Pathogen reduction of whole blood: utility and feasibility.

OBJECTIVES: To collect information on pathogen reduction applied to whole blood. BACKGROUND: Pathogen reduction (PR) of blood components has been developed over the past two decades, and pathogen-reduced fresh-frozen plasma and platelet concentrates are currently in clinical use. High cost and incomplete coverage of components make PR out of reach for low- and middle-income countries (LMIC). However, should PR become applicable to whole blood (WB), the main product transfused in sub-Saharan Africa, and be compatible with the preparation of clinically suitable components, cost would be minimised, and a range of safety measures in place at high cost in developed areas would become redundant. METHODS: All articles called with "pathogen reduction", "pathogen inactivation" and "whole blood" were retrieved from Medline. References in articles were utilised. RESULTS: One such PR technology (PRT) applied to WB has been developed and has shown efficacious against viruses, bacteria and parasites in vitro; and has been able to inactivate nucleated blood cells whilst retaining the ability to prepare components with acceptable characteristics. The efficacy of this WB PRT has been demonstrated in vivo using the inactivation of Plasmodium falciparum as a model and showing a high degree of correlation between in vitro and in vivo data. Obtaining further evidence of efficacy on other suitable targets is warranted. Shortening of the process, which is currently around 50 min, or increasing the number of units simultaneously processed would be necessary to make PRT WB conducive to LMIC blood services' needs. CONCLUSIONS: Even if not 100% effective against agents that are present in high pathogen load titres, WB PRT could massively impact blood safety in LMIC by providing safer products at an affordable cost.

Efficiency of riboflavin and ultraviolet light treatment against high levels of biofilm-derived Staphylococcus epidermidis in buffy coat platelet concentrates.

BACKGROUND AND OBJECTIVES: Staphylococcus epidermidis forms surface-attached aggregates (biofilms) in platelet concentrates (PCs), which are linked to missed detection during PC screening. This study was aimed at evaluating the efficacy of riboflavin-UV treatment to inactivate S. epidermidis biofilms in buffy coat (BC) PCs. MATERIALS AND METHODS: Biofilm and non-biofilm cells from S. epidermidis ST-10002 and S. epidermidis AZ-66 were individually inoculated into whole blood (WB) units (~106 colony-forming units (CFU)/ml) (N = 4-5). One spiked and three unspiked WB units were processed to produce a BC-PC pool. Riboflavin was added to the pool which was then split into two bags: one for UV treatment and the second was untreated. Bacterial counts were determined before and after treatment. In vitro PC quality was assessed by flow cytometry and dynamic light scattering. RESULTS: Bacterial counts were reduced during BC-PC production from ~106 CFU/ml in WB to 103 -104 CFU/ml in PCs (P < 0·0001). Riboflavin-UV treatment resulted in significantly higher reduction of S. epidermidis AZ-66 than strain ST-10002 (≥3·5 log reduction and 2·6-2·8 log reduction, respectively, P < 0·0001). Remaining bacteria post-treatment were able to proliferate in PCs. No differences in S. epidermidis inactivation were observed in PCs produced from WB inoculated with biofilm or non-biofilm cells (P > 0·05). Platelet activation was enhanced in PCs produced with WB inoculated with biofilms compared to non-biofilm cells (P < 0·05). CONCLUSION: Riboflavin-UV treatment was similarly efficacious in PCs produced from WB inoculated with S. epidermidis biofilm or non-biofilm cells. Levels of biofilm-derived S. epidermidis ≥103 CFU/ml were not completely inactivated; however, further testing is necessary with lower (real-life) bacterial levels.

Riboflavin and ultraviolet light: impact on dengue virus infectivity.

BACKGROUND: Dengue viruses (DENV 1-4) are emerging across the world, and these viruses pose a risk to transfusion safety. Pathogen inactivation may be an alternative approach for managing the risk of DENV transfusion transmission. This study aimed to investigate the ability of riboflavin and UV light to inactivate DENV 1-4 in platelet concentrates. MATERIALS AND METHODS: DENV 1-4 were spiked into buffy coat-derived platelet concentrates in additive solution (SSP+) before being treated with riboflavin and UV light. Infectious virus was quantified pre- and posttreatment, and the reduction in viral infectivity was calculated. RESULTS: All four DENV serotypes were modestly reduced after treatment. The greatest amount of reduction in infectivity was observed for DENV-4 (1·81 log reduction) followed by DENV-3 (1·71 log reduction), DENV-2 (1·45 log reduction) and then DENV-1 (1·28 log reduction). CONCLUSION: Our study demonstrates that DENV 1-4 titres are modestly reduced following treatment with riboflavin and UV light. With the increasing number of transfusion-transmitted cases of DENV around the globe, and the increasing incidence and geographical distribution of DENV, additional approaches for maintaining blood safety may be required in the future.

Development of a mitochondrial DNA real-time polymerase chain reaction assay for quality control of pathogen reduction with riboflavin and ultraviolet light.

BACKGROUND AND OBJECTIVES: Transfusion is associated with a risk of infection and alloimmunization. Pathogen reduction using riboflavin and UV light (Mirasol treatment) inactivates pathogens and leucocytes. With increasing adoption of the technology in clinical use, regulatory agencies have recommended the introduction of quality control measures to monitor pathogen reduction efficacy. We sought to develop a real-time PCR-based assay to document the impact of pathogen reduction on the mitochondrial genome in blood components. MATERIALS AND METHODS: DNA was extracted from platelet and plasma components before and after treatment with riboflavin and UV light. Inhibition of PCR amplification of mitochondrial DNA (mtDNA) in short- and long-amplicon target regions, ranging from under 200 base pairs (bp) to over 1800 bp, was measured in treated relative to untreated components. RESULTS: Pathogen reduction of platelets using riboflavin and UV light resulted in inhibition of PCR amplification of long-amplicon mtDNA targets, demonstrating approximately 1 log reduction of amplification relative to untreated products. Amplification of short-amplicon mtDNA targets was not affected by treatment. Evaluation of 110 blinded platelet samples from the PREPAReS clinical trial resulted in prediction of treatment status with 100% accuracy. Pathogen reduction of plasma components resulted in similar levels of PCR inhibition, while testing of 30 blinded plasma samples resulted in prediction of treatment status with 93% accuracy. CONCLUSION: A differential sized amplicon real-time PCR assay of mitochondrial DNA effectively documents nucleic acid damage induced by Mirasol treatment of platelets. The use of the assay for plasma product pathogen reduction requires further investigation.

Establishment of the first international repository for transfusion-relevant bacteria reference strains: ISBT working party transfusion-transmitted infectious diseases (WP-TTID), subgroup on bacteria.

BACKGROUND: Bacterial contamination of platelet concentrates (PCs) still remains a significant problem in transfusion with potential important clinical consequences, including death. The International Society of Blood Transfusion Working Party on Transfusion-Transmitted Infectious Diseases, Subgroup on Bacteria, organised an international study on Transfusion-Relevant Bacteria References to be used as a tool for development, validation and comparison of both bacterial screening and pathogen reduction methods. MATERIAL AND METHODS: Four Bacteria References (Staphylococcus epidermidis PEI-B-06, Streptococcus pyogenes PEI-B-20, Klebsiella pneumoniae PEI-B-08 and Escherichia coli PEI-B-19) were selected regarding their ability to proliferate to high counts in PCs and distributed anonymised to 14 laboratories in 10 countries for identification, enumeration and bacterial proliferation in PCs after low spiking (0·3 and 0·03 CFU/ml), to simulate contamination occurring during blood donation. RESULTS: Bacteria References were correctly identified in 98% of all 52 identifications. S. pyogenes and E. coli grew in PCs in 11 out of 12 laboratories, and K. pneumoniae and S. epidermidis replicated in all participating laboratories. The results of bacterial counts were very consistent between laboratories: the 95% confidence intervals were for S. epidermidis: 1·19-1·32 × 10(7) CFU/ml, S. pyogenes: 0·58-0·69 × 10(7) CFU/ml, K. pneumoniae: 18·71-20·26 × 10(7) CFU/ml and E. coli: 1·78-2·10 × 10(7) CFU/ml. CONCLUSION: The study was undertaken as a proof of principle with the aim to demonstrate (i) the quality, stability and suitability of the bacterial strains for low-titre spiking of blood components, (ii) the property of donor-independent proliferation in PCs, and (iii) their suitability for worldwide shipping of deep frozen, blinded pathogenic bacteria. These aims were successfully fulfilled. The WHO Expert Committee Biological Standardisation has approved the adoption of these four bacteria strains as the first Repository for Transfusion-Relevant Bacteria Reference Strains and, additionally, endorsed as a project the addition of six further bacteria strain preparations suitable for control of platelet contamination as the next step of enlargement of the repository.

The effect of pathogen reduction technology (Mirasol) on platelet quality when treated in additive solution with low plasma carryover.

BACKGROUND AND OBJECTIVES: Pathogen reduction technologies (PRT) for platelets are now compatible with both plasma and platelet additive solutions (PAS). The aim of this study was to examine the effect of PRT on the platelet storage lesion, in the presence of PAS with low plasma carryover. MATERIALS AND METHODS: PRT-treated (Mirasol) and untreated buffy coat-derived platelet concentrates prepared in 28% plasma/PAS-IIIM were evaluated using in vitro cell quality parameters on days 1, 2, 5, and 7 post-collection. RESULTS: At day 5, there were no significant differences between control and PRT treated platelets for swirl, viability, pO(2) , pCO(2) , mean platelet volume and adenosine diphosphate-induced aggregation. PRT treatment did not affect the functional integrity of the mitochondria. However, PRT resulted in a decrease in pH and enhancement of platelet glycolysis and activation, evidenced by increased glucose consumption and lactate production rates, increased expression of CD62P, CD63, annexin V staining and increased secretion of cytokines (P < 0.05). Hypotonic shock response and aggregation in response to collagen were also significantly reduced in PRT treated platelets (P < 0.05). CONCLUSION: Despite the observed differences in platelet metabolism and activation observed following PRT treatment in PAS and low plasma carryover, the results suggest that treatment and storage of platelets in PAS is no more detrimental to platelets than treatment and storage in plasma.

Characterization of plasma protein activity in riboflavin and UV light-treated fresh frozen plasma during 2 years of storage at -30 degrees C.

BACKGROUND: The Mirasol Pathogen Reduction Technology System (PRT) for Plasma (CaridianBCT) is based on a riboflavin and UV light treatment process resulting in pathogen inactivation due to irreversible, photochemically induced damage of nucleic acids. This study evaluated the in vitro protein quality of plasma products treated with riboflavin and UV light following treatment and subsequent storage for up to 104 weeks at -30 degrees C. MATERIALS AND METHODS: Apheresis and whole blood-derived plasma products were combined with riboflavin solution and exposed to ultraviolet light. Treated plasma was then flash frozen, within 8 h of collection, stored at -30 degrees C for up to 104 weeks and analysed at different stages of storage using standard coagulation assays. Results were compared with paired, untreated units stored for the same intervals. RESULTS: The average percent protein retention for all time-points in PRT-treated plasma samples after 36, 69, 87 and 104 weeks of storage at -30 degrees C in comparison with controls held under similar conditions were: Total Protein, 101%, Factor VIII, 79%, Fibrinogen, 78%, Factor II, 87%, Factor XII, 86%, Factor X, 84% and Factor IX, 81%. Anticoagulant and inhibitor proteins showed between 90% and 100% retention after 1 year (52 weeks) and 69 weeks of storage. No clinically relevant complement activation was observed in treated and stored samples. CONCLUSION: Riboflavin and UV light-treated plasma demonstrates reductions in several plasma coagulation factors following treatment. This reduction in activity levels is noted immediately after treatment and remains relatively constant during 2 years of storage at -30 degrees C.

Pathogen reduction technology (Mirasol) treated single-donor platelets resuspended in a mixture of autologous plasma and PAS.

BACKGROUND AND OBJECTIVES: Mirasol pathogen reduction technology (PRT) for platelet concentrates uses riboflavin and ultraviolet light. Previously, we described increased metabolism and activation for PRT platelets stored in 100% plasma. To improve platelet quality, we resuspended platelets in a mixture of plasma and platelet additive solution (PAS). MATERIALS AND METHODS: Single-donor platelets were resuspended in plasma and split into an untreated control and a PRT-treated single product. One hundred and fifty millilitre PAS (SSP+) was added to both. Over 7 days, we assayed pH, glucose consumption-, lactate production rate and CD62p with and without TRAP. RESULTS: On day 5, PRT units showed a significantly lower pH (7.087 +/- 0.105 vs. 7.288 +/- 0.200) accompanied by a higher lactate production (0.104 +/- 0014 vs. 0.063 +/- 0.017 mmol/10(12)/h) and glucose consumption rate (0.039 +/- 0005 vs. 0.028 +/- 0.009 mmol/10(12) platelets/h). CD62p expression was higher in treated units (44.5 +/- 13.0 vs. 16.5 +/- 7.6%). CONCLUSION: In comparison to PRT platelets resuspended in 100% plasma, a mixture of plasma and PAS improves pH and platelet metabolism but not platelet activation. Prolonged shelf-life for up to 7 days may be possible

Fermi surface changes across the Néel phase boundary of NdB6.

We report de Haas-van Alphen measurements in both the antiferromagetic and paramagnetic regimes of NdB6, which are shown to be separated by a second order upper critical field for antiferromagnetic ordering of H_{c} approximately 30 T when the magnetic field is parallel to [001]. The Fermi surface changes across the transition provide an ideal example of a system in which the effect of a one-dimensional magnetic periodic potential on doubling the unit cell (as originally predicted by Slater [Phys. Rev. 82, 538 (1951)]) can be tuned by varying only the magnetic field. The Fermi surface within the paramagnetic phase resembles that observed in other hexaborides such as LaB6 but with additional exchange splitting effects and weak correlations.

Pathogen inactivation of Leishmania donovani infantum in plasma and platelet concentrates using riboflavin and ultraviolet light.

BACKGROUND AND OBJECTIVES: Leishmania is transmitted by the bite of the phlebotomine sandfly or by transfusion of infected blood products. Leishmaniasis currently poses a significant problem in several parts of the world, and is an emerging problem in others. The Mirasol PRT technology is based on the use of riboflavin and ultraviolet light to generate chemical reactions in the nucleic acids of pathogens, which prevents replication and leads to inactivation. The intent of this study was to examine the ability of the Mirasol PRT System to kill the Leishmania parasite in human plasma and platelet concentrates. MATERIALS AND METHODS: In visceral Leishmaniasis, amastigotes are present in the blood and in the reticuloendothelial system within monocytes. For each unit of plasma or platelets treated, isolated mononuclear cells obtained from 100 ml of normal donor whole blood were incubated with 1.0 x 10(8) Leishmania donovani infantum promastigotes to produce amastigote-laden macrophages. The infected macrophages were added to 250 ml of human plasma or to 250 ml of platelet concentrates. Infected units were cultured pretreatment in 10-fold serial dilutions to determine the limits of detection. Thirty millilitres of 500 microM riboflavin was added to each unit, which was then illuminated with 5.9 J/cm2 of ultraviolet light (6.24 J/ml). After treatment and after 2 months of frozen storage, plasma units were cultured in 10-fold serial dilutions. Platelets were cultured on the day of treatment and on day 5 of storage post-illumination. RESULTS: A 5 log reduction of Leishmania was demonstrated in five of six units of plasma, and a 7 log reduction of Leishmania was demonstrated in one plasma unit. A 5 log reduction of Leishmania was demonstrated in five of six units of platelets, and a 6 log reduction of Leishmania was demonstrated in one unit. CONCLUSIONS: There is no donor screen for Leishmania and other pathogens constantly emerging in our blood supply. The Mirasol PRT System for Platelets and Plasma is an effective means of killing Leishmania and other emerging pathogens in these blood products.

Effects of a new pathogen-reduction technology (Mirasol PRT) on functional aspects of platelet concentrates.

BACKGROUND: Several strategies are being developed to reduce the risk of pathogen transmission associated with platelet (PLT) transfusion. STUDY DESIGN AND METHODS: The impact of a new technology for pathogen reduction based on riboflavin plus illumination (Mirasol PRT, Navigant Biotechnologies, Inc.) at 6.2 and 12.3 J per mL on functional and biochemical characteristics of PLTs was evaluated. PLT concentrates (PCs) obtained by apheresis were treated with Mirasol PRT and stored at 22 degrees C. Modifications in major PLT glycoproteins (GPIbalpha, GPIV, and GPIIb-IIIa), adhesive ligands (von Willebrand factor [VWF], fibrinogen [Fg], and fibronectin), activation antigens (P-selectin and LIMP), and apoptotic markers (annexin V binding and factor [F]Va) were analyzed by flow cytometry. Adhesive and cohesive PLT functions were evaluated with well-established perfusion models. Studies were performed on the preparation day (Day 0) and during PCs storage (Days 3 and 5). RESULTS: Levels of glycoproteins remained stable during storage in PCs treated with 6.2 J per mL pathogen reduction technology (PRT) and similar to those observed in nontreated PCs. When 12.3 J per mL PRT was applied, however, levels of GPIbalpha moderately decreased on Days 3 and 5. VWF, Fg, and FVa were not modified in their expression levels, either by treatment or by storage period. Fibronectin appeared more elevated in all PRT samples. A progressive increase in P-selectin and LIMP expression and in annexin V binding was observed during storage of PRT-treated PCs. Functional studies indicated that 6.2 J per mL Mirasol PRT-treated PLTs preserved adhesive and cohesive functions to levels compatible with those observed in the respective control PCs. CONCLUSION: PLT function was well preserved in PCs treated with 6.2 J per mL Mirasol PRT and stored for 5 days.

4f-electron localization in CexLa 1-xM In5 with M=Co, Rh, or Ir.

de Haas-van Alphen measurements on Ce(x)La(1-x)MIn(5) yield contrasting types of behavior that depend on whether M=Co and Ir or M=Rh. A stronger x-dependent scattering in the case of M=Co and Ir is suggestive of a stronger relative coupling, J/W, of the conduction electrons to the 4f electrons, which would then account for the development of a heavy composite Fermi-liquid state as x-->1. The failure of a composite Fermi-liquid state to form for any x in the case of M= Rh is shown to be inconsistent with theoretical models that propose antiferromagnetism to result from spin-density-wave formation.

Pathogen reduction of buffy coat platelet concentrates using riboflavin and light: comparisons with pathogen-reduction technology-treated apheresis platelet products.

BACKGROUND AND OBJECTIVES: A pathogen-reduction technology (PRT) system using riboflavin and light has been developed for the treatment of platelet concentrates (PC) obtained by either buffy coat preparation (BCPC) or apheresis procedures (APPC). The aim of this study was to evaluate the effects of the treatment process on in vitro cell quality and on riboflavin conversion in PC. MATERIALS AND METHODS: BCPC were prepared with the Compomat G4 from whole blood which had been stored overnight after collection. APPC were obtained using the TRIMA apheresis procedure. Both PC products had been stored for 18-24 h prior to PRT treatment. BCPC and APPC were treated with PRT on day 2 and day 1 of shelf-life, respectively. The treated PCs were then maintained for an additional 5 days after the PRT treatment. A panel of cell quality assays and high-performance liquid chromatography (HPLC) analysis were performed. RESULTS: Cell counts and plasma lactate dehydrogenase (LDH) levels during storage indicated that PRT did not induce significant cell lysis. Acceleration of a decrease in glucose and an increase in lactate was observed for treated PCs, but no significant differences were observed between treated BCPC and APPC. The pH of treated samples remained above 7.0, although was lower than that of the control. Platelet morphology of BCPC and APPC was well preserved. P-selectin expression indicated significant platelet activation when compared with control PC (BCPC on day 6: 39% vs. 12%; APPC on day 5: 35% vs. 18%). Both P-selectin expression and microparticle formation were not significantly different between treated BCPC and APPC during storage. The JC-1 assay also displayed no loss of mitochondria integrity during the storage of treated products. Approximately 20% of riboflavin converted into photoproducts, including lumichrome. CONCLUSIONS: PRT treatment had an effect on the development of the normal platelet storage lesion at a level which seems tolerable for clinical usage.

Electron-spin domains: magnetic enhancement of superconductivity.

An inhomogeneous superconducting state, not yet conclusively identified, was predicted by Fulde and Ferrell and Larkin and Ovchinnikov (FFLO) to arise in superconductors with strong Pauli limiting, a consequence of the electrons' Zeeman (spin) energy in a magnetic field. Radovan et al. propose that the observed cascades of steps in magnetization of the heavy fermion superconductor CeCoIn5, within the recently discovered second low-temperature state, are due to transitions between Landau-level (LL) states with different m-quanta vortices, expected under certain conditions when the magnetic field is swept within the FFLO state. The authors then conclude that the observed steps in magnetization constitute a proof that the low-temperature state in CeCoIn5 is indeed an FFLO state. We argue that this interpretation of the observed steps in magnetization cannot be supported on either quantitative or qualitative grounds.

Magnetization in the ultraquantum limit.

The magnetization below and far above the quantum limit for small Fermi surface orbits has been measured in the metallic compound LaRhIn(5). The magnetization due to a pocket of Fermi surface that comprises less than 1 part in 10(4) of the total Brillouin zone volume, and for which the quantum limit is approximately 7 T, leads to the appearance of an overall sample magnetic moment at fields between 7 and 32 T. This moment arises from diamagnetic currents produced by electrons in the ultraquantum limit. A model calculation of the origin and magnitude of the effect is in excellent agreement with the measured field dependence of the induced magnetization.

The use of riboflavin for the inactivation of pathogens in blood products.

BACKGROUND AND OBJECTIVES: In recent years, the desire to develop methods to inactivate pathogens in blood components has continued to grow. Several of these proposed approaches have been introduced or are currently in clinical studies. The use of chemical inactivating agents must be considered in terms of the current safety of the blood supply and the potential risks that the introduction of new chemical entities into blood components may carry. The impact which these treatment procedures have on the in vitro and in vivo performance of these products must also be considered relative to the potential benefit of the pathogen inactivation potential they offer. This paper will discuss one possible approach for inactivating pathogens in blood using vitamin B2, Riboflavin, and light. MATERIALS AND METHODS: We have used Riboflavin for treating plasma and platelets and evaluated protein quality and platelet function in vitro. Initial toxicology tests to assess the impact of infusion of photoproducts generated in these processes have also been conducted in rodents. Cytotoxicity evaluations have been used to assess the possible impact of photoproduct toxicity in vivo. Virus and bacteria spiking studies using a variety of human and animal model pathogens have been conducted in order to asses the efficacy of this process. RESULTS: Initial toxicology assessment of the photoproducts of Riboflavin generated under the proposed treatment conditions have been favorable. Virus and bacteria clearance studies have demonstrated efficacy of the procedure against a wide range of human and animal pathogens, including intracellular HIV-1. Studies with platelet and plasma function indicated reductions in vitro comparable to other proposed treatment approaches. CONCLUSION: The use of Riboflavin in a photochemical decontamination process for blood components shows promise.

The Radio Afterglow and the Host Galaxy of the X-Ray-rich GRB 981226.

We report the discovery of a radio transient VLA 232937.2-235553, coincident with the proposed X-ray afterglow for the gamma-ray burst GRB 981226. This gamma-ray burst (GRB) has the highest ratio of X-ray to gamma-ray fluence of all the GRBs detected by BeppoSAX so far, and yet no corresponding optical transient was detected. The radio light curve of VLA 232937.2-235553 is qualitatively similar to that of several other radio afterglows. At the subarcsecond position provided by the radio detection, optical imaging reveals an extended R=24.9 mag object, which we identify as the host galaxy of GRB 981226. Afterglow models that invoke a jetlike geometry for the outflow or that require an ambient medium with a radial density dependence, such as that produced by a wind from a massive star, are both consistent with the radio data. Furthermore, we show that the observed properties of the radio afterglow can explain the absence of an optical transient without the need for large extinction local to the GRB.

AIDS and behaviour change in Zambia.

PIP: AIDS-related deaths and funerals have become routine, everyday events in Zambia, with many families having lost half or more of their members. In this context, many organizations in the country are fighting HIV/AIDS, working to encourage people to adopt HIV/AIDS and STD risk reduction behaviors. Six Zambian AIDS organizations convened for a 2.5-day workshop in Lusaka in September to exchange ideas and discuss their work with young people. Participants discussed health education with youths, community home-based care, and the peer education and life-skills training approach pioneered by the Copperbelt Health Education Project (CHEP). Although adolescents are highly vulnerable, two organizations have found them open to sympathetic health education and willing to become peer educators. However, once in the field, peer educators must remain integrated within the community and their target audiences. Youth-friendly, confidential reproductive health services integrated into community clinics are urgently needed. Nursing staff must avoid being aggressive, insensitive, and judgmental. CHEP will make life skills a priority over the next 2 years, and plans to train at least 150 people, including all of its own staff. It was also noted at the workshop that young people are not passive recipients of health messages, but active service providers and shapers of policy.^ieng

High-temperature weak ferromagnetism in a low-density free-electron gas.

The magnetic properties of the ground state of a low-density free-electron gas in three dimensions have been the subject of theoretical speculation and controversy for seven decades. Not only is this a difficult theoretical problem to solve, it is also a problem which has not hitherto been directly addressed experimentally. Here we report measurements on electron-doped calcium hexaboride (CaB6) which, we argue, show that-at a density of 7× 1019 electrons cm-3-the ground state is ferromagnetically polarized with a saturation moment of 0.07 µB per electron. Surprisingly, the magnetic ordering temperature of this itinerant ferromagnet is 600 K, of the order of the Fermi temperature of the electron gas.

Photochemical and photophysical studies of 3-amino-6-iodoacridine and the inactivation of lambda phage.

The photochemistry and photophysics of 3-amino-6-iodoacridine (Acr-I) was studied. Photolysis (350 nm) of Acr-I (free base) generates products consistent with a free radical intermediate in methanol, benzene and carbon tetrachloride. The Acr-I hydrochloride is shown to bind to calf thymus DNA and to the self-complementary dinucleotide cytidylyl-(3'-5')-guanosine (CpG) miniduplex in a manner similar to that of proflavine (Acr-NH2), a known DNA intercalator. The Acr-I is shown to more efficiently nick supercoiled plasmid DNA pBR322 upon 350 nm or 420 nm photolysis than Acr-NH2. The efficiency of Acr-I-sensitized DNA nicking is not oxygen dependent. Photolysis of the Acr-I/(CpG)2 complex leads to cleavage of the dinucleotide and to cytidine base release by selective damage to a specific ribose moiety. Dinucleotide cleavage occurs equally well in the presence or absence of oxygen, thereby eliminating a singlet oxygen- or peroxyl radical-mediated process. Photolysis of Acr-I in the presence of a mononucleotide (GMP) or a non-self-complementary dinucleotide (uridylyl-[3'-5']-cytidine-UpC) does not lead to fragmentation and base release. Similarly, photolysis of the Acr-NH2/(CpG)2 complex does not lead to fragmentation and base release. The data indicate that photolysis of an iodinated intercalator bound to CpG or plasmid DNA generates an intercalated aryl radical and that the reactive intermediate initiates a sequence of reactions that efficiently nick nucleic acids. The inactivation of lambda phage sensitized by Acr-I with UV (350 nm) light is oxygen independent but with visible (420 nm) light is strongly oxygen dependent. The Acr-I fluoresces more intensely when excited at 446 than at 376 nm. Thus, UV photolysis may lead to C-I bond homolysis and free radical formation, a process that is not energetically feasible with visible light. The results demonstrate the difficulty of extrapolating model studies involving simple molecules and DNA to understanding the mechanism of viral inactivation with a particular sensitizer.