Miracle-dz/UniFAR-FTUs huggingface dataset:
CFTR Cl− channel and CFTR‐associated ATP channel: distinct pores regulated by common gates

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel that is regulated by phosphorylation of the R domain and ATP hydrolysis at two nucleotide‐binding domains (NBDs). It is controversial whether CFTR conducts ATP or whether CFTR might be closely associated with a separate ATP conductance. To characterize ATP channels associated with CFTR, we analyzed Cl− and ATP single channel‐currents in excised inside‐out membrane patches from MDCK epithelial cells transiently expressing CFTR. With 100 mM ATP in the pipette and 140 mM Cl− in the bath, ATP channels were associated with CFTR Cl− channels in two‐thirds of patches that included CFTR. CFTR Cl− channels and CFTR‐associated ATP channels had slope conductances of 7.4 pS and 5.2 pS, respectively, and had distinct reversal potentials and sensitivities to channel blockers. CFTR‐associated ATP channels exhibited slow gating kinetics that depended on the presence of protein kinase A and cytoplasmic ATP, similar to CFTR Cl− channels. Gating kinetics of the ATP channels as well as the CFTR Cl− channels were similarly affected by non‐hydrolyzable ATP analogues and mutations in the CFTR R domain and NBDs. Our results indicate that phosphorylation‐ and nucleotide‐hydrolysis‐dependent gating of CFTR is directly involved in gating of an associated ATP channel. However, the permeation pathways for Cl− and ATP are distinct and the ATP conduction pathway is not obligatorily associated with the expression of CFTR.
Genetically altered animal models in the kallikrein-kinin system

Abstract Transgenic and gene-targeting technologies allowing the generation of genetically altered animal models have greatly advanced our understanding of the function of specific genes. This is also true for the kallikrein-kinin system (KKS), in which some, but not yet all, components have been functionally characterized using such techniques. The first genetically altered animal model for a KKS component was supplied by nature, the brown Norway rat carrying an inactivating mutation in the kininogen gene. Mice deficient in tissue kallikrein, B1 and B2 receptors, some kinin-degrading enzymes, and factor XII followed, together with transgenic rat and mouse strains overexpressing tissue kallikrein, B1 and B2 receptors, and degrading enzymes. There are still no animal models with genetic alterations in plasma kallikrein, kininases I and some other degrading enzymes. The models have confirmed an important role of the KKS in cardiovascular pathology, inflammation, and pain, and have partially elucidated the distinct function of the two receptors. This created the basis for rational decisions concerning the putative use of kinin receptor agonists and antagonists in therapeutic applications. However, a more thorough analysis of the existing models and the generation of new, more sophisticated transgenic models will be necessary to clarify the still elusive issue as to where and by which mechanisms the kinins exert their actions.
Alteration of postantibiotic effect during one dosing interval of tobramycin, simulated in an in vitro pharmacokinetic model

The kinetics of the postantibiotic effect (PAE) during one dosing interval of tobramycin against Staphylococcus aureus and Pseudomonas aeruginosa was investigated. We determined the PAE at different time points during this dosing interval of 12 h in an in vitro pharmacokinetic model simulating human pharmacokinetics in which the half-life of tobramycin was adjusted to 2.4 +/- 0.2 h. Using an enzymatic method to inactivate tobramycin, we determined PAEs in samples extracted from the model at 1, 5, 8, and 12 h, corresponding with tobramycin concentrations of 20, 5, 2, and 1 times the MIC for the test organism. The PAE decreased significantly from 2.5 h at 1 h to 0 h at 12 h. No change in MIC was observed for the strains during the experiments. We conclude that the PAE decreases with decreasing tobramycin concentrations during a 12-h dosing interval and completely disappears after the concentration has reached the MIC for the test organism. On the basis of these observations, the emphasis that is placed on the PAE in discussions about the optimal dosing interval in aminoglycoside therapy is questionable.
Reliability Analysis of Wide-Area Measurement System

As a key technology in smart grid, the wide-area measurement system (WAMS) will gradually become an important guarantee for security and stability of future power systems. This paper presents a quantified reliability evaluation method for the backbone communication network in WAMS and the overall WAMS from a hardware reliability viewpoint. The whole WAMS is modeled using a hierarchical structure. Markov modeling and state enumeration techniques are combined to perform the reliability evaluation. The WAMS in the IEEE 14-bus system is used as an example to demonstrate the application of the presented method in reliability assessment of overall WAMS.
The Quaternary Structure of Chicken Acetylcholinesterase and Butyrylcholinesterase; Effect of Collagenase and Trypsin

Abstract: Acetylcholinesterase (EC 3.1.1.7.; AChE) and butyrylcholinesterase (EC 3.1.1.8.; BuChE) from chicken muscle exist as sets of structurally homologous forms with very similar properties. The collagenase sensitivity and aggregation properties of the‘heavy’forms of both enzymes indicate that they possess a collagen‐like tail, and their stepwise dissociation by trypsin confirms that they correspond to triple (A12) and double (A8) collagen‐tailed tetramers. In addition to this dissociating effect, trypsin digests an important fraction of the catalytic units of AChE, in a progressive manner, removing as much as 30% of the enzyme's mass, without inactivation of the tetramers and of the tailed molecules. The trypsin‐modified AChE forms closely resemble the corresponding mammalian AChE forms in their hydrodynamic properties. It is not known whether the trypsin‐digestible peptides, which do not appear to be involved in the ionic or hydrophobic interactions of the enzymes, are a fragment of the catalytic subunit or whether they constitute distinct polypeptides.
CCL26 Participates in the PRL-3–Induced Promotion of Colorectal Cancer Invasion by Stimulating Tumor-Associated Macrophage Infiltration

Both phosphatase of regenerating liver-3 (PRL-3) and tumor-associated macrophages (TAM) influence cancer progression. Whether PRL-3 plays a critical role in colorectal cancer invasion and metastasis by inducing TAM infiltration remains unclear. In the current study, we investigated the effects of chemokine ligand 26 (CCL26) on TAM infiltration and colorectal cancer invasion and the underlying mechanism in colorectal cancer cells by overexpressing or silencing PRL-3. We found that PRL-3 upregulated CCL26 expression correlatively and participated in cell migration, according to the results of gene ontology analysis. In addition, IHC analysis results indicated that the PRL-3 and CCL26 levels were positively correlated and elevated in stage III and IV colorectal cancer tissues and were associated with a worse prognosis in colorectal cancer patients. Furthermore, we demonstrated that CCL26 induced TAM infiltration by CCL26 binding to the CCR3 receptor. When LoVo-P and HT29-C cells were cocultured with TAMs, CCL26 binding to the CCR3 receptor enhanced the invasiveness of LoVo-P and HT29-C cells by mobilizing intracellular Ca2+of TAMs to increase the expression of IL6 and IL8. In addition, IHC results indicated that protein levels of CCR3 and TAMs counts were higher in stage III and IV colorectal cancer tissues and correlated with CCL26. Moreover, similar results were observed in vivo using mice injected with LoVo-P and HT29-C cells. These data indicate that PRL-3 may represent a potential prognostic marker that promotes colorectal cancer invasion and metastasis by upregulating CCL26 to induce TAM infiltration. Mol Cancer Ther; 17(1); 276–89. ©2017 AACR.
CpG Oligodeoxynucleotides Activate Innate Immune Response that Suppresses Infectious Bronchitis Virus Replication in Chicken Embryos

Abstract The understanding of innate immune modulation by pathogens and immune-modulating agents, including synthetic oligodeoxynucleotides (CpG ODNs), has offered several new approaches to improve prophylactic and therapeutic strategies against infectious diseases in humans and animals. However, in this regard not much work has been done in avian medicine. In the present study, we analyzed the kinetics of interferon (IFN), cytokine, and chemokine mRNA expression in chicken embryonic spleen at 6 hr, 24 hr, 48 hr, and 72 hr after administration of CpG ODN 2007 (B-class) in 18-day-old chicken embryos. Our data showed enhanced expression of IFN-γ; interleukin (IL)-1β, IL-6, and IL-8; and oligoadenyl synthetase A mRNA after CpG ODN administration. In addition, CpG ODN administration to chicken embryos 24 hr before the challenge with infectious bronchitis virus (IBV) was capable of limiting IBV propagation in different embryonic tissues. Based on the kinetics and type of cytokines induced after in ovo administration of CpG ODN, it may be speculated that in ovo administration of CpG ODNs may enhance resistance from viral infection in neonatal chicks and that CpG ODNs may contribute toward the development of more effective and safer poultry vaccines including in ovo vaccines.
An Efficient Implementation of the ITU-R Channel Model for Device-to-Device Simulation

To evaluate 4G cellular systems, a system-level simulation (SLS) with the ITU-R channel model is often used. For the evaluation of the next generation communication systems, a SLS including a device-to-device (D2D) system is needed. However, as the number of multi-paths in a D2D link is squared compared to the link between a base station and a mobile station, the simulation run-time has to increase greatly. In this paper, we propose the ITU-R channel model extension to the D2D channel and the Doppler response-based fast fading channel generation as a realization method for the D2D channel. The proposed method can significantly reduce the simulation run-time.
On the orienting value of attitudes: attitude accessibility as a determinant of an object's attraction of visual attention.

Four experiments tested the hypothesis that objects toward which individuals hold attitudes that are highly accessible from memory (i.e., attitude-evoking objects) are more likely to attract attention when presented in a visual display than objects involving less accessible attitudes. In Experiments 1 and 2, Ss were more likely to notice and report such attitude-evoking objects. Experiment 3 yielded evidence of incidental attention; Ss noticed attitude-evoking objects even when the task made it beneficial to ignore the objects. Experiment 4 demonstrated that inclusion of attitude-evoking objects as distractor items interfered with Ss' performance of a visual search task. Apparently, attitude-evoking stimuli attract attention automatically. Thus, accessible attitudes provide the functional benefit of orienting an individual's visual attention toward objects with potential hedonic consequences.
Prevalence of PIK3CA mutations and the SNP rs17849079 in Arab breast cancer patients

Carcinomas initiate and progress due to genetic and epigenetic alterations in epithelial cells. However, recently, these alterations have also been reported in stromal fibroblasts. The gain-of-function mutations in the PI3K p110 catalytic subunit (PIK3CA) have been identified in many cancers with a current global incidence of 26% (18–40%) in breast carcinomas. We analyzed the mutational frequency of PIK3CA of three hotspots (exons 1, 9, and 20) in 81 primary invasive breast cancers (BC) and 25 cultured breast cancer-associated fibroblast (CAF) samples by Sanger sequencing in Arab breast cancer patients. Associations between the incidence of any PIK3CA mutation and several clinicopathologic characteristics were assessed using chi-square tests for categorical or t test for continuous variables. Furthermore, survival curves were estimated using the Kaplan–Meier method with the log rank test to evaluate the significance of their differences. We identified a total of 21 PIK3CA missense mutations with a frequency of 25.9%. The majority of the mutations, 17 out of 21 (81%), were in exon 20 (p.His1047Arg, p.His1047Lys, p.Thr1025Ala, p.Gly1049Arg, p.Asp1056Asn) while the remainder, 4 out of 21 (19%) were in exon 9 (p.Glu545Lys). PIK3CA mutations were significantly associated with lower grade and hormone receptor positivity. Although there was a favorable trend in overall survival for patients whose tumor harbored PIK3CA mutations, the difference was not statistically significant (P = 0.10). However, we did not detect any somatic mutations in CAFs. Furthermore, we have shown a high prevalence (8.2-fold) of a silent variant (SNP, rs17849079) in the Arab breast cancer population compared with disease-free individuals.
Microarray analysis of genes controlled by progesterone in human endometrial stromal cells in vitro

The steroid hormone progesterone is a key factor in establishment and maintenance of pregnancy in the human endometrium. To obtain a global view and identify new target genes for progesterone in human endometrial stromal cells in short-term (3 days) culture ,we used a screening strategy to analyze the expression of nearly 1000 human genes by DNA microarray analysis. The results showed that six genes were up-regulated (at least a two-fold increase) ,and 27 genes were down-regulated (at least a two-fold decrease) after progesterone treatment compared with control. Progesterone stimulated the expression of the interleukin (IL)-1 receptor type 1 ,fibulin-1 ,fibulin-2 ,microsomal glutathione S-transferase 1 ,fumarylacetoacetate hydrolase and orphan G protein-coupled receptor (RDC1). Progesterone inhibited the expression of insulin-like growth factor binding protein-5 ,heparin-binding epidermal growth factor-like growth factor ,and IL-13 receptor α2. In addition ,progesterone inhibited the expression of genes involved in immune modulators ,DNA/chromatin-related proteins ,signal transduction ,transcription factors ,transport proteins ,enzyme ,receptor and structural proteins. Our results demonstrate that microarray analysis can be used to identify progesterone-regulated genes in endometrial stromal cells ,thus contributing to a more detailed understanding of the molecular mechanisms in response to progesterone in the endometrium during the preparatory period for implantation.
Interaction of calpastatin with calpain: a review

Abstract Calpastatin is a multiheaded inhibitor capable of inhibiting more than one calpain molecule. Each inhibitory domain of calpastatin has three subdomains, A, B, and C; A binds to domain IV and C binds to domain VI of the calpains. Crystallographic evidence shows that binding of C to domain VI involves hydrophobic interactions at a site near the first EF-hand in domain VI. Sequence homology suggests that binding of A to calpain domain IV also involves hydrophobic interactions near the EF1- hand of domain IV. Neither subdomain A nor C have inhibitory activity without subdomain B, but both increase the inhibitory activity of B. Subdomain B peptides have no inhibitory activity unless they contain at least 13 amino acids, and inhibitory activity increases with the number of amino acid residues, suggesting that inhibition requires interaction over a large area of the calpain molecule. Although subdomain B inhibition kinetically is competitive in nature, subdomain B does not seem to interact with the active site of the calpains directly, but may bind to domain III of the calpains and act to block access to the active site. It is possible that subdomain B binds to calpain only after it has been activated by Ca[2+].
First order diplexer using SIW-based circular cavity resonator

A design of Substrate Integrated Waveguide (SIW) diplexer is proposed. The diplexer is formed using two SIW circular cavity resonators designed individually and combined through a T-junction. The circular cavity structure using TM010 mode is employed in the design of this diplexer. To prove the concept, the diplexer is fabricated using Rogers RT5880 with dielectric constant, □r = 2.2 and height of substrate 1.57 mm. The diplexer is fabricated with standard printed circuit board technology and will be operating at 2.4 GHz and 2.6 GHz each suitable for LTE/WiFi applications. The performances of the proposed design are verified through both simulation and measurement. The measured results are in good agreement with simulated result. Slight frequency shift and losses are still in acceptable range.
Optimisation of 9T SRAM bit cell geometry for high speed memories

in this paper, 9T bit cell is designed and simulated to verify the design. The design and simulation study results are presented here. 9T SRAM bit cell is designed with 65nm CMOS technology, obtaining optimum transistor geometries for the bit cell. Leakage current for the designed bit cell is estimated for variations in transistor geometries, VDD and temperature.
The Chaotic Behavior of Foreign Exchange Rates

This paper explores the use of a measure of chaotic behavior, the correlation dimension, in explaining the unpredictable fluctuations in foreign exchange rates. The resulting calculations indicate that the Singapore dollar has a smaller correlation dimension than four European currencies, consistent with the view that the Singapore dollar is a highly managed currency. We also utilize the correlation dimension to determine the impact of the stock market crash of October 19, 1987 on the five currencies. The four European currencies exhibit a statistically significant decrease in their correlation dimensions, while the Singapore dollar displays no significant change. This is consistent with a hypothesis of a an intervention in the management of the European currencies.
Lyme borreliosis in Ontario: determining the risks.

In this issue of CMAJ Satyendra Banerjee and colleagues highlight the possibility of exposure to Lyme borreliosis in Ontario. [1][1] What is the likelihood of encountering the blacklegged tick, Ixodes scapularis , the vector of Lyme borreliosis, in eastern Canada? Is this likelihood changing? And
Deep fat of the face revisited

The midfacial deep fatty tissue has been divided into the buccal and parapharyngeal fat pads although the former carries several extensions in adults. Using histological sections of 15 large human fetuses, we demonstrated that the parapharyngeal fat pad corresponds to the major content of the prestyloid compartment of the parapharyngeal space or, simply, the prestyloid fat. The buccal and prestyloid fatty tissues were separated by the medial and lateral pterygoid muscles. In these tissues, superficial parts, corresponding to the lower body and the masseteric extension of the adult buccal fat pad, were well encapsulated and showed the most advanced stage of histogenesis. As the sphenoid bone was not fully developed even in the largest specimens, the temporal, infratemporal, and pterygopalatine fossae joined to provide a large space for a single, large upper extension of the buccal fat pad. In the intermediate part of the extension course, the larger specimens carried a narrower part between the maxilla and the temporalis muscle. The single, upper extension appeared to divide into several extensions, as seen in adults. The periocular fat was clearly separated from the upper extension of the buccal fat pad by the sheet‐like orbitalis muscle. A communication between the prestyloid fat and the buccal fat pad likely occurred through a potential space along the lingual nerve immediately superior to the deep part of the submandibular gland. At this site, therefore, the prestyloid fat may be injured or infected when the buccal fat pad is treated surgically. Clin. Anat. , 2013. © 2012 Wiley Periodicals, Inc.
Intraocular pressure and influencing systemic health parameters in a Korean population

Aim: To evaluate the relationship between intraocular pressure (IOP) and systemic health parameters such as age, gender, body mass index (BMI), total cholesterol, high density lipoprotein (HDL), and triglyceride (TG) in a Korean population. Materials and Methods: A total of 30,893 healthy subjects underwent automated multiphasic tests, including non-contact tonometry, automated perimetry, fundus photography, and blood samplings for total cholesterol, HDL, and TG. Seven age groups were divided by decades ranging from 20 to 29 years to 80 + years. The association between IOP and BMI, plasma lipid profiles was examined using cross-sectional analysis. Results: The mean age of subjects was 47.7 years. The mean IOP of subjects was 15.4 ± 3.2 mmHg for both eyes. The mean IOP of men was significantly higher than women (P = 0.000). By multiple linear regression analysis, IOP was positively associated with gender (male), BMI, total cholesterol, and TG and negatively associated with age (P = 0.000). BMI, total cholesterol, and TG had significantly positive correlations with IOP after adjusting for age, gender, and other variables which can influence the IOP (P = 0.000). Conclusions: In a Korean population, the mean IOP, total cholesterol, TG, and BMI values of men were higher than women. IOP was found to increase with total cholesterol, TG, BMI, and to decrease with only age regardless of sex.
Strengthening Strategic Reward Framework in Health Systems: A Survey of Narok County, Kenya.

BACKGROUND Rewards are used to strengthen good behavior among employees based on the general assumption that rewards motivate staff to improve organizational productivity. However, the extent to which rewards influence motivation among health workers (HWs) has limited information that is useful to human resources (HRs) instruments. This study assessed the influence of rewards on motivation among HWs in Narok County, Kenya. METHODS This was a cross-sectional study done in two sub-counties of Narok County. Data on the rewards availability, rewards perceptions and influence of rewards on performance, as well as motivation level of the HWs, was collected using a self-administered questionnaire with HWs. SPSS version 21 was used to analyze descriptive statistics, and factor analysis and multivariate regression using Eigen vectors was used to assess the relationship between the reward intervention and HWs' motivation. RESULTS A majority of HWs 175 (73.8%) had not received a reward for good performance. Only 3 (4.8%) of the respondents who received rewards were not motivated by the reward they received. Overall, reward significantly predicted general motivation (p-value = 0.009). CONCLUSION In Narok County, the HR's instruments have not utilized the reward system known to motivate employees. In the study area, hard work was not acknowledged and rewarded accordingly. In addition, there were not sufficient opportunities for promotion in the county. An increased level of reward has the potential to motivate HWs to perform better. Therefore, providing rewards to employees to increase motivation is a strategy that the Narok County health system and its HR management should utilize.