Konjungsi Dalam Lirik Lagu-lagu Kelompok Band Avenged Sevenfold Pada Album Nightmare

This research is entitled “Conjunction in the Songs' lyiric of Avenged Sevenfold Group Band in the album “Nightmare” that is also known as A7x. In the aspect of function, conjunction is divided into coordinative conjunction and subordinative conjunction. The object of this study is to see the conjunctions in the lyirics and see the function and meaning of the conjunctions. The method used is descriptive, and the concepts of Payne (2011), and Quirk and Greenbaum (1999). The result of this research shows that, the coordinate conjunctions found are and, but, or, for, so and still. Meanwhile the subordinate conjunctions found are where, when, that, before, how, as long as, as soon as, since, if, because, while, until, than, once, and as. Coordinate conjunctions connect words, phrases, clauses, and sentences. Meanwhile subordinate conjunctions connect clauses as in the concept. Besides, the subordinate conjunctions found also connect phrase and clause, and clause and sentence where these two things are not appropriate with the concept used, and the meaning of the conjunctions are fit to the concept

Characterizing Search Behavior in Productivity Software

Complex software applications expose hundreds of commands to users through intricate menu hierarchies. One of the most popular productivity software suites, Microsoft Office, has recently developed functionality that allows users to issue free-form text queries to a search system to quickly find commands they want to execute, retrieve help documentation or access web results in a unified interface. In this paper, we analyze millions of search sessions originating from within Microsoft Office applications, collected over one month of activity, in an effort to characterize search behavior in productivity software. Our research brings together previous efforts in analyzing command usage in large-scale applications and efforts in understanding search behavior in environments other than the web. Our findings show that users engage primarily in command search, and that re-accessing commands through search is a frequent behavior. Our work represents the first large-scale analysis of search over command spaces and is an important first step in understanding how search systems integrated with productivity software can be successfully developed

<i>P. berghei</i> telomerase subunit TERT is essential for parasite survival

Telomeres define the ends of chromosomes protecting eukaryotic cells from chromosome instability and eventual cell death. The complex regulation of telomeres involves various proteins including telomerase, which is a specialized ribonucleoprotein responsible for telomere maintenance. Telomeres of chromosomes of malaria parasites are kept at a constant length during blood stage proliferation. The 7-bp telomere repeat sequence is universal across different Plasmodium species (GGGTTT/CA), though the average telomere length varies. The catalytic subunit of telomerase, telomerase reverse transcriptase (TERT), is present in all sequenced Plasmodium species and is approximately three times larger than other eukaryotic TERTs. The Plasmodium RNA component of TERT has recently been identified in silico. A strategy to delete the gene encoding TERT via double cross-over (DXO) homologous recombination was undertaken to study the telomerase function in P. berghei. Expression of both TERT and the RNA component (TR) in P. berghei blood stages was analysed by Western blotting and Northern analysis. Average telomere length was measured in several Plasmodium species using Telomere Restriction Fragment (TRF) analysis. TERT and TR were detected in blood stages and an average telomere length of ~950 bp established. Deletion of the tert gene was performed using standard transfection methodologies and we show the presence of tert− mutants in the transfected parasite populations. Cloning of tert- mutants has been attempted multiple times without success. Thorough analysis of the transfected parasite populations and the parasite obtained from extensive parasite cloning from these populations provide evidence for a so called delayed death phenotype as observed in different organisms lacking TERT. The findings indicate that TERT is essential for P. berghei cell survival. The study extends our current knowledge on telomere biology in malaria parasites and validates further investigations to identify telomerase inhibitors to induce parasite cell death

The expected and unexpected roles of Plasmodium telomere-associated proteins : Telomerase, SIR2A and SIR2B

Telomere begrenzen die Enden eukaryotischer Chromosomen und sind mit einer als Telosomen bezeichneten Gruppe von Proteinen bedeckt, die die Telomere vor deren Abbau schützen und somit die Stabilität des Genoms sicherstellen. In Plasmodium wurde ein hoch konserviertes Telosom Protein identifiziert, das histone (protein) deacetylase silent information regulator 2 Protein (PfSIR2A) und sein Homolog SIR2B. Das P. falciparum SIR2A Protein scheint eine kritische Rolle bei der Regulation von Multigen Familien (z. B. var Gene) zu spielen, die in den Prozess der Antigenvariation involviert sind, ein Mechanismus der es pathogenen Organismen erlaubt ihre Oberflächenantigene zu verändern um dem Immunsystem ihres Wirts zu entgehen. Eine Deletion von Pfsir2a oder Pfsir2b führt zur Hochregulierung der Transkription bestimmter var Gene in den jungen asexuellen Blutstadien. Orthologe der beiden sir2 Gene von P. falciparum wurden in allen Plasmodium Arten gefunden, deren Genome bis dato sequenziert wurden, einschliesslich dem des Nagerparasiten P. berghei. Drei P. berghei Zelllinien wurden generiert und geklont: Pbsir2a, Pbsir2b, Pbsir2a/b. In der Maus wurden keine Veränderungen beim Wachstum der asexuellen Blutstadien, der Vermehrungsrate oder der Virulenz der drei mutierten Parasitenlinien beobachtet. Die Analyses des Transkriptoms der asexuellen Blutstadien der Doppel-Nullmutante (Pbsir2a/b) zeigte eine Deregulierung von Genfamilien in der sub-telomer Region (bir, Pb-fam), die mit dem Prozess der Antigenvariation in Verbindung stehen und bestätigte die Art der Genregulation durch SIR2, die für P. falciparum gezeigt wurde. Die Deletion von Pbsir2b hatte keinerlei Effekt auf das Wachstum der Parasiten während des gesamten Lebenszyklus, weshalb eine essenzielle Rolle des SIR2B Proteins für die Entwicklung der Moskito und Leberstadien ausgeschlossen werden kann. Die Deletion des Pbsir2a Gens führte jedoch zu einer unerwarteten Blockade der Entwicklung der Parasiten im Moskito beim Übergang vom Ookineten zum Oozysten Stadium. Bei der Analyse transgener Parasiten die eine GFP-markierte Form von PbSIR2A exprimieren, beobachteten wir eine bisher nicht charakterisierte Lokalisierung ausserhalb des Zellkerns am apikalen Pol der Ookinete. Morphologische Studien und die Untersuchung der Verteilung und Konzentration mehrerer micronemaler Proteine sowie einleitende Untersuchungen des Acetylierungsstatus von Proteinen in den mutierten Ookineten deuten auf eine aberrante Funktion des apikallen Apparates hin, welche womöglich einen minimalen Effekt auf die Motilität der Ookinete hat. Diese Ergebnisse weisen auf eine mögliche Funktion von SIR2A während der Anheftung/ Invasion/ Durchquerung der Ookinete durch die Mitteldarmwand des Moskitos hin. Ein weiteres Protein das für die Funktion der Telomere kritisch ist, ist das hoch konservierte Telomerase Holoenzym, welches für den Erhalt der Länge der Telomere wichtig ist. Bei jeder Zellteilung werden die Telomere aufgrund des Problems der End-Replikation verkürzt. Die Ribonukleoprotein Telomerase Reverse Transkriptase (TERT) ist die zentrale Untereinheit des Telomerase Komplexes und fügt den G-reichen 3’ Enden der Chromosomen neue repetitive Oligomere hinzu. Dadurch wird ein vorzeitiges Altern und letztendlich der Zelltod (verzögerter lethaler Phenotyp) verhindert, wie er in TERT und TR- defizienten Pflanzenzellen, Hefen, Protozoen und Säugerzellen beschrieben wurde, bei denen die Telomerase in erster Linie für den Erhalt funktioneller Telomere verantwortlich ist. Die Länge der Telomere in Plasmodium ist stabil während der Blutzellstadien und die Aktivität der TERT ist nachweisbar während der Trophozoiten- und Schizontenstadien, in denen die Replikation der DNA stattfindet. TERT wurde weithin als mögliches Zielmolekül für die Entwicklung von Medikamenten beispielsweise gegen Krebszellen untersucht und eine Inhibierung des Tumorwachstums konnte gezeigt werden. Vorläufige, bisher nicht publizierte Daten über den Effekt von Nucleosid-Analogen auf P.falciparum in vitro Kulturen zeigen einen lethalen Effekt auf die Blutstadien der Parasiten nach 3-5 Zyklen bei micromolaren Konzentrationen (A. Scherf, Institute Pasteur). Eine kürzlich veröffentlichte Evaluierung verschiedener Komponenten deutet auf eine hohe anti-plasmodiale Aktivität von Delarvidine in vitro gegen Leberstadien von P. yoelii hin. Zusätzlich zu diesen Daten kann ein negativer Effekt durch das Fehlen von TERT bei Deletionsversuchen in P. berghei beobachtet werden. Obwohl die Anwesenhiet von tert- Parasiten in der anfänglichen Population direkt nach der Transfektion beobachtet wurde, konnten keine tert- Klone gewonnen werden. Dies ist in Übereinstimmung mit dem verzögerten lethalen Phenotyp, der in anderen Organismen beobachtet wurde. Die gewonnenen Resultate zeigen das TERT für die Entwicklung von Plasmodium essentiell ist und kennzeichnen Anti-Telomerase Medikamente als mögliche Hilfsmittel bei der Behandlung von Malaria Erkrankungen

Pathogenesis of Alzheimer's disease : focus on amyloid â-peptide, homocysteine and metals

Alzheimer's disease (AD) is a complex dementia disorder. It is characterized by the neuronal and synaptic loss, presence of neurofibrillary tangles and senile plaques, composed of amyloid â-peptide (Aâ) in the brain. Biochemical and genetic studies implicate a central role for Aâ in the pathogenesis of AD, however how amyloid leads to neurodegeneration is still unknown. The present work focused on investigating the role of Aâ in AD and other relevant neurological and psychiatric disorders. The study was based on the analysis of Aâ in cell culture media and post-mortem brain tissue. In paper I, we measured Aâ in cell culture media from cells transfected with APP mutations causing familial AD. We could see that mutations in familial AD are primarily pathogenic through their effect on APP processing and not through altered cell signaling. In paper II, we compared the levels of Aâ in the brain of elderly schizophrenics with and without dementia versus controls. We demonstrated that in the brains from people with schizophrenia and dementia there is no increase of Aâ. Thus the pathogenic pathway of dementia in elderly schizophrenics is different from that seen in AD. Additionally, in schizophrenia cases with AD neuropathology, levels of brain Aâ were decreased as compared to 'pure' AD cases. This may be explained by high smoking prevalence among schizophrenics, the use of neuroleptic drugs or could be a result of the disease state per se. In paper III, we further investigated the hypothesis that stimulation of nicotinic receptors may diminish arnyloidosis in the brain. We could prove that deposition of Aâ is attenuated in the cortex of normal elderly people that used to smoke tobacco. However, the mechanism of this attenuation is unknown. Metals have been implicated in AD pathogenesis and some metal chelators have shown therapeutic promise in animal and human studies. In paper IV, we studied the interaction of human brain Aâ with biometals, such as zinc, copper, aluminium, iron and manganese. We extracted and measured cortical Aâ in AD patients and control groups. The levels of the metals were assessed in a parallel set of samples. We found that zinc is strongly elevated in AD brains and is correlated with Aâ and dementia severity. In paper V, we focused on other important factors in AD pathogenesis, such as homocysteine and vitamin B status. We compared plasma homocysteine levels in controls, AD patients and in patients with mild cognitive impairment. We observed hyperhomocysteinemia in AD. We also confirmed that ApoE 4 allele is a risk factor in the development of sporadic AD. We did not find any evidence that polymorphism of the enzyme involved in homocysteine biogenesis, methylenetetrahydrofolate reductase (MTHFR), has a clinical significance in these groups. In summary, these studies suggest a multifactoral pathogenesis of AD, where Aâ, zinc and homocysteine are important factors. They also give insight into targets to develop therapeutic strategies for treatment of dementia. Those include: substances stimulating nicotinic receptors, metals chelators, anti- hyperhomocysteinemia therapies, and anti-Aâ strategies

COVID-19 prevalence and mortality in longer-term care facilities

This essay considers the factors that have contributed to very high COVID-19 mortality in longer-term care facilities (LTCFs). We compare the demographic characteristics of LTCF residents with those of community-dwelling older adults, and then we review the evidence regarding prevalence and infection fatality rates (IFRs), including links to frailty and some comorbidities. Finally, we discuss policy measures that could foster the physical and mental health and well-being of LTCF residents in the present context and in potential future pandemics

Fucoidan Inhibits Smooth Muscle Cell Proliferation and Reduces Mitogen-activated Protein Kinase Activity

AbstractObjectives and design: fucoidan has previously been shown to inhibit the proliferation of arterial smooth muscle cells both in animal models and in vitro. However, the mechanisms behind the anti-proliferative effects of this polysulfated polysaccharide are not known in detail. Here, the inhibitory effect of fucoidan on rat aortic smooth muscle cell proliferation was examined and compared with the effects of heparin after stimulation with fetal calf serum, platelet-derived growth factor BB, basic fibroblast growth factor, heparin-binding epidermal growth factor, and angiotensin II. Materials and methods: the cultures were analysed with respect to cell proliferation and DNA synthesis by cell counting and measurement of3H-thymidine incorporation. Phosphorylation of mitogen-activated protein kinase and nuclear translocation of phosphorylated mitogen-activated protein kinase were studied by immunoblotting and immunocytochemistry. Results: fucoidan was shown to be a more potent inhibitor of smooth muscle cell proliferation than heparin. Fucoidan also reduced growth factor-induced activation of mitogen-activated protein kinase and prevented nuclear translocation of phosphorylated mitogen-activated protein kinase. Conclusion: fucoidan is a more potent anti-proliferative polysulphated polysaccharide than heparin and may mediate its effects through inhibition of the mitogen-activated protein kinase pathway in a similar manner as heparin