The B-cell transmembrane protein CD72 binds to and is an in vivo substrate of the protein tyrosine phosphatase SHP-1

BACKGROUND: Signals from the B-cell antigen receptor (BCR) help to determine B-cell fate, directing either proliferation, differentiation, or growth arrest/apoptosis. The protein tyrosine phosphatase SHP-1 is known to regulate the strength of BCR signaling. Although the B-cell co-receptor CD22 binds SHP-1, B cells in CD22-deficient mice are much less severely affected than those in SHP-1-deficient mice, suggesting that SHP-1 may also regulate B-cell signaling by affecting other signaling molecules. Moreover, direct substrates of SHP-1 have not been identified in any B-cell signaling pathway. RESULTS: We identified the B-cell transmembrane protein CD72 as a new SHP-1 binding protein and as an in vivo substrate of SHP-1 in B cells. We also defined the binding sites for SHP-1 and the adaptor protein Grb2 on CD72. Tyrosine phosphorylation of CD72 correlated strongly with BCR-induced growth arrest/apoptosis in B-cell lines and in primary B cells. Preligation of CD72 attenuated BCR-induced growth arrest/death signals in immature and mature B cells or B-cell lines, whereas preligation of CD22 enhanced BCR-induced growth arrest/apoptosis. CONCLUSIONS: We have identified CD72 as the first clear in vivo substrate of SHP-1 in B cells. Our results suggest that tyrosine-phosphorylated CD72 may transmit signals for BCR-induced apoptosis. By dephosphorylation CD72. SHP-1 may have a positive role in B-cell signaling. These results have potentially important implications for the involvement of CD72 and SHP-1 in B-cell development and autoimmunity.     

Relay performance in DSG islands

During field tests to confirm the existence of ferroresonant conditions in distribution system generators (DSGs), a number of voltage and frequency relays were installed and their performance monitored while exposed to the highly distorted waves resulting from these conditions. While the general performance of relay groups was satisfactory, certain problem areas became apparent. The field tests and evaluation method are described, the test results are reported, and the problem areas are discussed     

Driver's exposure to distractions in their natural driving environment

Unobtrusive video camera units were installed in the vehicles of 70 volunteer drivers over 1-week time periods to study drivers’ exposure to distractions. The video data were coded based on a detailed taxonomy of driver distractions along with important contextual variables and driving performance measures. Results show distractions to be a common component of everyday driving. In terms of overall event durations, the most common distractions were eating and drinking (including preparations to eat or drink), distractions inside the vehicle (reaching or looking for an object, manipulating vehicle controls, etc.), and distractions outside the vehicle (often unidentified). Distractions were frequently associated with decreased driving performance, as measured by higher levels of no hands on the steering wheel, eyes directed inside rather than outside the vehicle, and lane wanderings or encroachments. Naturalistic driving studies can provide a useful supplement to more controlled laboratory and field studies to further our understanding of the effects of all types of distractions on driving safety.     

Intrinsic carrier multiplication in layered Bi2O2Se avalanche photodiodes with gain bandwidth product exceeding 1 GHz

Emerging layered semiconductors present multiple advantages for optoelectronic technologies including high carrier mobilities, strong light-matter interactions, and tunable optical absorption and emission. Here, metal-semiconductor-metal avalanche photodiodes (APDs) are fabricated from Bi₂O₂Se crystals, which consist of electrostatically bound [Bi₂O₂]²⁺ and [Se]²⁻ layers. The resulting APDs possess an intrinsic carrier multiplication factor up to 400 at 7 K with a responsivity gain exceeding 3,000 A/W and bandwidth of ~ 400 kHz at a visible wavelength of 515.6 nm, ultimately resulting in a gain bandwidth product exceeding 1 GHz. Due to exceptionally low dark currents, Bi₂O₂Se APDs also yield high detectivities up to 4.6 × 10¹⁴ Jones. A systematic analysis of the photocurrent temperature and bias dependence reveals that the carrier multiplication process in Bi₂O₂Se APDs is consistent with a reverse biased Schottky diode model with a barrier height of ~ 44 meV, in contrast to the charge trapping extrinsic gain mechanism that dominates most layered semiconductor phototransistors. In this manner, layered Bi₂O₂Se APDs provide a unique platform that can be exploited in a diverse range of high-performance photodetector applications.

     

Localized surface plasmon resonance biosensor using silver nanostructures fabricated by glancing angle deposition

Glancing angle deposition was used to produce approximately 150-nm-thick silver nanoparticle films, which were evaluated as localized surface plasmon resonance (LSPR) biosensors. The films have a strong extinction peak around 368 nm in air due to LSPR. As the refractive index of the surrounding environment is increased, the extinction peak red-shifts with a linear dependence. The films were functionalized with 11-amino-1-undecanethiol and rabbit immunoglobulin G (rIgG) to allow for the detection of anti-rIgG binding. Binding of biomolecules to the nanoparticle surface increases the local refractive index and results in a red-shifting of the extinction peak. The wavelength shift at varying concentrations of anti-rIgG was measured and fit to the Langmuir isotherm. This yielded approximate values for the saturation response, Delta lambda max = 29.4 +/- 0.7 nm, and the surface confined binding constant, Ka = (2.7 +/- 0.3) x 10(6) M(-1). The response to nonspecific binding was also investigated.     

Integration of MHD Plants into Electric Utility Systems

This paper considers the behavior of an MHD/steam-comined cylce plant under the dynamic operating conditions prescribed by the transient stability regime (50 msc to 10 sec after a disturbance on a power system). Using a three-phase fault to ground to test the model developed, it is shown that: (1) in this regime, the MHD generator acts as a current source to provide damping and consequent increased network stability; (2) the low energy storage capability of the MED generator reduces fault currents and plant surges relative to those of a similarly rated conventional plant; and (3) load tripping introduces special requirements which are discussed in the paper.     

An integrated network component architecture

To deploy large-scale, interactive, distributed systems, we need architectures that support integration of new and existing components and allow dynamic configuration of component connections. The architecture presented in this article builds connection mechanisms into the components, which facilitates composition and the construction of flexible, scalable systems     

De novo non-alcoholic fatty liver disease following orthotopic liver transplantation

Non-alcoholic fatty liver disease (NAFLD) is an increasingly recognized clinico-pathologic entity typically associated with obesity, type II diabetes and hyperlipidemia. It has been noted to recur after orthotopic liver transplantation (OLT). We report four patients who developed de novo NAFLD within 3 months of OLT without the typical predisposing factors of diabetes mellitus or obesity. Three of the four patients underwent OLT for hepatitis C-related cirrhosis, and the other for alcoholic cirrhosis. Examination of the liver explants revealed no evidence of steatosis. No surreptitious alcohol use or a drug-induced process could be identified in these patients. Treatment of recurrent hepatitis C infection in one patient with interferon and ribavirin led to sustained suppression of the viral RNA to undetectable levels, but no improvement in histology or liver enzymes. All four patients had histologic evidence of preservation injury on the initial post-OLT biopsies, but the significance of this finding in relationship to the development of NAFLD is unknown. NAFLD can develop without any of the known predisposing conditions after transplantation, and this raises further questions about the pathogenesis of this condition.     

Nucleic acids. 16. Orally active derivatives of ara-cytidine

Water-soluble derivatives of ara-cytidine (cytarabine, Cytosar) were prepared and tested for antitumor, immunosuppressive, and antiarthritic activities in animals after oral administration. The compounds tested included the 5'-palmitate, 5'-benzoate, and 5'-adamantoate esters of ara-cytidine, made water soluble by use of their hydrochloride salts of peptidyl derivatives, and two basic 5' esters (5'-nicotinoate and 5'-quinuclidinate) as their hydrochloride salts. Five of the compounds had antitumor activity superior to that found with ara-cytidine itself after oral administration in the L1210 leukemic mouse assay. One of these, 5'-adamantoyl-ara-cytidine hydrochloride, had antitumor activity after oral administration approaching that achieved with parenterally administered ara-cytidine.