Micro electro mechanical cantilever with electrostatically controlled tip contact

A micro-electro-mechanical system (MEMS) cantilever that lifts from the surface by electrostatic force is described. The design is composed of three conductors: a fixed buried plate, a fixed surface plate, and a moveable cantilever. All have the same square shape and are arranged parallel in a vertical stack with aligned edges. The surface plate and cantilever are biased at the same potential, and the buried plate is oppositely biased. Theoretical analysis based on values of position-dependent coefficients of capacitance and electrostatic induction from finite element method demonstrates the sign of the force on the cantilever and determines its magnitude. Video microscopy and electrical measurements demonstrate the electrostatic lifting of the cantilever in a fabricated MEMS device. The vertical displacement of the cantilever is quantified from changes in optical interference fringes, and the displacement magnitude agrees with expectations based on estimated strengths of upward electrostatic force and downward elastic restoring force

Saliva, a bodily fluid with recognized and potential diagnostic applications

Human whole saliva is a bodily fluid that can be obtained easily by noninvasive techniques. Specimens can be collected by the patient also at home in order to monitor health status and variations of several analytes of clinical interest. The contributions to whole saliva include secretions from salivary glands and, among others, from the gingival crevicular fluid that derives from the epithelial mucosa. Therefore, saliva is currently a relevant diagnostic fluid for many substances, including steroids, nonpeptide hormones, therapeutic drugs, and drugs of abuse. This review at first briefly describes the different contributions to whole saliva. A section illustrates the procedures for the collection, handling, and storage of salivary specimens. Another section describes the present use of whole saliva for diagnostic purposes and its specific utilization for the diagnosis of several local and systemic diseases. The final sections illustrate the future opportunities offered by various not conventional techniques with a focus on the most recent –omic investigations. It describes the various issues that have to be taken into account to avoid false positives and negatives, such as the strength of the experimental plan, the adequacy of the number of samples under study, and the proper choice of controls

Service Failure-Recovery In Online Shops In Iran

Present article focuses on service failure and recovery in the online shops in Iran. The article investigates interaction between service failure and online shops readiness for service recovery and resulting impact on customer reaction. The data was collected by an e-questionnaire from 615 Iranian online shoppers. The findings suggest, although many online shops are severely breaching few fundamental business principles, defection is not happening as vast as in other similar studies. Furthermore, winning the customers back via service recovery seems to be depended rather on the process than the outcome of service recovery, which is very similar to the findings of another study in Chinese environment. Discussion of the findings suggests the researchers and managers to be conscious of the possible impact of the culture and environment on customer’s responses to service failure and service recovery states

A Catalog of Coding Sequence Variations in Salivary Proteins’ Genes Occurring during Recent Human Evolution

Saliva houses over 2000 proteins and peptides with poorly clarified functions, including proline-rich proteins, statherin, P-B peptides, histatins, cystatins, and amylases. Their genes are poorly conserved across related species, reflecting an evolutionary adaptation. We searched the nucleotide substitutions fixed in these salivary proteins’ gene loci in modern humans compared with ancient hominins. We mapped 3472 sequence variants/nucleotide substitutions in coding, noncoding, and 5′-3′ untranslated regions. Despite most of the detected variations being within noncoding regions, the frequency of coding variations was far higher than the general rate found throughout the genome. Among the various missense substitutions, specific substitutions detected in PRB1 and PRB2 genes were responsible for the introduction/abrogation of consensus sequences recognized by convertase enzymes that cleave the protein precursors. Overall, these changes that occurred during the recent human evolution might have generated novel functional features and/or different expression ratios among the various components of the salivary proteome. This may have influenced the homeostasis of the oral cavity environment, possibly conditioning the eating habits of modern humans. However, fixed nucleotide changes in modern humans represented only 7.3% of all the substitutions reported in this study, and no signs of evolutionary pressure or adaptative introgression from archaic hominins were found on the tested genes

Top-Down Proteomics of Human Saliva Highlights Anti-inflammatory, Antioxidant, and Antimicrobial Defense Responses in Alzheimer Disease

Alzheimer disease (AD) is the most prevalent neurodegenerative disease in the elderly, characterized by accumulation in the brain of misfolded proteins, inflammation, and oxidative damage leading to neuronal cell death. By considering the viewpoint that AD onset and worsening may be influenced by environmental factors causing infection, oxidative stress, and inflammatory reaction, we investigated the changes of the salivary proteome in a population of patients with respect to that in healthy controls (HCs). Indeed, the possible use of saliva as a diagnostic tool has been explored in several oral and systemic diseases. Moreover, the oral cavity continuously established adaptative and protective processes toward exogenous stimuli. In the present study, qualitative/quantitative variations of 56 salivary proteoforms, including post-translationally modified derivatives, have been analyzed by RP-HPLC-ESI-IT-MS and MS/MS analyses, and immunological methods were applied to validate MS results. The salivary protein profile of AD patients was characterized by significantly higher levels of some multifaceted proteins and peptides that were either specific to the oral cavity or also expressed in other body districts: (i) peptides involved in the homeostasis of the oral cavity; (ii) proteins acting as ROS/RNS scavengers and with a neuroprotective role, such as S100A8, S100A9, and their glutathionylated and nitrosylated proteoforms; cystatin B and glutathionylated and dimeric derivatives; (iii) proteins with antimicrobial activity, such as α-defensins, cystatins A and B, histatin 1, statherin, and thymosin β4, this last with a neuroprotective role at the level of microglia. These results suggested that, in response to injured conditions, Alzheimer patients established defensive mechanisms detectable at the oral level. Data are available via ProteomeXchange with identifier PXD021538

Investigation by top-down high-performance liquid chromatography-mass spectrometry of glutathionylation and cysteinylation of salivary S100A9 and cystatin B in preterm newborns

Glutathionylation and cysteinylation can be involved in the protection of critical cysteines from irreversible oxidative damages. S100A9 long and cystatin B, proteins highly represented in the saliva of preterm and at-term newborns, can undergo these modifications. Levels of S100A9 long and cystatin B and their glutathionylated and cysteinylated derivatives have been determined by a top-down platform based on high-performance liquid chromatography-electrospray ionization-mass spectrometry in 100 salivary samples serially collected from 17 preterm newborns with different postconceptional age at birth (178-226 days) and in 90 salivary samples collected from at-term newborns and babies. Results showed that: (1) S100A9 long and cystatin B were mainly present as unmodified forms in extremely preterm newborn; (2) the percentage of the S-thiolated derivatives of both proteins increased with increasing the postconceptional age; (3) the greatest variation occurred up to about 280 days of postconceptional age. Interestingly, differences in the levels of the S-thiolated derivatives only depended on the postconceptional age and not on whether the infant was born preterm or at-term. Inadequate levels of cysteine and glutathione might be responsible for the low level of S-thiolated derivatives measured in preterm newborns. Data are available via ProteomeXchange with identifier PXD025517

Improving Phase Change Memory Performance with Data Content Aware Access

A prominent characteristic of write operation in Phase-Change Memory (PCM) is that its latency and energy are sensitive to the data to be written as well as the content that is overwritten. We observe that overwriting unknown memory content can incur significantly higher latency and energy compared to overwriting known all-zeros or all-ones content. This is because all-zeros or all-ones content is overwritten by programming the PCM cells only in one direction, i.e., using either SET or RESET operations, not both. In this paper, we propose data content aware PCM writes (DATACON), a new mechanism that reduces the latency and energy of PCM writes by redirecting these requests to overwrite memory locations containing all-zeros or all-ones. DATACON operates in three steps. First, it estimates how much a PCM write access would benefit from overwriting known content (e.g., all-zeros, or all-ones) by comprehensively considering the number of set bits in the data to be written, and the energy-latency trade-offs for SET and RESET operations in PCM. Second, it translates the write address to a physical address within memory that contains the best type of content to overwrite, and records this translation in a table for future accesses. We exploit data access locality in workloads to minimize the address translation overhead. Third, it re-initializes unused memory locations with known all-zeros or all-ones content in a manner that does not interfere with regular read and write accesses. DATACON overwrites unknown content only when it is absolutely necessary to do so. We evaluate DATACON with workloads from state-of-the-art machine learning applications, SPEC CPU2017, and NAS Parallel Benchmarks. Results demonstrate that DATACON significantly improves system performance and memory system energy consumption compared to the best of performance-oriented state-of-the-art techniques.Comment: 18 pages, 21 figures, accepted at ACM SIGPLAN International Symposium on Memory Management (ISMM

Pathogenicity locus determinants and toxinotyping of Clostridioides difficile isolates recovered from Iranian patients

Little is known about the toxin profiles, toxinotypes and variations of toxin Clostridioides difficile C (tcdC) in Iranian C. difficile isolates. A total of 818 stool specimens were obtained from outpatients (n = 45) and hospitalized patients (n = 773) in Tehran, Iran, from 2011 to 2017. The 44 C. difficile isolates were subjected to PCR of toxin C. difficile A (tcdA), toxin C. difficile B (tcdB), tcdA 3�-end deletion, toxinotyping and sequencing of the tcdC gene. Thirty-eight isolates (86.36) were identified as tcdA and tcdB positive, and the remaining six isolates (13.63) were nontoxigenic. All tcdA- and tcdB-positive isolates yielded an amplicon of 2535 bp by PCR for the tcdA 3� end. Fourteen (36.84), seventeen (44.73) and seven (18.43) isolates belonged to wild-type, toxin C. difficile C subclone3 (tcdC-sc3) and tcdC-A genotype of tcdC, respectively. Thirty-one isolates (81.57) belonged to toxinotype 0, and seven isolates (18.42) were classified as toxinotype V. This study provides evidence for the circulation of historical and hypervirulent isolates in the healthcare and community settings. Furthermore, it was also demonstrated that the tcdC-A genotype and toxinotype V are not uncommon among Iranian C. difficile isolates. © 201

Pannexin 3 deletion reduces fat accumulation and inflammation in a sex-specific manner

Background: Pannexin 3 (PANX3) is a channel-forming glycoprotein that enables nutrient-induced inflammation in vitro, and genetic linkage data suggest that it regulates body mass index. Here, we characterized inflammatory and metabolic parameters in global Panx3 knockout (KO) mice in the context of forced treadmill running (FEX) and high-fat diet (HFD). Methods: C57BL/6N (WT) and KO mice were randomized to either a FEX running protocol or no running (SED) from 24 until 30 weeks of age. Body weight was measured biweekly, and body composition was measured at 24 and 30 weeks of age. Male WT and KO mice were fed a HFD from 12 to 28 weeks of age. Metabolic organs were analyzed for a panel of inflammatory markers and PANX3 expression. Results: In females there were no significant differences in body composition between genotypes, which could be due to the lack of PANX3 expression in female white adipose tissue, while male KOs fed a chow diet had lower body weight and lower fat mass at 24 and 30 weeks of age, which was reduced to the same extent as 6 weeks of FEX in WT mice. In addition, male KO mice exhibited significantly lower expression of multiple pro-inflammatory genes in white adipose tissue compared to WT mice. While on a HFD body weight differences were insignificant, multiple inflammatory genes were significantly different in quadriceps muscle and white adipose tissue resulting in a more anti-inflammatory phenotype in KO mice compared to WT. The lower fat mass in male KO mice may be due to significantly fewer adipocytes in their subcutaneous fat compared to WT mice. Mechanistically, adipose stromal cells (ASCs) cultured from KO mice grow significantly slower than WT ASCs. Conclusion: PANX3 is expressed in male adult mouse adipose tissue and may regulate adipocyte numbers, influencing fat accumulation and inflammation