Myeloma stem cells in autografting in multiple myeloma

Autologous transplantation has been used increasingly over the last 10 years for the treatment of multiple myeloma. As is the case in other cancers treated by high-dose therapy and stem cell rescue, the contribution of occult tumor cells in the graft to relapse posttransplant remains to be resolved. In this report, we review the biology and differentiation of plasma cells in the context of their significance as an origin of relapse in multiple myeloma.     

THE INFLUENCE OF LOAD MISALIGNMENT DURING UNIAXIAL LOW-CYCLE FATIGUE TESTING—II: APPLICATIONS

Abstract— Models for predicting scatter bands due to bending have been applied to four alloys, namely AISI 316L, Nimonic 101, 9 Cr-1 Mo, and IN 718. The alloys were tested extensively by 26 laboratories in an international round robin exercise sponsored by the Community Bureau of Reference (BCR) of the EC. After initially selecting data for analysis on the basis of their confirmed conformance to the ASTM bending criterion, it has been shown that in all four materials a major fraction of the data scatter could be attributed to bending. Furthermore, at the lowest strain range the predicted bending component represents the highest proportion of the experimental interlaboratory scatter. Many laboratories did not report any measure of bending and so could not be used in the initial analysis. However, a further interesting deduction from the models is that the entire BCR data-set can be encompassed within a scatter band based upon a bending criterion that is twice the allowable ASTM limit. Differences in the extent of scatter between materials at a given total strain range can be attributed to the gradient of the logarithmic plot of total strain range as a function of lifetime.     

A dynamic packet reservation multiple access scheme for wireless ATM

The dynamic packet reservation multiple access (DPRMA) scheme, a medium access control protocol for wireless multimedia applications, is proposed and investigated. DPRMA allows the integration of multiple traffic types through a single access control mechanism that permits users to specify their immediate bandwidth requirements. The primary feature of DPRMA is the dynamic matching of the traffic source generation rates with the assigned portion of the channel capacity. This is accomplished by a control algorithm that regulates the actual amount of channel capacity assigned to users. To support multimedia communication, channel capacity assignments are prioritized by traffic type. The performance of the scheme is evaluated and the scheme is shown to perform well in a system with voice, video conferencing, and data users present. It is also shown to provide improved performance over a system with a modified version of the packet reservation multiple access (PRMA) scheme. Furthermore, several system parameters are studied and optimized.     

Retarding Thermal Degradation in Hybrid Perovskites by Ionic Liquid Additives

Recent years have witnessed considerable progress in the development of solar cells based on lead halide perovskite materials. However, their intrinsic instability remains a limitation. In this context, the interplay between the thermal degradation and the hydrophobicity of perovskite materials is investigated. To this end, the salt 1‐(4‐ethenylbenzyl)‐3‐(3,3,4,4,5,5,6,6,7,7,8,8,8‐tridecafluorooctylimidazolium iodide (ETI), is employed as an additive in hybrid perovskites, endowing the photoactive materials with high thermal stability and hydrophobicity. The ETI additive inhibits methylammonium (MA) permeation in methylammonium lead triiodide (MAPbI₃) occurring due to intrinsic thermal degradation, by inhibiting out‐diffusion of the MA⁺ cation, preserving the pristine material and preventing decomposition. With this simple approach, high efficiency solar cells based on the unstable MAPbI₃ perovskite are markedly stabilized under maximum power point tracking, leading to greater than twice the preserved efficiency after 700 h of continuous light illumination and heating (60 °C). These results suggest a strategy to tackle the intrinsic thermal decomposition of MAI, an essential component in all state‐of‐the‐art perovskite compositions.     

Mitigating Ion Migration with an Ultrathin Self-Assembled Ionic Insulating Layer Affords Efficient and Stable Wide-Bandgap Inverted Perovskite Solar Cells

Wide-bandgap perovskite solar cells (PSCs) are attracting increasing attention because they play an irreplaceable role in tandem solar cells. Nevertheless, wide-bandgap PSCs suffer large open-circuit voltage (V_OC) loss and instability due to photoinduced halide segregation, significantly limiting their application. Herein, a bile salt (sodium glycochenodeoxycholate, GCDC, a natural product), is used to construct an ultrathin self-assembled ionic insulating layer firmly coating the perovskite film, which suppresses halide phase separation, reduces V_OC loss, and improves device stability. As a result, 1.68 eV wide-bandgap devices with an inverted structure deliver a V_OC of 1.20 V with an efficiency of 20.38%. The unencapsulated GCDC-treated devices are considerably more stable than the control devices, retaining 92% of their initial efficiency after 1392 h storage under ambient conditions and retaining 93% after heating at 65 °C for 1128 h in an N₂ atmosphere. This strategy of mitigating ion migration via anchoring a nonconductive layer provides a simple approach to achieving efficient and stable wide-bandgap PSCs.     

Maternal Fructose Intake Causes Developmental Reprogramming of Hepatic Mitochondrial Catalytic Activity and Lipid Metabolism in Weanling and Young Adult Offspring

Excess dietary fructose is a major public health concern, yet little is known about its influence on offspring development and later-life disease when consumed in excess during pregnancy. To determine whether increased maternal fructose intake could have long-term consequences on offspring health, we investigated the effects of 10% w/v fructose water intake during preconception and pregnancy in guinea pigs. Female Dunkin Hartley guinea pigs were fed a control diet (CD) or fructose diet (FD; providing 16% of total daily caloric intake) ad libitum 60 days prior to mating and throughout gestation. Dietary interventions ceased at day of delivery. Offspring were culled at day 21 (D21) (weaning) and at 4 months (4 M) (young adult). Fetal exposure to excess maternal fructose intake significantly increased male and female triglycerides at D21 and 4 M and circulating palmitoleic acid and total omega-7 through day 0 (D0) to 4 M. Proteomic and functional analysis of significantly differentially expressed proteins revealed that FD offspring (D21 and 4 M) had significantly increased mitochondrial metabolic activities of β-oxidation, electron transport chain (ETC) and oxidative phosphorylation and reactive oxygen species production compared to the CD offspring. Western blotting analysis of both FD offspring validated the increased protein abundances of mitochondrial ETC complex II and IV, SREBP-1c and FAS, whereas VDAC1 expression was higher at D21 but lower at 4 M. We provide evidence demonstrating offspring programmed hepatic mitochondrial metabolism and de novo lipogenesis following excess maternal fructose exposure. These underlying asymptomatic programmed pathways may lead to a predisposition to metabolic dysfunction later in life.     

A mass spectrometric and molecular modelling study of cisplatin binding to transferrin

A combination of mass spectrometry, UV/Vis spectroscopy and molecular modelling techniques have been used to characterise the interaction of cisplatin with human serum transferrin (Tf). Mass spectrometry indicates that cisplatin binds to the hydroxy functional group of threonine 457, which is located in the iron(III)-binding site on the C-terminal lobe of the protein. UV/Vis spectroscopy confirms the stoichiometry of binding and shows that cisplatin and iron(III) binding are competitive. The binding of cisplatin has been modelled by using molecular dynamic simulations and the results suggest that cisplatin can occupy part of both the iron(III)- and carbonate-binding sites in the C-terminal lobe of the protein. Combined, the studies suggest that cisplatin binding sterically restricts iron(III) binding to the C-terminal lobe binding site, whereas the N-terminal lobe binding site appears to be unaffected by the cisplatin interaction, possibly allowing the iron(III)-induced conformational change necessary for binding to a Tf receptor.     

The Pharmacology and Therapeutic Utility of Sodium Hydroselenide

Metabolically active gasotransmitters (nitric oxide, carbon monoxide and hydrogen sulfide) are important signalling molecules that show therapeutic utility in oxidative pathologies. The reduced form of selenium, hydrogen selenide (HSe⁻/H₂Se), shares some characteristics with these molecules. The simple selenide salt, sodium hydroselenide (NaHSe) showed significant metabolic activity, dose-dependently decreasing ex vivo O₂ consumption (rat soleus muscle, liver) and transiently inhibiting mitochondrial cytochrome C oxidase (liver, heart). Pharmacological manipulation of selenoprotein expression in HepG2 human hepatocytes revealed that the oxidation status of selenium impacts on protein expression; reduced selenide (NaHSe) increased, whereas (oxidized) sodium selenite decreased the abundance of two ubiquitous selenoproteins. An inhibitor of endogenous sulfide production (DL-propargylglycine; PAG) also reduced selenoprotein expression; this was reversed by exogenous NaHSe, but not sodium hydrosulfide (NaHS). NaHSe also conferred cytoprotection against an oxidative challenge (H₂O₂), and this was associated with an increase in mitochondrial membrane potential. Anesthetized Wistar rats receiving intravenous NaHSe exhibited significant bradycardia, metabolic acidosis and hyperlactataemia. In summary, NaHSe modulates metabolism by inhibition of cytochrome C oxidase. Modification of selenoprotein expression revealed the importance of oxidation status of selenium therapies, with implications for current clinical practice. The utility of NaHSe as a research tool and putative therapeutic is discussed.     

Multi‐objective risk assessment of freshwater inflow on ecosystem sustainability in San Antonio bay,Texas

Abstract:

San Antonio Bay is located on the coast of Texas between Galveston Bay and Corpus Christi Bay and is the primary bay in the Guadalupe Estuary. Three rivers feed San Antonio Bay from two river basins, including the Blanco and Guadalupe Rivers in the Guadalupe River Basin and the San Antonio River in the San Antonio River Basin. The Canyon Reservoir regulates the flow of fresh water in the middle and lower reaches of the Guadalupe River. These inflows are a primary regulator of salinity and, thus, the productivity of commercially important estuarine species. Increasing demand for water has prompted plans for an increased diversion of 49.3 million m³ (40,000 acre‐feet) from the reservoir. An additional amount of 61.6 million m³ (50,000 acre‐feet) from the mouth of the river is to be pumped back to San Antonio to relieve over‐pumping of the Edwards Aquifer. Because the Guadalupe River Basin contributes 58.1 percent of the freshwater inflow to the estuary, it is not known what the impact of these actions will have on the ecological integrity of the San Antonio Bay. Water resource management in the San Antonio Basin consists of decision making under risk and uncertainty related to randomness in the critical parameters such as the salinity in the bay, biological productivity, and total flow into the bay. The aim of this study is to investigate the trade‐offs between the competing objectives of maximizing biological productivity in the bay and minimizing flow using Stochastic Compromise Programming (SCP). The SCP model solves a multi‐objective function subject to constraints that must be maintained at three different prescribed levels of probability providing a global set of solutions for the water resource management problem under input uncertainty. The SCP model provides information on the trade‐offs among the objective function value, tolerance values of the constraint at the prescribed levels of probability, which could be valuable to policy makers in risk assessment. Solutions were found using three distance functions. Model outputs may suggest the minimum amount of freshwater needed to maximize biological productivity of the bay at specified risk level for assessing the impact of upcoming diversion program. Results indicate that current flows in the Guadalupe River are of sufficient volume to satisfy harvest requirements.