Nonhydrolyzable Heptose Bis- and Monophosphate Analogues Modulate Pro-inflammatory TIFA-NF-κB Signaling

d -Glycero-d -manno-heptose-1β,7-bisphosphate (HBP) and d -glycero-d -manno-heptose-1β-phosphate (H1P) are bacterial metabolites that were recently shown to stimulate inflammatory responses in host cells through the activation of the TIFA-dependent NF-κB pathway. To better understand structure-based activity in relation to this process, a family of nonhydrolyzable phosphonate analogues of HBP and H1P was synthesized. The inflammation modulation by which these molecules induce the TIFA-NF-κB signal axis was evaluated in vivo at a low-nanomolar concentration (6 nM) and compared to that of the natural metabolites. Our data showed that three phosphonate analogues had similar stimulatory activity to HBP, whereas two phosphonates antagonized HBP-induced TIFA-NF-κB signaling. These results open new horizons for the design of pro-inflammatory and innate immune modulators that could be used as vaccine adjuvant.     

An evolutionary algorithm for large traveling salesman problems

This work proposes an evolutionary algorithm, called the heterogeneous selection evolutionary algorithm (HeSEA), for solving large traveling salesman problems (TSP). The strengths and limitations of numerous well-known genetic operators are first analyzed, along with local search methods for TSPs from their solution qualities and mechanisms for preserving and adding edges. Based on this analysis, a new approach, HeSEA is proposed which integrates edge assembly crossover (EAX) and Lin-Kernighan (LK) local search, through family competition and heterogeneous pairing selection. This study demonstrates experimentally that EAX and LK can compensate for each other's disadvantages. Family competition and heterogeneous pairing selections are used to maintain the diversity of the population, which is especially useful for evolutionary algorithms in solving large TSPs. The proposed method was evaluated on 16 well-known TSPs in which the numbers of cities range from 318 to 13509. Experimental results indicate that HeSEA performs well and is very competitive with other approaches. The proposed method can determine the optimum path when the number of cities is under 10,000 and the mean solution quality is within 0.0074% above the optimum for each test problem. These findings imply that the proposed method can find tours robustly with a fixed small population and a limited family competition length in reasonable time, when used to solve large TSPs.     

Reliability investigation of 0.07-/spl mu/m InGaAs-InAlAs-InP HEMT MMICs with pseudomorphic In/sub 0.75/Ga/sub 0.25/As channel

The authors have investigated the reliability performance of G-band (183 GHz) monolithic microwave integrated circuit (MMIC) amplifiers fabricated using 0.07-/spl mu/m T-gate InGaAs-InAlAs-InP HEMTs with pseudomorphic In/sub 0.75/Ga/sub 0.25/As channel on 3-in wafers. Life test was performed at two temperatures (T/sub 1/ = 200 /spl deg/C and T/sub 2/ = 215 /spl deg/C), and the amplifiers were stressed at V/sub ds/ of 1 V and I/sub ds/ of 250 mA/mm in a N/sub 2/ ambient. The activation energy is as high as 1.7 eV, achieving a projected median-time-to-failure (MTTF) /spl ap/ 2 /spl times/ 10/sup 6/ h at a junction temperature of 125 /spl deg/C. MTTF was determined by 2-temperature constant current stress using /spl Delta/G/sub mp/ = -20% as the failure criteria. The difference of reliability performance between 0.07-/spl mu/m InGaAs-InAlAs-InP HEMT MMICs with pseudomorphic In/sub 0.75/Ga/sub 0.25/As channel and 0.1-/spl mu/m InGaAs-InAlAs-InP HEMT MMICs with In/sub 0.6/Ga/sub 0.4/As channel is also discussed. The achieved high-reliability result demonstrates a robust 0.07-/spl mu/m pseudomorphic InGaAs-InAlAs-InP HEMT MMICs production technology for G-band applications.     

Length of maternity leave and quality of mother-infant interactions

The aim of this study was to assess the association between the length of maternity leave and the quality of mother-infant interactions; 198 employed mothers of 4-month-old infants were interviewed and videotaped in their homes during a feeding time. Hierarchical multiple regression analyses indicated a direct association between shorter length of leave and more negative affect and behavior in maternal interactions with their infants. Infant and mother stressor/protective variables added significantly in predicting the quality of the mother-infant relationship. There were also significant interaction effects between the length of leave and these variables. Mothers who either reported more depressive symptoms or who perceived their infant as having a more difficult temperament and who had shorter leaves, compared with mothers who had longer leaves, were observed to express less positive affect, sensitivity, and responsiveness in interactions with their infants. The public policy implications of the relation between length of maternity leave, maternal and infant individual differences, and the quality of mother-infant interactions are discussed.     

Cadaver lungs for transplantation. Effect of ventilation with alveolar gas

In an effort to increase the donor pool for lung transplantation (LTX), we have demonstrated the feasibility of LTX from circulation-arrested cadavers in a canine LTX model. We hypothesized that ventilation of the cadaver lung with alveolar gas (20% O2, 5% CO2, balance N2) (AG) would be superior to ventilation with 100% oxygen (O2) after circulatory arrest of the donor. Twelve mongrel dogs were intubated, heparinized and euthanized by pentothal injection and ventilated with AG (n=6) or O2 (n=6). Four hours later, donor animals underwent sternotomy, and the lungs were flushed with cold modified Euro-Collins solution, harvested, and stored inflated in ice slush. Left lung allotransplantation was performed, and recipients were made dependent o n the transplanted lung by occlusion of the contralateral bronchus and pulmonary artery. Recipient animals were ventilated with an FiO2 of 0.4 and followed for 8 hr. Total ischemic time was 7.9 hr for both groups. Pulmonary edema developed in all recipients of AG lungs; one recipient survived the 8-hr observation period with poor oxygenation. In contrast, three of six recipients of O2-ventilated lungs survived for 8-hr with excellent gas exchange. Specimens of donor lungs before and after transplant were evaluated histologically utilizing trypan blue exclusion as an indicator of cell viability. At the time of organ retrieval 4 hr after death, 6% of cells were nonviable in the O2-ventilated cadaver lungs. Circulation-arrested cadaver lungs ventilated with 100% O2 prior to organ retrieval have superior pulmonary function after transplant compared with lungs ventilated with AG. Ventilation of cadaver lungs with AG induces pulmonary injury in this model. retrieval of donor lungs from circulation-arrested cadavers has potential for increasing the pulmonary donor pool.     

Implementation of computerized social work data base/assessments

The Department of Veterans Affairs, Social Work Service has designed, developed and implemented the Social Work Information Management System (SWIMS) which provides for the collection and reporting of both administrative and clinical information. This paper describes the implementation of one component of SWIMS, the automated Social Work Data Base/Assessment. The discussion details the implementation process and discusses issues encountered in the implementation of a computerized documentation system.