can play variegated roles in the regulation of Vav1 signaling. Unlike the case of the tyrosine phosphorylation step, this new regulatory layer is not conserved in other Vav family paralogs.

This paper and its future companion papers, were aimed to develop a set of efficient and accurate enough modular tools to build a simulation test bed for the stability analysis of interacting VAV (variable air volume air-conditioning system) control loops. By providing the correlation equations between the heat flow and temperature of the two opposite surfaces, the wall model was expected to link adjacent zones effectively and efficiently. In part 1, the development of an optimal simplified 3R2C (composed of three resistances and two capacitances) thermal network model of building envelope, i.e., the wall model, was descripted. The verification showed that the simplification of one-dimensional heat conduction through a typical wall of heavy construction was acceptable. The accuracy of the optimal simplified 3R2Cmodel was satisfying, and outperformed that of the optimal 4R3C model as well as two 3R2C models which were normally used in practical applications. First and foremost, the room dimensions of the test bed with the boundary conditions in numerical scheme were designed under the principle of similarity. After validation of the numerical scheme with the high-cited scaled experiment, a series of numerical test cases simulating the potential oscillations in practical applications, were conducted. Then, the long neglected concerned frequency range within which heat flow transfer through extern wall, was determined. Finally, the part of solid wall was separated with the part of indoor air, and was developed into a flexible wall module of 3R2C model based on frequency domain regression. [ABSTRACT FROM AUTHOR]

RHO GTPases are a class of small molecules involved in the regulation of several cellular processes that belong to the RAS GTPase superfamily. The RHO family of GTPases includes several members that are further divided into two different groups: typical and atypical. Both typical and atypical RHO GTPases are critical transducers of intracellular signaling and have been linked to human cancer. Significantly, both gain-of-function and loss-of-function mutations have been described in human tumors with contradicting roles depending on the cell context. The RAS family of GTPases that also belong to the RAS GTPase superfamily like the RHO GTPases, includes arguably the most frequently mutated genes in human cancers (K-RAS, N-RAS, and H-RAS) but has been extensively described elsewhere. This review focuses on the role of RHO family GTPases in human lymphoma initiation and progression.

Myeloid phagocytes have evolved to rapidly recognize invading pathogens and clear them through opsonophagocytic killing. The adenylate cyclase toxin (CyaA) of Bordetella pertussis and the edema toxin (ET) of Bacillus anthracis are both calmodulin-activated toxins with adenylyl cyclase activity that invade host cells and massively increase the cellular concentrations of a key second messenger molecule, 3’,5’-cyclic adenosine monophosphate (cAMP). However, the two toxins differ in the kinetics and mode of cell entry and generate different cAMP concentration gradients within the cell. While CyaA rapidly penetrates cells directly across their plasma membrane, the cellular entry of ET depends on receptor-mediated endocytosis and translocation of the enzymatic subunit across the endosomal membrane. We show that CyaA-generated membrane-proximal cAMP gradient strongly inhibits the activation and phosphorylation of Syk, Vav, and Pyk2, thus inhibiting opsonophagocytosis. By contrast, at similar overall cellular cAMP levels, the ET-generated perinuclear cAMP gradient poorly inhibits the activation and phosphorylation of these signaling proteins. Hence, differences in spatiotemporal distribution of cAMP produced by the two adenylyl cyclase toxins differentially affect the opsonophagocytic signaling in myeloid phagocytes.

• Evaluation three high-performance HVAC controllers in a VAV cooling system. • Integrated three controllers with the medium-sized office building model in Modelica. • Compared the performance in terms of energy efficiency and thermal comfort. • Demonstrated the comparable performance of GDL36 with two intelligent controllers. The design, commissioning, and retrofit of heating, ventilation, and air-conditioning (HVAC) control systems are crucially important for energy efficiency. However, designers and control contractors adopt ad-hoc control sequences based on diffused and fragmented information; therefore, most of the existing control sequences are diverse and sub-optimal. ASHRAE Guideline 36 (GDL36), High-performance Sequences of Operation (SOO) for HVAC Systems, was thus developed to provide standardized and high-performance rule-based HVAC control sequences with the main focus on maximizing energy efficiency. However, only limited studies verify the performance of these high-performance rules-based control and most of these studies focus on the single-zone systems. In this Modelica-based simulation study, the high-performance rule-based control sequences from GDL36 were compared to the state-of-the-art intelligent controllers (i.e., optimization-based controller (OBC) and deep reinforcement-learning-based controller (DRLC)) in terms of the energy efficiency and thermal comfort. The performance evaluation was conducted in a medium-sized office building with a multi-zone Variable Air Volume (VAV) cooling system. The OBC and DRLC replaced the GDL36 airside supervisory level control loops. In other words, the optimal supply air temperature (SAT) and static differential pressure (DP) setpoints were determined by the optimization problems in OBC and trained control policy by DRLC. The OBC and DRLC were formulated to minimize the HVAC energy consumption and zone air temperature violation. The OBCs with different control intervals and DRLCs with different hyperparameters in the Proximal Policy Optimization (PPO) algorithm were exploited and fine-tuned. The simulation results show that the GDL36 has a comparable energy performance (within a 3% deviation) with DRLC in the cases with high or mild cooling loads. It also has a comparable energy performance (within a 3% deviation) with OBC in the case of a high cooling load. However, the case with GDL36 consumed 7% more energy in the testing shoulder period. For the thermal comfort metric, the GDL36 has slightly more zone air temperature violations in all testing scenarios compared to the two intelligent controllers. From this case study, we can conclude that the GDL36 has demonstrated its comparable performance in terms of energy efficiency and thermal comfort with the two intelligent controllers. The GDL36 airside SOO is good enough considering the complexity and tuning efforts of the intelligent controllers. [ABSTRACT FROM AUTHOR]

An important discussion on the application of the Axiomatic Design Theory (ADT) is how to address coupled designs. Coupled designs are somewhat usual in engineering and call for solutions in the field of ADT. This paper addresses a class of designs where one or more functional requirements can be fulfilled by design parameters of the type “the higher the better”. A good example of this kind of designs is one of the most widespread types of air conditioning systems for office applications: the variable air volume (VAV) system. A VAV system controls the air temperature of multiple rooms by adjusting the flow of cooled air that is supplied by the VAV box that serves each room of the office. The essential functional requirements (FRs) of any modern air conditioning system are: “to control the air temperature”, and “to provide indoor air quality (IAQ)” to each served room. The drawback of the VAV systems is that the renewal of the stale air depends on the heat loading of all the rooms, which makes it a coupled design. This paper shows how this coupled design can be decoupled by using a design parameter (the outdoor airflow), which value may be set large enough to fulfil the related functional requirement (the IAQ). The VAV application serves as an example of the application of a new proposed theorem of the ADT that allows decoupling a matrix equation. [ABSTRACT FROM AUTHOR]

Damper opening prediction under demand flowrate is the key for the novel feed-forward control method of damper opening and fan frequency, which is widely applied in the VAV system as well as many other processes. This paper proposed a novel damper opening prediction algorithm under demand air flowrate, and a novel air flowrate control method based on this prediction algorithm, which are both verified by the case simulation. The novel prediction algorithm is based on duct network impedance model, and the maximum opening prediction error can be less than ±1° by 5 groups sample identification. The novel flowrate control method does not need static pressure measurement, and can reduce airflow fluctuation time by 55% and fan power consumption by 21.6% compared with constant static pressure setting method, which is potential to replace the static pressure setting method in VAV air conditioning system. The work of this paper provides the basic algorithm and control method for energy saving control of the duct or pipe network in HVAC system. • A novel prediction algorithm of VAV terminal damper opening is proposed. • The prediction algorithm has high-precision and simple calculation processes. • Air flowrate control based on the algorithm does not need pressure measurement. • Flow fluctuation and fan power can be reduced by 55% and 21.6% respectively. [ABSTRACT FROM AUTHOR]

In recent years, a large number of secure voting protocols have been proposed in the literature. Often these protocols contain flaws, but because they are complex protocols, rigorous formal analysis has proven hard to come by. Rivest's ThreeBallot and Vote/Anti-Vote/Vote (VAV) voting systems are important because they aim to provide security (voter anonymity and voter verifiability) without requiring cryptography. In this paper, we construct CSP models of ThreeBallot and VAV, and use them to produce the first automated formal analysis of their anonymity properties. Along the way, we discover that one of the crucial assumptions under which ThreeBallot and VAV (and many other voting systems) operate-the short ballot assumption-is highly ambiguous in the literature. We give various plausible precise interpretations and discover that in each case, the interpretation either is unrealistically strong or else fails to ensure anonymity. We give a revised version of the short ballot assumption for ThreeBallot and VAV that is realistic but still provides a guarantee of anonymity. [ABSTRACT FROM AUTHOR]

The energy required to maintain comfortable indoor environmental conditions is a significant percentage (35%) of the overall energy consumption in office buildings. In the modern-day realization of climate change and global warming potential, the reduction of energy consumption in office buildings (particularly energy consumed using cooling and mechanical ventilation systems) and maintaining indoor environmental conditions, is an essential design requirement particularly for buildings located in hot, arid climates. The mixed-mode ventilation (MMV) strategies have been effectively used in the past for saving energy as well as maintaining indoor air quality for the occupants by sustaining adequate indoor environmental conditions. It has been found that mixed-mode buildings have the potential to save 40% HVAC energy by optimizing window operation schedules, and up to 75% by alternating natural and mechanical ventilation. However, to successfully optimize these strategies, it is imperative to understand what factors affect the performance of mixed-mode buildings in terms of energy savings and comfort of the occupants. A comprehensive literature review was conducted covering the past two decades (1996–2016) to analyze the use of MMV systems in office buildings. The study provides the reader with an impression of which practical objectives have been pursued, what progress has been made in the past two decades, and what the future challenges are for using MMV systems in office buildings. [ABSTRACT FROM AUTHOR]

Sleep is evolutionarily conserved and required for organism homeostasis and survival. Despite this importance, the molecular and cellular mechanisms underlying sleep are not well understood. Caenorhabditis elegans exhibits sleep-like behavioral quiescence and thus provides a valuable, simple model system for the study of cellular and molecular regulators of this process. In C. elegans, epidermal growth factor receptor (EGFR) signaling is required in the neurosecretory neuron ALA to promote sleep-like behavioral quiescence after cellular stress. We describe a novel role for VAV-1, a conserved guanine nucleotide exchange factor (GEF) for Rho-family GTPases, in regulation of sleep-like behavioral quiescence. VAV-1, in a GEF-dependent manner, acts in ALA to suppress locomotion and feeding during sleep-like behavioral quiescence in response to cellular stress. Additionally, VAV-1 activity is required for EGF-induced sleep-like quiescence and normal levels of EGFR and secretory dense core vesicles in ALA. Importantly, the role of VAV-1 in promoting cellular stress–induced behavioral quiescence is vital for organism health because VAV-1 is required for normal survival after cellular stress. [ABSTRACT FROM AUTHOR]

Small GTPases of the Ras superfamily are capable of activating E2F-dependent transcription leading to cell proliferation, but the molecular mechanisms are poorly understood. In this study, using immortalized chicken DT40 B cell lines to investigate the role of the Vav/Rac signalling cascade on B cell proliferation, it is shown that the proliferative response triggered by B cell receptor activation is dramatically reduced in the absence of Vav3 expression. Analysis of this proliferative defect shows that in the absence of Vav3 expression, retinoblastoma protein ( RB) phosphorylation and the subsequent E2F activation do not take place. By combining pharmacological and genetic approaches, phosphatidylinositol-3-kinase and phospholipase Cγ2 ( PLCγ2) were identified as the key regulatory signalling molecules upstream of the Vav3/Rac pathway leading to RB phosphorylation and E2F transcription factor activation. Additionally, vav3 −/− and plcγ 2 −/− DT40 B cells were not able to activate the RB-E2F complex wild-type phenotype when these genetically modified cells were transfected with constitutively active forms of RhoA or Cdc42. However, when these knockout cells were transfected with different constitutively active versions of PLCγ, Vav or Rac1, not only activation of the RB-E2F complex wild-type phenotype was recovered but also the cellular proliferation. Furthermore, by evaluating the effect of two known effector mutants of Rac1 (Rac1Q61L/F37A and Rac1Q61L/Y40C), the RB-E2F complex activation dependency on p21-activated kinase ( PAK) and protein kinase Cε ( PKCε) activities was established, being independent of both actin cytoskeleton reorganization and Ras activity. These results suggest that PAK1 and PKCε may be potential therapeutic targets to stop uncontrolled B cell proliferation mediated by the Vav/Rac pathway. [ABSTRACT FROM AUTHOR]

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Organ shaping and patterning depends on the coordinated regulation of multiple processes. The Drosophila compound eye provides an excellent model to study the coordination of cell fate and cell positioning during morphogenesis. Here, we find that loss of vav oncogene function during eye development is associated with a disorganised retina characterised by the presence of additional cells of all types.We demonstrate that these defects result from two distinct roles of Vav. First, and in contrast to its well-established role as a positive effector of the EGF receptor (EGFR), we show that readouts of the EGFR pathway are upregulated in vav mutant larval eye disc and pupal retina, indicating that Vav antagonises EGFR signalling during eye development. Accordingly, decreasing EGFR signalling in vav mutant eyes restores retinal organisation and rescues most vav mutant phenotypes. Second, using live imaging in the pupal retina, we observe that vav mutant cells do not form stable adherens junctions, causing various defects, such as recruitment of extra primary pigment cells. In agreement with this role in junction dynamics, we observe that these phenotypes can be exacerbated by lowering DE-Cadherin or Cindr levels. Taken together, our findings establish that Vav acts at multiple times during eye development to prevent excessive cell recruitment by limiting EGFR signalling and by regulating junction dynamics to ensure the correct patterning and morphogenesis of the Drosophila eye. [ABSTRACT FROM AUTHOR]