Miracle-dz/UniFAR-FTUs huggingface dataset:
in the Cystic Fibrosis AirwaysGalectin-9 Pathway - Dysregulation of TIM-3

The T-cell Ig and mucin domain-containing molecules (TIMs) have emerged as promising therapeutic targets to correct abnormal immune function in several autoimmune and chronic inﬂammatory conditions. It has been reported that proinﬂammatory cytokine dysregulation and neutrophil-dominated inﬂammation are the main causes of morbidity in cystic ﬁbrosis (CF). However, the role of TIM receptors in CF has not been investigated. In this study, we demonstrated that TIM-3 is constitutively overexpressed in the human CF airway, suggesting a link between CF transmembrane conductance regulator (CFTR) function and TIM-3 expression. Blockade of CFTR function with the CFTR inhibitor-172 induced an upregulation of TIM-3 and its ligand galectin-9 in normal bronchial epithelial cells. We also established that TIM-3 serves as a functional receptor in bronchial epithelial cells, and physiologically relevant concentrations of galectin-9 induced TIM-3 phosphorylation, resulting in increased IL-8 production. In addition, we have demonstrated that both TIM-3 and galectin-9 undergo rapid proteolytic degradation in the CF lung, primarily because of neutrophil elastase and proteinase-3 activity. Our results suggest a novel intrinsic defect that may contribute to the neutrophil-dominated immune response in the CF airways. The Journal of Immunology , 2011, 186: 000–000. 2 h. Fragmentation patterns suggest that various proteases are involved in this degradation at different stages. A systematic study of the proteases involved in TIM-3 degradation revealed that serine proteases, speciﬁcally NE and PR3, are involved in the initial cleavage of TIM-3 in the extracellular domain, an effect that would lead to inactivation of the receptor.
ROLE OF PARAOXONASE ENZYME STATUS IN CORONARY HEART DISEASE IN THE AL- QUWAYIYAH REGION OF SAUDI ARABIA

Background: Coronary Heart Disease (CHD) is a principal cause of mortality and disability globally. Dyslipidemia and lipid peroxidation are considered an independent risk factor for CHD. Serum Paraoxonase (PON) enzyme is almost exclusively located on the high density lipoprotein (HDL). It will protect against LDL oxidative modification in atherosclerotic lesions and atherogenic indexes in CHD patients and healthy peoples. Methods: An open randomized study was case controlled in design. The present study included 60 patients suffering from CHD and 65 age and sex matched healthy controls were included during the period of December 2016 to October 2017. Various parameters like lipid profile, lipid peroxidation marker i.e. malondialdehyde (MDA) and antioxidant enzyme PON levels were measured and compared. Results: Increased levels of MDA concentration, total cholesterol, triglycerides, LDL-cholesterol, while decreased levels of HDL- C and PON were significantly low (p<0.001) in CHD patients compared to normal healthy controls. Conclusion: The study showed strong evidence of CHD associated with low activity of PON and HDL-C and significantly a high level of lipids and lipid peroxides concentrations, atherogenic index, atherogenic coefficient and cardiac risk ratios may be involved in the early pathogenesis of CHD. The present study illustrated that the PON is an important enzyme in oxidant - antioxidant status of atherosclerosis with its antioxidant effect.
Understanding the early evolutionary stages of a tandem D. melanogaster -specific gene family: a structural and functional population study

Gene families underlie genetic innovation and phenotypic diversification. However, our understanding of the early genomic and functional evolution of tandemly arranged gene families remains incomplete as paralog sequence similarity hinders their accurate characterization. The D. melanogaster -specific gene family Sdic is tandemly repeated and impacts sperm competition. We scrutinized Sdic in 20 geographically diverse populations using reference-quality genome assemblies, read-depth methodologies, and qPCR, finding that ~90% of the individuals harbor 37 copies as well as evidence of population differentiation. In strains with reliable gene annotations, copy number variation (CNV) and differential transposable element insertions distinguish one structurally distinct version of the Sdic region per strain. All 31 annotated copies featured protein-coding potential and, based on the protein variant encoded, were categorized into 13 paratypes differing in their 3’ ends, with 3-5 paratypes coexisting in any strain examined. Despite widespread gene conversion, the only copy present in all strains has functionally diverged at both coding and regulatory levels under positive selection. Contrary to artificial tandem duplications of the Sdic region that resulted in increased male expression, CNV in cosmopolitan strains did not correlate with expression levels, likely as a result of differential genome modifier composition. Duplicating the region did not enhance sperm competitiveness, suggesting a fitness cost at high expression levels or a plateau effect. Beyond facilitating a minimally optimal expression level, Sdic CNV acts as a catalyst of protein and regulatory diversity, showcasing a possible evolutionary path recently formed tandem multigene families can follow toward long-term consolidation in eukaryotic genomes.
Fiorini, Luke Anthony and Griffiths, Amanda and Houdmont, Jonathan (2018) Reasons for presenteeism in nurses working in geriatric settings: a qualitative study. (4). 9-16.

Objective: To explore the perceived causes of presenteeism in nurses on geriatric wards. Background: Presenteeism, deﬁned as working when unwell, is associated with lost productivity and increased absenteeism. It is more commonly reported by employees in the healthcare sector than other sectors. Methods: An exploratory, qualitative study using semi-structured interviews, thematically analysed. Data collected via 18 recorded interviews with nurses working with patients on geriatric medical wards in Malta. Results: Four major themes emerged that related to nurses’ decisions to engage in presenteeism: illness perceptions, which included participants’ views and experiences of their own health complaints; attitudes to their employing organisation, co-workers and patients; organisational aspects such as culture and administrative arrangements; and personal reasons including illness behaviour preference and personal circumstances. Conclusions: Nurses’ decisions to attend work when unwell were reported as dependent upon four themes. Further studies are warranted to determine if ﬁndings are applicable to nurse populations other than those represented in this study. Implications: Workplace health promotion initiatives should target nurses’ management of their own health, particularly if they have chronic illnesses. Workplace policies and arrangements should be examined with a view to controlling presenteeism.
A review of the promising new advances in the combat against cholesterol trafficking defect and consequent occurrence of the rare Niemann-Pick type C disease

Introduction: The rare, often neglected, and incurable Niemann-Pick type C (NPC) disease is alysosomal storage disorder that occurs in many communities across the world, affecting largely youngsters. The slow neurodegeneration caused by this disease is the primary and eventual cause of death for NPC patients in most cases. Since NPC still remains incurable, extensive focus and considerable efforts have been made by biomedical researchers in order to combat its many intricacies including but not limited to lipid homeostasis that leads to neurological consequences for NPC patients. Objectives and Method: This review summarizes recent and most relevant studies and triages the important aspects of NPC which need to be addressed and are of immediate concern to the scientific community. Extensive literature review was conducted using the PubMed database and biomedical literature from MEDLINE to identify the most recent and relevant research and emphasis was put on identifying promising new ways by which NPC and cholesterol trafficking defect may be combated. Results and Conclusions: Many neuronal and non-neuronal studies have been carriedouton lipid trafficking alterations to advance the knowledge of NPC. It has been observed that β-cyclodextrin therapy, substrate reduction therapy with Miglustat, and histone deacetylase (HDAC) inhibitors have proven to be the most promising therapeutic agents in this regard but other treatment options are also available as revealed by literature review. However, further studies are warranted in order to identify or lessen the nebulous correlation between lipid trafficking defects and the clinical manifestations of NPC. Considering the difficulty in NPC diagnosis and effective treatment for NPC, it is imperative for researchers to well aware of potential therapeutic targets, agents and strategies that might be useful in the near future. A better understanding of NPC and its evaluation on potential treatment options would have a significant effect on the therapy and management of NPC patients.
In mature cortex, activation of the cholinergic system induces oscillatory network activity and facilitates synaptic plasticity. We used an in vitro preparation of the intact cerebral cortex and cortical slices of the neonatal rat to study carbachol (CCh, ≥30 μM)-induced

oscillatory network activity and facilitates synaptic plasticity. We used an in vitro preparation of the intact cerebral cortex and cortical slices of the neonatal rat to study carbachol (CCh, ≥30 μM)-induced network oscillations during the early postnatal period. Multi-site extracellular recordings revealed CCh-induced transient beta oscillations with an average duration of 4.6 ± 0.2 s, amplitude of 123 ± 7.4 μV and frequency of 17.7 ± 0.5 Hz. These oscillations propagated uniformly at 0.5–1.5 mm/s over the cortex and were reversibly blocked by tetrodotoxin (TTX) and atropine, indicating that they depended on action potentials and activation of muscarinic receptors. The activity was not blocked by bicuculline methiodide or gabazine, but was reversibly abolished by kynurenic acid, indicating that activation of glutamate receptors, but not GABA-A receptors, was required. CNQX caused a significant decrease in the power of the Fourier frequency spectrum of the CCh-induced oscillations and CPP or MK-801 completely blocked the activity, indicating a contribution of AMPA/kainate receptors and an essential role of NMDA receptors. Oscillations were synchronized between sites separated horizontally by ∼1 mm and for delays of 2–8 ms. Synchronized activity between neighboring recording sites was very stable over repeated applications of CCh. Whole-cell recordings from morphologically identified pyramidal neurons in the intact cortex revealed a close temporal correlation between CCh-induced membrane oscillations and local field potential recordings. In contrast, CCh-induced oscillations recorded in coronal neocortical slices were smaller in amplitude and frequency, suggesting that a widespread network of intracortical axonal connections is required for their generation.
Piezoelectric Vibrational Energy Harvesting

Cantilever piezoelectric energy harvesting from ambient vibrations is a viable solution for powering wireless sensors and low-power electronics. However, the greatest issue preventing these systems from being widely used is their poor reliability. With the aim to maximise their power output, the devices are often operated close the fracture strength, which results in cracks in the brittle piezoceramic layer. Tapered cantilevers are suggested to improve the mechanical reliability. A relative comparison is made between tapered piezoelectric cantilevers and conventional rectangular cantilevers in terms of reliability and power output. Tensional strains causing fractures show serious reduction of power output and eigenfrequency. Moreover, for large accelerations causing deflections lower than the fracture strength, electrical degradation takes place. Experiments show that tapered cantilevers have a higher power output per unit area. Keywords—Mechanical reliability, PZT, vibration energy harvester, tapered cantilever
VI. Nomenclature and Classification of Purinoceptors *

the and A 2a and the human A 2b receptor, each of these is to the corresponding rat receptor. The rabbit A 2 receptor also homologous, and genomic cloning revealed that the receptor gene has an intron 1993). The chicken P2yl receptor has 362 amino acids and the mouse P2u receptor et 1993) has 373 amino acids. The approximate start positions of the transmembrane helices, as designated on the basis of hydropathy plots, are shown by the symbols TM1 to TM7. increase potency at P 2Y receptors. The nitro derivative may discriminate between forms of P 2X receptors. N 6 -methyl ATP may discriminate between forms of P 2Y receptors. The structures of some compounds—suramin, pyridoxalphosphate-6-azophenyl-2 ′ ,4 ′ -disulfonic acid (PPADS), and Reactive Blue—that have antagonistic properties are also shown.
Soy Isoﬂavones Alter Expression of Genes Associated with Cancer Progression, Including Interleukin-8, in Androgen-Independent PC-3 Human Prostate Cancer Cells 1

High consumption of soy isoﬂavones in Asian diets has been correlated with a lower incidence of clinically important cases of prostate cancer. The chemopreventive properties of these diets may result from an interaction of several types of isoﬂavones, including genistein and daidzein. The present study investigated the effects of a soy isoﬂavone concentrate (ISF) on growth and gene expression proﬁles of PC-3 human prostate cancer cells. Trypan blue exclusion and [ 3 H]-thymidine incorporation assays showed that ISF decreased cell viability and caused a dose-dependent inhibition of DNA synthesis, respectively, with 50% inhibition (IC 50 ) of DNA synthesis at 52 mg/L ( P ¼ 0.05). The glucoside conjugates of genistein and daidzein in ISF were converted to bioactive free aglycones in cell culture in association with the inhibition of DNA synthesis. Flow cytometry and Western immunoblot analyses showed that ISF at 200 mg/L caused an accumulation of cells in the G 2 /M phase of the cell cycle ( P , 0.05) and decreased cyclin A by 20% ( P , 0.05), respectively. The effect of ISF on the gene expression proﬁle of PC-3 cells was analyzed using Affymetrix oligonucleotide DNA microarrays that interrogate ; 17,000 human genes. Of the 75 genes altered by ISF, 28 were upregulated and 47 were downregulated (P , 0.05). Further analysis showed that IL-8, matrix metalloproteinase 13, inhibin b A, follistatin, and ﬁbronectin mRNA levels were signiﬁcantly reduced, whereas the expression of p21 CIP1 , a major cell cycle inhibitory protein, was increased. The effects of ISF on the expression of IL-8 and p21 CIP1 mRNA and protein were validated at high and low ISF concentrations. Our data show that ISF inhibits the growth of PC-3 cells through modulation of cell cycle progression and the expression of genes involved in cell cycle regulation, metastasis, and angiogenesis. J. Nutr. 136: 75–82, 2006.
CEO characteristics and earnings management: evidence from Indonesia

The CEO has an important role as a decision maker in the company and is responsible for the company's performance. This study was conducted to measure the effect of CEO on earnings management in 495 samples of non-financial companies listed on the Indonesia Stock Exchange in 2017-2019 using panel regression analysis with classical assumption testing. The results of panel regression examiners show that there is no significant effect between female CEOs and CEO turnover on earnings management proxies with discretionary accruals. Meanwhile, CEO tenure and company size show a significant negative relationship with earnings management. On the other hand, leverage and return on assets have a significant positive effect on earnings management. In addition, there is no significant influence between company age and Market to Book ratio on earnings management.
Selective Activation of Estrogen Receptor- (cid:1) Target Genes by 3,3 (cid:1) -Diindolylmethane

(cid:1) -Diindolylmethane (DIM) is a natural compound found in cruciferous vegetables that has an-tiproliferative and estrogenic activity. However, it is not clear whether the estrogenic effects are mediated through estrogen receptor (ER) (cid:1) , ER (cid:2) , or both ER subtypes. We investigated whether DIM has ER subtype selectivity on gene transcription. DIM stimulated ER (cid:2) but not ER (cid:1) activation of an estrogen response element upstream of the luciferase reporter gene. DIM also selectively activated multiple endogenous genes through ER (cid:2) . DIM did not bind to ER (cid:2) , indicating that it activates genes by a ligand-independent mechanism. DIM causes ER (cid:2) to bind regulatory elements and recruit the steroid receptor coactivator (SRC)-2 coactivator, which leads to the activation of ER target genes. Silencing of SRC-2 inhibited the activation of ER target genes, demonstrating that SRC-2 is required for transcriptional activation by DIM. Our results demonstrate that DIM is a new class of ER (cid:2) -selective compounds, because it does not bind to ER (cid:2) , but instead it selectively recruits ER (cid:2) and coactivators to target genes. ( Endocrinology 151:
Does Manipulation Help Increase the Productivity of Employees?

The aim of this study is to investigate the relationship between Machiavellian Personality and Job Performance in Sales Personnels. The study utilized a quantitative cross-sectional design using the Machiavellian Personality Scale (MPS) (Dahling et al., 2009) and the Individual Work Performance Questionnaire (IWPQ) (Koopmans et al., 2015), which was administered to participants as a paper pencil test. The results indicated a significantly higher level Machiavellianism results in better Job performance in sales Personnels.
The conserved positive charge in the transmembrane domain of HIV gp41 contributes to its trimerization

: The transmembrane (TM) domain of HIV glycoprotein gp41 anchors the envelope (Env) spike in the viral membrane and is highly conserved. The mid-span arginine 696 is particularly conserved, and the only other residue found in this position is lysine. Seeking to examine the role of this conserved positive charge in the structure and function of the gp41 TM domain, we synthesized a series of peptides corresponding to this region. Analysis of the peptides in a previously validated fluorescence assay in model membranes showed that the native TM domain is trimeric. Peptides in which the intramembrane arginine was mutated to alanine showed significantly lower trimerization propensity. In contrast, this mutation in the context of infectious pseudovirus caused only modest decreases in viral stability and infectivity. We propose a model to explain the importance of this charge to gp41 structure and to HIV infection. Graphical Abstract: Our the isolate 37 °C the mutation activation energy the stable This reduced stability of CH505 R696A experimentally as a reduced infectivity half-life at 37 °C. We propose that the TM domain in the viral membrane acts as a reservoir of potential energy that contributes to the series of structural rearrangements upon engagement of the virus with CD4 on the target cell and that disruption of these interactions may reduce or abrogate viral infectivity in an Env dependent manner. Our work suggests that the conserved positive charge at position 696 helps promote trimerization of this domain. The wild-type TM domain in model membranes exists in equilibrium between monomeric and trimeric states, with the trimeric form favored under physiological conditions. Previous reports suggest that the folded structure of the trimeric Env spikes require each gp41 TM domain to be spatially distal from the others in the unliganded state of the virus 3 , but form a tight trimer in the CD4-bound state. The energetic penalty of positioning an arginine in an isolated, membrane-embedded TM domain is at least partially relieved by trimerization, providing an element of the driving force for the gp41 rearrangements that ultimately lead to viral fusion.
RATIONAL SURFACES WITH K 2 > 0

The main but not all of the results in this paper concern rational surfaces X for which the self-intersection K 2 X of the anticanonical class − K X is positive. In particular, it is shown that no superabundant numerically e(cid:11)ective divisor classes occur on any smooth rational projective surface X with K 2 X > 0. As an application, it follows that any 8 or fewer (possibly in(cid:12)nitely near) points in the projective plane P 2 are in good position. This is not true for 9 points, and a characterization of the good position locus in this case is also given. Moreover, these results are put into the context of conjectures for generic blowings up of P 2 . All results are proven over an algebraically closed (cid:12)eld of arbitrary characteristic.
Luminescence and Luminescence Kinetics of Gd3Ga5O12Polycrystals Doped with Cr3+and Pr3+

In this paper spectroscopic investigations of Gd3Ga5O12 (GGG) polycrystals, containing Cr and intentionally doped with Pr of concentrations 0.5, 1 and 1.5 mol% are presented. We have measured the steady state luminescence and luminescence excitation spectra, as well as the time resolved spectra and luminescence kinetics. The main goal was to investigate the excitation energy transfer from lattice to impurity and between impurities. We found that relative intensity of Cr and GGG lattice luminescence decreased when material was doped with Pr. On the other hand, time resolved spectroscopy and luminescence decay measurements showed that the Cr and GGG lattice luminescence decays were independent of Pr content. The lifetime of Pr luminescence related to D2→ H4 and P0→ H4 transitions decreased with concentration of Pr, which was attributed to the concentration luminescence quenching. No energy transfer between GGG lattice defects and Cr, and Pr ions was observed. We proposed the model of radiative recombination of electron and hole, which took place through three independent pathways: by GGG host emission that peaked at 12750 cm−1, by Cr luminescence that peaked at 15400 cm−1, and by Pr luminescence.
Economic dispatch model for wind power integrated system considering the dispatchability of power to gas

Power-to-gas (P2G) technology opens up another perspective for effective, long-term, large-scale energy storage, so that it can promote large-scale wind power integration. Under this background, this study introduces P2G technology into the economic dispatch model of wind power integrated systems. First, an uncertainty interval model of wind power is built based on the probability distribution of wind power prediction error. Then, considering P2G's function of absorbing surplus wind power and undertaking downward spinning reserve, the factors that influence P2G's ability in enhancing the accommodation of wind power are analysed through theoretical derivation. Consequently, the relationship between the maximum wind power integration and the power delivered to the P2G facilities under a given capacity of P2G can be further understood. Moreover, an economic dispatch model incorporating wind power, P2G facilities and battery energy storage systems is established and a feasible region relaxation algorithm is proposed to deal with the non-smooth functions in the proposed model. Case studies are conducted on a modified IEEE 39-bus system. The results verify the correctness of theoretic analysis and show that the proposed model can help to reduce wind power curtailment and enhance the security and economy of the power system.