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Variation in vectorial capacity for human malaria among Anopheles mosquito species is determined by many factors, including behavior, immunity, and life history. To investigate the genomic basis of vectorial capacity and explore new avenues for vector control, we sequenced the genomes of 16 anopheline mosquito species from diverse locations spanning ~100 million years of evolution. Comparative analyses show faster rates of gene gain and loss, elevated gene shuffling on the X chromosome, and more intron losses, relative to Drosophila. Some determinants of vectorial capacity, such as chemosensory genes, do not show elevated turnover but instead diversify through protein-sequence changes. This dynamism of anopheline genes and genomes may contribute to their flexible capacity to take advantage of new ecological niches, including adapting to humans as primary hosts.

Introduction Low melting point metals are often encapsulated in a hermetic container, irradiated and the container transferred to hot-cell for material removal and processing. An important process of this kind is the production of 82Sr from rubidium (melting point: 39.5 °C.) This new concept departures completely form the encapsulated targets approach and allows an almost continues production by the irradiation of the bulk metal. As well, eliminated is the target transfer. By placing the target material dissolution chamber right in the target station, only the dissolution product is pumped to the hotcell for further processing. Material and Methods Some of the disadvantages of the encapsulated target are: 1. Complicated transfer system that is ex-pensive to install, slow and prone to failures. 2. Complex and expensive encapsulation procedure. 3. Loss of production time during the lengthy target changing. 4. Capsule geometry is constrained by the encapsulating process and transfer demands compromising heat transfer and beam power. To avoid the difficulties of liquid metal handling, metal salts are often used instead (rubidium chloride is one example). This creates other problems and limits the beam currents and production yields. In the system described, the liquid metal is transferred (by gravity) from a bulk container to an irradiation chamber. The chamber, made out of nickel-plated silver, holds the correct quantity of rubidium for one irradiation run. Because of the geometry of the chamber and the efficient cooling, up to 40KW of beam power can be delivered to the target. The chamber is equipped with thermocouples and a liquid-metal level detector and is entirely of welded/brazed construction. The alloy foil that forms the beam window is electron-beam welded to the chamber front ring. At the end of irradiation the irradiated liquid metal is gravity fed into a reaction chamber situ-ated below the irradiation chamber, and a new load of fresh rubidium released into the irradia-tion chamber. The liquid-metal transfer and the irradiation components are shown on FIG. 1, and the sectional view on FIG. 2. Appropriate chemicals (n-butanol in the case of rubidium) are delivered to the reaction chamber and the irradiated metal dissolved. The liquid dissolution product is transferred back to the hotcell. Since all steps of the reaction involve liquids, only small diameter tubes connect the target station with the hotcell. The transfer is fast and simple. The bulk liquid-metal storage container can be constructed to hold enough material for 10 or more runs. When empty, it is replaced with a pre-loaded one. The container is connected to the target system with one coupling and the exchange takes a short time. A robotic bottle exchange can be implemented if desired. The station is equipped with its own vacuum system, beam diagnostic (consisting of a four-sector mask) and a collimation. The target chamber and each of the beam intercepting components are electrically insulated to allow beam current monitoring. Constructed entirely out of metal and ceramic the target core assembly does not suffer from radiation damage. The use of aluminum, silver and alumina reduce component activation. Results and Conclusion A large part of the station design is based on the well proven construction of high current solid target system and is using the same, or similar components. Test was performed to optimize the liquid-metal transfer and the chamber filling with the correct volume, while leaving some room for expansion. A process for niobium coating of sliver is investi-gated. Niobium is known to provide good corro-sion resistance against liquid metals. Thermal modelling of the target and flow analysis of the cooling geometry is under way.

Thermal separation is defined as a mass transfer process driven by molecular forces. The process involves the heat transfer between two phases with different composition. In general, thermal separation occurs when heat is generated in the system additionally to the already existing phases. In a second phase the mass is transferred in the system (adsorption) and at the end of this step the separation is completed. The thermal separation can be achieved in temperature or concentration gradient function of system configuration [1]. Thermo-chromatography is a process in which the separation occurs in gase-ous phase. By passing a heated gas through a column a thermal gradient is created with a continuously decreasing temperature along the column. The separation occurs based on the different volatilization temperatures, the less volatile species will condense on the column walls at the higher temperatures and the highly volatile compounds will condense at lower temperatures. Parameters like temperature, carrier flow rate, column geometry and length have impact on the absorption of the compound on the column material affecting the separation efficiency. The thermal separation has been used for separation of Molybdenum (Mo) and Technetium (Tc) by either sublimation in the case of 94mTc {2,3,4] or dry distillation in the case of 99mTc from neutron irradiated MoO3 [5]. The thermal separation process has been used in the development of a new type of Mo/Tc generators starting from the MoO3 as target material for production of 99mTc in linear accelerators [6]. Dry distillation has become a standard procedure for separation of radioiodine from tellurium targets [7]. The present paper describes the thermal separation of a three component system (Cu/Mo/Tc) used as a target in the production of 99mTc through the 100Mo(p,2n) reaction. Material and Methods The separation method involves the use of oxygen as a carrier gas and oxidation agent. The method is based on the different volatilization temperatures of Tc formed oxides and the MoO3 formed in the system during the oxidation. In the presence of oxygen the existing Tc is oxidized to its anhydride as Tc2O7 (b.p. 319 ⁰C; m.p. 110.9 ⁰C) following the reaction: 4Tc + 7O2 →2Tc2O7 The T2O7 has a saturated vapor pressure of 310 ⁰C whilst Mo is completely oxidized to MoO3 having a sublimation temperature at 750 ⁰C. The initial experimental setup comprised a quartz tube (6 mm internal diameter, 40 cm long) which is introduced into a horizontal tube furnace (model 55035A, Lindberg). The left end of the quartz tube is connected to a pure oxygen supply which flows through the separation tube at a rate of 10 mL/min. The other end of the tube is opened to the atmosphere and protected with quartz wool. The quartz tube is heated over a length of 23 cm at a temperature of 850 ⁰C. The heated carrier gas is flowing on the tube length and the temperature gradient is created along the tube from 850 ⁰C to room temperature. During the process, the oxygen carries out the Tc oxides to a lower temperature and Tc2O7 is deposited in the cooler region of the tube in a similar manner as described by Tachimory [5]. The temperature gradient is calibrated by meas-uring the temperature inside the tube at each centimeter along its length (FIG. 1). The radioactivity counting is performed by scan-ning the tube along its length every 2 centimeters by using a detection system shown in figure 2. The system comprises a GM tube coupled to a computer controlled linear actuator (Velmex Unislide). The tube is placed at a distance of approximately 25 mm from the collimator of GM. Preliminary testing using Mo powder Prior to testing the three component separation, a reference test was performed by using 120 mg of natural Mo powder (Alpha Aesar, 99.9 %) soaked with 50 MBq NaTcO4 (Cardinal Health, radiochemical purity >95 %). After evaporation the dried powder was introduced into a quartz tube (6 mm ID, 40 mm long) and heated up to 850 ⁰C in the presence of oxygen flowing at a rate of 10 mL/min. Three component separation The targets prepared for the production of 99mTc by a cyclotron were comprised of copper (Cu) (C101, oxygen free) support having a Mo layer deposited on the surface in an elliptical form as described in literature [8,9]. About 60 to 250 mg of Mo (99.9%, Alpha Aesar) was deposited on the target surface. 70 MBq of Tc (Cardinal Health) as NaTcO4 (> 99 % radiochemical purity) was deposited on the Mo insert to mimic the conditions created during proton irradiation. The Tc spike was evaporated to dryness and the Cu/Mo/Tc target was then introduced into the experimental setup. The process was allowed to continue for 20 min. The experiment was carried out by inserting the target plates in a quartz tube (CanSci, Canada) of similar design to those described by Fonslet for the separation of radio-iodine from TeO2 targets [7]. The quartz tube can be seen in FIG. 2 and illustrated with dimensions indicated in FIG. 3. Separation of in-situ cyclotron produced Tc by irradiation of Mo targets with a proton beam. A third set of experiments have been performed for in-situ generated Tc by irradiation of circular targets containing approximately 60 mg Mo deposited on a copper support. The targets were irradiated for 30 min with a proton beam with the energy of 15 MeV and a current of 50 µA. The separation was performed using similar experimental conditions as previously described. The quartz tube was scanned in length by using a RadioTLC scanning system calibrated for 99mTc and 99Mo isotopes. After the thermal separation was completed 99mTc was recovered as NaTcO4 by selectively washing the quartz tube with 1 M NaOH (Fisher) solution. The presence of Mo in the NaTcO4 solution was verified by a colorimetric strip test (EM-Quant Mo test kit, Millipore). The presence of copper was qualitatively analyzed by adding a few drops of concentrated NH4OH (Fisher) solution and checking the formation of Schweitzer reagent. Results Thermal separation of Tc-Mo powder After 20 min the deposition of MoO3 was ob-served as yellow crystals in the region of tem-perature of 770 ⁰C, which is in accordance with the results reported in the literature [5]. The activity of 99mTc was detected at about 5 cm from the exit of the tube furnace in a temperature range starting with 310 ⁰C and ending at 46 ⁰C (FIG. 4).

Introduction Alternative methods for producing the medical imaging isotope 99mTc are actively being developed around the world in anticipation of the imminent shutdown of the National Research Universal (NRU) reactor in Chalk River, Ontario, Canada and the high flux reactor (HFR) in Petten, Holland that together currently produce up to 80 % of the world’s supply through fission. The most promising alternative methods involve accelerators that focus Bremsstrahlung radiation or protons on metallic targets comprised of 100Mo and a supporting material used to conduct heat away during irradiation. As an example, the reaction 100Mo(p,2n)99mTc provides a direct route that can be incorporated into routine production in regional nuclear medicine centers that possess medical cyclotrons for production of other isotopes, such as those used for Positron Emission Tomography (PET). The targets used to produce 99mTc are subject to a number of operational constraints. They must withstand the temperatures generated by the irradiation and be fashioned to accommodate temperature gradients from in situ cooling. The targets must be resilient, which means they cannot disintegrate during irradiation or post processing, because of the radioactive nature of the products. Yet, the targets must be easily post-processed to separate the 99mTc. In addition, the method used to manufacture the targets must not be wasteful of the 100Mo, because of its cost (~$2/mg). Any manufacturing process should be able to function remotely in a shielded space to accommodate the possibility of radioactive recycled target feedstock. There are a number of methods that have been proposed for large-scale target manufacturing including electrophoretic deposition, pressing and sinter-ing, electroplating and carburization [1]. How to develop these methods for routine production is an active business [2,3]. From the industrial perspective, plasma spraying showed promising results initially [4], but the process became very expensive requiring customized equipment in order to reduce losses because of overspray,which also required a large inventory of expen-sive feedstock. In this paper we report the ex-perimental validation of an industrial process for production of targets comprising a Mo layer and a copper support. Materials and methods Target Design Targets have been manufactured for irradiation at 15 MeV. Two targets are shown in FIG. 1: one as-manufactured and another after irradiation; no visible changes were observed following irradiation. The supporting circular copper (C101) disks have diameters of 24 mm and thickness of 1.6 mm. The molybdenum in the center of the target is fully dense with thickness 230 μm determined from SEM cross-sections.Targets have also been manufactured for irradi-ation in a general-purpose target holder designed to be attached to all makes of cyclotrons found in regional nuclear medicine centers. The elliptical targets were designed for high-volume production of 99mTc with 15 MeV protons at currents of 400 µA with 15% collimation [4]. The elliptical shape reduces the heat flux associated with high current sources. The cooling channels on the back of the target are designed to with-stand the high temperature generated during Irradiation. A thermal simulation of expected temperatures during irradiation is shown in FIG. 3. The center of the target is expected to reach 260 oC during irradiation. The elliptical targets were formed from a 27 mm C101 copper plate with width 22 mm and length 55 mm. The molybdenum in the center of the target is fully dense with thickness 60 m de-termined from SEM cross-sections. FIG. 4 shows the molybdenum deposition in the center of the target in a form of an ellipse (38×10 mm). Results and Conclusions Circular targets have been produced and suc-cessfully irradiated for up to 5 h with a proton beam with energy 15 MeV and current 50 µA. (FIG. 1). The targets were resilient. Before irradi-ation the targets were subjected to mechanical shock tests and thermal gradients with no ob-servable effect. After irradiation there was no indication of any degradation. The manufacturing process produced 20 consistently reproducible targets within an hour with a molybdenum loss of less than 2 %. After irradiation the targets were chemically processed and the products characterized by Ge-HP gamma spectrometry. Only Tc isotopes were found. No other contami-nants were identified after processing. The de-tails of the separation and purification are de-scribed elsewhere [5]. Circular targets suitable for low-volume produc-tion of 99mTc have been manufactured and test-ed. The targets have been shown to meet the required operation constraints: the targets are resilient withstanding mechanical shock and irradiation conditions; they are readily produced with minimal losses; and post-processing after irradiation for 5 h has been shown to produce 99mTc. Elliptical targets suitable for high-volume pro-duction of 99mTc with high power cyclotrons have been manufactured (FIG. 4). Like the circular targets, the elliptical targets are readily pro-duced with minimal losses and are able to with-stand mechanical shock and thermal gradients; however, they have yet to be irradiated.

Under conditions of low ionic strength and a pH ranging between about 3.7 and 5.0, solutions of purified coat proteins of cowpea chlorotic mottle virus (CCMV) form spherical multishell structures in the absence of viral RNA. The outer surfaces of the shells in these structures are negatively charged, whereas the inner surfaces are positively charged due to a disordered cationic N-terminal domain of the capsid protein, the arginine-rich RNA-binding motif that protrudes into the interior. We show that the main forces stabilizing these multishells are counterion release combined with a lower charge density in the RNA-binding motif region of the outer shells due to their larger radii of curvature, arguing that these compensate for the outer shells not being able to adopt the smaller, optimal, radius of curvature of the inner shell. This explains why the structures are only stable at low ionic strengths at pHs for which the outer surface is negatively charged and why the larger outer shells are not observed separately in solution. We show how to calculate the free energy of shells of nonoptimal radius of curvature from the elastic properties of the native shell. The spacing between shells is determined mainly by the entropic elasticity of the RNA-binding motifs. Although we focus on CCMV multishells, we also predict the solution conditions under which multishells formed by CCMV coat protein mutants with a lower RNA-binding motif charge are stable, and we examine other viruses as well. We conclude that at a given surface charge density, the boundaries separating regions of stable multishells with different numbers of shells shift to lower ionic strengths upon either increasing the length of the RNA-binding motif, increasing the stiffness of the shells, or decreasing the charge per RNA-binding motif.

We show that when a heat-shock-driven gene that encodes the yeast FLP recombinase is injected into preblastoderm Drosophila embryos, it promotes intermolecular recombination between two coinjected plasmids that bear the specific recombination target sequence, FRT. Minimal, 34-bp FRT sites in the two plasmids are sufficient for their cointegration. The reaction is efficient enough to produce detectable recombinants when one of the plasmids is present in as little as 1000 molecules per embryo. This is comparable to the concentration of unique chromosomal sites, raising the possibility that integration of injected plasmid DNA into FRT-bearing fly chromosomes may also be achievable. Since integrants might be stabilized against the reverse excision reaction if the recombinase could be provided in a sharp pulse, it is encouraging that efficient plasmid cointegration is also achieved when in vitro synthesized FLP RNA rather than DNA is injected into the embryos.