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Non-communicable diseases (NCDs) such as cardiovascular disease, cancers, diabetes and obesity are responsible for about two thirds of mortality worldwide, and all of these ailments share a common low-intensity systemic chronic inflammation, endoplasmic reticulum stress (ER stress), and the ensuing Unfolded Protein Response (UPR). These adaptive mechanisms are also responsible for significant metabolic changes that feedback with the central clock of the suprachiasmatic nucleus (SCN) of the hypothalamus, as well as with oscillators of peripheral tissues. In this review we attempt to use a systems biology approach to explore such interactions as a whole; to answer two fundamental questions: (1) how dependent are these adaptive responses and subsequent events leading to NCD with their state of synchrony with the SCN and peripheral oscillators? And, (2) How could modifiers of the activity of SCN for instance, food intake, exercise, and drugs, be potentially used to modulate systemic inflammation and ER stress to ameliorate or even prevent NCDs?
Content available remote Protein Disulfide Isomerase Superfamily in Disease and the Regulation of Apoptosis
Cellular homeostasis requires the balance of a multitude of signaling cascades that are contingent upon the essential proteins being properly synthesized, folded and delivered to appropriate subcellular locations. In eukaryotic cells the endoplasmic reticulum (ER) is a specialized organelle that is the central site of synthesis and folding of secretory, membrane and a number of organelletargeted proteins. The integrity of protein folding is enabled by the presence of ATP, Ca++, molecular chaperones, as well as an oxidizing redox environment. The imbalance between the load and capacity of protein folding results in a cellular condition known as ER stress. Failure of these pathways to restore ER homeostasis results in the activation of apoptotic pathways. Protein disulfide isomerases (PDI) compose a superfamily of oxidoreductases that have diverse sequences and are localized in the ER, nucleus, cytosol, mitochondria and cell membrane. The PDI superfamily has multiple functions including, acting as molecular chaperones, protein-binding partners, and hormone reservoirs. Recently , PDI family members have been implicated in the regulation of apoptotic signaling events. The complexities underlying the molecular mechanisms that define the switch from pro-survival to pro-death response are evidenced by recent studies that reveal the roles of specific chaperone proteins as integration points in signaling pathways that determine cell fate. The following review discusses the dual role of PDI in cell death and survival during ER stress.
Content available remote Non-invasive inspection of heat exchanger tubes
Two well-known methods for inspection of tubes and pipes are Acoustic Pulse Reflectometry (APR) and Guided Waves (GW). Both are based on probing the tubes/pipes using long range acoustic waves, either through the air in the tubes (APR) or the tube walls (GW). Both methods share the advantage of being non-traversing, enabling very short inspection times, on the order of 10 seconds per tube. In addition, each method has complementary advantages and disadvantages. APR for example can detect blockages and very small pinholes but is in sensitive to Outer Diameter (OD) defects. GW, on the other hand, can detect OD faults but can not easily distinguish pitting from through-holes. As opposed to APR, which has been applied to tube inspection for several years, GW has been used mainly for screening applications in large diameter pipes. In this paper we firs present several recent developments in GW, giving an implementation that can fit into tubes as small as 3/4” and capable of detecting, classification and sizing of defects. We term this implementation Ultrasonic Pulse Reflectometry (UPR). We then show how a combined system containing both APR and UPR in a single probe provides a comprehensive solution to tube inspection, enabling very rapid inspection and capable of detecting all typical tube defects.
Dwie znane metody inspekcji rur i przewodów rurowych to Acoustic Pulse Reflectometry (APR) oraz GuidedWaves(GW). Obie metody oparte są na próbkowaniu rur/ przewodów za pomocą długich fal akustycznych, albo za pośrednictwem powietrza w rurach (APR) lub ścian rurowych(GW). Obie metody mają taką zaletę że, umożliwiają bardzo krótki czas kontroli, rzędu 10 sekund na rurę. Ponadto, każda z tych metod ma wady i zalety komplementarne. APR dla przykładu może wykryć blokad i bardzo małe kratery, ale jest niewrażliwa na wady na średnicy zewnętrznej (OD).Metoda GW, z drugiej strony, może wykryć błędy na średnicy zewnętrznej (OD), ale nie może z łatwością odróżnić wżerów od otworów przelotowych. W przeciwieństwie do APR, która jest stosowana do inspekcji rur przez kilka lat, GW był używany głównie do przesiewania aplikacji w rur o dużej średnicy. W tym artykule najpierw przedstawimy kilka wdrożeń i zastosowań GW, które mogą pasować do rurek tak małych, jak 3/4” i być zdolne do wykrywania, klasyfikacjii wielkości wad. Będzie to implementacja Ultrasonic Reflectometry Pulse(UPR). Następnie pokażemy, jak łączyć układy zawierające zarówno APR oraz UPR w jedno kompleksowe stanowisko do inspekcji rur, umożliwiające bardzo szybką kontrolę i zdolne do wykrywania wszystkich typowych uszkodzeń rur.
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