Sensitivity of High-Speed Lightwave System Receivers Using InAlAs Avalanche Photodiodes

Calculations based on a rigorous analytical model are carried out to compare the sensitivity of optical receivers that use InP and In0.52Al0.48As avalanche photodiodes (APDs). The model includes the effects of intersymbol interference, tunneling current, avalanche noise and its correlation with the stochastic avalanche duration, dead space, and transimpedance amplifier noise. For a 10-Gb/s system with a bit-error rate of 10-12, the optimum receiver sensitivity predicted for In0.52Al0.48As and InP APDs is -28.6 and -28.1 dBm, respectively, corresponding to a reduction of 11% in optical signal power for receivers using In0.52Al0.48As APDs. Thus, considering overall receiver sensitivity, the improvement offered by In0.52Al0.48As APDs over InP is modest

1,25-Dihydroxyvitamin D Induces Lipoprotein Lipase Expression in 3T3-L1 Cells in Association with Adipocyte Differentiation

1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] is known to modulate the development of hone and other mesenchymal cell types. Since osteoblasts and adipocytes are thought to arise in bone marrow from a common progenitor, this work examined the effects of 1,25-(OH)2D3 on adipocyte development, and in particular on the expression of lipoprotein lipase (LPL), which is an early marker for the differentiated adipocyte. 3T3-L1 preadipocytes were cultured in the presence of 1.25-(OH)2D3 (10-9 to 10-7 M) for up to 7 days. LPL activity was measured in the medium and cell extracts, and LPL messenger RNA levels were measured by Northern blotting. When compared to control cells, 10-7 M 1,25-(OH)2D3 increased medium LPL activity by 2- to 3-fold and cellular LPL by 1.5-fold. Significant increases in medium and cellular LPL were observed at 10-9 M and were maximal at 10-7 M. Along with the increase in LPL activity, there was an increase in LPL messenger RNA by 2- fold at 5 days, and by 5-fold at 7 days. In addition to an increase in LPL, 1,25-(OH)2D3 increased expression of aP2, an adipocyte-specific marker associated with differentiation. After the addition of 1,25-(OH)2D3, there was a decrease in 3T3-L1 cell number, which is consistent with differentiation, and a decrease in vitamin D receptors. Finally, these cells developed a different morphology. 1,25-(OH)2D3-treated cells assumed a rounded appearance, although without detachment from the dish and without the degree of lipid accumulation usually associated with the addition of insulin, isobutylmethylxanthine, and dexamethasone. It is concluded that 1,25- (OH)2D3 induced LPL expression in 3T3-L1 cells through an induction of differentiation-dependent mechanism(s). These findings suggest an important role for 1,25-(OH)2D3 in normal adipocyte differentiation

Optimization of InP APDs for High-Speed Lightwave Systems

Calculations based on a rigorous analytical model are carried out to optimize the width of the indium phosphide avalanche region in high-speed direct-detection avalanche photodiode-based optical receivers. The model includes the effects of intersymbol interference (ISI), tunneling current, avalanche noise, and its correlation with the stochastic avalanche duration, as well as dead space. A minimum receiver sensitivity of -28 dBm is predicted at an optimal width of 0.18 mum and an optimal gain of approximately 13, for a 10 Gb/s communication system, assuming a Johnson noise level of 629 noise electrons per bit. The interplay among the factors controlling the optimum sensitivity is confirmed. Results show that for a given transmission speed, as the device width decreases below an optimum value, increased tunneling current outweighs avalanche noise reduction due to dead space, resulting in an increase in receiver sensitivity. As the device width increases above its optimum value, the receiver sensitivity increases as device bandwidth decreases, causing ISI to dominate avalanche noise and tunneling current shot noise

The Expression of TNFα by Human Muscle: Relationship to Insulin Resistance

TNFα is overexpressed in the adipose tissue of obese rodents and humans, and is associated with insulin resistance. To more closely link TNF expression with whole body insulin action, we examined the expression of TNF by muscle, which is responsible for the majority of glucose uptake in vivo. Using RT-PCR, TNF was detected in human heart, in skeletal muscle from humans and rats, and in cultured human myocytes. Using competitive RT-PCR, TNF was quantitated in the muscle biopsy specimens from 15 subjects whose insulin sensitivity had been characterized using the glucose clamp technique. TNF expression in the insulin resistant subjects and the diabetic patients was fourfold higher than in the insulin sensitive subjects, and there was a significant inverse linear relationship between maximal glucose disposal rate and muscle TNF (r = -0.60, P \u3c 0.02). In nine subjects, muscle cells from vastus lateralis muscle biopsies were placed into tissue culture for 4 wk, and induced to differentiate into myotubes. TNF was secreted into the medium from these cells, and cells from diabetic patients expressed threefold more TNF than cells from nondiabetic subjects. Thus, TNF is expressed in human muscle, and is expressed at a higher level in the muscle tissue and in the cultured muscle cells from insulin resistant and diabetic subjects. These data suggest another mechanism by which TNF may play an important role in human insulin resistance

Tissue-Specific Expression of Human Lipoprotein Lipase: EFFECT OF THE 3′-UNTRANSLATED REGION ON TRANSLATION

Lipoprotein lipase (LPL) is a central enzyme in lipoprotein metabolism and is expressed predominantly in adipose tissue and muscle. In these tissues, the regulation of LPL is complex and often opposite in response to the same physiologic stimulus. In addition, much regulation of LPL occurs post-transcriptionally. The human LPL cDNA is characterized by a long 3′-untranslated region, which has two polyadenylation signals. In this report, human adipose tissue expressed two LPL mRNA species (3.2 and 3.6 kb) due to an apparent random choice of sites for mRNA polyadenylation, whereas human skeletal and heart muscle expressed predominantly the longer 3.6-kb mRNA form. To determine whether there was any functional significance to this tissue-specific mRNA expression, poly(A)-enriched RNA from adipose tissue and muscle were translated in vitro, and the poly(A)-enriched RNA from muscle was more efficiently translated into LPL protein. The increased translatability of the 3.6-kb form was also demonstrated by cloning the full-length 3.2- and 3.6-kb LPL cDNA forms, followed by in vitro translation of in vitro prepared transcripts. To confirm that this increased efficiency of translation occurred in vivo, Chinese hamster ovary cells were transfected with the 3.2- and 3.6-kb LPL cDNAs. Cells transfected with the 3.6-kb construct demonstrated increased LPL activity and synthesis, despite no increase in levels of LPL mRNA. Thus, human muscle expresses the 3.6-kb form of LPL due to a non-random choice of polyadenylation signals, and this form is more efficiently translated than the 3.2-kb form

Epstein Barr virus genomes reveal population structure and type 1 association with endemic Burkitt lymphoma [preprint]

Endemic Burkitt lymphoma (eBL), the most prevalent pediatric cancer in sub-Saharan Africa, is associated with malaria and Epstein Barr virus (EBV). In order to better understand the role of EBV in eBL, we improved viral DNA enrichment methods and generated a total of 98 new EBV genomes from both eBL cases (N=58) and healthy controls (N=40) residing in the same geographic region in Kenya. Comparing cases and controls, we found that EBV type 1 was significantly associated with eBL with 74.5% of patients (41/55) versus 47.5% of healthy children (19/40) carrying type 1 (OR=3.24, 95% CI=1.36 - 7.71, P=0.007). Controlling for EBV type, we also performed a genome-wide association study identifying 6 nonsynonymous variants in the genes EBNA1, EBNA2, BcLF1, and BARF1 that were enriched in eBL patients. Additionally, we observed that viruses isolated from plasma of eBL patients were identical to their tumor counterpart consistent with circulating viral DNA originating from the tumor. We also detected three intertypic recombinants carrying type 1 EBNA2 and type 2 EBNA3 regions as well as one novel genome with a 20 kb deletion resulting in the loss of multiple lytic and virion genes. Comparing EBV types, genes show differential variation rates as type 1 appears to be more divergent. Besides, type 2 demonstrates novel substructures. Overall, our findings address the complexities of EBV population structure and provide new insight into viral variation, which has the potential to influence eBL oncogenesis

Integrative microRNA and mRNA deep-sequencing expression profiling in endemic Burkitt lymphoma

BACKGROUND: Burkitt lymphoma (BL) is characterized by overexpression of the c-myc oncogene, which in the vast majority of cases is a consequence of an IGH/MYC translocation. While myc is the seminal event, BL is a complex amalgam of genetic and epigenetic changes causing dysregulation of both coding and non-coding transcripts. Emerging evidence suggest that abnormal modulation of mRNA transcription via miRNAs might be a significant factor in lymphomagenesis. However, the alterations in these miRNAs and their correlations to their putative mRNA targets have not been extensively studied relative to normal germinal center (GC) B cells. METHODS: Using more sensitive and specific transcriptome deep sequencing, we compared previously published small miRNA and long mRNA of a set of GC B cells and eBL tumors. MiRWalk2.0 was used to identify the validated target genes for the deregulated miRNAs, which would be important for understanding the regulatory networks associated with eBL development. RESULTS: We found 211 differentially expressed (DE) genes (79 upregulated and 132 downregulated) and 49 DE miRNAs (22 up-regulated and 27 down-regulated). Gene Set enrichment analysis identified the enrichment of a set of MYC regulated genes. Network propagation-based method and correlated miRNA-mRNA expression analysis identified dysregulated miRNAs, including miR-17~95 cluster members and their target genes, which have diverse oncogenic properties to be critical to eBL lymphomagenesis. Central to all these findings, we observed the downregulation of ATM and NLK genes, which represent important regulators in response to DNA damage in eBL tumor cells. These tumor suppressors were targeted by multiple upregulated miRNAs (miR-19b-3p, miR-26a-5p, miR-30b-5p, miR-92a-5p and miR-27b-3p) which could account for their aberrant expression in eBL. CONCLUSION: Combined loss of p53 induction and function due to miRNA-mediated regulation of ATM and NLK, together with the upregulation of TFAP4, may be a central role for human miRNAs in eBL oncogenesis. This facilitates survival of eBL tumor cells with the IGH/MYC chromosomal translocation and promotes MYC-induced cell cycle progression, initiating eBL lymphomagenesis. This characterization of miRNA-mRNA interactions in eBL relative to GC B cells provides new insights on miRNA-mediated transcript regulation in eBL, which are potentially useful for new improved therapeutic strategies

Neurocysticercosis in Oregon, 1995–2000

The unexpected death of a teenager from neurocysticercosis prompted an investigation of this disease in Oregon. We found 89 hospitalizations, 43 newly diagnosed cases, and 6 deaths from 1995 to 2000. At least five cases occurred in persons who had not traveled or lived outside the United States. Enhanced surveillance for neurocysticercosis is warranted