Restoration of X-ray and etoposide resistance, Ku-end binding activity and V(D) J recombination to the Chinese hamster sxi-3 mutant by a hamster Ku86 cDNA

Ku is a heterodimeric protein composed of 86 and 70 kDa subunits that binds preferentially to the double-stranded ends of DNA. Recent molecular characterization of ionizing-radiation sensitive (IRs) mutants belonging to the XRCC5 complementation group demonstrated the involvement of Ku in DNA double-strand break (DSB) repair and lymphoid V(D)J recombination. Here, we describe the isolation of a full-length hamster cDNA encoding the large subunit of the Ku heterodimer and demonstrate that the stable expression of this cDNA can functionally restore IR, Ku DNA end-binding activity and V(D)J recombination proficiency in the Chinese hamster IRs sxi-3 mutant. Moreover, we also demonstrate that sxi-3 cells are hypersensitive to etoposide, a DNA topoisomerase II inhibitor, and that resistance to this drug was restored by the Ku86 cDNA. These experiments suggest that a defect in the large subunit of the heterodimeric Ku protein is the sole factor responsible for the known defects of sxi-3 cells and our data of further support the role of Ku in DNA DSB repair and V(D)J recombination.     

Zoonotic Brugian lymphadenitis. An unusual case with florid monocytoid B-cell proliferation

Human infection with a zoonotic Brugia species in the United States is uncommon. Positive identification of the filarial nematode is required for histopathologic diagnosis. Many cases may go unrecognized because of the nonspecific clinical manifestations and the nondiagnostic histologic changes occurring in involved lymph nodes. A case of zoonotic Brugia lymphadenitis is described in a patient from Rhode Island, in which a small nongravid female worm was identified in a lymph node biopsy specimen. The lymph node also showed a spectrum of reaction changes including the presence of florid monocytoid B-cell proliferation, which has not been described in association with zoonotic Brugian filariasis.     

Cystic fibrosis. Gastrointestinal complications and gene therapy

The gastrointestinal and nutritional complications of cystic fibrosis are diverse. As longevity improves in patients with cystic fibrosis, management of these complications is becoming increasingly important . This article provides overviews of the molecular aspects of the pathogenesis of cystic fibrosis, the current status of gene therapy, and a review of the gastrointestinal manifestations and nutritional care.     

Medicine and science in the life of Luigi Galvani (1737-1798)

The c-Raf-1 kinase is converted into an oncoprotein by functional inactivation of its NH2-terminal regulatory domain and into a dominant-interfering protein by mutations that eliminate catalytic activity. This report describes a systematic charged residue-to-alanine scanning mutagenesis of the ATP-binding subdomain of the c-raf-1 gene. Two temperature-sensitive mutations were found, which were then used to construct both conditionally active and conditionally dominant-defective alleles. Stable cell lines overexpressing both types of mutants were isolated, and their phenotypes were examined. Ectopic expression of Raf-1 activity in quiescent cells was not sufficient to elicit S-phase entry, but the Raf signal could be efficiently complemented by the progression factor insulin-like growth factor I. The results point to a function of Raf-1 in the platelet-derived growth factor and epidermal growth factor pathways, leading to the establishment of competence for cell cycle entry. Ectopic expression of the dominant-defective activity in quiescent cells efficiently blocked entry into S phase. Effects of the dominant-defective protein could be detected minutes after the shift to the restrictive conditions and resulted in the rapid down-regulation of the mitogen-activated protein kinase pathway. Taken together, the phenotypes of the conditionally active and conditionally dominant-defective mutants point to a critical function of Raf-1 at very early times during exit from G0 and entry into G1.     

Use of highly overcoupled couplers to detect shifts in Braggwavelength [strain sensors]

The authors present a technique for detecting Bragg wavelength shifts using highly overcoupled couplers (HOCC). An HOCC of 60%/nm was fabricated with 626 cycles. With our HOCC, a 5 μW LED and a 95% reflective Bragg grating we were able to detect 10 μstrain (Δλ=0.01 nm)     

DARYN-a distributed decision-making algorithm for railway networks:modeling and simulation

The state of the art in scheduling “point-to-point” trains in a railway network utilizes the principles of centralized decision-making. The major difficulty of this approach is that the execution time and the memory requirements increase nonlinearly as the system grows in size. The present paper introduces a new approach, “DARYN”, wherein the overall decision process is analyzed and distributed onto every natural entity of the system. In DARYN, the decision process for every train is executed by an on-board processor that negotiates, dynamically and progressively, for temporary ownership of the tracks with the respective station controlling the tracks, through explicit processor to processor communication primitives. This processor then computes its own route utilizing the results of its negotiation, its knowledge of the track layout of the entire system, and its evaluation of the cost function. Every station's decision process is also executed by a dedicated processor that, in addition, maintains absolute control over a given set of tracks and participates in the negotiation with the trains. Presently, DARYN utilizes a simple cost function. However, if one chooses to increase the complexity of the cost function, DARYN's advantage over the traditional approach increases due to its enormous available computational power. Given that the current microprocessors such as MC68030, MC88000, Intel 486, and Intel 860 are powerful yet relatively inexpensive, a network of concurrently executing processors may offer superior price-performance quotient over a single high performance computer     

Ohmic contact and transport properties of II–VI Green/Blue laser diodes

The employment of the Zn(Se,Te) pseudo-graded contacting scheme to p-type ZnSe-based alloys contributes directly to the recent demonstration of room temperature continuous-wave operation of II– VI green-blue laser diodes. Contact ohmicity is maintained down to cryogenic temperatures which enabled the investigation of electrical transport properties associated with the p-type nitrogen-doped ZnSe, Zn(S,Se), and (Zn,Mg)(S,Se). The observation of both persistent photoconductivity and a metastable population of holes which are in thermodynamic equilibrium with hydrogenic acceptors having reduced activation energy suggests the presence of a DX-like behavior for holes in p-type (Zn,Mg)(S,Se).     

Performance implications of internet channels in financial services: A comprehensive perspective

Advances in information technology (IT) have forced financial services firms to explore new organizational forms and deliver service innovation. Given the obvious differences in the business model in which the financial services sector provides online services, it is natural to ask whether the emergence of Internet channels leads to superior achievement. Using a sample of twenty-four Taiwanese publicly traded financial services firms from 1997 to 2003, this empirical study attempts to assess the Internet channel??s effect on firm performance by means of applying event study methodology and data envelopment analysis. Results show that the magnitudes of average abnormal returns are uniformly positive and increase the operating efficiency of firms following announcements via Internet channels. This work therefore concludes that Internet channels have positive influences on firm performance.     

Usable optimistic fair exchange

Fairly exchanging digital content is an everyday problem. It has been shown that fair exchange cannot be achieved without a trusted third party (called the Arbiter). Yet, even with a trusted party, it is still non-trivial to come up with an efficient solution, especially one that can be used in a p2p file sharing system with a high volume of data exchanged.We provide an efficient optimistic fair exchange mechanism for bartering digital files, where receiving a payment in return for a file (buying) is also considered fair. The exchange is optimistic, removing the need for the Arbiter’s involvement unless a dispute occurs. While the previous solutions employ costly cryptographic primitives for every file or block exchanged, our protocol employs them only once per peer, therefore achieving an O(n) efficiency improvement when n blocks are exchanged between two peers. Our protocol uses very efficient cryptography, making it perfectly suitable for a p-2-p file sharing system where tens of peers exchange thousands of blocks and they do not know beforehand which ones they will end up exchanging. Therefore, our system yields up to one-to-two orders of magnitude improvement in terms of both computation and communication (40 s vs. 42 min, 1.6 MB vs. 200 MB). Thus, for the first time, a provably secure (and privacy-respecting when payments are made using e-cash) fair exchange protocol can be used in real bartering applications (e.g., BitTorrent) [14] without sacrificing performance.