Light-wave dynamic control of magnetism.

The enigmatic interplay between electronic and magnetic phenomena observed in many early experiments and outlined in Maxwell's equations propelled the development of modern electromagnetism1. Today, the fully controlled evolution of the electric field of ultrashort laser pulses enables the direct and ultrafast tuning of the electronic properties of matter, which is the cornerstone of light-wave electronics2-7. By contrast, owing to the lack of first-order interaction between light and spin, the magnetic properties of matter can only be affected indirectly and on much longer timescales, through a sequence of optical excitations and subsequent rearrangement of the spin structure8-16. Here we introduce the regime of ultrafast coherent magnetism and show how the magnetic properties of a ferromagnetic layer stack can be manipulated directly by the electric-field oscillations of light, reducing the magnetic response time to an external stimulus by two orders of magnitude. To track the unfolding dynamics in real time, we develop an attosecond time-resolved magnetic circular dichroism detection scheme, revealing optically induced spin and orbital momentum transfer in synchrony with light-field-driven coherent charge relocation17. In tandem with ab initio quantum dynamical modelling, we show how this mechanism enables the simultaneous control of electronic and magnetic properties that are essential for spintronic functionality. Our study unveils light-field coherent control of spin dynamics and macroscopic magnetic moments in the initial non-dissipative temporal regime and establishes optical frequencies as the speed limit of future coherent spintronic applications, spin transistors and data storage media.

Giant and Controllable Valley Currents in Graphene by Double Pumped THz Light.

The field of valleytronics considers the creation and manipulation of "valley states", charge excitations characterized by a particular value of the crystal momentum in the Brillouin zone. Here we show, using the example of minimally gapped (≤40 meV) graphene, that there exist lightforms that create almost perfect valley contrasting current states (up to ∼80% valley purity) in the absence of a valley contrasting charge excitation. These "momentum streaked" THz waveforms act by deforming the excited state population in momentum space such that current flows at one valley yet is blocked at the conjugate valley. This approach both unlocks the potential of graphene as a materials platform for valleytronics, as gaps of 10-40 meV are robustly found in useful experimental contexts such as graphene/hBN systems, while simultaneously providing a tool toward ultrafast light control of valley currents in diverse minimally gapped matter, including many topological insulator systems.

Light-Shaping of Valley States.

The established paradigm to create valley states, excitations at local band extrema ("valleys"), is through selective occupation of specific valleys via circularly polarized laser pulses. Here we show a second way exists to create valley states, not by valley population imbalance but by "light-shaping" in momentum space, i.e. controlling the shape of the distribution of excited charge at each valley. While noncontrasting in valley charge, such valley states are instead characterized by a valley current, identically zero at one valley and finite and large at the other. We demonstrate that these (i) are robust to quantum decoherence, (ii) allow lossless toggling of the valley state with successive femtosecond laser pulses, and (iii) permit valley contrasting excitation both with and without a gap. Our findings open a route to robust ultrafast and switchable valleytronics in a wide scope of 2d materials, bringing closer the promise of valley-based electronics.

Mutual Modulation of the Activities of Human CYP2D6 and Four UGTs during the Metabolism of Propranolol.

Cytochromes P450 (CYP) and UDP-glucuronosyltransferases (UGT) are two enzyme families that play an important role in drug metabolism, catalyzing either the functionalization or glucuronidation of xenobiotics. However, their mutual interactions are poorly understood. In this study, the functional interactions of human CYP2D6 with four human UGTs (UGT1A7, UGT1A8, UGT1A9, and UGT2A1) were investigated using our previously established co-expression model system in the fission yeast Schizosaccharomyces pombe. The substrate employed was propranolol because it is well metabolized by CYP2D6. Moreover, the CYP2D6 metabolite 4-hydroxypropranolol is a known substrate for the four UGTs included in this study. Co-expression of either UGT1A7, UGT1A8, or UGT1A9 was found to increase the activity of CYP2D6 by a factor of 3.3, 2.1 or 2.8, respectively, for the conversion of propranolol to 4-hydroxypropranolol. In contrast, UGT2A1 co-expression did not change CYP2D6 activity. On the other hand, the activities of all four UGTs were completely suppressed by co-expression of CYP2D6. This data corroborates our previous report that CYP2D6 is involved in functional CYP-UGT interactions and suggest that such interactions can contribute to both adverse drug reactions and changes in drug efficacy.

Expected and Unexpected Products from the Biochemical Oxidation of Bacterial Alkylquinolones with CYP4F11.

2-Alkylquinolones are a class of microbial natural products primarily produced in the Pseudomonas and Burkholderia genera that play a key role in modulating quorum sensing. Bacterial alkylquinolones were synthesized and then subjected to oxidative biotransformation using human cytochrome P450 enzyme CYP4F11, heterologously expressed in the fission yeast Schizosaccharomyces pombe. This yielded a range of hydroxylated and carboxylic acid derivatives which had undergone ω-oxidation of the 2-alkyl chain, the structures of which were determined by analysis of NMR and MS data. Oxidation efficiency depended on chain length, with a chain length of eight or nine carbon atoms proving optimal for high yields. Homology modeling suggested that Glu233 was relevant for binding, due to the formation of a hydrogen bond from the quinolone nitrogen to Glu233, and in this position only the longer alkyl chains could come close enough to the heme moiety for effective oxidation. In addition to the direct oxidation products, a number of esters were also isolated, which was attributed to the action of endogenous yeast enzymes on the newly formed ω-hydroxy-alkylquinolones. ω-Oxidation of the alkyl chain significantly reduced the antimicrobial and antibiofilm activity of the quinolones.

Deciphering the biotransformation mechanism of dialkylresorcinols by CYP4F11.

Cytochrome P450 enzymes (CYPs) are one of the most important classes of oxidative enzymes in the human body, carrying out metabolism of various exogenous and endogenous substrates. In order to expand the knowledge of these enzymes' specificity and to obtain new natural product derivatives, CYP4F11, a cytochrome P450 monooxygenase, was used in the biotransformation of dialkylresorcinols 1 and 2, a pair of antibiotic microbial natural products. This investigation resulted in four biotransformation products including two oxidative products: a hydroxylated derivative (3) and a carboxylic acid derivative (4). In addition, acetylated (5) and esterified products (6) were isolated, formed by further metabolism by endogenous yeast enzymes. Oxidative transformations were highly regioselective, and took place exclusively at the ω-position of the C-5 alkyl chain. Homology modeling studies revealed that optimal hydrogen bonding between 2 and the enzyme can only be established with the C-5 alkyl chain pointing towards the heme. The closely-related CYP4F12 was not capable of oxidizing the dialkylresorcinol 2. Modeling experiments rationalize these differences by the different shapes of the binding pockets with respect to the non-oxidized alkyl chain. Antimicrobial testing indicated that the presence of polar groups on the side-chains reduces the antibiotic activity of the dialkylresorcinols.

GeneXpert Ultra in Urine Samples for Diagnosis of Extra-Pulmonary Tuberculosis.

Extra-pulmonary tuberculosis (EPTB) continues to be difficult to diagnose. Novel biomarkers in biological specimens offer promise. Detection of Mycobacterium tuberculosis (Mtb) DNA in urine could prove useful in diagnosis of EPTB, possibly due to disseminated disease or micro-abscesses reported in kidneys. The current study was designed to detect Mtb DNA in stored urine samples from patients with EPTB. Diagnosis of EPTB was reached using Microbiological Reference Standards (MRS) on samples from the disease site using WHO Recommended Diagnostics (WRD), [smear microscopy, liquid culture (MGIT-960)] and GX (molecular WRD, mWRD) and Comprehensive reference standards [CRS, clinical presentation, microbiological reference standards, radiology, histopathology]. GX-Ultra was performed on urine samples stored in -80oC deep freezer, retrospectively. Of 70 patients, 51 (72.9%) were classified as confirmed TB, 11 (15.7%) unconfirmed TB, and 8 (11.4%) unlikely TB. GX-Ultra in urine samples demonstrated sensitivity of 52.9% and specificity of 57.9% against MRS, and higher sensitivity of 56.5% and specificity of 100% against CRS. The sensitivity and specificity of GX-Ultra in urine was 53.6% and 75% for pus sample subset and 52.2% and 53.3% for fluid sample subset. Urine being non-invasive and easy to collect, detection of Mtb DNA using mWRD in urine samples is promising for diagnosis of EPTB.

Nanomechanical Spectroscopy of 2D Materials.

We introduce a nanomechanical platform for fast and sensitive measurements of the spectrally resolved optical dielectric function of 2D materials. At the heart of our approach is a suspended 2D material integrated into a high Q silicon nitride nanomechanical resonator illuminated by a wavelength-tunable laser source. From the heating-related frequency shift of the resonator as well as its optical reflection measured as a function of photon energy, we obtain the real and imaginary parts of the dielectric function. Our measurements are unaffected by substrate-related screening and do not require any assumptions on the underling optical constants. This fast (τrise ∼ 135 ns), sensitive (noise-equivalent power = 90⁣pW√Hz), and broadband (1.2-3.1 eV, extendable to UV-THz) method provides an attractive alternative to spectroscopic or ellipsometric characterization techniques.

Role of alternatives to antibiotics in mitigating the antimicrobial resistance crisis.

Antimicrobial resistance (AMR) is a burgeoning challenge of global priority, warranting immediate action to prevent the explosion of multidrug-resistant (MDR) pathogens. Indiscriminate antimicrobial use is the most important driver for AMR. AMR has led to depletion of the antibiotic pipeline and developing new antibiotics is extremely challenging due to technical and financial issues and also resistance emerges as soon any new antibiotic is introduced. At present, preserving the power of existing antibiotics by prudent use and curtailing spread of pathogens by infection prevention and control (biosecurity) in both humans and animals are the best available options to defer AMR crisis. Meanwhile, to reduce dependence on antibiotics, other alternatives such as vaccines, antibodies, pattern recognition receptors, probiotics, bacteriophages, peptides, phytochemicals, metals, and antimicrobial enzymes are being explored. This review provides an overview of various promising, potential and under investigative strategies as alternatives to antibiotics.

Optimum dose of oral folic acid supplementation in transfusion-dependent thalassemia: a randomized controlled trial.

AIM AND OBJECTIVES: We compared the effect of different doses of oral folic acid (FA) supplementation (5 mg/day vs. 2.5 mg/day vs. 5 mg/week) on the proportion of children with folate excess (serum folate >20 ng/ml) and plasma homocysteine (Hcys) excess (>15 µmol/l) in transfusion-dependent thalassemia (TDT). MATERIALS AND METHODS: Children with TDT aged 5-18 years received oral FA in doses of 5 mg/day (Group 1), 2.5 mg/day (Group 2) and 5 mg/week (Group 3) for 9 months, after a wash-off period of 8 weeks. Folate levels (Serum and RBC) and plasma Hcys levels were measured after the therapy. RESULTS: Ninety children were randomized to receive one of the three interventions (30 per group). After wash-off period, the median serum folate levels were significantly lower and five children developed folate deficiency; the median [interquartile range (IQR)] serum folate levels (ng/dl) were comparable in the three groups [Group 1: 6.5 (3.3-14.2), Group 2: 5.1 (2.6-10.5) and Group 3: 4.8 (3.4-10.0)]. After 9 months of intervention, the median (IQR) serum folate levels (ng/ml) were comparable in all participants [Group 1: 18.0 (6.5-28), Group 2: 13.5 (6.4-24.5) and Group 3: 9.7 (5.3-22.5); p = 0.11]. Proportion of children with serum folate excess was 40%, 26.7% and 26.7% in Group 1, Group 2 and Group 3 (p = 0.48). Proportion of children with RBC folate excess was 92%, 86.7% and 86.7% in Group 1, Group 2 and Group 3 (p = 0.79). Hyperhomocysteinemia was seen in eight children with no significant difference between median Hcys levels in the groups (p = 0.75). CONCLUSION: Folic acid supplementation is recommended in TDT with 5 mg weekly dose being adequate.

The Ethnic Identity Scale: Affirmation, really?

OBJECTIVE: The Ethnic Identity Scale (EIS) was developed to distinguish between process and content components of ethnic-racial identity (ERI). However, the affirmation subscale is composed entirely of negatively worded items, measuring negative feelings about one's ethnic-racial group, rather than positive feelings as widely conceptualized. Addressing this gap, the present study examined the psychometric validity of a revised EIS with positively and negatively worded items to determine whether affirmation is best represented as a unidimensional construct, a bidimensional construct, or a combination of the two. METHOD: The sample consisted of 280 college students (75.5% female; Mage = 20.95 years; SD = 1.98 years). The largest ethnic-racial group consisted of Black or African Americans (68.2%), followed by Asian/Asian Americans (12.1%), Hispanic/Latinos (9.6%), and other ethnic-racial groups (10%). RESULTS: Confirmatory factor analysis provided evidence for both unidimensionality and multidimensionality. Indeed, although positively worded and negatively worded items of "affirmation" loaded onto a general factor representing affirmation, there was still a significant amount of variance captured by the negative ERI affect specific factor, indicating the presence of multidimensionality. In addition, results indicated that negative ERI affect, over and above the general ERI affirmation factor, predicted psychosocial functioning. CONCLUSIONS: The present study expands our understanding of the multidimensionality of ERI, highlighting the need for examination of how we measure ERI affect at the very least, and possibly how we conceptualize it within the broader ERI literature. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Ab Initio Study of Helicity-Dependent Light-Induced Demagnetization: From the Optical Regime to the Extreme Ultraviolet Regime.

We use ab initio real-time time-dependent density functional theory to investigate the effect of optical and extreme ultraviolet (XUV) circularly polarized femtosecond pulses on the magnetization dynamics of ferromagnetic materials. We demonstrate that the light induces a helicity-dependent reduction of the magnitude of the magnetization. In the XUV regime, where the 3p semicore states are involved, a larger helicity dependence persisting even after the passage of light is exhibited. Finally, we were able to separate the part of the helicity-dependent dynamics due to the absorption from the part due to the inverse Faraday effect. Doing so, we show that the former has, overall, a greater impact on the magnetization than the latter, especially after the pulse and in the XUV regime. This work hints at the yet experimentally unexplored territory of the XUV light-induced helicity-dependent dynamics, which, according to our prediction, could magnify the helicity-dependent dynamics already exhibited in the optical regime.

Spin/Valley Coupled Dynamics of Electrons and Holes at the MoS2-MoSe2 Interface.

The coupled spin and valley degrees of freedom in transition metal dichalcogenides (TMDs) are considered a promising platform for information processing. Here, we use a TMD heterostructure MoS2-MoSe2 to study optical pumping of spin/valley polarized carriers across the interface and to elucidate the mechanisms governing their subsequent relaxation. By applying time-resolved Kerr and reflectivity spectroscopies, we find that the photoexcited carriers conserve their spin for both tunneling directions across the interface. Following this, we measure dramatically different spin/valley depolarization rates for electrons and holes, ∼30 and <1 ns-1, respectively, and show that this difference relates to the disparity in the spin-orbit splitting in conduction and valence bands of TMDs. Our work provides insights into the spin/valley dynamics of photoexcited carriers unaffected by complex excitonic processes and establishes TMD heterostructures as generators of spin currents in spin/valleytronic devices.

Perfect and Controllable Nesting in Minimally Twisted Bilayer Graphene.

Parallel ("nested") regions of a Fermi surface (FS) drive instabilities of the electron fluid, for example, the spin density wave in elemental chromium. In one-dimensional materials, the FS is trivially fully nested (a single nesting vector connects two "Fermi dots"), while in higher dimensions only a fraction of the FS consists of parallel sheets. We demonstrate that the tiny angle regime of twist bilayer graphene (TBLG) possesses a phase, accessible by interlayer bias, in which the FS consists entirely of nestable "Fermi lines", the first example of a completely nested FS in a two-dimensional (2D) material. This nested phase is found both in the ideal as well as relaxed structure of the twist bilayer. We demonstrate excellent agreement with recent STM images of topological states in this material and elucidate the connection between these and the underlying Fermiology. We show that the geometry of the Fermi lines network is controllable by the strength of the applied interlayer bias, and thus TBLG offers unprecedented access to the physics of FS nesting in 2D materials.

Soil carbon pool and dynamics of different fractions in subalpine temperate coniferous forests of Western Himalaya, India.

Natural forests have the ability to sequester atmospheric carbon for a long time and fix it into the soil through a variety of processes such as decomposition and root respiration. The changing environment of alpine forests alters the characteristics of soil carbon, causing it to be divided into several components. The current study looked at soil carbon fractions and how they changed over time, both annually and seasonally, at different depths and along an altitudinal gradient. Seasonal sampling was carried out at three depths, with standard procedures employed to estimate the results of soil carbon fractions. The results showed that the surface layer (10 cm) had the highest value of all soil qualities such as SOC, Fraction I, Fraction II, Fraction III, SOM and active pool of carbon than the subsurface (20 cm and 30 cm) layers with autumn dominating the seasons. Site 1 had the highest value and Site 4 lowest, indicating that altitudinal variance had a direct relationship with distinct soil fractions. On an annual basis, the corresponding soil carbon fraction variation was examined, revealing the maximum retention capability at 30 cm of depth. According to the findings, the soils of the Western Himalayas have a high potential for carbon sequestration and conversion into various fractions, with significant annual and seasonal change due to changing environmental conditions.

Identification of new probe substrates for human CYP20A1.

CYP20A1 is a well-conserved member of the human cytochrome P450 enzyme family for which no endogenous or xenobiotic substrate is known. We have recently shown that this enzyme has moderate activity towards two proluciferin probe substrates. In order to facilitate the search for physiological substrates we have tested nine additional proluciferins in this study and identified three such probe substrates that give much higher product yields. Using one of these probes, we demonstrate inhibition of CYP20A1 activity by 1-benzylimidazole, ketoconazole and letrozole. Finally, we show that the combination of two common single nucleotide polymorphisms (SNPs) of CYP20A1 leads to an enzyme (CYP20A1Leu97Phe346) with reduced activity.

Laser-Induced Intersite Spin Transfer.

Laser pulses induce spin-selective charge flow that we show to generate dramatic changes in the magnetic structure of materials, including a switching of magnetic order from antiferromagnetic (AFM) to transient ferromagnetic (FM) in multisub-lattice systems. The microscopic mechanism underpinning this ultrafast switching of magnetic order is dominated by spin-selective charge transfer from one magnetic sublattice to another. Because this spin modulation is purely optical in nature (i.e., not mediated indirectly via the spin-orbit interaction) this is one of the fastest means of manipulating spin by light. We further demonstrate this mechanism to be universally applicable to AFM, FM, and ferri-magnets in both multilayer and bulk geometry and provide three rules that encapsulate early-time magnetization dynamics of multisub-lattice systems.

Treatment and outcomes in children with multidrug-resistant tuberculosis: A systematic review and individual patient data meta-analysis.

BACKGROUND: An estimated 32,000 children develop multidrug-resistant tuberculosis (MDR-TB; Mycobacterium tuberculosis resistant to isoniazid and rifampin) each year. Little is known about the optimal treatment for these children. METHODS AND FINDINGS: To inform the pediatric aspects of the revised World Health Organization (WHO) MDR-TB treatment guidelines, we performed a systematic review and individual patient data (IPD) meta-analysis, describing treatment outcomes in children treated for MDR-TB. To identify eligible reports we searched PubMed, LILACS, Embase, The Cochrane Library, PsychINFO, and BioMedCentral databases through 1 October 2014. To identify unpublished data, we reviewed conference abstracts, contacted experts in the field, and requested data through other routes, including at national and international conferences and through organizations working in pediatric MDR-TB. A cohort was eligible for inclusion if it included a minimum of three children (aged <15 years) who were treated for bacteriologically confirmed or clinically diagnosed MDR-TB, and if treatment outcomes were reported. The search yielded 2,772 reports; after review, 33 studies were eligible for inclusion, with IPD provided for 28 of these. All data were from published or unpublished observational cohorts. We analyzed demographic, clinical, and treatment factors as predictors of treatment outcome. In order to obtain adjusted estimates, we used a random-effects multivariable logistic regression (random intercept and random slope, unless specified otherwise) adjusted for the following covariates: age, sex, HIV infection, malnutrition, severe extrapulmonary disease, or the presence of severe disease on chest radiograph. We analyzed data from 975 children from 18 countries; 731 (75%) had bacteriologically confirmed and 244 (25%) had clinically diagnosed MDR-TB. The median age was 7.1 years. Of 910 (93%) children with documented HIV status, 359 (39%) were infected with HIV. When compared to clinically diagnosed patients, children with confirmed MDR-TB were more likely to be older, to be infected with HIV, to be malnourished, and to have severe tuberculosis (TB) on chest radiograph (p < 0.001 for all characteristics). Overall, 764 of 975 (78%) had a successful treatment outcome at the conclusion of therapy: 548/731 (75%) of confirmed and 216/244 (89%) of clinically diagnosed children (absolute difference 14%, 95% confidence interval [CI] 8%-19%, p < 0.001). Treatment was successful in only 56% of children with bacteriologically confirmed TB who were infected with HIV who did not receive any antiretroviral treatment (ART) during MDR-TB therapy, compared to 82% in children infected with HIV who received ART during MDR-TB therapy (absolute difference 26%, 95% CI 5%-48%, p = 0.006). In children with confirmed MDR-TB, the use of second-line injectable agents and high-dose isoniazid (15-20 mg/kg/day) were associated with treatment success (adjusted odds ratio [aOR] 2.9, 95% CI 1.0-8.3, p = 0.041 and aOR 5.9, 95% CI 1.7-20.5, p = 0.007, respectively). These findings for high-dose isoniazid may have been affected by site effect, as the majority of patients came from Cape Town. Limitations of this study include the difficulty of estimating the treatment effects of individual drugs within multidrug regimens, only observational cohort studies were available for inclusion, and treatment decisions were based on the clinician's perception of illness, with resulting potential for bias. CONCLUSIONS: This study suggests that children respond favorably to MDR-TB treatment. The low success rate in children infected with HIV who did not receive ART during their MDR-TB treatment highlights the need for ART in these children. Our findings of individual drug effects on treatment outcome should be further evaluated.