Characterizations of Pneumocystis carinii and rat lung lipids: glyceryl ethers and fatty alcohols

Pneumocystis carinii carinii and rat lung phospholipids contained 3-6% 1-alkyl-2-acyl glycerols composed of the glyceryl ether species, 1-O-octadecyl glycerol (batyl alcohol), 1-O-octadec-9-enyl glycerol (selachyl alcohol), 1-O-hexadecyl glycerol (chimyl alcohol), and 1-O-hexadec-9-enyl glycerol. Of the major phospholipid classes, phosphatidylinositol (PI) and phosphatidylserine contained the highest percentage of alkyl acyl glycerols. Methylprednisolone treatment caused an increase in alkyl acyl PI of rat lung lipids from 12% to 45%. As the PI concentration in lung phospholipids increases in rats treated with methylprednisolone, the increase in alkyl acyl PI was substantial; the proportions of alkyl acyl phosphatidylethanolamine and alkyl acyl lyso phosphatidylcholine (PC) also increased. Pneumocystis phospholipids contained higher proportions of alkyl acyl PC than the phospholipids of the lungs from normal and immunosuppressed uninfected rats. The glyceryl ether compositions of P. carinii carinii PC and lyso PC were similar, which suggests that lyso PC in the organism is derived by phospholipase A2 action on PC. This was not the case for PC and lyso PC of the lung controls. Analysis of the free fatty alcohols, precursors of glyceryl ethers identified only saturated species in P. carinii carinii and rat lung controls. Thus, the introduction of a double bond in the alcohol moiety of glyceryl ethers occurs after formation of the ether linkage between fatty alcohol and the glyceryl backbone.     

BDN-GWMNN: Internet of Things (IoT) Enabled Secure Smart City Applications

Nowadays, next-generation networks such as the Internet of Things (IoT) and 6G are played a vital role in providing an intelligent environment. The development of technologies helps to create smart city applications like the healthcare system, smart industry, and smart water plan, etc. Any user accesses the developed applications; at the time, security, privacy, and confidentiality arechallenging to manage. So, this paper introduces the blockchain-defined networks with a grey wolf optimized modular neural network approach for managing the smart environment security. During this process, construction, translation, and application layers are created, in which user authenticated based blocks are designed to handle the security and privacy property. Then the optimized neural network is applied to maintain the latency and computational resource utilization in IoT enabled smart applications. Then the efficiency of the system is evaluated using simulation results, in which system ensures low latency, high security (99.12%) compared to the multi-layer perceptron, and deep learning networks.

     

A Novel Triple-Action Inhibitor Targeting B-Cell Receptor Signaling and BRD4 Demonstrates Preclinical Activity in Chronic Lymphocytic Leukemia

B-cell chronic lymphocytic leukemia (CLL) results from intrinsic genetic defects and complex microenvironment stimuli that fuel CLL cell growth through an array of survival signaling pathways. Novel small-molecule agents targeting the B-cell receptor pathway and anti-apoptotic proteins alone or in combination have revolutionized the management of CLL, yet combination therapy carries significant toxicity and CLL remains incurable due to residual disease and relapse. Single-molecule inhibitors that can target multiple disease-driving factors are thus an attractive approach to combat both drug resistance and combination-therapy-related toxicities. We demonstrate that SRX3305, a novel small-molecule BTK/PI3K/BRD4 inhibitor that targets three distinctive facets of CLL biology, attenuates CLL cell proliferation and promotes apoptosis in a dose-dependent fashion. SRX3305 also inhibits the activation-induced proliferation of primary CLL cells in vitro and effectively blocks microenvironment-mediated survival signals, including stromal cell contact. Furthermore, SRX3305 blocks CLL cell migration toward CXCL-12 and CXCL-13, which are major chemokines involved in CLL cell homing and retention in microenvironment niches. Importantly, SRX3305 maintains its anti-tumor effects in ibrutinib-resistant CLL cells. Collectively, this study establishes the preclinical efficacy of SRX3305 in CLL, providing significant rationale for its development as a therapeutic agent for CLL and related disorders.     

Purification and characterization of a DNA helicase from Saccharomyces cerevisiae

A novel DNA helicase, scHelI, has been purified from whole cell extracts of Saccharomyces cerevisiae using biochemical assays to monitor the fractionation. The enzyme unwinds partial duplex DNA substrates, as long as 343 base pairs in length, in a reaction that is dependent on either ATP or dATP hydrolysis. scHelI also catalyzes a single-stranded DNA-dependent ATP hydrolysis reaction; the apparent Km for ATP is 325 microM. The unwinding reaction on circular partial duplex substrates is biphasic, with a fast component occurring within 5 min of the initiation of the reaction and a slow component continuing to 60 min. This is in contrast to the ATP hydrolysis reaction, which exhibits linear kinetics for 60 min. The direction of the unwinding reaction is 5' to 3' with respect to the strand of DNA on which the enzyme is bound. The unwinding reaction is strongly stimulated by the addition of Escherichia coli single-stranded DNA-binding protein when long partial duplex substrates are used. The enzymatic activity of scHelI copurifies with a polypeptide of 135 kDa as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The polypeptide sediments as a monomer in a glycerol gradient in the presence of 0.2 M NaCl.     

Antimicrobial activity of polysiloxane coatings containing quaternary ammonium-functionalized polyhedral oligomeric silsesquioxane

An array of quaternary ammonium functionalized-polyhedral oligomeric silsesquioxane (Q-POSS) compounds with different alkyl chain lengths and counter ions were synthesized using a two-step process. First, octasilane POSS was functionalized with dimethylamino groups by hydrosilylation with allyldimethylamine. Next, partial quaternization of the tertiaryamino-functional POSS was achieved using an alkyl halide to produce the Q-POSS. Alkyl chain length of the Q-POSS compounds varied from –C₁₂H₂₅ to –C₁₈H₃₇ and the counter ions varied between chlorine, bromine, and iodine. Moisture-cured polysiloxane coatings were prepared by dispersing Q-POSS molecules into a solution blend of silanol-terminated polydimethylsiloxane, methylacetoxysilane, and a catalyst. To evaluate the utility of the Q-POSS molecules as a broad-spectrum antimicrobial additive, the antimicrobial activity of the coatings toward the Gram-negative bacterium, Escherichia coli, the Gram-positive bacterium, Staphylococcus aureus, and the opportunistic fungal pathogen, Candida albicans, was determined using an agar plating method. The results obtained showed that both the composition of the Q-POSS and the composition of the polysiloxane matrix affected antimicrobial properties. Compositions were identified that inhibited the growth of all three microorganisms on the coating surface. Surface Raman spectroscopic analysis was performed on selected set of coatings to understand the relative concentration of Q-POSS molecules at the coating surface.     

An enhanced adaptive Q-tuning scheme for a 100-MHz fully symmetric OTA-based bandpass filter

A tuning scheme for continuous-time high-Q biquad filters is presented. An improvement over the existing implementation of the modified-LMS Q-tuning scheme is proposed and efficiently combined with the frequency tuning based on phase-locked loops. The proposed scheme takes much less area without compromising the accuracy achieved previously. The proposed unified Q- and f/sub 0/-tuning scheme does not require the Q-tuning loop to be slower than the f/sub 0/-tuning loop. The optimal case is to have equal speeds for both loops. Also, a low-voltage pseudo-differential operational transconductance amplifier with inherent common-mode feedforward is introduced. The structure is fully symmetric and suitable for high-frequency applications. An experimental test chip is fabricated in standard CMOS 0.5-/spl mu/m technology, with a bandpass filter of center frequency 100 MHz and Q of 20, along with the proposed tuning scheme. The measured Q-tuning error is around 1%. Expected and experimental results are in good agreement.