Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of the native and fibrillar conformation of the human Nα‐acetyltransferase ARD1

ARD1 (arrest‐defective protein 1), together with NAT1 (N‐acetyltransferase protein 1), is part of the major Nα‐acetyltransferase complex in eukaryotes responsible for α‐acetylation of proteins and peptides. Protein acetylation has been implicated in gene expression regulation and protein–protein interaction. We characterized the native folded and misfolded conformation of hARD1. Structural characterization of native hARD1 using size exclusion chromatography, circular dichroism, and fluorescence spectroscopy shows the protein consists of a compact globular region comprising two thirds of the protein and a flexible unstructured C terminus. In addition, hARD1 forms protofilaments under physiological conditions of pH and temperature, as judged by electron microscopy and staining with the dyes Congo red and thioflavin T. The process is accelerated by thermal denaturation and high protein concentrations. Limited proteolysis of aggregated hARD1 revealed a resistant fragment whose sequence matched a region contained within the acetyl transferase domain.
Out-of-plane microwire force sensor arrays with embedded p-n diodes by selective vapor-liquid-solid growth

We proposed a concept of force sensor arrays with vertically integrated, out-of-plane, high-aspect ratio, IC-compatible silicon wires. The proposed structure gives whisker-like force sensor arrays that one end of the wire is affixed on the substrate with another end free to be touched, even though the sensing wire-element has two terminal electrodes. We fabricated the sensor array based on 3-µm-diameter, 30-µm-length p-silicon wires (1 Ω·cm) on n-silicon substrate (3–6 Ω·cm), that results in the p-n diode systems at each wire-base. When the individual wire-tip contacts with an object, the wire exhibits the change in the electrical conductance of both the p-silicon wire body and the embedded p-n diode due to the compressive force. The proposed microwire force sensor array has the possibility for numerous measurements, such as multisite contact force, shear force, surface roughness, slip, etc., with small detection area (∼20 µm2) and high spatial resolution (10–100 µm in pitch). This wire-based force sensor could also be used in fingertips of a robot hand that performs the grasping and the manipulating motions to handle objects.
A cascaded NPC/H-Bridge inverter with simplified control strategy and minimum component count

Multilevel topologies have emerged as a viable technique for medium and high voltage inverters but in the low voltage range they have failed to attract much interest due to their increased cost associated with the additional components and complicated control. This paper proposes a new and simplified control strategy for a nine- cascaded Neutral-Point —Clamped (NPC)/H-Bridge PWM inverter. The new control strategy is achieved by decomposing the nine level output into four separate and independent three- level NPC PWM output. By combining the three- level NPC PWM back to back using DC sources and properly phase shifting the modulating wave and carrier a simplified control strategy is achieved with reduced number of components. The control strategy is applied on cascaded NPC/H-bridge inverter that combines features from NPC inverter and cascaded H-Bridge inverter. A theoretical harmonic analysis of the proposed control is carried out using double Fourier principle. Verification of the analytical results is done using MATLAB simulation.
Reflections on the national patient-reported outcome measures (PROMs) programme: Where do we go from here?

Derek Kyte, Paul Cockwell, Mauro Lencioni, Magdalena Skrybant, Maria von Hildebrand, Gary Price, Katie Squire, Shena Webb, Olivia Brookes, Hilary Fanning, Tim Jones and Melanie Calvert Centre for Patient-Reported Outcomes Research, University of Birmingham, Birmingham B15 2TT, UK Institute of Applied Health Research, University of Birmingham, Birmingham B15 2TT, UK University Hospitals Birmingham, NHS Foundation Trust, Birmingham B15 2TT, UK Institute of Inflammation and Aging, University of Birmingham B15 2TT, UK Corresponding author: Melanie Calvert. Email: m.calvert@bham.ac. uk
Altered expression of cytokine signaling pathway genes in peripheral blood cells of alcohol dependent subjects: preliminary findings.

BACKGROUND Preclinical and clinical studies have implicated changes in cytokine and innate immune gene-expression in both the development of and end-organ damage resulting from alcohol dependence. However, these changes have not been systematically assessed on the basis of alcohol consumption in human subjects. METHODS Illumina Sentrix Beadchip (Human-6v2) microarrays were used to measure levels of gene-expression in peripheral blood in 3 groups of subjects: those with alcohol dependence (AD, n = 12), heavy drinkers (HD; defined as regular alcohol use over the past year of at least 8 standard drinks/wk for women and at least 15 standard drinks/wk for men, n = 13), and moderate drinkers (MD; defined as up to 7 standard drinks/wk for women and 14 standard drinks/wk for men, n = 17). RESULTS Four hundred and thirty-six genes were differentially expressed among the 3 groups of subjects (false discovery rate corrected p-value < 0.05). Two hundred and ninety-one genes differed between AD and MD subjects, 240 differed between AD and HD subjects, but only 6 differed between HD and MD subjects. Pathway analysis using DAVID and GeneGO Metacore(®) software showed that the most affected pathways were those related to T-cell receptor and Janus kinase-Signal transducer and activator of transcription (JAK-Stat) signaling. CONCLUSIONS These results suggest the transition from heavy alcohol use to dependence is accompanied by changes in the expression of genes involved in regulation of the innate immune response. Such changes may underlie some of the previously described changes in immune function associated with chronic alcohol abuse. Early detection of these changes may allow individuals at high risk for dependence to be identified.
The Challenge of Access to the Pontomesencephalic Junction: An Anatomical Study of Lateral Approach and Exposure

We quantitatively compared relative merits of lateral approaches to the pontomesencephalic junction (PMJ): anterior petrosectomy, subtemporal transtentorial, posterior petrosectomy, and retrosigmoid transtentorial. In dissected cadaveric heads, lengths of exposure were measured anteriorly from CN V along the pontomesencephalic sulcus (PMS); posterosuperiorly along the lateral mesencephalic sulcus (LMS); and posteroinferiorly along the interpeduncular sulcus (IPS). Subtemporal transtentorial approach provided best anterior exposure along the PMS (23.8 ± 4.5 mm). Posterosuperior exposures were comparable for all approaches except anterior petrosectomy (limited). Posteroinferior exposure was most with subtemporal transtentorial approach (13.2 ± 2.8 mm). CN V entry/exit point was identified through all approaches, except for subtemporal transtentorial; shortest surgical depth with posterior petrosectomy was 43.7 ± 5.5 mm. PMS-LMS-IPS convergence point: reached through all approaches, except for anterior petrosectomy (limited); shortest surgical depth with posterior petrosectomy was 40.3 ± 4.3 mm. Anterior petrosectomy provides direct anterolateral views of the pons not afforded by subtemporal approach. Subtemporal transtentorial approach provides optimal posterolateral view to the PMJ and cerebellar peduncles. Retrosigmoid transtentorial approach offers wide exposure of the lateral surface, limited on the posteroinferior PMJ by the cerebellum. The small opening of posterior petrosectomy creates an awkward corridor to anterior PMJ targets but provides a direct and shortest route to the cerebellar peduncles.
Thiamine deficiency alters APP but not presenilin‐1 immunoreactivity in vulnerable brain regions

PRESENILIN-1 (PS-1) and amyloid precursor protein (APP) have been linked to the pathogenesis of Alzheimer's disease. While APP accumulation is well documented in several models of brain injury, the role of PS-1 levels in neurodegeneration, if any, remains to be elucidated. The current studies examined PS-1 and APP expression in brain following thiamine deficiency (TD), a nutritional model associated with impaired oxidation and selective neurodegeneration. TD did not alter PS-1 immunoreactivity in any region of rodent brain before or after cell loss. In contrast, APP immunoreactivity accumulated in swollen neurites within, or around lesions in rats, or in abnormal clusters in mice. Thus, alterations in APP but not PS-1 levels are involved in TD-induced neurodegeneration.
Cytoplasmic maturation of the snRNAs

The snRNAs are abundant and stable components of the interphase nucleus. Aqueous and non‐aqueous cell fractionation demonstrate that the snRNAs appear transiently in the cytoplasm shortly after transcription, before returning permanently to the interphase nucleus. In pulse label and chase experiments, the newly synthesized snRNA species appear in the cytoplasm after 1 min of labeling and then return to the interphase nucleus after approximately 15 min in the cytoplasm. In order to study the maturation and intracellular transport of these particles, a battery of metabolic inhibitors and alterations in cell culture conditions were investigated for their ability to interfere with the return of the newly synthesized snRNAs to the nucleus. A wide range of inhibitors of the cytoskeleton did not interfere with this process. Only the inhibition of protein synthesis and exposure of cells to medium of at least twice the normal tonicity block the return of the snRNAs to the nucleus. Immunofluorescent staining of cells exposed to hypertonic medium identifies discrete foci in the cytoplasm that stain with the Sm antiserum, directed against proteins associated with the snRNAs. Using a detergent extraction procedure that preserves the cytoskeleton, the newly synthesized snRNAs in the cytoplasm fractionate as soluble complexes. These data are consistent with the hypothesis that the snRNAs partition into the interphase nucleus because of a preferential solubility and the existence of specific binding sites.
Biotransformation of butylated hydroxytoluene (BHT) to BHT-quinone methide in rats.

2, 6-Di-tert-butyl-4-methylene-2, 5-cyclohexadien-1-one (BHT-quinone methide, BHT-QM) was detected in the bile of rats given butylated hydroxytoluene (BHT). The biliary excretion of BHT-QM during 24 h after administration of BHT, 3, 5-di-tert-butyl-4-hydroxybenzyl alcohol (BHT-alcohol), or 2, 6-di-tert-butyl-4-hydroxy-4-methyl-2, 5-cyclohexadien-1-one (4-hydroxy-BHT) was determined by high-performance liquid chromatography. BHT-alcohol gave about 7 times as much BHT-QM as did BHT, but no BHT-QM was detected after administration of 4-hydroxy-BHT. This result suggests that the transformation of BHT to BHT-QM proceeds mainly through BHT-alcohol. Although 1, 2-bis (3, 5-di-tert-butyl-4-hydroxyphenyl) ethane (BHT-dimer) has been reported as a biliary metabolite of BHT in rats, most of the BHT-dimer seems to be formed artificially by dimerization of BHT-QM during the isolation process.
Role of chemokines and their receptors in chronic lymphocytic leukemia

Chemokines produced in distinct tissue microenvironments sustain migration of mature lymphocytes in lymphoglandula. Chemokine receptors expressed on chronic lymphocytic leukemia (CLL) cells regulate the migration of the leukemia cells within the bone marrow (BM), lymphoid organs in collaboration with chemokines. Chemokines form a pro-survival circuitry by regulating leukocyte trafficking, maintaining extended lymphocyte survival. Therefore, chemokines in tumor cell–microenvironment interactions represent a target for treatment of CLL. AMD3100 disrupts the CLL/microenvironment interactions and influences CXCL12/CXCR4 survival signaling. Fostamatinib, ibrutinib, and GS-1101 as B-cell receptor (BCR)-related kinase inhibitors inhibit BCR- and chemokine-receptor-signal-regulated kinase and have a good clinical response in CLL. Lenalidomide, sorafenib, and dasatinib are other additional drugs associated with chemokine in microenvironment. Inhibiting signaling through chemokine and microenvironment associated signaling are emerging as innovative therapeutic targets in CLL. In this article, we reviewed the role of chemokines in CLL microenvironment and novel therapeutics targeting CLL microenvironment.
The Spirochete FlaA Periplasmic Flagellar Sheath Protein Impacts Flagellar Helicity

ABSTRACT Spirochete periplasmic flagella (PFs), including those fromBrachyspira (Serpulina),Spirochaeta, Treponema, andLeptospira spp. , have a unique structure. In most spirochete species, the periplasmic flagellar filaments consist of a core of at least three proteins (FlaB1, FlaB2, and FlaB3) and a sheath protein (FlaA). Each of these proteins is encoded by a separate gene. Using Brachyspira hyodysenteriae as a model system for analyzing PF function by allelic exchange mutagenesis, we analyzed purified PFs from previously constructedflaA::cat,flaA::kan, andflaB1::kan mutants and newly constructed flaB2::cat andflaB3::cat mutants. We investigated whether any of these mutants had a loss of motility and altered PF structure. As formerly found withflaA::cat,flaA::kan, andflaB1::kan mutants,flaB2::cat andflaB3::cat mutants were still motile, but all were less motile than the wild-type strain, using a swarm-plate assay. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis indicated that each mutation resulted in the specific loss of the cognate gene product in the assembled purified PFs. Consistent with these results, Northern blot analysis indicated that each flagellar filament gene was monocistronic. In contrast to previous results that analyzed PFs attached to disrupted cells, purified PFs from a flaA::cat mutant were significantly thinner (19.6 nm) than those of the wild-type strain and flaB1::kan,flaB2::cat, andflaB3::cat mutants (24 to 25 nm). These results provide supportive genetic evidence that FlaA forms a sheath around the FlaB core. Using high-magnification dark-field microscopy, we also found thatflaA::cat andflaA::kan mutants produced PFs with a smaller helix pitch and helix diameter compared to the wild-type strain and flaB mutants. These results indicate that the interaction of FlaA with the FlaB core impacts periplasmic flagellar helical morphology.
Genome-wide responses of a pathogenic bacterium to its host.

abundance and processing; and (c) protein expression, modification, and localization. Of these, a wealth of information bears on gene transcriptional regulation. Data from completed bacterial genome sequences suggest a direct relationship between the breadth of environmental conditions encountered by a bacterium and the number of genes in its genome that are predicted to encode transcriptional regulatory factors (2). Escherichia coli is particularly well endowed, presumably reflecting environmental transitions in and out of the intestinal tract (3). On closer examination of this species, we now recognize an immense degree of genomic heterogeneity among different serovars and pathovars.
A fault diagnosis method for diesel engine based on Adaptive Network-based Fuzzy Inference System

Combines fuzzy logic inference system with Neural Network, a fault diagnosis method for diesel engine based on Adaptive Network-based Fuzzy Inference System (ANFIS) is studied. The theory and arithmetic and structure of this system are introduced, and a fault model for the fuel injection system of a diesel engine is built with the help of Matlab Fuzzy Toolbox. Simulation results demonstrate that the proposed approach can efficiently diagnose the faults and is better than the fault diagnosis method based on BP neural network.
How do differences in species and part consumption affect diet nutrient concentrations? A test with red colobus monkeys in Kibale National Park, Uganda

Within a primate species, diet can be highly variable in composition, even at small spatial scales within the same forest, or temporally, suggesting that primates use different plant species and parts to meet similar nutritional needs. To test whether such differences in the plant species and parts that primates eat affects the nutrient concentrations that they obtain, we observed feeding of seven groups of red colobus monkeys (Procolobus rufomitratus) residing in Kibale National Park, Uganda. The different groups consumed mostly young leaves from many of the same plant species, but spent different amounts of time feeding on them. As protein and fibre are suggested to be important determinants of colobine food choice and abundance, we analysed multiple samples of 47 food species for protein and fibre. Despite the differences in the plant species and parts eaten, the protein and fibre concentrations for the seven red colobus groups were similar. Our results suggest that colobus monkeys eating diets with differing amounts of species and parts may ultimately receive similar concentrations of nutrients.
Inflammation and Coagulation: Linked Processes Potentially Regulated Through a Common Pathway Mediated by Protein C

Unraveling the biochemical basis of the complex process of blood coagulation has been the focus of intense investigation for more than 30 years. During this period of time, considerable progress has been made in elucidating the structure and assembly of the coagulation complexes (for a review, see ref. 1). From our perspective, the framework of the biochemical basis of the assembly of the coagulation complexes provided the basis for examining the potential cross talk between inflammatory injury and coagulation. The importance of the linkage between inflammation and coagulation is manifest most dramatically in gram negative septic shock. During this process, leukocytes, platelets and monocytes are activated, cytokines are liberated, fibrinogen is consumed and massive vascular damage ensues. In this process, tissue factor is formed de novo and protein C is activated (for a review, see ref. 2). While each of these events definitely occur in the shock process, the influence of each event on other events and their relative contribution to the vascular damage and death are only beginning to emerge. The development of quantitative binding and kinetic assays has led to a second important advance — the appreciation of the roles of endothelial cells, neutrophils, monocyte/macrophage and platelets in these processes (1). In particular, cellular activation now appears to be central to the control of blood coagulation. It is cellular activation that probably constitutes a major link between inflammation, coagulation and vascular damage. This chapter will review our concepts of how these diverse processes may be linked. Our interests have focused on inflammation-coagulation interactions in three areas: 1) E. coli induced shock and disseminated intravascular coagulation (DIC); 2) venous thrombosis; and 3) reperfusion injury. The basic approach that has been taken is to combine basic information with clinical observations to design specific physiological experiments to test the relative importance of particular regulatory molecules on each of the above processes.
Development of a spherical parallel manipulator as a haptic device for a tele-operation system: Application to robotic surgery

In tele-operation applications, especially in surgery, haptic devices need to exhibit a high degree of rigidity and accuracy. This paper deals with the development of a spherical parallel manipulator (SPM) that enables the satisfaction of those characteristics. The parallel architecture enables the use of this kind of robot as master in a tele-operation system. Moreover, the SPM has a center of rotation that makes it a natural candidate and more adapted to minimally invasive surgery application. However, the parallel manipulator presents a poor behavior in singular configuration.
Power Quality Improvement in Autonomous Microgrids Using Multi-functional Voltage Source Inverters: A Comprehensive Review

Multi-functional voltage source inverters (VSIs) have attracted increasing attention in recent years for their advantageous auxiliary services for power quality enhancement in autonomous microgrids. These types of VSIs can not only achieve a proper control scheme in autonomous mode but also cope with the prescribed power quality and stability requirements. These functionalities are integrated within the same device, thereby significantly improving the cost-effectiveness of microgrids while decreasing the investment and bulk compared with those of multiple devices with independent functionalities. Control strategies for power quality enhancement in autonomous microgrids using multi-functional VSIs are comprehensively reviewed in this paper. In addition, such VSIs are discussed in detail, and comparisons of which are also provided. Lastly, a number of future research directions for multi-functional VSIs are recommended.
Parent‐child communications about consumption and advertising in China

The current study examines how mainland Chinese parents communicate with their children about consumption and advertising. A survey of 1,665 parents of children aged six to 14 in Beijing, Nanjing and Chengdu was conducted in December 2001 to March 2002. Using Moore and Moschis’s typology of family communication patterns, Chinese parents are classified into four types including laissez‐faire, protective, pluralistic, and consensual parents. Results indicated Chinese parents are classified primarily as consensual in type with both high socio‐ as well as concept‐oriented communication. Family communication patterns differ among parents of different demographic groups as well as among different dyad relationships. Parents with a higher education level and families with a higher household income engaged more frequently in concept‐oriented communication. Pluralistic and consensual parents discussed with children about television commercials more often than laissez‐faire and protective parents. Consensual parents perceived they have a greater influence on children’s attitude toward advertising than laissez‐faire parents. Implication for marketers and advertisers are discussed.
Regulation of apoptosis by ubiquitination

Summary: Cell elimination through apoptosis, or programmed cell death, is an evolutionarily conserved central tenet of biology from embryological development to immune homeostasis. While many of the apoptotic signaling pathways have been elucidated, the relationship between ubiquitin and apoptosis is only beginning to be defined. In the past decade, many reports of polyubiquitin conjugation of key pro‐ and anti‐apoptotic molecules have characterized ubiquitin as an essential regulatory modification targeting proteins for proteasomal degradation. However, recent work relating monoubiquitination and nonclassical polyubiquitin conjugation to apoptotic molecules has added an additional level of diversity to the role of ubiquitin in apoptotic regulation beyond degradation. This review focuses on the direct effects of ubiquitination on apoptosis‐signaling molecules.
Role of cholesterol in fusion of Semliki Forest virus with membranes

The low pH-triggered membrane fusion activity of Semliki Forest virus is dependent on the presence of cholesterol in the target membrane. When liposomes containing phospholipids and cholesterol analogs were used, fusion activity was observed with steroids which did not have a planar nucleus or an isooctyl side chain at C-17, but fusion activity was not observed when analogs which lacked the 3 beta-OH group were used. Binding of virus to liposomes at low pH was similarly, but not totally, dependent on the presence of a 3 beta-OH sterol.