Changes in Escherichia coli to enteric protozoa ratios in rivers: Implications for risk-based assessment of drinking water treatment requirements.

Minimum treatment requirements are set in response to established or anticipated levels of enteric pathogens in the source water of drinking water treatment plants (DWTPs). For surface water, contamination can be determined directly by monitoring reference pathogens or indirectly by measuring fecal indicators such as Escherichia coli (E. coli). In the latter case, a quantitative interpretation of E. coli for estimating reference pathogen concentrations could be used to define treatment requirements. This study presents the statistical analysis of paired E. coli and reference protozoa (Cryptosporidium, Giardia) data collected monthly for two years in source water from 27 DWTPs supplied by rivers in Canada. E. coli/Cryptosporidium and E. coli/Giardia ratios in source water were modeled as the ratio of two correlated lognormal variables. To evaluate the potential of E. coli for defining protozoa treatment requirements, risk-based critical mean protozoa concentrations in source water were determined with a reverse quantitative microbial risk assessment (QMRA) model. Model assumptions were selected to be consistent with the World Health Organization (WHO) Guidelines for drinking-water quality. The sensitivity of mean E. coli concentration trigger levels to identify these critical concentrations in source water was then evaluated. Results showed no proportionalities between the log of mean E. coli concentrations and the log of mean protozoa concentrations. E. coli/protozoa ratios at DWTPs supplied by small rivers in agricultural and forested areas were typically 1.0 to 2.0-log lower than at DWTPs supplied by large rivers in urban areas. The seasonal variations analysis revealed that these differences were related to low mean E. coli concentrations during winter in small rivers. To achieve the WHO target of 10-6 disability-adjusted life year (DALY) per person per year, a minimum reduction of 4.0-log of Cryptosporidium would be required for 20 DWTPs, and a minimum reduction of 4.0-log of Giardia would be needed for all DWTPs. A mean E. coli trigger level of 50 CFU 100 mL-1 would be a sensitive threshold to identify critical mean concentrations for Cryptosporidium but not for Giardia. Treatment requirements higher than 3.0-log would be needed at DWTPs with mean E. coli concentrations as low as 30 CFU 100 mL-1 for Cryptosporidium and 3 CFU 100 mL-1 for Giardia. Therefore, an E. coli trigger level would have limited value for defining health-based treatment requirements for protozoa at DWTPs supplied by small rivers in rural areas.

Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis.

Treating KRAS-mutant lung adenocarcinoma (LUAD) remains a major challenge in cancer treatment given the difficulties associated with directly inhibiting the KRAS oncoprotein. One approach to addressing this challenge is to define mutations that frequently co-occur with those in KRAS, which themselves may lead to therapeutic vulnerabilities in tumors. Approximately 20% of KRAS-mutant LUAD tumors carry loss-of-function mutations in the KEAP1 gene encoding Kelch-like ECH-associated protein 1 (refs. 2, 3, 4), a negative regulator of nuclear factor erythroid 2-like 2 (NFE2L2; hereafter NRF2), which is the master transcriptional regulator of the endogenous antioxidant response. The high frequency of mutations in KEAP1 suggests an important role for the oxidative stress response in lung tumorigenesis. Using a CRISPR-Cas9-based approach in a mouse model of KRAS-driven LUAD, we examined the effects of Keap1 loss in lung cancer progression. We show that loss of Keap1 hyperactivates NRF2 and promotes KRAS-driven LUAD in mice. Through a combination of CRISPR-Cas9-based genetic screening and metabolomic analyses, we show that Keap1- or Nrf2-mutant cancers are dependent on increased glutaminolysis, and this property can be therapeutically exploited through the pharmacological inhibition of glutaminase. Finally, we provide a rationale for stratification of human patients with lung cancer harboring KRAS/KEAP1- or KRAS/NRF2-mutant lung tumors as likely to respond to glutaminase inhibition.

Application of in vivo measurements for the management of cyanobacteria breakthrough into drinking water treatment plants.

The increasing presence of potentially toxic cyanobacterial blooms in drinking water sources and within drinking water treatment plants (DWTPs) has been reported worldwide. The objectives of this study are to validate the application of in vivo probes for the detection and management of cyanobacteria breakthrough inside DWTPs, and to verify the possibility of treatment adjustment based on intensive real-time monitoring. In vivo phycocyanin YSI probes were used to monitor the fate of cyanobacteria in raw water, clarified water, filtered water, and chlorinated water in a full scale DWTP. Simultaneous samples were also taken for microscopic enumeration. The in vivo probe was successfully used to detect the incoming densities of high cyanobacterial cell number into the clarification process and their breakthrough into the filtered water. In vivo probes were used to trace the increase in floating cells over the clarifier, a robust sign of malfunction of the coagulation-sedimentation process. Pre-emptive treatment adjustments, based on in vivo probe monitoring, resulted in successful removal of cyanobacterial cells. The field results on validation of the probes with cyanobacterial bloom samples showed that the probe responses are highly linear and can be used to trigger alerts to take action.

Species-dependence of cyanobacteria removal efficiency by different drinking water treatment processes.

Accumulation and breakthrough of several potentially toxic cyanobacterial species within drinking water treatment plants (DWTP) have been reported recently. The objectives of this project were to test the efficiency of different treatment barriers in cyanobacterial removal. Upon observation of cyanobacterial blooms, intensive sampling was conducted inside a full scale DWTP at raw water, clarification, filtration and oxidation processes. Samples were taken for microscopic speciation/enumeration and microcystins analysis. Total cyanobacteria cell numbers exceeded World Health Organisation and local alert levels in raw water (6,90,000 cells/mL). Extensive accumulation of cyanobacteria species in sludge beds and filters, and interruption of treatment were observed. Aphanizomenon cells were poorly coagulated and they were not trapped efficiently in the sludge. It was also demonstrated that Aphanizomenon cells passed through and were not retained over the filter. However, Microcystis, Anabaena, and Pseudanabaena cells were adequately removed by clarification and filtration processes. The breakthrough of non toxic cyanobacterial cells into DWTPs could also result in severe treatment disruption leading to plant shutdown. Application of intervention threshold values restricted to raw water does not take into consideration the major long term accumulation of potentially toxic cells in the sludge and the risk of toxins release. Thus, a sampling regime inside the plant adapted to cyanobacterial occurrence and intensity is recommended.

Syntheses and characterization of six quaternary uranium chalcogenides A2M4U6Q17 (A = Rb or Cs; M = Pd or Pt; Q = S or Se).

The A(2)M(4)U(6)Q(17) compounds Rb(2)Pd(4)U(6)S(17), Rb(2)Pd(4)U(6)Se(17), Rb(2)Pt(4)U(6)Se(17), Cs(2)Pd(4)U(6)S(17), Cs(2)Pd(4)U(6)Se(17), and Cs(2)Pt(4)U(6)Se(17) were synthesized by the high-temperature solid-state reactions of U, M, and Q in a flux of ACl or Rb(2)S(3). These isostructural compounds crystallize in a new structure type, with two formula units in the tetragonal space group P4/mnc. This structure consists of a network of square-planar MQ(4), monocapped trigonal-prismatic UQ(7), and square-antiprismatic UQ(8) polyhedra with A atoms in the voids. Rb(2)Pd(4)U(6)S(17) is a typical semiconductor, as deduced from electrical resistivity measurements. Magnetic susceptibility and specific heat measurements on single crystals of Rb(2)Pd(4)U(6)S(17) show a phase transition at 13 K, the result either of antiferromagnetic ordering or of a structural phase transition. Periodic spin-polarized band structure calculations were performed on Rb(2)Pd(4)U(6)S(17) with the use of the first principles DFT program VASP. Magnetic calculations included spin-orbit coupling. With U f-f correlations taken into account within the GGA+U formalism in calculating partial densities of states, the compound is predicted to be a narrow-band semiconductor with the smallest indirect and direct band gaps being 0.79 and 0.91 eV, respectively.

Single-crystal structures, optical absorptions, and electronic distributions of thorium oxychalcogenides ThOQ (Q = S, Se, Te).

The compounds ThOS, ThOSe, and ThOTe have been synthesized, and their structures have been determined by means of single-crystal X-ray diffraction methods. All three compounds adopt the PbFCl structure type in the tetragonal space group D(4h)(7) - P4/nmm. More precise crystallographic data have been obtained for ThOS and ThOSe, which had previously only been known from X-ray powder diffraction data. ThOS, ThOSe, and ThOTe are yellow-, orange-, and black-colored, respectively. From single-crystal optical absorption measurements the band gaps are 2.22, 1.65, and 1.45 eV, respectively. Optical band gaps, ionic charges, and densities of states were calculated for the three compounds with the use of Density Functional methods.

Oxidation state of uranium in A6Cu12U2S15 (A = K, Rb, Cs) compounds.

Black single crystals of A(6)Cu(12)U(2)S(15) (A = K, Rb, Cs) have been synthesized by the reactive flux method. These isostructural compounds crystallize in the cubic space group Ia ̅3d at room temperature. The structure comprises a three-dimensional framework built from US(6) octahedra and CuS(3) trigonal planar units with A cations residing in the cavities. There are no S-S bonds in the structure. To elucidate the oxidation state of U in these compounds, various physical property measurements and characterization methods were carried out. Temperature-dependent electrical resistivity measurement on a single crystal of K(6)Cu(12)U(2)S(15) showed it to be a semiconductor. These three A(6)Cu(12)U(2)S(15) (A = K, Rb, Cs) compounds all exhibit small effective magnetic moments, < 0.58 µ(B)/U and band gaps of about 0.55(2) eV in their optical absorption spectra. From X-ray absorption near edge spectroscopy (XANES), the absorption edge of A(6)Cu(12)U(2)S(15) is very close to that of UO(3). Electronic band structure calculations at the density functional theory (DFT) level indicate a strong degree of covalency between U and S atoms, but theory was not conclusive about the formal oxidation state of U. All experimental data suggest that the A(6)Cu(12)U(2)S(15) family is best described as an intermediate U(5+)/U(6+) sulfide system of (A(+))(6)(Cu(+))(12)(U(5+))(2)(S(2-))(13)(S(-))(2) and (A(+))(6)(Cu(+))(12)(U(6+))(2)(S(2-))(15).

Structure, properties, and theoretical electronic structure of UCuOP and NpCuOP.

The compounds UCuOP and NpCuOP have been synthesized and their crystal structures were determined from low-temperature single-crystal X-ray data. These isostructural compounds crystallize with two formula units in space group P4/nmm of the tetragonal system. Each An atom (An = U or Np) is coordinated to four O and four P atoms in a distorted square antiprism; each Cu atom is coordinated to four P atoms in a distorted tetrahedron. Magnetic susceptibility measurements on crushed single crystals indicate that UCuOP orders antiferromagnetically at 224(2) K. Neutron diffraction experiments at 100 and 228 K show the magnetic structure of UCuOP to be type AFI (+ - + -) where ferromagnetically aligned sheets of U atoms in the (001) plane order antiferromagnetically along [001]. The electrical conductivity of UCuOP exhibits metallic character. Its electrical resistivity measured in the ordered region with the current flowing within the tetragonal plane is governed by the scattering of the conduction electrons on antiferromagnetic spin-wave excitations. The electrical resistivity of single-crystalline NpCuOP shows semimetallic character. It is dominated by a pronounced hump at low temperatures, which likely arises owing to long-range magnetic ordering below about 90 K. Density of state analyses using the local spin-density approximation show covalent overlap between AnO and CuP layers of the structure and dominant contributions from 5f-actinide orbitals at the Fermi level. Calculations on a 2 × 2 × 2 supercell of NpCuOP show ferromagnetic ordering within the Np sheets and complex coupling between these planes. Comparisons of the physical properties of these AnCuOP compounds are made with those of the family of related tetragonal uranium phosphide compounds.

First-principles investigations of Ti-substituted hydroxyapatite electronic structure.

The electronic structure of Ti-substituted hydroxyapatite is investigated using density functional theory within a periodic slab model. Two sorption mechanisms have been considered: i.e., Ti(4+) and Ti(OH)(2)(2+) as the likely species to exchange with Ca(2+). Ti(4+) has a small ionic radius compared to Ca(2+) and can dope into both distinct sites, showing no site preference; however, when two H were removed from the OH channel to obtain charge compensation, preferential site II substitution appears, accompanied with a large O shift forming a strong Ti-O bond. The species Ti(OH)(2)(2+) displays a strong site preference: substitution by Ti(OH)(2)(2+) on the hydroxyl channel (site II) is exothermic and favored strongly over the Ca column (site I). Ti(OH)(2)(2+) substitution for Ca(2+) induces a large geometry relaxation and distortion, especially within the OH channel and Ca(2+) column, with a considerable shift of Ti compared to the Ca sites in pure HA. These results are consistent with the experimental observation that material synthesis with high Ti doping (atomic ratio > 0.1) shows irregular particles formation with reduced crystallinity. The calculated cell shape and volume relaxations indicate that the volume and cell parameters both expand in all the substituted HA models. The site preference and volume expansion differences found are attributed to the metal ion shift caused in meeting the requirement of strong Ti-O coordination in site I and site II polyhedra.

The structure of strontium-doped hydroxyapatite: an experimental and theoretical study.

First-principles modeling combined with experimental methods were used to study hydroxyapatite in which Sr2+ is substituted for Ca2+. Detailed analyses of cation-oxygen bond distributions, cation-cation distances, and site 1-oxygen polyhedron twist angles were made in order to provide an atomic-scale interpretation of the observed structural modifications. Density functional theory periodic band-structure calculations indicate that the Ca2+ to Sr2+ substitution induces strong local distortion on the hydroxyapatite lattice: the nearest neighbor Sr-O bond structures in both cationic sites are comparable to pure SrHA, while Sr induces more distortion at site 2 than site 1. Infrared vibrational spectroscopy (FTIR) and extended X-ray absorption fine structure (EXAFS) analysis suggest increasing lattice disorder and loss of OH with increasing Sr content. Rietveld refinement of synchrotron X-ray diffraction patterns shows a preference for the Ca1 site at Sr concentrations below 1 at.%. The ideal statistical occupancy ratio Sr2/Sr1=1.5 is achieved for approximately 5 at.%; for higher Sr concentrations occupation of the Ca2 site is progressively preferred.

Separation and molecular-level segregation of complex alkane mixtures in metal-organic frameworks.

In this computational work we explore metal-organic frameworks (MOFs) for separating alkanes according to the degree of branching. We show that the structure MOF-1 shows an adsorption hierarchy for a 13-component light naphtha mixture precisely as desired for increasing the research octane number of gasoline. In addition we report an unusual molecular-level segregation of molecules based on their degree of branching.

Syntheses, structures, physical properties, and electronic properties of some AMUQ3 compounds (A = alkali metal, M = Cu or Ag, Q = S or Se).

The seven new isostructural quaternary uranium chalcogenides KCuUS 3, RbCuUS 3, RbAgUS 3, CsCuUS 3, CsAgUS 3, RbAgUSe 3, and CsAgUSe 3 were prepared from solid-state reactions. These isostructural materials crystallize in the layered KZrCuS 3 structure type in the orthorhombic space group Cmcm. The structure is composed of UQ 6 octahedra and MQ 4 tetrahedra that share edges to form (2) infinity[UMQ 3 (-)] layers. These layers stack perpendicular to [010] and are separated by layers of face- and edge-sharing AQ 8 bicapped trigonal prisms. There are no Q-Q bonds in the structure, so the formal oxidation states of A/U/M/Q may be assigned as 1+/4+/1+/2-, respectively. CsCuUS 3 shows semiconducting behavior with thermal activation energy E a = 0.14 eV and sigma 298 = 0.3 S/cm. From single-crystal absorption measurements in the near IR range, the optical band gaps of these compounds are smaller than 0.73 eV. The more diffuse 5f electrons play a much more dominant role in the optical properties of the AMUQ 3 compounds than do the 4f electrons in the AMLnQ 3 compounds (Ln = rare earth). Periodic DFT spin band-structure calculations on CsCuUS 3 and CsAgUS 3 establish two energetically similar antiferromagnetic spin structures and show magnetic interactions within and between the layers of the structure. Density-of-states analysis shows M-Q orbital overlap in the valence band and U-Q orbital overlap in the conduction band.

Initial stages of hydration and Zn substitution/occupation on hydroxyapatite (0001) surfaces.

The initial stages of the hydration process have been simulated on a single-Ca(I) terminated hydroxyapatite (0001) surface in step-by-step fashion using periodic slab density functional theory (DFT). Adsorption configurations and energetic properties have been described at different H(2)O coverage. At low H(2)O coverage, oxygen prefers to form CaO bonds with surface Ca cations, but as coverage increases, H(2)O tends to loosely float on the already-formed water layer. The height of the first layer H(2)O relative to the surface is found to be 1.6A. The hydration process does not cause the decomposition of surface phosphate groups and hydroxyl channel, but does affect the energetics of subsequent Zn substitution and occupation on Ca(I) and Ca(II) sites. The Ca(II) vacancy site is found to be energetically more favorable for occupation due to less spatial constraint. This suggested mechanism of preferential occupation is different from previous attempts to explain the cation substitution site preference in bulk by ionic radius and electronegativity differences.

A structural analysis of lead hydroxyvanadinite.

Hydroxyvanadinite, Pb(10)(VO(4))(6)(OH)(2), was prepared by the co-precipitation method and analyzed by X-ray absorption spectroscopy (XANES, EXAFS), infrared spectroscopy, Raman scattering and X-ray diffraction (XRD). The results showed that the structure is very similar to that of vanadinite, Pb(10)(VO(4))(6)Cl(2), with space group P6(3)/m (176) and cell parameters a = 10.2242(3) A and c = 7.4537(2) A. A Rietveld refinement of the structure was performed using vanadinite as the starting model and fixing the geometry of the vanadate ion as a rigid body. First-principles Density Functional embedded cluster models are developed to analyze electronic structures, bonding, and densities of states. Interaction of Pb with the OH channel anion is examined in detail, as an important structural feature. A periodic band structure approach was used to obtain a further estimate of relaxed atomic coordinates.

Synthesis and structural characterization of some selenoruthenates and telluroruthenates.

The reaction of solid [RuClCp(PPh(3))(2)] with TeSe(3)(2-) or Se(n)(2-) in DMF leads to the formation of [RuCp(PPh(3))(mu(2)-Se(2))](2) (1). In the structure of this compound the two bridging Se(2) groups lead to a six-membered Ru(2)Se(4) ring in a chair conformation. Attached to each Ru center is a PPh(3) ligand in an equatorial position and a Cp ring in an axial position. The compound is diamagnetic. The compound [Ru(2)Cp(2)(mu(3)-Se(2))(mu(3)-Se)](2) (2) is obtained under similar conditions in the presence of air. This structure comprises a centrosymmetric Ru(4)Se(6) dimer formed from the two bridging Se groups and the two bridging Se(2) groups. Each Ru center is pi-bonded to a Cp ring. The reaction of solid [RuClCp(PPh(3))(2)] with a Te(n)(2-) polytelluride solution in DMF leads to the diamagnetic compound [(RuCp(PPh(3)))(2)(mu(2)-(1,4-eta:3,6-eta)Te(6))] (3). Here the Ru centers are bound to a bridging Te(6) chain at the 1, 4, 3, and 6 positions, leading to a bicyclic Ru(2)Te(6) ring. Each Ru atom is bound to a Cp ring and a PPh(3) group. This dimer possesses a center of symmetry. The structure of 3 is the first example of a bicyclic complex where fusion occurs along a Te-Te bond. If the same reaction is carried out in DMF/CH(2)Cl(2), rather than DMF, then [(RuCp(PPh(3)))(2)(mu(2)-(1,4-eta:3,6-eta)Te(6))].CH(2)Cl(2) (4) is obtained. In the solid state it possesses the same Ru(2)Te(6) structural unit as does 3, but the unit lacks a crystallographically imposed center of symmetry. The electronic structures of 3 and 4 have been analyzed with the use of first principles density functional theory. Bond order analysis indicates that the Te-Te bond where fusion occurs has a shared bonding charge of about (2)/(3) of that found for Te-Te single bonds.

Syntheses, structure, some band gaps, and electronic structures of CsLnZnTe3 (Ln=La, Pr, Nd, Sm, Gd, Tb, Dy, Ho, Er, Tm, Y).

Eleven new quaternary rare-earth tellurides, CsLnZnTe3 (Ln=La, Pr, Nd, Sm, Gd, Tb, Dy, Ho, Er, Tm, and Y), were prepared from solid-state reactions at 1123 K. These isostructural materials crystallize in the layered KZrCuS3 structure type in the orthorhombic space group Cmcm. The structure is composed of LnTe6 octahedra and ZnTe4 tetrahedra that share edges to form [LnZnTe3] layers. These layers stack perpendicular to [010] and are separated by layers of face- and edge-sharing CsTe8 bicapped trigonal prisms. There are no Te-Te bonds in the structure of these CsLnZnTe3 compounds so the formal oxidation states of Cs/Ln/Zn/Te are 1+/3+/2+/2-. Optical band gaps of 2.13 eV for CsGdZnTe3 and 2.12 eV for CsTbZnTe3 were deduced from single-crystal optical absorption measurements. A first-principles calculation of the density of states and the frequency-dependent optical properties was performed on CsGdZnTe3. The calculated band gap of 2.1 eV is in good agreement with the experimental value. A quadratic fit for the lanthanide contraction of the Ln-Te distance is superior to a linear one if the closed-shell atom is included.

Structural analysis of porphyrin molecular squares using molecular mechanics and density-functional methods.

"Molecular squares" formed from Re(CO)(3)Cl corners and porphyrin sides have potential applications as hosts for catalytic sites and as building blocks for membranes. In these materials, knowledge of the conformations of the squares is important. Molecular-mechanics (MM) and density-functional (DF) calculations have been used iteratively in this work to find the minimum-energy configurations of several porphyrin molecular squares. MM predicts that the steric and torsional interactions at connecting junctures of the square framework determine the overall geometry. Torsional degrees of freedom around these junctures were therefore analyzed using DF methods, giving further insight and helping choose among MM force-field options. Single-point DF calculations on the entire squares showed that the energy and conformation of the entire square could be reliably obtained by performing DF calculations on the critical elements of the square and then piecing them together. This "piecewise" strategy allows for both the major torsional motions and the most important local relaxations of large supramolecular species such as molecular squares.