Portfolio size effect in retirement accounts : what does it imply for lifecycle asset allocation funds?

Lifecycle funds offered by retirement plan providers allocate aggressively to risky asset classes when the employee participants are young, gradually switching to more conservative asset classes as they grow older and approach retirement. This approach focuses on maximizing growth of the accumulation fund in the initial years and preserving its value in the later years. The authors simulate terminal wealth outcomes based on conventional lifecycle asset allocation rules as well as on contrarian strategies that reverse the direction of asset switching. The evidence suggests that the growth in portfolio size over time significantly impacts the asset allocation decision. Due to the portfolio size effect that is observed by the authors, the terminal value of accumulation in retirement accounts is influenced more by the asset allocation strategy adopted in later years relative to that adopted in early years. By mechanistically switching to conservative assets in the later years of a plan, lifecycle strategies sacrifice significant growth opportunity and prove counterproductive to the participant's wealth accumulation objective. The authors' conclude that this sacrifice does not seem to be compensated adequately in terms of reducing the risk of potentially adverse outcomes.

The p38 mitogen-activated protein kinase regulates interleukin-1beta-induced IL-8 expression via an effect on the IL-8 promoter in intestinal epithelial cells

Several lines of evidence implicate the p38 mitogen-activated protein kinase (p38 MAPK) in the proinflammatory response to bacterial agents and cytokines. Equally, the transcription factor, nuclear factor (NF)-kappaB, is recognized to be a critical determinant of the inflammatory response in intestinal epithelial cells (IECs). However, the precise inter-relationship between the activation of p38 MAPK and activation of the transcription factor NF-kappaB in the intestinal epithelial cell (IEC) system, remains unknown. Here we show that interleukin (IL)-1beta activates all three MAPKs in Caco-2 cells. The production of IL-8 and monocyte chemotactic protein 1 (MCP-1) was attenuated by 50% when these cells were preincubated with the p38 MAPK inhibitor, SB 203580. Further investigation of the NF-kappaB signalling system revealed that the inhibitory effect was independent of the phosphorylation and degradation of IkappaBalpha, the binding partner of NF-kappaB. This effect was also independent of the DNA binding of the p65 Rel A subunit, as well as transactivation, determined by an NF-kappaB luciferase construct, using both SB 203580 and dominant-negative p38 MAPK. Evaluation of IL-8 and MCP-1 RNA messages by reverse transcription-polymerase chain reaction (RT-PCR) revealed that the inhibitory effect of SB 203580 was associated with a reduction in this parameter. Using an IL-8-luciferase promoter construct, an effect of p38 upon its activation by both pharmacological and dominant-negative p38 construct co-transfection was demonstrated. It is concluded that p38 MAPK influences the expression of chemokines in intestinal epithelial cells, through an effect upon the activation of the chemokine promoter, and does not directly involve the activation of the transcription factor NF-kappaB

Reverse engineering and finite element analysis of a 3-wheeler automotive structure

Auto rickshaws (3-wheelers) are the most sought after transport among the urban and rural poor in India. The assembly of the vehicle involves assemblies of several major components. The L-angle is the component that connects the front panel with the vehicle floor. Current L-angle part has been observed to experience permanent deformation failure over period of time. This paper studies the effect of the addition of stiffeners on the L-angle to increase the strength of the component. A physical model of the L-angle was reversed engineered and modelled in CAD before static loading analysis were carried out on the model using finite element analysis. The modified L-angle fitted with stiffeners was shown to be able to withstand more load compare to previous design.

Identification of early-stage colorectal cancer patients at risk of relapse post-resection by immunobead reverse transcription-PCR analysis of peritoneal lavage fluid for malignant cells

Purpose: Colorectal cancer patients diagnosed with stage I or II disease are not routinely offered adjuvant chemotherapy following resection of the primary tumor. However, up to 10% of stage I and 30% of stage II patients relapse within 5 years of surgery from recurrent or metastatic disease. The aim of this study was to determine if tumor-associated markers could detect disseminated malignant cells and so identify a subgroup of patients with early-stage colorectal cancer that were at risk of relapse. Experimental Design: We recruited consecutive patients undergoing curative resection for early-stage colorectal cancer. Immunobead reverse transcription-PCR of five tumor-associated markers (carcinoembryonic antigen, laminin γ2, ephrin B4, matrilysin, and cytokeratin 20) was used to detect the presence of colon tumor cells in peripheral blood and within the peritoneal cavity of colon cancer patients perioperatively. Clinicopathologic variables were tested for their effect on survival outcomes in univariate analyses using the Kaplan-Meier method. A multivariate Cox proportional hazards regression analysis was done to determine whether detection of tumor cells was an independent prognostic marker for disease relapse. Results: Overall, 41 of 125 (32.8%) early-stage patients were positive for disseminated tumor cells. Patients who were marker positive for disseminated cells in post-resection lavage samples showed a significantly poorer prognosis (hazard ratio, 6.2; 95% confidence interval, 1.9-19.6; P = 0.002), and this was independent of other risk factors. Conclusion: The markers used in this study identified a subgroup of early-stage patients at increased risk of relapse post-resection for primary colorectal cancer. This method may be considered as a new diagnostic tool to improve the staging and management of colorectal cancer. © 2006 American Association for Cancer Research.

Inhibitors of human immunodeficiency virus type 1 reverse transcriptase target distinct phases of early reverse transcription

Early HIV-1 reverse transcription can be separated into initiation and elongation phases. Here we show, using PCR analysis of negative-strand strong-stop DNA [(−)ssDNA] synthesis in intact virus, that different reverse transcriptase (RT) inhibitors affect distinct phases of early natural endogenous reverse transcription (NERT). The effects of nevirapine on NERT were consistent with a mechanism of action including both specific and nonspecific binding events. The nonspecific component of this inhibition targeted the elongation reaction, whereas the specific effect seemed principally to be directed at very early events (initiation or the initiation-elongation switch). In contrast, foscarnet and the nucleoside analog ddATP inhibited both early and late (−)ssDNA synthesis in a similar manner. We also examined compounds that targeted other viral proteins and found that Ro24-7429 (a Tat antagonist) and rosmarinic acid (an integrase inhibitor) also directly inhibited RT. Our results indicate that NERT can be used to identify and evaluate compounds that directly target the reverse transcription complex.

The effect of Tenofovir on vitamin D metabolism in HIV-infected adults is dependent on sex and ethnicity

Background: Tenofovir has been associated with renal phosphate wasting, reduced bone mineral density, and higher parathyroid hormone levels. The aim of this study was to carry out a detailed comparison of the effects of tenofovir versus non-tenofovir use on calcium, phosphate and, vitamin D, parathyroid hormone (PTH), and bone mineral density. Methods: A cohort study of 56 HIV-1 infected adults at a single centre in the UK on stable antiretroviral regimes comparing biochemical and bone mineral density parameters between patients receiving either tenofovir or another nucleoside reverse transcriptase inhibitor. Principal Findings: In the unadjusted analysis, there was no significant difference between the two groups in PTH levels (tenofovir mean 5.9 pmol/L, 95% confidence intervals 5.0 to 6.8, versus non-tenofovir; 5.9, 4.9 to 6.9; p = 0.98). Patients on tenofovir had significantly reduced urinary calcium excretion (median 3.01 mmol/24 hours) compared to non-tenofovir users (4.56; p,0.0001). Stratification of the analysis by age and ethnicity revealed that non-white men but not women, on tenofovir had higher PTH levels than non-white men not on tenofovir (mean difference 3.1 pmol/L, 95% CI 5.3 to 0.9; p = 0.007). Those patients with optimal 25-hydroxyvitamin D (.75 nmol/L) on tenofovir had higher 1,25-dihydroxyvitamin D [1,25(OH)2D] (median 48 pg/mL versus 31; p = 0.012), fractional excretion of phosphate (median 26.1%, versus 14.6;p = 0.025) and lower serum phosphate (median 0.79 mmol/L versus 1.02; p = 0.040) than those not taking tenofovir. Conclusions: The effects of tenofovir on PTH levels were modified by sex and ethnicity in this cohort. Vitamin D status also modified the effects of tenofovir on serum concentrations of 1,25(OH)2D and phosphate.

Restoration of native folding of single-stranded DNA sequences through reverse mutations: an indication of a new epigenetic mechanism

We used in vivo (biological), in silico (computational structure prediction), and in vitro (model sequence folding) analyses of single-stranded DNA sequences to show that nucleic acid folding conservation is the selective principle behind a high-frequency single-nucleotide reversion observed in a three-nucleotide mutated motif of the Maize streak virus replication associated protein (Rep) gene. In silico and in vitro studies showed that the three-nucleotide mutation adversely affected Rep nucleic acid folding, and that the single-nucleotide reversion [C(601)A] restored wild-type-like folding. In vivo support came from infecting maize with mutant viruses: those with Rep genes containing nucleotide changes predicted to restore a wild-type-like fold [A(601)/G(601)] preferentially accumulated over those predicted to fold differently [C(601)/T(601)], which frequently reverted to A(601) and displaced the original population. We propose that the selection of native nucleic acid folding is an epigenetic effect, which might have broad implications in the evolution of plants and their viruses.

Effect of overload cycles on thin steel roof claddings during cyclonic winds

During an investigation on thin steel roof claddings under simulated cyclonic wind loading, it was found that trapezoidal roof claddings behaved quite differently to corrugated (arc and tangent type) roof claddings due to the presence of overload cycles. The overload cycles caused a reduction in fatigue life for corrugated roofing whereas the reverse occurred for trapezoidal roofing. This contrasting behavior of the two crest-fixed roof claddings was investigated using small scale roofing models instead of the commonly used large scale two-span roof claddings. It was found that overload cycles formed a weaker locally dimpled mechanism around the fastener holes of corrugated roofing and thus accelerated the fatigue-caused pull-through failure. In contrast, a stronger deformed shape was formed in trapezoidal roofing which delayed the pull-through failure. Both laboratory testing and finite element analysis of small scale models were used to study the contrasting behavior of roof claddings.

Research on injury compensation and health outcomes : ignoring the problem of reverse causality led to a biased conclusion

Objective This study highlights the serious consequences of ignoring reverse causality bias in studies on compensation-related factors and health outcomes and demonstrates a technique for resolving this problem of observational data. Study Design and Setting Data from an English longitudinal study on factors, including claims for compensation, associated with recovery from neck pain (whiplash) after rear-end collisions are used to demonstrate the potential for reverse causality bias. Although it is commonly believed that claiming compensation leads to worse recovery, it is also possible that poor recovery may lead to compensation claims—a point that is seldom considered and never addressed empirically. This pedagogical study compares the association between compensation claiming and recovery when reverse causality bias is ignored and when it is addressed, controlling for the same observable factors. Results When reverse causality is ignored, claimants appear to have a worse recovery than nonclaimants; however, when reverse causality bias is addressed, claiming compensation appears to have a beneficial effect on recovery, ceteris paribus. Conclusion To avert biased policy and judicial decisions that might inadvertently disadvantage people with compensable injuries, there is an urgent need for researchers to address reverse causality bias in studies on compensation-related factors and health.

Effect of defoliation interval and height on the growth and quality of Arachis pintoi cv. Amarillo

The effect of defoliation on Amarillo (Arachis pintoi cv. Amarillo) was studied in a glasshouse and in mixed swards with 2 tropical grasses. In the glasshouse, Amarillo plants grown in pots were subjected to a 30/20°C or 25/15°C temperature regime and to defoliation at 10-, 20- or 30-day intervals for 60 days. Two field plot studies were conducted on Amarillo with either irrigated kikuyu (Pennisetum clandestinum) in autumn and spring or dryland Pioneer rhodes grass (Chloris gayana) over summer and autumn. Treatments imposed were 3 defoliation intervals (7, 14 and 28 days) and 2 residual heights (5 and 10 cm for kikuyu; 3 and 10 cm for rhodes grass) with extra treatments (56 days to 3 cm for both grasses and 21 days to 5 cm for kikuyu). Defoliation interval had no significant effect on accumulated Amarillo leaf dry matter (DM) at either temperature regime. At the higher temperature, frequent defoliation reduced root dry weight (DW) and increased crude protein (CP) but had no effect on stolon DW or in vitro organic matter digestibility (OMD). On the other hand, at the lower temperature, frequent defoliation reduced stolon DW and increased OMD but had no effect on root DW or CP. Irrespective of temperaure and defoliation, water-soluble carbohydrate levels were higher in stolons than in roots (4.70 vs 3.65%), whereas for starch the reverse occured (5.37 vs 9.44%). Defoliating the Amarillo-kikuyu sward once at 56 days to 3 cm produced the highest DM yield in autumn and sprong (582 and 7121 kg/ha DM, respectively), although the Amarillo component and OMD were substantially reduced. Highest DM yields (1726 kg/ha) were also achieved in the Amarillo-rhodes grass sward when defoliated every 56 days to 3 cm, although the Amarillo component was unaffected. In a mixed sward with either kikuyu or rhodes grass, the Amarillo component in the sward was maintained up to a 28-day defoliation interval and was higher when more severely defoliated. The results show that Amarillo can tolerate frequent defoliation and that it can co-exist with tropical grasses of differing growth habits, provided the Amarillo-tropical grass sward is subject to frequent and severe defoliation.

Antifertility effect of tamoxifen as tested in the female bonnet monkey (Macaca radiata)

The administration of a potent antiestrogen, tamoxifen at a dose of 3 mg/kg body weight/day orally post-coitally to cycling mated bonnet monkeys(Macaca radiata) from days 18–30 of cycle resulted in inhibition of establishment of pregnancy in 9 out of 10 monkeys. Tamoxifen effect was not due to interference with luteal function. The effect was specific to tamoxifen as exogenously administered progesterone could not reverse it. In addition to suggesting a role for estrogen in maintenance of early pregnancy in the primate the present study could be a prelude to the development of an effective post-ovulatory approach for regulation of fertility in the human female

A numerical study of the effect of loading conditions on tubular hydroforming

In this work, the mechanics of tubular hydroforming under various types of loading conditions is investigated. The main objective is to contrast the effects of prescribing fluid pressure or volume flow rate, in conjunction with axial displacement, on the stress and strain histories experienced by the tube and the process of bulging. To this end, axisymmetric finite element simulations of free hydroforming (without external die contact) of aluminium alloy tubes are carried out. Hill’s normally anisotropic yield theory along with material properties determined in a previous experimental study [A. Kulkarni, P. Biswas, R. Narasimhan, A. Luo, T. Stoughton, R. Mishra, A.K. Sachdev, An experimental and numerical study of necking initiation in aluminium alloy tubes during hydroforming, Int. J. Mech. Sci. 46 (2004) 1727–1746] are employed in the computations. It is found that while prescribed fluid pressure leads to highly non-proportional strain paths, specified fluid volume flow rate may result in almost proportional ones for the predominant portion of loading. The peak pressure increases with axial compression for the former, while the reverse trend applies under the latter. The implication of these results on failure by localized necking of the tube wall is addressed in a subsequent investigation.

The role of phospholipid transfer protein and cholesteryl ester transfer protein in reverse cholesterol transport

In atherosclerosis, cholesterol accumulates in the vessel wall, mainly in the form of modified low-density lipoprotein (LDL). Macrophages of the vessel wall scavenge cholesterol, which leads to formation of lipid-laden foam cells. High plasma levels of high-density lipoprotein (HDL) protect against atherosclerosis, as HDL particles can remove peripheral cholesterol and transport it to the liver for excretion in a process called reverse cholesterol transport (RCT). Phospholipid transfer protein (PLTP) remodels HDL particles in the circulation, generating prebeta-HDL and large fused HDL particles. In addition, PLTP maintains plasma HDL levels by facilitating the transfer of post-lipolytic surface remnants of triglyceride-rich lipoproteins to HDL. Most of the cholesteryl ester transfer protein (CETP) in plasma is bound to HDL particles and CETP is also involved in the remodeling of HDL particles. CETP enhances the heteroexchange of cholesteryl esters in HDL particles for triglycerides in LDL and very low-density lipoprotein (VLDL). The aim of this thesis project was to study the importance of endogenous PLTP in the removal of cholesterol from macrophage foam cells by using macrophages derived from PLTP-deficient mice, determine the effect of macrophage-derived PLTP on the development of atherosclerosis by using bone marrow transplantation, and clarify the role of the two forms of PLTP, active and inactive, in the removal of cholesterol from the foam cells. In addition, the ability of CETP to protect HDL against the action of chymase was studied. Finally, cholesterol efflux potential of sera obtained from the study subjects was compared. The absence of PLTP in macrophages derived from PLTP-deficient mice decreased cholesterol efflux mediated by ATP-binding cassette transporter A1. The bone marrow transplantation studies showed that selective deficiency of PLTP in macrophages decreased the size of atherosclerotic lesions and caused major changes in serum lipoprotein levels. It was further demonstrated that the active form of PLTP can enhance cholesterol efflux from macrophage foam cells through generation of prebeta-HDL and large fused HDL particles enriched with apoE and phospholipids. Also CETP may enhance the RCT process, as association of CETP with reconstituted HDL particles prevented chymase-dependent proteolysis of these particles and preserved their cholesterol efflux potential. Finally, serum from high-HDL subjects promoted more efficient cholesterol efflux than did serum derived from low-HDL subjects which was most probably due to differences in the distribution of HDL subpopulations in low-HDL and high-HDL subjects. These studies described in this thesis contribute to the understanding of the PLTP/CETP-associated mechanisms underlying RCT.

Effect of specific FSH or LH deprivation on testicular function of the adult rat

While the need for FSH in initiating spermatogenesis in the immature rat is well accepted, its requirement for maintenance of spermatogenesis in adulthood is questioned. In the current study, using gonadotropin antisera to neutralize specifically either endogenous FSH or LH, we have investigated the effect of either FSH or LH deprivation for a 10-day period on (i) testicular macromolecular synthesis in vitro, (ii) the activities of testicular germ cell specific LDH-X and hyaluronidase enzymes, and finally (iii) on the concentration of sulphated glycoprotein (SGP-2), one of the Sertoli cell marker proteins. Both immature (35-day-old) and adult (100-day-old) rats have been used in this study. Since LH deprivation leads to a near total blockade of testosterone production, the ability of exogenous testosterone supplementation to override the effects of LH deficiency has also been evaluated. Deprivation of either of the gonadotropins significantly affected in vitro RNA and protein synthesis by both testicular minces as well as single cell preparations. Fractionation of dispersed testicular cells preincubated with labelled precursors of RNA and protein on Percoll density gradient revealed that FSH deprivation affected specifically the rate of RNA and protein synthesis of germ cell and not Leydig cell fraction. LH but not FSH deprivation inhibited [3H]thymidine incorporation into DNA. The inhibitory effect of LH could mostly be overriden by testosterone supplementation. LDH-X and hyaluronidase activities of testicular homogenates of adult rats showed significant reduction (50%; P less than .05) following either FSH or LH deprivation. Again testosterone supplementation was able to reverse the LH inhibitory effect.

Comparison of the effect of processing parameters and degradation on the DC and microwave properties of thin films and polycrystalline bulk high-Tc superconducting materials

The sharp increase in microwave power loss (the reverse of what has previously been reported) at the transition temperature in high-Tc superconducting systems such as YBaCu oxide (polycrystalline bulk and thin films obtained by the laser ablation technique) and BiPbSrCaCu oxide is reported. The differences between DC resistivity ( rho ) and the microwave power loss (related to microwave surface resistance) are analysed from the data obtained by a simultaneous measurement set-up. The influence of various parameters, such as preparation conditions, thickness and aging of the sample and the probing frequency (6-18 GHz), on the variation of microwave power loss with temperature is outlined.