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Personalized, individualized, targeted therapy has successfully found entrance in the palliative treatment of lung cancer as they enable a personalized and individualized strategy going ahead with biomarker testing. Due to the crescending amount of predictive molecular and immunhistochemical analyses at different time points during therapy the need for more and actual tumor tissue increases; however these samples cannot always be obtained without major discomfort for the patients. Therefore, analyses from blood, the so called "liquid biopsy", is an alternative or additional method. Activating mutations in the EGFR gene and the inhibitory mutation T790 M can already be detected from blood during clinical routine. This review presents the status of liquid biopsy for diagnosis, prognosis and as predictive parameter during the course of therapy in lung cancer and gives an outlook on future developments.

Therapeutic decisions for breast cancer are increasingly becoming based on subtype-specific gene expression tests. For bladder cancer very similar subtypes have been identified by genome-wide mRNA analysis, which as for breast cancer differ with respect to the prognosis and response to therapy on the basis of their hormone dependency. At the DNA level, however, the type of mutations and their frequencies within the subtypes are strikingly different between bladder and breast cancers. It will be interesting to see whether possible driver mutations can serve as therapeutic targets in both indications. In contrast, the apparent hormone dependency of a substantial number of bladder carcinomas suggests that hormonal and anti-hormonal treatment can be valid therapy options similar to breast cancer. Moreover, gender-specific differences with respect to the incidence and aggressiveness of male compared to female bladder cancers can be explained by hormonal effects. Together with forthcoming immunomodulatory therapies these multiple therapy options raise and give new hope to efficiently combat this aggressive disease.

Though tobacco smoking is the leading cause of lung cancer, during the last decades the prevalence increased in never smoking patients, especially in women. Sex steroid hormones and particularly the estrogen receptors (ERs) seem to play an important but still underestimated role in non-small cell lung cancer (NSCLC). Beside long existing hints that hormone replacement therapy (HRT) increases the risk of lung tumors recent analyses on cell lines, xenografts and human tumors of both sexes gave clear evidence of ER expression and proliferation in NSCLC. Most recently, the expression of ERs apparently has prognostic and predictive value. Recently, an intracellular "cross-talk" between the ER and the epithelial growth factor receptor (EGFR) could be demonstrated. EGFR are important targets of approved tyrosinkinases (TKIs), like gefitinib, erlotinib or afatinib. Currently, clinical studies are enrolling lung tumor patients for combination treatment with EGFR TKI and antihormonal drugs, e. g. fulvestrant.

The immunodominant region of the Plasmodium falciparum circumsporozoite protein is comprised mainly of a series of tetrapeptide repeats that can, depending on the starting cadence chosen, be described as (NANP)n, (ANPN)n, (NPNA)n or (PNAN)n in one-letter amino acid code. Data from several studies suggest that the NPNA cadence alone is structurally correct, in that each NPNA tetrapeptide effectively forms a structural unit initiated by an Asx-Pro turn. To explore this idea further and to assess the immunological relevance of peptide conformation as it relates to the cadence of these tetrapeptide repeats, we used ELISA to compare the abilities of monoclonal antibodies (MAbs) produced against P. falciparum sporozoites to recognize repeat-related heptapeptides expressed on the surface of filamentous bacteriophage. Having included representatives of both NANP and NPNA cadences and other peptides in which the number and location of Asx-Pro sequences varied, we provide evidence that Asx-Pro sequences play an important role in peptide conformation and antibody recognition, that peptide conformation is influenced by the cadence of the tetrapeptide repeats and that peptide conformation is important to the abilities of these MAbs to recognize their epitopes.

A theoretical model of the stress-strain-temperature response of a thermally driven. shape memory alloy (SMA) composite actuator under applied load is developed. The actuator is assumed to be constructed from a thin layer of SMA bonded to a layer of elastomer. The model is developed by considering an energy balance on the SMA and force equilibrium for both SMA and the composite. It includes the martensite fraction of the SMA as a state variable which describes the phase transition process and the constitutive relation of the SMA. Closed-form solutions for the stress-strain-temperature response are obtained by assuming that heat conduction in the axial direction is negligible. Parametric studies are conducted to show how the material properties of the elastomer and geometric dimensions of the actuator affect the thermal and stress responses of the actuator. Finally, the actuation force as a function of the heating power is predicted by the model.

It has been shown, that smoking results in a lower yield of surfactant associated phospholipids in bronchoalveolar lavage (BAL). Indirect evidence suggests impaired secretion. In the present study, we investigated the influence of cigarette smoke on surfactant secretion in cultured rat alveolar type II cells. Smoke exposure was achieved by bubbling the smoke of four cigarettes through Dulbecco's modified Eagle's medium (DMEM) which was adjusted to a reference absorption value of 1.36 at 320 nm. Cells were preincubated with various dilutions of cigarette smoke-treated medium for 30 min, and were then exposed to this medium for 2 h. After this time, secretion of 3H-choline-labelled phosphatidylcholine (PC) was measured as a marker of surfactant secretion. A 10 fold dilution of cigarette smoke-treated medium inhibited PC secretion stimulated by a combination of terbutaline, adenosine triphosphate and 12-O-tetradecanoylphorbol-13-acetate by over 50%, but did not alter basal secretion. Exposure to less concentrated cigarette smoke-treated medium resulted in less inhibition. Cellular injury was not observed with the concentrations of cigarette smoke-treated medium used in this study. The gas phase of cigarette smoke was not inhibitory at comparable concentrations. Longer exposure to cigarette smoke-treated medium resulted in increased inhibition of PC secretion. The cigarette smoke ingredients, nicotine and benzo[a]pyrene, failed to inhibit PC secretion. Secretion of type II cells exposed to cigarette smoke-treated medium at lower temperatures was not affected. Addition of antioxidants to medium and cells during the preincubation and secretion period did not alter cigarette smoke-treated medium-induced inhibition of stimulated PC secretion. These results demonstrate a direct inhibitory effect of cigarette smoke constituents on surfactant secretion in type II cells. Inhibition is mediated by compounds contained predominantly in the particulate phase of cigarette smoke. Inactivation of the inhibitory effect by lower temperatures suggests involvement of processes such as enzymatic bioactivation or active transport mechanisms.

A thermally driven force/displacement actuator may be fabricated from a composite consisting of a shape memory alloy (SMA) and an elastomer. A simple onedimensional device is described where a thin layer of SMA overlays an elastomer which is in turn bonded to a heat sink. A thermal response model is developed which includes the martensite fraction of the SMA, in addition to the effects of heat capacity of the composite and conductive resistance of the elastomer. Solutions, in terms of temperature-composition-time trajectories, for free response are obtained using different phase transition models. Calculations for a device consisting of Nitinol overlaying a typical elastomer show that rapid response, coupled with small power consumption, may be achieved if device size is kept small.

Subcooled flow boiling experiments with water at 0.2atm pressure assess the utility of fine filament screen-laminate enhanced surfaces as high performance boiling surfaces. Experiments are conducted on vertically oriented, multi-layer copper laminates in distilled water. The channel Reynolds number is varied from 2,000 to 20,000; and, subcooling ranges from 2K to 35K. Boiling performance is documented for ten different surfaces having pore hydraulic diameters ranging from 39μm to 105μm, and surface area enhancement ratios ranging from 5 to 37. Heat flux of up to 453W/cm2 is achieved at 35K subcooling at a channel Reynolds number of 6,000, which represents a 3.5-fold increase in Critical Heat Flux (CHF) over that of saturated pool boiling on the same surface. Results show that CHF is strongly correlated with subcooling; and the effect of subcooling is more pronounced as flow intensity is increased. It is found that CHF enhancement due to subcooling and flow intensity is intrinsically linked to the surface area enhancement ratio, which has an optimum that depends on the degree of subcooling. High speed video imagery (1200fps) and long range microscopy are use to document bubble dynamics. Boiling mechanisms inherent to subcooling, enhanced surface geometry, and CHF are discussed.Copyright © 2010 by ASME

Saturated pool boiling on vertically oriented, copper, wavy-fin surfaces in water at reduced pressures is investigated. A lamination of fine-filament, wire mesh is an effective surface enhancement for boiling since the surface can be configured to provide a very high density of potential bubble nucleation sites. Two surfaces are considered: a 0.75mm thick 4-layer laminate with approximately 4000 pores per cm2 and a 0.42mm thick 8-layer laminate with approximately 26,000 pores per cm2 . The results show that the 8-layer laminate outperforms the 4-layer laminate. At reduced pressures a reduction in performance is seen for both surfaces. A semi-empirical boiling model is developed. The model predicts the boiling performance of our data within an error of 30%. The model shows that shorter fins improve boiling performance.Copyright © 2010 by ASME

A study on adult anopheline ecology and malaria vector incrimination was carried out from 1986 to 1989 during irrigation development in an area of the Mahaweli Project in eastern Sri Lanka. Eleven potential vector species were collected resting indoors or by using human or bovid bait, and from light trap catches. Overall, Anopheles vagus (Donitz), An. annularis (van der Wulp), and An. subpictus (Grassi) were the most prevalent, and An. culicifacies (Giles) and An. barbirostris (van der Wulp) were the least prevalent species. The abundance of An. aconitus (Donitz), An. jamesii (Theobald), An. pallidus (Theobald), and An. subpictus increased after irrigation development, while An. annularis, An. barbirostris, An. culicifacies and An. varuna (Iyengar) decreased. Populations of An. nigerrimus (Giles), An. tessellatus (Theobald), and An. vagus did not change substantially. Seven species were infected with malaria parasites, as determined by enzyme-linked immunosorbent assays (ELISA) done on mosquito head-thorax triturates. The main species involved were An. annularis, at peak abundance during the 1986-1987 period of development leading to the onset of irrigation, and An. subpictus, during times of seasonal abundance in the post-irrigation period of 1988 to 1989. Although occurring at low abundance, An. culicifacies was involved in malaria transmission irregularly throughout the study period. While there was strong ELISA-based evidence implicating An. subpictus as a major post-irrigation vector, confirmation of its vector status must await dissection and ELISA-based evidence of P. vivax and P. falciparum sporozoite infection rates in salivary glands.

The use of repellents in protecting people against vector-borne diseases is predicated on the assertion that reducing human/vector contact will reduce the incidence of disease. The methods that have been used in developing countries have been simple to apply and relatively cheap. This article will discuss the use of repellents for protection against vector-borne disease in Southeast Asia and the Southwest Pacific region.

The susceptibility to two coindigenous Plasmodium vivax GrassiFeletti phenotypes VK210 and VK247 of three colonized Anopheles albimanus Wiedemann strains (white-striped, green and brown) from southern Mexico was investigated. Mosquitoes of the three strains were simultaneously fed with P. vivax-infected patient blood and examined 1 wk later for the presence of oocysts. The circumsporozoite protein phenotype type (VK210 and VK247) was determined by immunoflorescence of salivary gland sporozoites using monoclonal antibodies. The proportions of specimens infected and the number of oocyst per mosquito indicated that all mosquito strains were more susceptible to the phenotype VK210 than to VK247, but the white-striped strain was more susceptible to both parasite phenotypes than the other two strains.

Nebulization of an aqueous mixture of primaquine diphosphate and albumin into heated vegetable oil produces spherical particles with an average size of 6 microm. The microparticles are relatively stabile in buffers of pH 7.2 and 4.5 and completely degrade when exposed to proteolytic enzymes such as trypsin. Pharmacokinetic evaluation of the albumin-encapsulated primaquine diphosphate shows significantly higher levels in mouse liver tissue relative to free drug 2-48 h post-IP administration. Higher AUC (2.8x), lower steady-state volume of distribution (10x) and slower half-life (2.5x) relative to an equivalent dose of free primaquine diphosphate suggest liver targeting and sustained release of the drug from the microparticles.

Two field trials for commercially available and experimental mosquito traps variously baited with light, carbon dioxide, octenol, or combinations of these were evaluated in a malarious area at Paekyeon-Ri near Tongil-Chon (village) and Camp Greaves, Paju County, Kyonggi Province, Republic of Korea. The host-seeking activity for common mosquito species was determined using hourly aspirator collections from a human- and propane lantern-baited Shannon trap. The total number of mosquitoes and number of each species captured during the test were compared using 8 x 8 and 5 x 5 Latin square designs based on trap location. Significant differences were observed for the total number of mosquitoes collected in the 8 x 8 test, such that counterflow geometry (CFG) with CO2or = CFG with CO2 and octenolor = Shannon trapor = Mosquito Magnet with octenolAmerican Biophysics Corporation (ABC) light trap with light, CO2 (500 ml/min), and octenolor = ABC light trap with light and dry iceor = ABC light trap with light and CO2ABC light trap with light only. A concurrent 5 x 5 test found significant differences in trap catch, where Mosquito Magnet with octenolNew Jersey light trapor = EPAR Mosquito Killer with CO2or = ABC light trap with light and dry iceCenters for Disease Control (CDC) light trap (manufactured by John W. Hock) with light and octenol. Significant differences in trap catch were noted for several species including: Aedes vexans, Anopheles sinensis, An. yatsushiroensis, An. lesteri, Culex pipiens, and Cx. orientalis. Traps baited with octenol captured significantly fewer Cx. pipiens than those not baited with octenol. Likewise, no Cx. orientalis were captured in octenol-baited traps. Host-seeking activity showed a similar bimodal pattern for all species captured. Results from these field trap evaluations can significantly enhance surveillance efforts. Significantly greater numbers of mosquitoes were captured with mosquito traps using counterflow technology (e.g., Mosquito Magnet and CFG traps) when compared to standard light and carbon dioxide-baited traps. Additionally, field evaluations demonstrate that various traps can be utilized for isolation and detection of arboviruses and other pathogens.

An extended-duration formulation of lambda-cyhalothrin (Demand CS) applied as either an ultra-low volume (ULV) or thermal fog spray from a new handheld sprayer (Terrier) against Aedes aegypti was evaluated in Honduras. Spray applications were made at the front door for 1 min or to each room for 15 sec, both for the ULV and thermal fog applications to houses in separate blocks for each treatment. The efficacy and duration of effectiveness of the spray was determined from sentinel caged mosquito mortality and collection of mosquitoes within houses with a backpack power aspirator. Sentinel caged mosquito mortality in both open and sequestered locations was 97-100% for all spray treatments, with control mortality less than 2%. Both ULV applications (front door and each room) provided 4 wk of significant control (P0.01) based on adult Ae. aegypti house collections.

Malaria remains the most serious vector-borne disease, affecting some 300-500 million people annually, transmitted by many species of Anopheles mosquitoes (Diptera: Culicidae). Monoclonal antibodies developed against specific circumsporozoite (CS) proteins of the main malaria parasites Plasmodium falciparum and P. vivax have been used previously for enzyme-linked immunosorbent assays (ELISA), widely employed for detection of malaria sporozoites in vector Anopheles for local risk assessment, epidemiological studies and targeting vector control. However, ELISA procedures are relatively slow and impractical for field use. To circumvent this, we developed rapid wicking assays that identify the presence or absence of specific peptide epitopes of CS protein of the most important P. falciparum and two strains (variants 210 and 247) of the more widespread P. vivax. The resulting assay is a rapid, one-step procedure using a 'dipstick' wicking test strip. In laboratory assessment, dipsticks identified 1 ng/ mL of any of these three CS protein antigens, with sensitivity nearly equal to the CS standard ELISA. We have developed and are evaluating a combined panel assay that will be both qualitative and quantitative. This quick and easy dipstick test (VecTest Malaria) offers practical advantages for field workers needing to make rapid surveys of malaria vectors.

Minist?rio da Sa?de. Funda??o Nacional de Sa?de. Instituto Evandro Chagas. Bel?m, PA, Brasil. Walter Reed Army Institute of Research. Washington, DC, USA. Minist?rio da Sa?de. Funda??o Nacional de Sa?de. Instituto Evandro Chagas. Bel?m, PA, Brasil. London School of Hygiene and Tropical Medicine. Department of Infectious and Tropical Diseases. Pathogen Molecular Biology and Biochemistry Unit. London, UK. London School of Hygiene and Tropical Medicine. Department of Infectious and Tropical Diseases. Pathogen Molecular Biology and Biochemistry Unit. London, UK. We conducted a survey to determine the vectors of malaria in six localities of Serra do Navio municipality, State of Amap?, from 1990 to 1991. Malaria infection rates of 29.3%, 6.2% and 20.4% were detected by human blood smears in Col?nia ?gua Branca, Porto Terezinha and Arrependido, respectively. There was no malaria infection detected in Serra do Navio. Fifteen species were identified among 3,053 anopheline mosquitoes collected by human bait and 64.4% were identified as Anopheles albitarsis s.l., 16.7% An. braziliensis, 9.5% An. nuneztovari and 5.8% An. triannulatus. An. darlingi, the main vector of malaria in the Amazon region of Brazil, was scare. Using enzyme-linked immunosorbent assay (ELISA), a total positive rate of 0.8% (23/2876) was found for six species: fifteen An. albitarsis s.l., four An. nuneztovari, and one of each: An. braziliensis, An. triannulatus, An. oswaldoi and An. rangeli. Nine of 23 positive mosquitoes were infected with Plasmodium malariae, eight with P. vivax VK210, three with P. vivax VK247 and three with P. falciparum. Since An. albitarsis s.l. was collected feeding on humans, was present in the highest density and was positive by ELISA for malaria sporozoites, it probably plays an important role in malaria transmission in this area.

A 63-year-old woman from Colonial Beach, Westmoreland County, VA, was diagnosed with Plasmodium falciparum malaria on July 19, 1998. The woman had no history of international travel, intravenous drug use, blood transfusion, or other risk factor for contracting the disease. She seldom left the county and generally spent her evenings indoors, leading to the conclusion that she had been bitten locally by an infected mosquito. Colonial Beach is host to a population of migrant agricultural laborers from areas in which malaria occurs, but a blood survey of 89 Haitians and Mexicans failed to find Plasmodium parasites, specific antibodies, or clinical cases of malaria. Mosquito surveys were conducted during 2 days (July 22 and 28, 1998) with carbon-dioxide-baited light traps, larval and pupal collections, and landing collections. Thirteen species of mosquitoes were identified morphologically, including 4 potential vectors: Anopheles crucians, An. punctipennis, An. smaragdinus (new state record), and An. quadrimaculatus s.s. (new state record). Identifications of the latter 2 species were confirmed by sequencing of the ITS2 DNA region from adults reared from locally collected larvae. Anopheles smaragdinus was the most common biting species among the potential vectors, although An. crucians was the most abundant in other kinds of collections. In addition, Ae. albopictus was collected in Westmoreland County for the 1st time.

Dried Anopheles farauti mosquitos caught in Solomon Islands in 1990 were examined for malaria sporozoites by ELISA and nested polymerase chain reaction (PCR). Only heads and thoraces were used. Plasmodium genus-specific nested PCR amplifications were carried out on all samples. Of the 402 pools of mosquitos that were processed, 30 were positive for malaria. Nest 1 products of positive samples were subjected to further PCR amplifications with species-specific primers for P. falciparum and P. vivax. Twenty pools were positive for P. vivax by PCR while only 7 were positive by ELISA. For P. falciparum 2 pools were positive by both ELISA and PCR, and one of these was a pool which was positive for P. vivax by PCR and ELISA. Thus the sensitivity of PCR for P. vivax was 100% while the specificity was 96.7%. For P. falciparum the sensitivity and specificity were 100%. The PCR technique is highly sensitive and can be used on dried mosquitos which makes it a valuable tool for determining sporozoite rates of mosquitos, even in remote areas.

Four repellents, N,N-diethyl-3-methyl-benzamide (deet), 2-hydroxy-methyl-cyclohexyl acetic acid lactone (CIC-4), and 2 piperidines (1-[3-cyclohexen-1-ylcarbonyl] piperidine [AI3-35765] and 1-[3-cyclohexen-1-ylcarbonyl]-2-methylpiperidine [AI3-37220]) were evaluated alone and in combination against Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus using a modified in vitro test system. This method was a valuable tool for comparing effective concentrations of the new compounds. Because of the controlled conditions of the test, it was possible to use the results of assays that had been conducted over a 5-year period and to perform the many replications necessary to evaluate combinations of compounds. The new candidate repellents were generally as effective as deet. Although speculative at this time, there was some evidence of synergistic interaction. Repellent combinations of CIC-4/AI3-37220/AI3-35767, deet/AI3-35765, and deet/AI3-37220/AI3-35765 against An. stephensi and CIC-4/AI3-35765, deet/AI3-37220/AI3-35765, AI3-37220/AI3-35765, and CIC-4/AI3-37220 against Ae. aegypti were more effective than the component compounds alone.

Malaria transmission by anopheline mosquitoes was studied in a traditional tank-irrigation-based rice-producing village in the malaria-endemic low country dry zone of northcentral Sri Lanka during the period August 1994-February 1997. Adult mosquitoes were collected from human and bovid bait catches, bovid-baited trap huts, indoor catches, and pit traps. Mosquito head-thoraces were tested for the presence of Plasmodium falciparum and P. vivax, and blood-engorged abdomens for the presence of human blood by ELISAs. House surveys were done at two-day intervals to record cases of blood film-confirmed malaria among the villagers. A total of 7,823 female anophelines representing 14 species were collected. Trends in anopheline abundance were significantly correlated with rainfall of the preceding month in An. annularis, An. barbirostris, An. subpictus, An. vagus, and An. varuna, but were not significant in An. culicifacies and An. peditaeniatus. Malaria parasite infections were seen in seven mosquito species, with 75% of the positive mosquitoes containing P. falciparum and 25% P. vivax. Polymorph PV247 was recorded from a vector (i.e., An. varuna) for the first time in Sri Lanka. Computations of mean number of infective vector (MIV) rates using abundance, circumsporozoite (CS) protein rate, and human blood index (HBI) showed the highest rate in An. culicifacies. A malaria outbreak occurred from October 1994 to January 1995 in which 45.5% of village residents experienced at least a single disease episode. Thereafter, malaria incidence remained low. Anopheles culicifacies abundance lagged by one month correlated positively with monthly malaria incidence during the outbreak period, and although this species ranked fifth in terms of abundance, infection was associated with a high MIV rate due to a high CS protein rate and HBI. Abundance trends in other species did not correlate significantly with malaria. It was concluded that An. culicifacies was epidemiologically the most important vector in the study area.

Immature Anopheles stephensi Liston were reared in untreated water and water containing eight 2-fold dilutions of rubidium (Rb) from 1,000 to 7.8 ppm to determine the concentration that allowed reliable detection and produced the least toxic effects as measured by adult emergence, weight, and survival. The amount of Rb detected in mosquitoes increased positively with increasing concentrations in the rearing water. Concentrationsor = 31.2 ppm Rb in the rearing water provided high and consistent detection levels ofor = 3,500 ppm Rb/mg of adult mosquito. There were no adverse effects of Rb on the weights of mosquitoes. However, increased Rb concentrations in the rearing water were associated with decreased emergence and survival. After 8 d, percentage emergence from Rb concentrations of 0-31.2 ppm wasor = 50%. At day 21, Rb concentrations of 0-31.2 ppm showedor = 29% reduction of female survival compared with controls. The recommended concentration for reliable Rb detection with minimal toxic effects in An. stephensi was 32 ppm.

This study examined U.S. Army soldiers' knowledge, attitudes, and practices regarding personal protection measures (PPMs) to prevent arthropod-related diseases and nuisance bites. Soldiers attending 1 of 13 U.S. Army training courses either completed a written questionnaire (N = 1,007) or participated in a group interview (N = 65). Respondents primarily used repellents to prevent nuisance insect bites (55%) rather than to prevent disease (38.7%). Less than one-third correctly identified the military-issue repellents to be used on skin (31.7%) or clothing (26.1%). More than half (57.6%) thought that commercial products were better than military-issue repellents, but most (74.2%) reported that they did not have enough or any information about the U.S. military's system of PPMs. Soldiers have poor knowledge of U.S. military doctrine regarding PPMs and still prefer to use commercial products. A focused strategy to ensure the appropriate use of PPMs by service members should be developed, implemented, and evaluated.

Measurements of fully-developed augmented convection and pressure drop of air flow in an isothermal, symmetrically grooved channel are reported for channel Reynolds numbers ranging from 800 to 5,000. Grooves, oriented transverse to the flow, are of triangular shape with dimensions that are comparable to the hydraulic diameter of the channel. The grooved section is designed to excite instabilities in the flow leading to increased mixing at sub-transitional Reynolds numbers. Local heat transfer measurements are made using a holographic interferometer. Interferograms, representative of the cross-span-average temperature of the air in the channel, are analyzed to produce data records of the air temperature distribution and the local heat flux along the grooved walls. Heat flux distributions are spatially averaged to produce a correlation of fully-developed Colburn j-factor for this surface configuration. A performance evaluation of the grooved surface applied to a simple heat exchanger shows that it provides thermal performance which is comparable to other surfaces commonly employed in compact heat exchangers.

The flow and heat transfer characteristics in the region of an asymmetric contraction in a two-dimensional channel are studied numerically. The contraction is in the form of a step on one of the channel walls. Channel wall-to-wall spacing ranges from 2 step heights to 10 step heights, with Reynolds numbers, based on channel hydraulic diameter, ranging from 500 to 2500. Separation and recirculation regions occur upstream from the contraction; the flow generally separates on the order of one step height upstream from the step and re-attaches approximately one-half the distance up the step face. In some cases there is a recirculation region on the top of the step, beginning just downstream from the leading edge of the step, and typically a few step heights in extent. Heat transfer is reduced in the recirculation regions, relative to that of a parallel-wall flow. In addition, there is heat transfer augmentation on the wall opposite the step, not only because of the contraction itself, but also enhanced by the flow around the recirculation regions. Correlations are reported for friction factor and for heat transfer augmentation and reduction, and results are reported for location of separation and reattachment points and for heat transfer across the entire region.

Direct numerical simulations of three-dimensional flow and augmented convection in a channel with symmetric, transverse grooves on two opposite walls are performed using the spectral element technique. The flow is driven by a constant pressure gradient. A method employing an exponentially decaying temperature scale is developed and used to calculate the fully developed heat transfer coefficient for constant temperature boundary conditions. Results are presented for the Reynolds number range 180 < Re < 1175. A series of flow transitions is observed as the Reynolds number is increased, from steady two-dimensional flow, to traveling two and three-dimensional wave structures, and finally to three-dimensional mixing. Periodic ejection of slow moving fluid from the grooves causes significant flow rate unsteadiness. Three-dimensional simulations predict friction factor and Nusselt number values to within 20% of measured values over the narrow Reynolds number range where overlapping data exists. Two-dimensional simulations are found to be inadequate to calculate transport in this channel for Re > 400.

Sugar meals of plant origin are an important component of the sand fly diet. We show that sugar solution baits have potential as vehicles for phlebotomine sand fly control. In the laboratory, adult Phlebotomus duboscqi Neveu-Lemaire and Sergentomyia schwetzi (Adler, Theodor, and Parrot) that have consumed an aqueous sucrose solution containing Bacillus sphaericus Neide toxins and are subsequently eaten by larvae produce significant larval death (P0.01). In the field, when vegetation near animal burrows and eroded termite mounds was sprayed with sucrose solution with or without incorporation of the larval toxicant B. sphaericus, 40% of female sand flies fed in situ. Dispersing B. sphaericus-carrier sand flies caused significant larval mortality (P0.01) in resting and breeding sites in animal burrows 10-30 m from the sprayed vegetation for 2-12 wk posttreatment. Also, adult sand fly populations breeding and resting inside animal burrows were significantly reduced (P0.01) following direct application of the sucrose/B. sphaericus solution to the burrow entrances. This control effect lasted 4-10 wk post-treatment. The effect was not seen for sand fly populations breeding and resting inside eroded termite mounds. This approach may be useful for the application of biological control agents against phlebotomine sand flies in biotypes where larvae and adults use the same habitats.

A field evaluation of the repellents N,N-diethyl-3-methylbenzamide (deet) and 1-(3-cyclohexen-1-yl-carbonyl)-2-methylpiperidine (AI3-37220, a piperidine compound) was conducted against Anopheles funestus and An. arabiensis in Kenya. Both repellents provided significantly more protection (P0.001) than the ethanol control. AI3-37220 was significantly more effective (P0.001) than deet in repelling both species of mosquitoes. After 9 h, 0.1 mg/cm2 of AI3-37220 provided 89.8% and 71.1% protection against An. arabiensis and An. funestus, respectively. Deet provided80% protection for only 3 h, and protection rapidly decreased after this time to 60.2% and 35.1% for An. arabiensis and An. funestus, respectively, after 9 h. Anopheles funestus was significantly less sensitive (P0.001) to both repellents than An. arabiensis. The results of this study indicate that AI3-37220 is more effective than deet in repelling anopheline mosquitoes in western Kenya.

A 21-month (1991-1992) assessment of malaria and the relative contribution of Anopheles punctulatus and An. koliensis to its transmission was conducted in Oksibil, a highland community in Irian Jaya, Indonesia. Nearly all (98%) of the 2577 Anopheles from indoor or outdoor human-landing collections were An. punctulatus. Nineteen (0.75%) of the 2518 An. punctulatus tested were positive when tested for malaria circumsporozoite protein (CSP) by ELISA: nine (45% of positives) for Plasmodium vivax-210, six (30%) for Plasmodium falciparum, three (15%) for P. vivax-247 and two (10%) for P. malariae. One mosquito was positive for both P. vivax 210 and P. falciparum. All 59 An. koliensis tested were negative. All mosquitoes positive for CSP were from indoor collections, 89% from the main houses and the remaining 11% from the traditional dwellings (bokams). These findings are discussed with respect to highland malaria epidemiology and transmission in the Oksibil Valley.Perennial malaria is a major health problem for most lowland and coastal populations of Irian Jaya, Indonesia. The highlands, however, are generally thought to be free of autochonthous malaria despite the presence of potential vectors up to 2250 m. The authors measured the prevalence of Anopheles punctulatus and A. koliensis during January 1991 to September 1992 in Oksibil, a highland community in Irian Jaya, and their relative contribution to the transmission of malaria. 98% of the 2577 Anopheles from indoor and outdoor human-landing collections were A. punctulatus. 19 (0.75%) of the 2518 A. punctulatus tested were positive when tested for malaria circumsporozoite protein (CSP) by ELISA: nine for Plasmodium vivax-210, six for P. falciparum, three for P. vivax-247, and two for P. malariae. One mosquito was positive for both P. vivax-210 and P. falciparum. All 59 A. koliensis tested were negative. All mosquitoes positive for CSP were from indoor collections, 89% from the main houses and the remaining 11% from the traditional dwellings. Study findings are discussed with respect to highland malaria epidemiology and transmission in Oksibil Valley.

A field experiment was conducted to compare the biting behavior of Plasmodium falciparum-infected and uninfected Anopheles on humans using mosquito repellents. Repellent formulations (5% [wt/vol] N,N-diethyl-3-methylbenzamide [deet] or 5% [wt/vol] AI3-37220, a piperidine compound, both in 100% ethanol, or 100% ethanol alone [as a control]) were applied to the lower legs of 3 collectors in each of 4 houses. Collectors caught mosquitoes over 6 collection nights. Mosquitoes were collected into vials after they initiated probing on the leg of a collector. Infected females made up the same proportion of the Anopheles funestus populations biting either repellent-protected or unprotected individuals. We conclude that repellent formulations are equally effective against Plasmodium-infected and uninfected An. funestus.

Differences in sensitivities of chloroquine-sensitive and chloroquine-resistant strains of Plasmodium berghei were observed following irradiation of the parasites. A dose of 15 kilorads from a cobalt-60 source killed the erythrocytic stages of the chloroquine-sensitive strain and no parasitemias were observed when mice were injected with these irradiated parasites. In contrast, when the chloroquine-resistant strain was irradiated with the same dose of cobalt-60 and injected into mice, an infection rate of 12.5% was observed, indicating that the latter strain was more resistant to inactivation by irradiation. Following injection of these irradiated strains of P. berghei into mice, significant decreases in mouse hepatic cytochrome P450 and benzo(a)pyrene hydroxylase activity, with no significant effect on N-demethylase activity, were observed. Serum glutamic-oxaloacetic transaminase (SGOT) and glutamic-pyruvic transaminase (SGPT) levels of mice injected with the irradiated parasites fell within the range of the serum enzyme levels in normal laboratory mice.

The mouse monoclonal antibody 2A10 (immunoglobulin G), which recognizes the (NANP)n repeat of Plasmodium falciparum circumsporozoite surface protein, was used to screen a filamentous phage epitope library expressing random amino acid hexamers. The sequences obtained were TNRNPQ, SNRNPQ, NND-NPQ, SNYNPQ, and QNDNPQ (single-letter amino acid designation). These peptides showed 50% homology with the native epitope (PNANPN) and therefore were considered to mimic its structure (mimotopes). Two of these mimotopes (TNRNPQ and NNDNPQ) inhibited the binding of monoclonal antibody 2A10 to the recombinant protein R32LR, which contains the amino acid sequence [(NANP)15NVDP]2. Immunization of mice and rabbits using the peptide (TNRNPQ)4 induced a humoral response that recognized R32LR by an enzyme-linked immunosorbent assay and P. falciparum sporozoites by an immunofluorescence assay. These results suggest that phage epitope libraries can be exploited to screen for mimotopes in the design of subunit vaccines against infectious agents.

Eight commercial repellents were tested against Aedes aegypti 0 and 4 h after application in serial dilution to volunteers and laboratory mice. Results were analyzed by multiple regression of percentage of biting (probit scale) on dose (logarithmic scale) and time. Empirical correction terms for conversion of values obtained in tests on mice to values expected in tests on human volunteers were calculated from data obtained on 4 repellents and evaluated with data obtained on 4 others. Corrected values from tests on mice did not differ significantly from values obtained in tests on volunteers. Test materials used in the study were dimethyl phthalate, butopyronoxyl, butoxy polypropylene glycol, MGK Repellent 11, deet, ethyl hexanediol, Citronyl, and dibutyl phthalate.

A comparative study of 3 ELISA protocols was performed for host blood meal identification in Aedes aegypti. In the sandwich-B ELISA, which used a combination of heavy and heavy+light chain conjugates, specificity was improved to such a degree that conjugates no longer required cross-adsorption with heterologous sera. Using the sandwich-B assay, human blood meals in laboratory reared Ae. aegypti could be detected longer after feeding (100% at 32 h and 80% at 42 h) than with a direct assay (100% at 20 h). Efficacy of the sandwich-B and direct ELISAs in field analyses was studied in parallel) using 80 field collected mosquitoes from Thailand. The sandwich-B assay was superior (88% detection rate) to the direct assay (41% detection rate) and was thus selected as the method of choice for future field studies.

Indoor resting Anopheles subpictus in a new irrigation scheme in Sri Lanka were investigated during 1989-1990 for malaria infection by dissection and ELISA, and human feeding rates by ELISA analysis of blood meals. Indoor resting abundance was 22.3 females per house per 15-min catch in April-June 1989, 2.2 in November-December 1989, and 7.5 in April-June 1990. ELISA-based malaria infection rates (Plasmodium vivax and P. falciparum combined) were 1.4% during April-June and 3.2% during November-December 1989, and 12.5% during April-June 1990. Dissection and ELISA confirmed the presence of oocysts and sporozoites of P. falciparum in 1990. Human blood was detected in 4.3, 0.8, and 5.2% of analyzed meals, respectively, during the three sampling periods. Estimates of the entomological inoculation rate (EIR) ranged from 0.00006 to 0.005 in different samples and vectorial capacity (VC) was 0.0005 for the 1990 sample. Thus, An. subpictus is incriminated as a vector of human malaria in Sri Lanka.

A strain of Plasmodium vivax from Thailand with a polymorphic repeat unit of the circumsporozoite protein was established in Saimiri sciureus boliviensis and 3 species of Aotus monkeys. All 11 attempts to transmit infection via sporozoite inoculation, 4 times to splenectomized S. sciureus boliviensis, 2 times to splenectomized Aotus nancymai, and 5 times to intact Saimiri monkeys, were successful. Anopheles freeborni, Anopheles stephensi, Anopheles dirus, and Anopheles gambiae mosquitoes were infected by feeding on parasitemic blood from a chimpanzee and an Aotus azarae boliviensis monkey. Our results indicate that this strain may be useful in antisporozoite vaccine trials.

A field and laboratory study was conducted to determine some of the parameters relevant to malaria transmission by Anopheles mosquitoes in Dajabon Province, Dominican Republic. Although all 4 species occurring in the area, i.e., An. albimanus, An. crucians, An. grabhamii and An. vestitipennis, were included in the investigations, most of the work focused on the first and last named species because of their abundance. Gonotrophic cycles were determined to be 2.6 and 3.2 days for An. albimanus and An. vestitipennis, respectively. Mean parity rates for the 2 species were 37.3 and 20.7%, respectively, in outdoor samples. The human blood index, as determined by ELISA, was 0.08 for An. albimanus and 0.12 for An. vestitipennis. Only An. albimanus was confirmed positive for Plasmodium falciparum circumsporozoite protein, using ELISA. The vectorial capacity of An. albimanus was determined to be 0.019 and that of An. vestitipennis 0.005.

Mosquitoes were collected with light traps baited with dry ice at 16 locations in Senegal during the rainy season of 1988. Of 62,055 mosquitoes identified, 1,384 (2.2%), representing 25 species in 4 genera, were bloodfed. Mosquito bloodmeals were screened by enzyme-linked immunosorbent assay against antisera to humans, bovines, goats, sheep and chickens. Overall, 88% of the bloodmeals tested were identified. Bloodmeals from 5 species of Culex mosquitoes comprised 82% of the number tested. Culex antennatus (36.6%) and Cx. tritaeniorhyncus (33.5%) were the most abundant. All Culex except those of the Cx. univittatus group fed most often on humans. Aedes species fed almost equally on all mammals tested, while species of Anopheles preferred cattle over humans, goats and sheep.

Deet and permethrin were evaluated as protectants against Plasmodium falciparum-infected, P. berghei-infected and uninfected Anopheles stephensi mosquitoes. Deet 50% effective dose (ED50) values were 3.2 micrograms/cm2 for P. falciparum-infected and 1.9 micrograms/cm2 for uninfected mosquitoes; permethrin values were 0.5 micrograms/cm2 and 0.6 micrograms/cm2, respectively. Deet ED50 values were 2.3 micrograms/cm2 for P. berghei-infected and 1.3 micrograms/cm2 for uninfected mosquitoes; the permethrin values were both 0.5 micrograms/cm2. There were no significant differences in the protective efficacy of deet or permethrin between malaria-infected and uninfected An. stephensi mosquitoes.

N,N-diethyl-3-methylbenzamide (DEET) has recently been reported to kill cercariae of Schistosoma mansoni in vitro. In addition, it blocked cercarial entry into mouse tail skin. We confirmed these results and compared the efficacy of DEET to a second insect repellent, 1-(3-Cyclohexen-1-yl-carbonyl)-2-methylpiperidine (AI3-37220), in preventing S. mansoni infections in mice. Both AI3-37220 and DEET conferred 100% protection against S. mansoni infection via percutaneous exposure to cercariae.

Field tests were conducted to compare the effectiveness of 2 repellent formulations of N,N-diethyl-3-methylbenzamide (deet) in combination with permethrin-impregnated military uniforms against Culex sitiens and Aedes vigilax in Thailand. Repellency was determined during a 2 h crepuscular period using volunteers who had been treated with repellents 6, 8, 10, and 12 h prior to the end of each test period. An extended-duration repellent formulation (EDRF) containing 35% deet repelled significantly more Ae. vigilax than 75% deet in ethanol. Although not statistically significant, the EDRF also resulted in fewer biting attempts by Cx. sitiens. Neither formulation provided complete protection against either species 4-12 h post-application, but both provided greater overall protection against Ae. vigilax. Volunteers who wore treated uniforms without repellents were attacked by significantly fewer mosquitoes than controls.

Deep inflation of the lung stimulates surfactant secretion by unknown mechanisms. The hypothesis that mechanical distension directly stimulates type II cells to secrete surfactant was tested by stretching type II cells cultured on silastic membranes. The intracellular Ca2+ concentration was measured in single cells, before and after stretching. A single stretch of alveolar type II cells caused a transient (less than 60 seconds) increase in cytosolic Ca2+ followed by a sustained (15 to 30 minutes) stimulation of surfactant secretion. Both Ca2+ mobilization and exocytosis exhibited dose-dependence to the magnitude of the stretch-stimulus. Thus, mechanical factors can trigger complex cellular events in nonneuron, nonmuscle cells and may be involved in regulating normal lung functions.