Response of the mechanical and chiral character of ethane to ultra-fast laser pulses.

A pair of simulated left and right circularly polarized ultra-fast laser pulses of duration 20 femtoseconds that induce a mixture of excited states are applied to ethane. The response of the electron dynamics is investigated within the next generation quantum theory of atoms in molecules (NG-QTAIM) using third-generation eigenvector-trajectories which are introduced in this work. This enables an analysis of the mechanical and chiral properties of the electron dynamics of ethane without needing to subject the C-C bond to external torsions as was the case for second-generation eigenvector-trajectories. The mechanical properties, in particular, the bond-flexing and bond-torsion were found to increase depending on the plane of the applied laser pulses. The bond-flexing and bond-torsion, depending on the plane of polarization, increases or decreases after the laser pulses are switched off. This is explainable in terms of directionally-dependent effects of the long-lasting superpositions of excited states. The chiral properties correspond to the ethane molecule being classified as formally achiral consistent with previous NG-QTAIM investigations. Future planned investigations using ultra-fast circularly polarized lasers are briefly discussed.

Tools for overcoming reliance on energy-based measures in chemistry: a tutorial review.

The vast majority of literature in the chemical sciences describes fundamental chemical and physical phenomena using scalar measures, such as the energy, even though many phenomena are beyond the scope of scalar-based considerations. This problem exists no matter how accurately the associated energies are calculated. The solution that is explained in this work is to remove the reliance on scalar quantum chemical measures and instead utilize the vector-based and full symmetry-breaking nature of next generation quantum theory of atoms in molecules (NG-QTAIM). The connection with experiment on neutral chiral molecules is explained. A selection of non-energy-based explanations are provided: the functioning of molecular devices, why the cis-effect is the exception rather than the rule, stereochemical phenomena including chiral discrimination, quantifying chiral character of formally achiral molecules, mixed S and R stereoisomer character and the effect of an applied electric field. Current and future developments along with suggestions for future avenues of investigation are discussed. This tutorial review provides the practical details required to implement NG-QTAIM for a range of phenomena that are not accessible with energy-based measures. Step-by-step worked examples are included with data sets and instructions for use of commercial and open-source software along with examples of how to interpret the results.

Dietitian and nutrition-related practices and resources in Australian and New Zealand PICUs: A clinician survey.

BACKGROUND: Recommendations to facilitate evidence-based nutrition provision for critically ill children exist and indicate the importance of nutrition in this population. Despite these recommendations, it is currently unknown how well Australian and New Zealand (ANZ) paediatric intensive care units (PICUs) are equipped to provide nutrition care. OBJECTIVES: The objectives of this project were to describe the dietitian and nutrition-related practices and resources in ANZ PICUs. METHODS: A clinician survey was completed as a component of an observational study across nine ANZ PICUs in June 2021. The online survey comprised 31 questions. Data points included reporting on dietetics resourcing, local feeding-related guidelines and algorithms, nutrition screening and assessment practices, anthropometry practices, and indirect calorimetry (IC) device availability and local technical expertise. Data are presented as frequency (%), mean (standard deviation), or median (interquartile range). RESULTS: Survey responses were received from all nine participating sites. Dietetics staffing per available PICU bed ranged from 0.01 to 0.07 full-time equivalent (median: 0.03 [interquartile range: 0.02-0.04]). Nutrition screening was established in three (33%) units, all of which used the Paediatric Nutrition Screening Tool. Dietitians consulted all appropriate patients (or where capacity allowed) in six (66%) units and on a request or referral basis only in three (33%) units. All units possessed a local feeding guideline or algorithm. An IC device was available in two (22%) PICUs and was used in one of these units. CONCLUSIONS: This is the first study to describe the dietitian and nutrition-related practices and resources of ANZ PICUs. Areas for potential improvement include dietetics full-time equivalent, routine nutrition assessment, and access to IC.

Scoring molecular wires subject to an ultrafast laser pulse for molecular electronic devices.

A nonionizing ultrafast laser pulse of 20-fs duration with a peak amplitude electric-field ±E = 200 × 10-4 a.u. was simulated. It was applied to the ethene molecule to consider its effect on the electron dynamics, both during the application of the laser pulse and for up to 100 fs after the pulse was switched off. Four laser pulse frequencies ω = 0.2692, 0.2808, 0.2830, and 0.2900 a.u. were chosen to correspond to excitation energies mid-way between the (S1 ,S2 ), (S2 ,S3 ), (S3 ,S4 ) and (S4 ,S5 ) electronic states, respectively. Scalar quantum theory of atoms in molecules (QTAIM) was used to quantify the shifts of the C1C2 bond critical points (BCPs). Depending on the frequencies ω selected, the C1C2 BCP shifts were up to 5.8 times higher after the pulse was switched off compared with a static E-field with the same magnitude. Next generation QTAIM (NG-QTAIM) was used to visualize and quantify the directional chemical character. In particular, polarization effects and bond strengths, in the form of bond-rigidity vs. bond-flexibility, were found, for some laser pulse frequencies, to increase after the laser pulse was switched off. Our analysis demonstrates that NG-QTAIM, in partnership with ultrafast laser irradiation, is useful as a tool in the emerging field of ultrafast electron dynamics, which will be essential for the design, and control of molecular electronic devices.

Diffusion of hydrophilic to hydrophobic forms of Nile red in aqueous C12EO10 gels by variable area fluorescence correlation spectroscopy.

Solute diffusion within lyotropic liquid crystal gels prepared from a series of water and decaethylene glycol monododecyl ether (C12EO10) mixtures was explored by variable area fluorescence correlation spectroscopy. Aqueous C12EO10 gels were prepared in concentrations ranging from 55 : 45 to 70 : 30 wt% of surfactant and water. Small angle X-ray scattering revealed that these gels comprise hexagonal mesophases of cylindrical micelles. Micelle spacing was found to decrease with increasing C12EO10 concentration. Three different Nile red (NR) dyes were employed as model solutes and were separately doped into the gels at nanomolar levels. These include a hydrophilic form of NR incorporating an anionic sulfonate group (NRSO3-), a hydrophobic form incorporating a fourteen-carbon alkane tail (NRC14), and commercial NR as an intermediate case. FCS data acquired from the gels revealed that NRSO3- diffused primarily in 3D. Its diffusion coefficient exhibited a monotonic decrease with increasing gel concentration and micelle packing density, consistent with confinement of its motions by its exclusion from the micelle cores. NRC14 exhibited the smallest diffusion coefficient, most likely due to its larger size and enhanced interactions with the micelle cores. NR yielded an intermediate diffusion coefficient and the most anomalous behavior of the three dyes, attributable to its facile partitioning between core and corona regions, and greater participation by 1D diffusion. The results of these studies afford an improved understanding of molecular mass transport through soft-matter nanomaterials like those being developed for use in drug delivery and membrane based chemical separations.

Next generation quantum theory of atoms in molecules for the design of emitters exhibiting thermally activated delayed fluorescence with laser irradiation.

The effect of a static electric (E)-field and an unchirped and chirped laser pulse field on the cycl[3.3.3]azine molecule was investigated using next-generation quantum theory of atoms in molecules (NG-QTAIM). Despite the magnitude of the E-field of the laser pulses being an order of magnitude lower than for the static E-field, the variation of the energy gap between the lowest lying singlet (S1 ) and triplet (T1 ) excited states was orders of magnitude greater for the laser pulse than for the static E-field. Insights into the response of the electronic structure were captured by NG-QTAIM, where differences in the inverted singlet-triplet gap due to the laser pulses were significant larger compared to those induced by the static E-field. The response of the S1 and T1 excited states, as determined by NG-QTAIM, switched discontinuously between weak and strong chemical character for the static E-field. In contrast, the response to the laser pulses, determined by NG-QTAIM, is to induce a continuous range of chemical character, indicating the unique ability of the laser pulses to induce polarization effects in the form of "mixed" bond types. Our analysis demonstrates that NG-QTAIM is a useful tool for understanding the response to laser irradiation of the lowest-lying singlet S1 and triplet T1 excited states of emitters exhibiting thermally activated delayed fluorescence. The chirped laser pulse led to more frequent instances of the desired outcome of an inverted singlet-triplet gap than the unchirped pulse, indicating its usefulness as a tool to design more efficient organic light-emitting diode devices.

The Cis-Effect Explained Using Next-Generation QTAIM.

We used next-generation QTAIM (NG-QTAIM) to explain the cis-effect for two families of molecules: C2X2 (X = H, F, Cl) and N2X2 (X = H, F, Cl). We explained why the cis-effect is the exception rather than the rule. This was undertaken by tracking the motion of the bond critical point (BCP) of the stress tensor trajectories Tσ(s) used to sample the Uσ-space cis- and trans-characteristics. The Tσ(s) were constructed by subjecting the C1-C2 BCP and N1-N2 BCP to torsions ± θ and summing all possible Tσ(s) from the bonding environment. During this process, care was taken to fully account for multi-reference effects. We associated bond-bending and bond-twisting components of the Tσ(s) with cis- and trans-characteristics, respectively, based on the relative ease of motion of the electronic charge density ρ(rb). Qualitative agreement is found with existing experimental data and predictions are made where experimental data is not available.

Chirality without Stereoisomers: Insight from the Helical Response of Bond Electrons.

The association between molecular chirality and helical characteristics known as the chirality-helicity equivalence is determined for the first time by quantifying a chirality-helicity measure consistent with photoexcitation circular dichroism experiments. This is demonstrated using a formally achiral SN 2 reaction and a chiral SN 2 reaction. Both the achiral and chiral SN 2 reactions possess significant values of the chirality-helicity measure and display a Walden inversion, i. e. an inversion of the chirality between the reactant and product. We also track the chirality-helicity measure along the reaction path and discover the presence of chirality at the transition state and two intermediate structures for both reactions. We demonstrate the need for the chirality-helicity measure to differentiate between steric effects due to eclipsed conformations and chiral behaviors in formally achiral species. We explain the significance of this work for asymmetric synthetic reactions including the intermediate structures where the Cahn-Ingold-Prelog (CIP) rules cannot be used.

A case of capillary malformation-arteriovenous malformation and Ebstein's anomaly in a child with EphB4 mutation.

Capillary malformation-arteriovenous malformation (CM-AVM) is a rare condition characterized by multiple cutaneous capillary malformations with potential associated arteriovenous malformations. RAS p21 protein activator 1 (RASA1) and ephrin type-B receptor 4 (EPHB4) genes are implicated. We present a child with CM-AVM, due to EPHB4 mutation, and Ebstein's anomaly. Although EPHB4 is a known effector of vascular remodeling, its contribution to cardiogenesis is still being explored. Further research is needed to determine causality of Ebstein's anomaly in the setting of CM-AVM due to EPHB4 mutation.

The positive environmental impact of virtual isotretinoin management.

BACKGROUND/OBJECTIVES: Other medical specialties have studied how their practices influence the environment, but environmental impact studies in the field of dermatology remain limited. With respect to dermatology, vehicle emissions by patients traveling to and from appointments are an important factor influencing climate change. This study was undertaken to determine the greenhouse gas emissions avoided by managing isotretinoin virtually at West Virginia University Hospital. METHODS: A retrospective cross-sectional study was conducted during the COVID-19 outbreak from March 25 to December 1, 2020, where travel data were acquired and converted to emission data. RESULTS: 5,137 kg of GHG emissions in CO2 equivalents were prevented by managing isotretinoin virtually during the study period. 49 400 kg of GHG emissions in CO2 equivalents would be prevented annually. This is the emission load released when 24 690 kg of coal are burned. CONCLUSIONS: Environmental impact studies in the field of dermatology remain limited. GHG emissions were significantly reduced by virtually managing isotretinoin at a single institution. The practice of dermatology could reduce its carbon footprint by managing isotretinoin virtually, even in non-pandemic periods. Given that isotretinoin management represents a small percentage of the overall carbon footprint associated with dermatology, dermatologists should identify other conditions amenable to virtual medicine to produce greater environmental impact.

Next-generation QTAIM for scoring molecular wires in E-fields for molecular electronic devices.

The effect of a varying, directional E x , E y , and E z electric field on the ethene molecule was investigated using next-generation quantum theory of atoms in molecules (QTAIM). Despite using low E-field strengths that are within the realm of experiment and do not measurably alter the molecular geometry, significant changes to the QTAIM properties were observed. Using conventional QTAIM, the shifting of the C─C and C─H bond critical points (BCPs) demonstrates polarization through an interchange in the size of the atoms involved in a bond, since a BCP is located on the boundary between a pair of bonded atoms. Next-generation QTAIM, however, demonstrates the polarization effect more directly with a change in morphology of the 3-D envelope around the BCP. Modest increases of ≈ 2% in the ellipticity ε of the BCP were uncovered when the C─C bond was aligned parallel or anti-parallel to the applied E x -field. Significant asymmetries were found in the response of the next-generation QTAIM 3-D paths of the C─H bonds to the applied E-field. When the E-field coincided with the C─C bond, the BCP moved in response and was accompanied by the envelope constructed from 3-D next-generation paths. The response displayed a polarization effect that increased with increasing magnitude of the E x -field parallel and anti-parallel to the C─C bond. Our analysis demonstrates that next-generation QTAIM is a useful tool for understanding the response of molecules to E-fields, for example, for the screening of molecular wires for the design of molecular electronic devices. © 2019 Wiley Periodicals, Inc.

3-D bond-paths of QTAIM and the stress tensor in neutral lithium clusters, Lim (m = 2-5), presented on the Ehrenfest force molecular graph.

In this investigation we set out to understand the origins of non-nuclear attractors (NNAs) found for neutral lithium clusters Lim (m = 2-5) on the QTAIM molecular graph but not on the Ehrenfest force F(r) molecular graph. Therefore, we pursued the stress tensor σ(r) without using the dependency on the QTAIM partitioning, since previously σ(r) was only calculated within the QTAIM partitioning, to see if any indication of NNA character can be determined. Because the stress tensor σ(r) lacks an associated scalar- or vector-field as is the case for QTAIM and the Ehrenfest F(r) partitioning schemes respectively, a stress tensor σ(r) partitioning scheme cannot be constructed. Therefore, to overcome this difficulty we use next generation QTAIM, constructed from the most preferred directions of electronic charge density accumulation, to calculate the stress tensor σ(r) 3-D bond-paths on the Ehrenfest force F(r) molecular graph. Using next generation 3-D bond-paths within the Ehrenfest force F(r) partitioning, we can classify the degree of NNA character in the absence of NNAs. A much higher degree of NNA character is found to be present for the stress tensor σ(r) 3-D bond-paths than for the corresponding QTAIM or Ehrenfest force F(r) 3-D bond-paths. The stabilizing effect of the NNA is demonstrated by undertaking Li2 bond-path compression and stretching distortions sufficient to cause the annihilation of the NNA. The compression and stretching distortions also lead to a large increase in the 3-D bond-path asymmetry and persistent bond-path torsion respectively.

Intramolecular mode coupling of the isotopomers of water: a non-scalar charge density-derived perspective.

The H2O/D2O/HDO isotopomers of water are presented in terms that enable bond-flexing, bond-twist and bond-anharmonicity to be quantified during the bending (Q1), symmetric-stretch (Q2) and anti-symmetric-stretch (Q3) normal modes of vibration. Bond-flexing was detected by the presence of curved bonding and the bond-anharmonicity was detected by the presence of motion of the bond critical point (BCP) relative to the oxygen atom. These 2-D scalar measures are unable to fully describe the 3-D nature of the normal modes of vibration and therefore any susceptibility towards normal mode coupling, or to fully distinguish the three isotopomers. To detect bond-twist a vector-based measure was used, in the form of the bond critical point (BCP) trajectory, constructed in terms of preferred directions of electronic motion, defined by the variation of the position of the BCP during the normal modes of vibration. The BCP trajectories describe the coupling of the intramolecular bending and symmetric-stretch normal modes as well as distinguishing all three isotopomers within the harmonic approximation. The coupling of the bending and symmetric-stretch normal modes are suggested to be facilitated by the absence of bond-twist that would disrupt the coupling between Sigma O-H bonds and hydrogen-bonding. Partial coupling was found for the mixed isotopomer HDO.

Chirality-Helicity Equivalence in the S and R Stereoisomers: A Theoretical Insight.

We located the unknown chirality-helicity equivalence in molecules with a chiral center, and as a consequence, the degeneracy of the S and R stereoisomers of lactic acid was lifted. An agreement was found with the naming schemes of S and R stereoisomers from optical experiments. This was made possible by the construction of the stress tensor trajectories in a non-Cartesian space defined by the variation of the position of the torsional bond critical point upon a structural change, along the torsion angle, θ, involving a chiral carbon atom. This was undertaken by applying a torsion θ, -180.0° ≤ θ ≤ +180.0° corresponding to clockwise and counterclockwise directions. We explain why scalar measures can at best only partially lift the degeneracy of the S and R stereoisomers, as opposed to vector-based measures that can fully lift the degeneracy. We explained the consequences for stereochemistry in terms of the ability to determine the chirality of industrially relevant reaction products.

The destabilization of hydrogen bonds in an external E-field for improved switch performance.

The effect of an electric field on a recently proposed molecular switch based on a quinone analogue was investigated using next-generation quantum theory of atoms in molecules (QTAIM) methodology. The reversal of a homogenous external electric field was demonstrated to improve the "OFF" functioning of the switch. This was achieved by destabilization of the H atom participating in the tautomerization process along the hydrogen bond that defines the switch. The "ON" functioning of the switch, from the position of the tautomerization barrier, is also improved by the reversal of the homogenous external electric field: this result was previously inaccessible. The "ON" and "OFF" functioning of the switch was visualized in terms of the response of the most preferred directions of motion of the electronic charge density to the applied external field. All measures from QTAIM and the stress tensor provide consistent results for the factors affecting the "ON" and "OFF" switch performance. Our analysis therefore demonstrates use for future design of molecular electronic devices. © 2019 Wiley Periodicals, Inc.

Stress Tensor Eigenvector Following with Next-Generation Quantum Theory of Atoms in Molecules: Excited State Photochemical Reaction Path from Benzene to Benzvalene.

In this investigation, we considered both the scalar and 3-D vector-based measures of bonding using next generation quantum theory of atoms in molecules (QTAIM), constructed from the preferred direction of electronic charge density accumulation, to better understand the photochemical reaction associated with of the formation of benzvalene from benzene. The formation of benzvalene from benzene resulted in two additional C-C bonds forming compared with the benzene. The creation of the additional C-C bonds was explained in terms of an increasing the favorability of the reaction process by maximizing the bonding density. The topological instability of the benzvalene structure was determined using the scalar and vector-based measures to explain the short chemical half-life of benzvalene in terms of the competition between the formation of unstable new C-C bonding that also destabilizes nearest neighbor C-C bonds. The explosive character of benzvalene is indicated by the unusual tendency of the C-C bonds to rupture as easily as weak bonding. The topological instability of the short strong C-C bonds was explained by the existence of measures from conventional and next generation QTAIM that previously have only been observed in weak interactions; such measures included twisted 3-D bonding descriptors.

Halogen and Hydrogen Bonding in Halogenabenzene/NH3 Complexes Compared Using Next-Generation QTAIM.

Next-generation quantum theory of atoms in molecules (QTAIM) was used to investigate the competition between hydrogen bonding and halogen bonding for the recently proposed (Y = Br, I, At)/halogenabenzene/NH3 complex. Differences between using the SR-ZORA Hamiltonian and effective core potentials (ECPs) to account for relativistic effects with increased atomic mass demonstrated that next-generation QTAIM is a much more responsive tool than conventional QTAIM. Subtle details of the competition between halogen bonding and hydrogen bonding were observed, indicating a mixed chemical character shown in the 3-D paths constructed from the bond-path framework set B. In addition, the use of SR-ZORA reduced or entirely removed spurious features of B on the site of the halogen atoms.

Non-nuclear attractors in small charged lithium clusters, Limq (m = 2-5, q = ±1), with QTAIM and the Ehrenfest force partitioning.

In this investigation we explore the function and existence of the non-nuclear attractor (NNA) for a series of small charged lithium clusters Limq (m = 2-5, q = ±1) using QTAIM and the Ehrenfest force F(r) partitioning schemes. The NNAs were found to be present in all of the Limq (m = 2-5, q = ±1) clusters for QTAIM, in contrast none were found for F(r). We discovered that the anionic and cationic lithium dimers are limiting cases for minimal and maximal impact of the NNA related to the relative sparseness of total charge density ρ(r) distributions respectively. Evidence is found that the NNA in the anionic dimer is in the process of being annihilated by two neighboring BCPs. We provide a measure of the size of the NNA and find for Limq (m = 2-5, q = ±1) that larger NNAs correlate with increased Li-Li separations. The NNA was determined to be a persistent feature by varying the Li separations for the cationic and anionic dimers. Very large Li separations failed to induce an NNA in the F(r) anionic dimer and therefore we conclude that F(r) is unable to detect NNAs. The metallicity ξ(rb) was also used to measure the sparseness of the distribution of ρ(r) and significant metallic character, on the basis of ξ(rb) > 1, was present for QTAIM but not for F(r), providing further evidence that F(r) cannot detect NNAs. Advantages of the use of Ehrenfest force F(r) partitioning scheme are discussed that include the design of nano-devices through tuning of the Ehrenfest potential VF(b) by the application of external forces such as a constant electric or strain field.

Cell cycle pathway dysregulation in human keratinocytes during chronic exposure to low arsenite.

BACKGROUND: Arsenic is naturally prevalent in the earth's crust and widely distributed in air and water. Chronic low arsenic exposure is associated with several cancers in vivo, including skin cancer, and with transformation in vitro of cell lines including immortalized human keratinocytes (HaCaT). Arsenic also is associated with cell cycle dysregulation at different exposure levels in multiple cell lines. In this work, we analyzed gene expression in HaCaT cells to gain an understanding of gene expression changes contributing to transformation at an early time point. METHODS: HaCaT cells were exposed to 0 or 100nM NaAsO2 for 7weeks. Total RNA was purified and analyzed by microarray hybridization. Differential expression with fold change≥|1.5| and p-value≤0.05 was determined using Partek Genomic Suite™ and pathway and network analyses using MetaCore™ software (FDR≤0.05). Cell cycle analysis was performed using flow cytometry. RESULTS: 644 mRNAs were differentially expressed. Cell cycle/cell cycle regulation pathways predominated in the list of dysregulated pathways. Genes involved in replication origin licensing were enriched in the network. Cell cycle assay analysis showed an increase in G2/M compartment in arsenite-exposed cells. CONCLUSIONS: Arsenite exposure induced differential gene expression indicating dysregulation of cell cycle control, which was confirmed by cell cycle analysis. The results suggest that cell cycle dysregulation is an early event in transformation manifested in cells unable to transit G2/M efficiently. Further study at later time points will reveal additional changes in gene expression related to transformation processes.