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We report here on the design, fabrication, and characterization of highly integrated parallel optical transceivers designed for Tb/s-class module-to-module data transfer through polymer waveguides integrated into optical printed circuit boards (o-PCBs). The parallel optical transceiver is based on a through-silicon-via silicon carrier as the platform for integration of 24-channel vertical cavity surface-emitting laser and photodiode arrays with CMOS ICs. The Si carrier also includes optical vias (holes) for optical access to conventional surface-emitting 850 nm optoelectronic devices. The 48-channel 3-D transceiver optochips are flip-chip soldered to organic carriers to form transceiver optomodules. Fully functional optomodules with 24 transmitter + 24 receiver channels were assembled and characterized with transmitters operating up to 20 Gb/s/ch and receivers up to 15 Gb/s/ch. At 15 Gb/s, the 48-channel optomodules provide a bidirectional aggregate bandwidth of 360 Gb/s. In addition, o-PCBs have been developed using a 48-channel flex waveguide assembly attached to FR4 electronic boards. Incorporation of waveguide turning mirrors and lens arrays facilitates optical coupling to/from the o-PCB. Assembly of optomodules to the o-PCB using a ball grid array process provides both electrical and optical interconnections. An initial demonstration of the full module-to-module optical link achieved >; 20 bidirectional links at 10 Gb/s. At 15 Gb/s, operation at a bit error ratio of <; 10- 12 was demonstrated for 15 channels in each direction, realizing a record o-PCB link with a 225 Gb/s bidirectional aggregate data rate. [ABSTRACT FROM PUBLISHER]

The effect of applying feed-forward equalization (FFE) on the transmitter side is studied for three different full optical links. In contrast to all previous works, the FFE settings are optimized for a complete link, rather than just the vertical-cavity surface-emitting laser output. The approach results in dramatic improvements in total link performance: >; 6 dB in sensitivity, 3X in timing margin, and 2X in power efficiency at 15 Gb/s, and a record 5.7 pJ/bit at 20 Gb/s. [ABSTRACT FROM PUBLISHER]

We report an 850-nm, vertical-cavity surface-emitting laser (VCSEL)-based optical link that achieves new benchmarks in speed and power efficiency. The laser diode driver and receiver ICs are fabricated in standard 90-nm bulk CMOS, and the gallium arsenide optoelectronic devices are commercial components. An operation at a bit-error rate less than 10-12 at 25 Gb/s is achieved, representing the highest speed reported to date for a CMOS-based full optical link. At 22 Gb/s, the link power efficiency is 3.8 pJ/bit and improves further at lower data rates, attaining a minimum of 2.6 pJ/bit at 15 Gb/s. The efficiency numbers reported here, which include a complete accounting of the power dissipation of all the components, are the best reported for any optical interconnect in any technology. This work demonstrates the scalability of VCSEL-based links in both efficiency and speed to meet the demanding requirements of next-generation exa-scale computing and large data center systems. [ABSTRACT FROM PUBLISHER]

Time-resolved photoluminescence measurements of excitons in GaAs-Ga1-xAlxAs quantum wells subject to an electric field perpendicular to the well plane have been made. With increasing field, both integrated luminescence (as previously reported) and luminescence lifetime decrease. Thus the electric field increases the exciton nonradiative decay rate. Estimates of several possible mechanisms suggest that Fowler–Nordheim tunneling is responsible for the quenching. With increasing pump laser intensities, larger electric fields are required to quench the lifetime because of exciton screening of the field. [ABSTRACT FROM AUTHOR]

A reduction of the GaAs surface recombination velocity due to a heavily carbon-doped GaAs overlayer is reported. Metalorganic molecular beam epitaxy using trimethylgallium, triethylgallium, and elemental arsenic sources has been used to grow an epitaxial structure consisting of 1000 nm of p=1×1017 cm-3 capped with 10 nm of p=1×1020 cm-3 GaAs. Time-resolved photoluminescence (PL) and PL excitation spectroscopy showed this p+/p structure to have a 3.2 ns carrier lifetime and strong band-edge PL emission, whose intensity was nearly constant over an excitation photon energy range of 1.5–3.3 eV. The same wafer with the p+ cap etched off exhibited a much shorter carrier lifetime and PL intensity that decreased exponentially with increasing photon energy, which is indicative of carrier losses to surface recombination. The specific contact resistivity of nonalloyed ohmic contacts to these heavily doped layers was observed to be in the mid 10-7 Ω cm2 range, independent of measurement temperature from 77 to 340 K, suggesting a tunneling contact due to the narrow surface depletion layer. [ABSTRACT FROM AUTHOR]

Electrical pulses shorter than 0.6 ps were generated by photoconductively shorting a charged coplanar transmission line with 80 fs laser pulses. After propagating 8 mm on the line the electrical pulses broadened to only 2.6 ps. [ABSTRACT FROM AUTHOR]

Optical fiber links have become ubiquitous for links at the metropolitan and wide area distance scales, and have become common alternatives to electrical links in local area networks and cluster networks. As optical technology improves and link frequencies continue to increase, optical links will be increasingly considered for shorter, higher-bandwidth links such as I/O, memory, and system bus links. For these links closer to processors, issues such as packaging, power dissipation, and components cost assume increasing importance along with link bandwidth and link distance. Also, as optical links move steadily closer to the processors, we may see significant differences in how servers, particularly high-end servers, are designed and packaged to exploit the unique characteristics of optical interconnects. This paper reviews the various levels of a server interconnect hierarchy and the current status of optical interconnect technology for these different levels. The potential impacts of optical interconnect technology on future server designs are also reviewed. [ABSTRACT FROM AUTHOR]

Background: Bevacizumab added to weekly paclitaxel resulted in improved progression free survival (PFS) and objective response rates (ORR) compared to weekly paclitaxel alone. Nab-paclitaxel and the platins are active in MBC. We conducted an efficacy and safety study of carboplatin, nab-paclitaxel and bevacizumab. Methods: A phase II open label prospective multi-site study enrolled patients (pts) who had measurable MBC according to RECIST 1.1 criteria and no prior chemotherapy for advanced disease. The primary endpoint was PFS with secondary endpoints of overall survival (OS), ORR, and safety. Pts initially received carboplatin AUC 6 day 1, 22,43, plus weekly nab-paclitaxel 100mg/m² and bevacizumab 15mg/m² day 1,22,43 of a 56 day cycle. This was later changed to carboplatin AUC 6 day 1, nab-paclitaxel 100mg/m² day 1,8,15, and bevacizumab 10mg/m² day 1,15 of a 28 day cycle. Thirty-two pts were required to detect an increase in median PFS from 6.7 to 10.5 mo with 80% power based on a one-sided p = 0.05. Kaplan-Meier analyses estimated PFS and OS. The log rank test was used for the comparison of survival curves between pts with triple negative MBC (TNBC) and pts with non-TNBC. Results: Thirty-two pts were enrolled between 2/2008 and 11/2011 by 1 academic and 5 community oncology practices. Two pts were ineligible due to non-measurable disease and not included in the response analyses. The median age was 58 years (range 35-81), 22 pts (69%) had an ECOG PS 0, 9 (28%) had a PS 1, 1 (3%) PS 2. Twenty-four (75%) pts had ER+ disease, 7 (22%) had TNBC, 1 (3%) had ER-HER2+ disease not eligible for trastuzumab-based therapy. Metastatic sites were bone (26%), liver (18%), loco-regional (16%), and lung (12%). One pt (3%) had bone and loco-regional disease only, 19 (59%) had visceral dominant disease. The median number of weeks on treatment was 28.9 (range 5-131). The median PFS in all pts was 13.6 months (mo) (95% CI 11.2-21.9), with a median OS of 26.8 mo (95% CI 13.3-41.2). The ORR (2 CR and 18 PR) was 66.7% (CI 47.2-82.7). There also were 6 (20%) unconfirmed PR and 3 (10%) stable disease, resulting in a clinical benefit rate of 96.7% (CI 82.78-99.92). There was no significant difference in PFS (median 13.6 vs 16.1mo, p = 0.37) or OS (median 13.6 vs 26.8mo, p = 0.32) in pts with TNBC versus non-TNBC disease. The most common toxicities of any grade (gr) include neutropenia and thrombocytopenia in 24 pts (75%) each, leukopenia and fatigue in 17 pts (53%) each, anemia in 15 (47%), and neuropathy in 10 (31%). Gr 4 neutropenia was seen in 7 pts (22%) without febrile neutropenia, and gr 4 thrombocytopenia occurred in 6 (19%). There were no pts with gr 4 sensory neuropathy. All pts required chemotherapy dose delays, 15 (47%) had chemotherapy dose reductions. Conclusions: The carboplatin, nab-paclitaxel and bevacizumab combination is highly effective with good tolerance in first line MBC. As the role of anti-angiogenic therapy in first line metastatic breast cancer is being clarified, this would be an attractive regimen to test in the (neo)adjuvant setting and together with novel molecular targeted agents. [ABSTRACT FROM AUTHOR]

Purpose: The 21-gene Recurrence Score (RS) assay has been validated to quantify the risk of distant recurrence in tamoxifen-treated patients with lymph node-negative, estrogen receptor-positive breast cancer and predict magnitude of chemotherapy benefit. This multicenter study was designed to prospectively examine whether RS affects physician and patient adjuvant treatment selection and satisfaction., Patients and Methods: Before and after obtaining the 21-gene RS assay, medical oncologists stated their adjuvant treatment recommendation and confidence in it. Patients also indicated their treatment choice pre- and post-RS assay. Patients completed measures for decisional conflict, anxiety, and quality of life., Results: Seventeen medical oncologists at one community and three academic practices consecutively enrolled 89 assessable patients. The medical oncologist treatment recommendation changed for 28 patients (31.%). Twenty-four patients (27%) changed their treatment decision. The largest change after the RS results was conversion from the medical oncologist's pretest recommendation for chemotherapy plus hormonal therapy (CHT) to post-test recommendation for hormone therapy (HT) in 20 cases (22.5%). Nine patients (10.1%) changed their treatment decision from CHT to HT. RS results increased medical oncologist confidence in their treatment recommendation in 68 cases (76%). Patient anxiety and decisional conflict were significantly lower after RS results., Conclusion: The results of this study indicate that the RS assay impacts medical oncologist adjuvant treatment recommendations, patient treatment choice, and patient anxiety.

Dendritic cells (DCs), generated ex vivo from blood mononuclear cells (PBMC) or CD34(+) stem cells, are being used to develop novel immunotherapies. To establish optimal DC generation, a direct comparison of the optimal cell source, culture conditions, and maturation stimuli was performed, utilizing phenotypic and functional assays as end points. Plastic adherent monocytes from PBMC were expanded in a serum-free medium (X-Vivo 10) for 7 days using GM-CSF/IL-4; CD34(+) cells were expanded for 14 days using GM-CSF/IL-4/ Flt3L, in either X-Vivo 10 alone or with albumin or autologous plasma. Expanded DC from both cell sources were matured for 7 days with CD40L or IFN-alpha/TNF-alpha. Starting from 2 x 10(7) monocytes, the optimal expansion/maturation process yielded 1.73 +/- 0.52 x 10(6) CD86(+) DC. Optimal expansion of CD34(+) cells (83.9 +/- 25.0-fold) was achieved using X-Vivo 10 with 5% plasma, matured with CD40L, and yielded 10.68 +/- 2.72 x 10(6) CD86(+) DC from 1 x 10(6) CD34(+) cells. Mature DC from PBMC or CD34(+) cells had similar enhanced expression of MHC class II HLA-DR, CD80, CD83, and CD86 and were potent stimulators of mixed lymphocyte reactions. Prior to maturation, all groups of DC actively phagocytosed apoptotic melanoma cells (approximately 50% of HLA-DR(+)). CD34(+) DC matured with CD40L or IFN-alpha/TNF-alpha had reduced phagocytic capability (34 and 31% of HLA-DR(+) DC, respectively). Similar expansion and functional activity was found using cryopreserved DC precursors, cultured in gas permeable bags. We conclude that both cell lineages produce potent mature DC, permitting exploration of the optimal clinical strategy to trigger anti-tumor immune responses in patients with malignancies., (Copyright 2000 Academic Press.)

In previous studies, a lutropin receptor mRNA binding protein implicated in the hormonal regulation of lutropin receptor mRNA stability was identified. This protein, termed LRBP-1, was shown by RNA gel electrophoretic mobility shift assay to specifically interact with lutropin receptor RNA sequences. The present studies have examined the specificity of lutropin receptor mRNA recognition by LRBP-1 and mapped the contact site by RNA footprinting and by site-directed mutagenesis. LRBP-1 was partially purified by cation-exchange chromatography, and the mRNA binding properties of the partially purified LRBP-1 were examined by RNA gel electrophoretic mobility shift assay and hydroxyl-radical RNA footprinting. These data showed that the LRBP-1 binding site is located between nucleotides 203 and 220 of the receptor open reading frame, and consists of the bipartite polypyrimidine sequence 5'-UCUC-X(7)-UCUCCCU-3'. Competition RNA gel electrophoretic mobility shift assays demonstrated that homoribopolymers of poly(rC) were effective RNA binding competitors, while poly(rA), poly(rG), and poly(rU) showed no effect. Mutagenesis of the cytidine residues contained within the LRBP-1 binding site demonstrated that all the cytidines in the bipartite sequence contribute to LRBP-1 binding specificity. Additionally, RNA gel electrophoretic mobility supershift analysis showed that LRBP-1 was not recognized by antibodies against two well-characterized poly(rC) RNA binding proteins, alphaCP-1 and alphaCP-2, implicated in the regulation of RNA stability of alpha-globin and tyrosine hydroxylase mRNAs. In summary, we show that partially purified LRBP-1 binds to a polypyrimidine sequence within nucleotides 203 and 220 of lutropin receptor mRNA with a high degree of specificity which is indicative of its role in posttranscriptional control of lutropin receptor expression.

Background: Rural physicians need access to quality medical information, but accessing information is difficult in rural settings. Digital health sciences libraries (DHSLs) offer the potential to make information more accessible to rural physicians. A telemedicine network was deployed to six rural hospitals in Iowa. Computers were installed allowing access to a DHSL and training sessions were held. The purpose of this study was to examine the barriers to use of a DHSL by rural physicians., Methods: Approximately one year after deployment of the telemedicine network, physicians were surveyed using a modified critical incident technique., Results: Seventy percent of the eligible physicians responded and 33% had used the DHSL. Primary barriers included insufficient training, being too time consuming to use, and distance of computers from physicians' practice sites. Non-DHSL users cited the difficulty of using the DHSL as their greatest barrier, while DHSL users cited the quality of the information resources., Conclusions: This study identifies a number of barriers that exist to rural physicians use of a DHSL. Potential solutions to these barriers are discussed. DHSLs will finally reach their potential when they can be delivered by easy to use handheld computers seamlessly integrated into the rural physician's workflow.

Background: Rural physicians need access to digital health sciences libraries (DHSLs) that is easy and reasonably rapid. The goal of this project was to study rural hospitals' access to a DHSL on the Internet, by comparing differing access speeds with differing costs and their acceptability for retrieving text, image, and video information in a DHSL., Methods: DHSL system response time was measured at three different times during the day over three different types of network connections (T1, Frame Relay, Modem). Text, image, and video information was retrieved. Costs were determined for installation and operation of the different types of network connections., Results: System response times were consistent at the three different testing times for each media type retrieved by each of the three network connection types. System response times for text retrieval met literature standards for all connections. Image retrieval met literature standards for T1 and Frame relay connections. No connection met literature standards for video retrieval., Conclusions: High speed access to DHSLs is preferable; Frame relay connections provide substantively similar service as T1 connections at less cost. However, access via modem to a DHSL can provide access to the majority of information--text--in a DHSL with an acceptable system response time.

To elucidate the molecular events associated with the regulation of luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptor mRNA stability during hCG-induced receptor down-regulation, we have identified an LH/hCG receptor-specific mRNA binding protein. Proteins were isolated from control and down-regulated rat ovary and were incubated with in vitro transcribed RNAs corresponding to the full-length LH/hCG receptor, as well as 5'- and 3'-truncated receptor forms. Resultant ribonucleoprotein complexes were analyzed by RNA gel mobility shift. A prominent Mr 50,000 ribonucleoprotein complex was identified with the following characteristics: 1) specificity for LH/hCG receptor open reading frame sequences located between nucleotides 102 and 282; 2) lack of competition by nonspecific RNAs; 3) a 3-fold increase in RNA binding activity during hCG-induced receptor down-regulation; and 4) limited tissue expression. This report describes the first evidence of an LH/hCG receptor mRNA binding protein, which we term LRBP-1, for luteinizing hormone receptor RNA binding protein-1. This protein is a candidate for a trans-acting factor involved in the hormonal regulation of LH/hCG receptor mRNA stability in rat ovary.

Objective: To assess the level of consensus among the administrative and health care leaders at rural Iowa hospitals regarding service gaps and priorities for developing telemedicine services., Methods: In the summer of 1994, a survey was conducted of all rural hospital chief executive officers, chiefs of medical staffs, and directors of nursing in Iowa concerning their perceptions of telemedicine services., Results: With the exception of teleradiology, few clinical specialties received high ratings as areas of need or priorities for the development of telemedicine. There was a general lack of agreement among respondents from the same hospital on such priorities. In contrast, respondents expressed higher priorities for the development of telemedicine-based educational services., Conclusions: The interest in teleradiology is consistent with the fact that teleradiology has been more thoroughly tested for medical efficacy than other telemedicine applications. Continuing medical education may represent another potential for widespread successful telemedicine application. Financial issues were reported as the greatest barriers to the development of telemedicine systems.