Miracle-dz/UniFAR-FTUs huggingface dataset:
High Mitotic Activity of Polo-like Kinase 1 Is Required for Chromosome Segregation and Genomic Integrity in Human Epithelial Cells*

Background: Polo-like kinase 1 (Plk1) has multiple functions and substrates in human mitosis. Results: Plk1 functions are separable via distinct thresholds of activity, and partial functional loss leads to chromosome missegregation. Conclusion: Plk1 has several distinct mitotic roles that are separable by chemical genetics. Significance: It is possible to dissect individual functions of a multifunctional enzyme using activity thresholds. Protein kinases play key roles in regulating human cell biology, but manifold substrates and functions make it difficult to understand mechanism. We tested whether we could dissect functions of a pleiotropic mitotic kinase, Polo-like kinase 1 (Plk1), via distinct thresholds of kinase activity. We accomplished this by titrating Plk1 activity in RPE1 human epithelial cells using chemical genetics and verifying results in additional lines. We found that distinct activity thresholds are required for known functions of Plk1 including (from low to high activity) bipolar spindle formation, timely mitotic entry, and formation of a cytokinesis cleavage furrow. Subtle losses in Plk1 activity impaired chromosome congression and produced severe anaphase dysfunction characterized by poor separation of chromosome masses. These two phenotypes were separable, suggesting that they stem from distinct phosphorylation events. Impaired chromosome segregation in anaphase was the most sensitive to modest loss in Plk1 activity. Mechanistically, it was associated with unpaired sister chromatids with stretched kinetochores, suggestive of merotelic attachments. The C-terminal Polo box domain of Plk1 was required for its anaphase function, although it was dispensable for forming a bipolar spindle. The ultimate effect of partial inhibition of Plk1 was the formation of micronuclei, an increase in tetraploid progeny, and senescence. These results demonstrate that different thresholds of Plk1 activity can elicit distinct phenotypes, illustrating a general method for separating pleiotropic functions of a protein kinase even when these are executed close in time.
Feasibility of Using One-Column-Varistor Arresters in 1000-kV UHV Substations

With the application of ultra-high-voltage (UHV) technology, how to reduce the construction cost of the UHV substations is becoming an important and emergent issue. In this paper, two kinds of one-column-varistor arresters are used to replace conventional four-column-varistor arresters for busbars or transformers or both of them. The switching overvoltage and lightning intruding overvoltage are calculated to evaluate the feasibility of using one-column-varistor arresters in UHV substations. At the same time, the energy absorbed by and current flowing through the arresters, and the thermal stability of these one-column-varistor arresters are analyzed to ensure their safe operations. It is shown that conventional one-column-varistor arresters can be used for busbars and transformers in UHV substations to replace conventional four-column-varistor arresters and could highly reduce the construction cost of the UHV substation, but the safety of the substation will remain the same.
Identification and functional analysis of two P450 enzymes of Gossypium hirsutum involved in DMNT and TMTT biosynthesis

Summary The homoterpenes (3E)‐4,8‐dimethyl‐1,3,7‐nonatriene (DMNT) and (E,E)‐4,8,12‐trimethyl‐1,3,7,11‐tridecatetraene (TMTT) are major herbivore‐induced plant volatiles that can attract predatory or parasitic arthropods to protect injured plants from herbivore attack. In this study, DMNT and TMTT were confirmed to be emitted from cotton (Gossypium hirsutum) plants infested with chewing caterpillars or sucking bugs. Two CYP genes (GhCYP82L1 and GhCYP82L2) involved in homoterpene biosynthesis in G. hirsutum were newly identified and characterized. Yeast recombinant expression and enzyme assays indicated that the two GhCYP82Ls are both responsible for the conversion of (E)‐nerolidol to DMNT and (E,E)‐geranyllinalool to TMTT. The two heterologously expressed proteins without cytochrome P450 reductase fail to convert the substrates to homoterpenes. Quantitative real‐time PCR (qPCR) analysis suggested that the two GhCYP82L genes were significantly up‐regulated in leaves and stems of G. hirsutum after herbivore attack. Subsequently, electroantennogram recordings showed that electroantennal responses of Microplitis mediator and Peristenus spretus to DMNT and TMTT were both dose dependent. Laboratory behavioural bioassays showed that females of both wasp species responded positively to DMNT and males and females of M. mediator could be attracted by TMTT. The results provide a better understanding of homoterpene biosynthesis in G. hirsutum and of the potential influence of homoterpenes on the behaviour of natural enemies, which lay a foundation to study genetically modified homoterpene biosynthesis and its possible application in agricultural pest control.
Suppression of MicroRNA-Silencing Pathway by HIV-1 During Virus Replication

MicroRNAs (miRNAs) are single-stranded noncoding RNAs of 19 to 25 nucleotides that function as gene regulators and as a host cell defense against both RNA and DNA viruses. We provide evidence for a physiological role of the miRNA-silencing machinery in controlling HIV-1 replication. Type III RNAses Dicer and Drosha, responsible for miRNA processing, inhibited virus replication both in peripheral blood mononuclear cells from HIV-1–infected donors and in latently infected cells. In turn, HIV-1 actively suppressed the expression of the polycistronic miRNA cluster miR-17/92. This suppression was found to be required for efficient viral replication and was dependent on the histone acetyltransferase Tat cofactor PCAF. Our results highlight the involvement of the miRNA-silencing pathway in HIV-1 replication and latency.
Test systems for dynamic stability studies in electric power system

Electric power system is one of the largest and complex infrastructures made by mankind during the last century. The total investment associated with it in trillions of dollars. As it is a very expensive, large and complex physical system, secure network operation without having any system wide instability issue and catastrophic consequences is sought. As a result power system educators and researchers are constantly scrutinizing power system with changing scenarios and coming up with the new solutions to keep the most important infrastructure intact in order to make the economy and society sustainable. It is tough, but not impossible, and expensive to build physical test power systems to perform various researches. Hence, the test power systems models have been playing a key role for better understanding, development, and deployment of new solutions in power system problems. There have been many test systems with varying complexities and sizes used all around the world. However, there is no common platform where the most of these test systems are documented so that the educators and researchers can chose an appropriate test system suitable for their studies. The paper presents a collection of commonly used test systems for various dynamic stability studies.
Ventricular shunt removal: the ultimate treatment of the slit ventricle syndrome.

OBJECT The aim of this study was to assess the effectiveness of an algorithm used to evaluate and prescribe treatment for patients having slit ventricle syndrome (SVS). METHODS All patients included in this protocol underwent fiberoptic intracranial pressure monitoring after removal or externalization of their ventricular shunt systems. A significant number of patients did not need extracranial cerebrospinal fluid (CSF) diversion and tolerated removal of their shunt systems without requiring further intervention. Patients who demonstrated a need for CSF drainage underwent an endoscopic third ventriculostomy, regardless of the putative cause of their hydrocephalus. Sixteen (72.7%) of 22 patients experienced resolution of or significant improvement in their SVS complaints after their inclusion in the protocol. Concomitantly, 14 (64%) of 22 patients were no longer shunt dependent after a mean follow-up period of 21.4 months. CONCLUSIONS A significant number of patients debilitated by SVS may experience improvement in their symptoms and undergo shunt removal according to this protocol, improving their quality of life and simplifying their medical follow up.
Different effects of proton pump inhibitors and famotidine on the clopidogrel metabolic activation by recombinant CYP2B6, CYP2C19 and CYP3A4

Inhibitory potential of proton pump inhibitors (PPIs) and famotidine, an H2 receptor antagonist, on the metabolic activation of clopidogrel was evaluated using recombinant CYP2B6, CYP2C19 and CYP3A4. Formation of the active metabolite from an intermediate metabolite, 2-oxo-clopidogrel, was investigated by liquid chromatography–tandem mass spectrometry and three peaks corresponding to the pharmacologically active metabolite and its stereoisomers were detected. Omeprazole potently inhibited clopidogrel activation by CYP2C19 with an IC50 of 12.8 μmol/L and more weakly inhibited that by CYP2B6 and CYP3A4. IC50 of omeprazole for CYP2C19 and CYP3A4 was decreased about two- and three-fold, respectively, by 30-min preincubation with NADPH. Lansoprazole, esomeprazole, pantoprazole, rabeprazole and rabeprazole thioether, a major metabolite, also inhibited metabolic activation by CYP2C19, with an IC50 of 4.3, 8.9, 48.3, 36.2 and 30.5 μmol/L, respectively. In contrast, famotidine showed no more than 20% inhibition of clopidogrel activation by CYP2B6, CYP2C19 and CYP3A4 at up to 100 μmol/L and had no time-dependent CYP2C19 and CYP3A4 inhibition. These results provide direct evidence that PPIs inhibit clopidogrel metabolic activation and suggest that CYP2C19 inhibition is the main cause of drug–drug interaction between clopidogrel and omeprazole. Famotidine is considered as a safe anti-acid agent for patients taking clopidogrel.
Molecular cytogenetic insights into the ageing syndrome Hutchinson-Gilford Progeria (HGPS)

Hutchinson-Gilford Progeria Syndrome (HGPS) is an extremely rare genetic disorder characterized by premature ageing in childhood and serves as a valuable model for the human ageing process in general. Most recently, point mutations in the lamin A (LMNA) gene on chromosome 1q have been associated with the disease, however how these mutations relate to the complex phenotype of HGPS remains to be established. It has been shown that fibroblasts from HGPS patients are frequently resistant to immortalization with telomerase (hTERT), consistent with the idea that the loss of a dominant acting HGPS gene is a pre-requisite for immortalization. In this study we report the first detailed cytogenetic analysis of hTERT-immortalised HGPS cell lines from three patients and one corresponding primary fibroblast culture. Our results provide evidence for a cytogenetic mosaicism in HGPS with a distinctive pattern of chromosome aberrations in all the HGP clones. Chromosome 11 alterations were observed at a high frequency in each immortalised HGPS cell line but were also present at a lower frequency in the corresponding primary cells. Moreover, we were able to identify the 11q13→q23 region as a potential site of breakage. Our results are therefore consistent with a role of chromosome 11 alterations in the escape from senescence observed in HGPS cells. In addition to this defined rearrangement, we consistently observed complex chromosomal rearrangements, suggesting that HGPS displays features of chromosomal instability.
Simulation and design of a chipless passive RFID tag

RFID is an object identification and tracking technology worth several billion dollars today. Chipless technology doesn't require communication protocols and IC, making it cheaper. Passive RFID Tags use backscattering technique to send information to the Reader. In this paper, we present a passive RFID Tag based on Ultra-wide band technology. The chipless RFID tag modeled uses passive elements, namely antennas and transmission lines in different architectural orders by varying the lengths and the number of the transmission lines. The unique identities of the tags are characterized by the number and the lengths of the transmission lines and hence a large number of tags can be manufactured economically with a finite number of transmission lines. The technology involves transmission of nanosecond duration pulses which enables high precision time of arrival (TOA) estimation of signal. The software tool used to simulate this system is Linux based open source software development toolkit called GNURadio. It has a predefined set of signal processing blocks and has the provision to code user defined blocks and enables us to represent the RFID system using standard programming languages namely C++ and Python.
Flexible Zinc Finger Requirement for Binding of the Transcriptional Activator Staf to U6 Small Nuclear RNA and tRNASec Promoters*

The transactivator Staf, which contains seven zinc finger motifs, exerts its effect on gene expression by binding to specific targets in small nuclear RNA (snRNA) and snRNA-type gene promoters. In this work, binding site selection allowed us to identify the 21-base pair ATTACCCATAATGCATYGCGG sequence as the high affinity consensus binding site for Staf. It shows a high sequence divergence with Staf-responsive elements in the Xenopus selenocysteine tRNA (tRNASec) and human U6 snRNA promoters. By using a combination of approaches, we analyzed the interaction of wild-type and truncated Staf zinc finger domains with the consensus,Xenopus tRNASec, and human U6 sites. Two main conclusions emerged from our data. First, the data clearly indicate that zinc finger 7 does not establish base-specific contacts in Staf-DNA complexes. The second conclusion concerns zinc finger 1, which is required for the binding to the XenopustRNASec site but is dispensable in the case of the human U6 site. Taking into account the sequence differences in the two sites, these findings demonstrate that Staf utilizes zinc finger 1 in a rather flexible manner, illustrating how a protein can interact with DNAs containing targets of different sequences.
A novel method to prepare multicellular spheroids from varied cell types

A simple method for preparing multicellular spheroids from varied cell types has been successfully developed by using a stepwise gradient surface in cell attachability or detachability. The surface was composed of poly‐N‐isopropylacrylamide (PNIPAAm), a temperature responsive polymer, as a cell detaching component, and collagen as a cell attaching component. The surface functions as a culture substratum at 37°C; then, when lowering the temperature of culture medium, the cells attached to it detach as a self‐supporting sheet. This is because PNIPAAm dissolves into the culture medium below the lower critical solution temperature (LCST; about 30°C), but it is insoluble above the LCST. The detached cell sheet forms a multicellular spheroid. The stepwise gradient surface which consisted of six different sectors was prepared by exposing a surface of the PNIPAAm‐collagen mixture to ultraviolet (UV) irradiation six times using a photomask, sliding the hole position in the photomask, and changing the energy of UV irradiation. This was because crosslinking of collagen depended on the energy of UV irradiation, then, cell attachability to and detachability from the surface were tightly controlled by changing the energy.
Objective Methods of Sample Selection in Acoustic Analysis of Voice

Objectives: In acoustic voice analysis, the fact that reproducible methods of sample selection have not been defined impedes research study generalizability and clinical assessment of treatment efficacy. Because perturbation results differ along a single signal, this study sought to establish objective methods of sample selection by use of a moving window to determine the most stable regions of phonation. Methods: Voice signals obtained from 21 patients affected by laryngeal conditions associated with Parkinson's disease were analyzed to study jitter, shimmer, signal-to-noise ratio, and correlation dimension parameters when various sample selection procedures were used. Objectively selected voice samples were chosen based upon 5%, 10%, and 20% variance from a signal's minimum perturbation value. The stability of these samples, defined by the standard deviations of the acoustic measurements, was compared to the stability of unselected samples and subjectively selected samples. Results: A significant decrease in standard deviation values of acoustic parameters was found in comparing the objectively selected samples (particularly those selected with 5% and 10% variance) to the subjectively selected and unselected samples. Conclusions: These results suggest that the development of an objective sample selection method may have significant effects on the stability and reliability of acoustic voice measurements.
Silicon-Organic Hybrid MZI Modulator Generating OOK, BPSK and 8-ASK Signals for Up to 84 Gbit/s

We report on high-speed multilevel signal generation and arbitrary pulse shaping with silicon-organic hybrid (SOH) Mach-Zehnder interferometer (MZI) modulators. Pure phase modulation exploiting the linear electrooptic effect allows the generation of multiple modulations formats at highest speed such as 40-Gbit/s on-off-keying (OOK) and binary-phase-shift keying (BPSK) and 28-Gbd 4-ASK and 8-ASK with data rates up to 84 Gbit/s. Additionally, beside NRZ pulse shaping, for the first time, Nyquist pulse shaping with silicon modulators is demonstrated to enable multiplexing at highest spectral efficiency.
Phylogeny and potential transmission routes of midgut‐associated endosymbionts of tsetse (Diptera: Glossinidae)

Many tsetse species (Diptera: Glossinidae) harbour two morphologically different intracellular endosymbiotic microorganisms associated with gut tissue: primary (P) and secondary (S) endosymbionts. The P‐endosymbionts of tsetse (Wigglesworthia glossinidia) are sequestered in specialized epithelial cells, bacteriocytes, which form a structure (bacteriome) in the anterior portion of the gut. Phylogenetic characterization of P‐endosymbionts from the three subgenera of genus Glossina has shown that these organisms constitute a distinct lineage within the γ‐subdivision of Proteobacteria and have evolved concordantly with their insect host species, suggesting an evolutionarily ancient association for this symbiosis. The S‐endosymbiont is a smaller (1–2 μm) gram‐negative rod and is harboured in midgut epithelial cells. Its phylogenetic characterization from Glossina morsitans morsitans had shown that it is a member of the family Enterobacteriaceae within the γ‐3 subdivision of the Proteobacteria, closely related to enteric bacteria. Some tsetse species harbour a third bacterium in their reproductive tissue, which was shown phylogenetically to belong to the Wolbachia pipientis assemblage of microorganisms.
Influence of solid lipid microparticle carriers on skin penetration of the sunscreen agent, 4‐methylbenzylidene camphor

The objective of this study was to prepare lipid microparticles (LMs) loaded with the sunscreen agent, 4‐methylbenzylidene camphor (4‐MBC), to achieve decreased skin penetration of this UV filter. The microparticles were produced by the melt dispersion technique using tristearin as lipidic material and hydrogenated phosphatidylcholine as the surfactant. The obtained microparticles were characterized by scanning electron microscopy and differential scanning calorimetry. Release of 4‐MBC from the LMs was found to be slower than its dissolution rate. The influence of the LMs' carrier system on percutaneous penetration was evaluated after their introduction in a model topical formulation (emulsion). In‐vitro measurements were performed with cellulose acetate membranes in Franz diffusion cells. The 4‐MBC release and diffusion was decreased by 66.7–77.3% with the LM formulation, indicating that the retention capacity of the microparticles was maintained after incorporation into the emulsion. In‐vivo human skin penetration of 4‐MBC was investigated by tape stripping, a technique for selectively removing the upper cutaneous layers. The amount of sunscreen penetrating into the stratum corneum was greater for the emulsion containing non‐encapsulated 4‐MBC (36.55% of the applied dose) compared with the formulation with the sunscreen‐loaded microparticles (24.57% of the applied dose). The differences between the two formulations were statistically significant in the first (2–4) horny layer strips. Moreover, the LMs' effect measured in‐vivo was less pronounced than in‐vitro. The increased 4‐MBC retention on the skin surface achieved by its incorporation in the LMs should enhance its efficacy and reduce the potential toxicological risk associated with skin penetration.
Mapping by admixture linkage disequilibrium in human populations: limits and guidelines.

Certain human hereditary conditions, notably those with low penetrance and those which require an environmental event such as infectious disease exposure, are difficult to localize in pedigree analysis, because of uncertainty in the phenotype of an affected patient's relatives. An approach to locating these genes in human cohort studies would be to use association analysis, which depends on linkage disequilibrium of flanking polymorphic DNA markers. In theory, a high degree of linkage disequilibrium between genes separated by 10-20 cM will be generated and persist in populations that have a history of recent (3-20 generations ago) admixture between genetically differentiated racial groups, such as has occurred in African Americans and Hispanic populations. We have conducted analytic and computer simulations to quantify the effect of genetic, genomic, and population parameters that affect the amount and ascertainment of linkage disequilibrium in populations with a history of genetic admixture. Our goal is to thoroughly explore the ranges of all relevant parameters or factors (e.g., sample size and degree of genetic differentiation between populations) that may be involved in gene localization studies, in hopes of prescribing guidelines for an efficient mapping strategy. The results provide reasonable limits on sample size (200-300 patients), marker number (200-300 in 20-cM intervals), and allele differentiation (loci with allele frequency difference of > or = .3 between admixed parent populations) to produce an efficient approach (> 95% ascertainment) for locating genes not easily tracked in human pedigrees.