Exploring high-throughput synchrotron X-Ray powder diffraction for the structural analysis of pharmaceuticals.

Synchrotron radiation offers a host of advanced properties, surpassing conventional laboratory sources with its high brightness, tunable phonon energy, photon beam coherence for advanced X-ray imaging, and a structured time profile, ideal for capturing dynamic atomic and molecular processes. However, these benefits come at the cost of operational complexity and expenses. Three decades ago, synchrotron radiation facilities, while technically open to all scientists, primarily served a limited community. Despite substantial accessibility improvements over the past two decades, synchrotron measurements still do not qualify as routine analyses. The intrinsic complexity of synchrotron science means experiments are pursued only when no alternatives suffice. In recent years, strides have been made in technology transfer offices, intermediate synchrotron-based analytical service companies, and the development of high-throughput synchrotron systems at various facilities, reshaping the perception of synchrotron science. This article investigates the practical application of synchrotron X-Ray Powder Diffraction (s-XRPD) techniques in pharmaceutical analysis. By utilizing concrete examples, we demonstrate how high-throughput systems have the potential to revolutionize s-XRPD applications in the pharmaceutical industry, rapidly generating XRPD patterns of comparable or superior quality to those obtained in state-of-the-art laboratory XRPD, all in less than 5 s. Additional cases featuring well-established pharmaceutical active ingredients (API) and excipients substantiate the concept of high throughput in pharmaceuticals, affirming data quality through structural refinements aligned with literature-derived unit cell parameters. Synchrotron data need not always be state-of-the-art to compete with lab-XRPD data. The key lies in ensuring user-friendliness, reproducibility, accessibility, cost-effectiveness, and the streamlined efforts associated with synchrotron instrumentation to remain highly competitive with their laboratory counterparts.

Effects of vitamin E and selenium administration on transportation stress in pregnant dairy heifers.

We investigated the effects of road transportation and administration of the vitamin E and selenium (ESe) on circulating cortisol, haptoglobin, blood metabolites, oxidative biomarkers, white blood cell profiles, and behaviors in pregnant dairy heifers. Forty pregnant Holstein heifers were randomly assigned to one of 4 treatments: no transportation and no ESe administration, no transportation and ESe administration, transportation and no administration, and transportation and ESe administration. The ESe (70 IU/kg dry matter feed of dl-α-tocopheryl acetate and 0.3 mg/kg dry matter feed of sodium selenite) was orally delivered once a day from 7 d before transportation to 3 d after transportation. The heifers were transported in trucks designed for cattle transportation. Blood was collected 1 h before transportation, immediately after transportation (IAT), and at 6, 24, and 48 h after transportation. Behaviors were recorded using a video camera for 2 consecutive days after transportation. Transported/non-ESe-administered heifers had greater cortisol at IAT, haptoglobin at 6 and 24 h after transportation, total oxidative status at 6 h after transportation, and nonesterified fatty acid levels, white blood cell numbers, and neutrophil percentages at IAT and 6 h after transportation in the blood than nontransported heifers. Transported/non-ESe-administered heifers had lower total antioxidative status levels at 48 h after transportation and lymphocyte percentages at IAT and 6 h after transportation than nontransported heifers. Lying time was shorter in transported heifers than nontransported/non-ESe-administered heifers. Transported/ESe-administered heifers had lower cortisol, total oxidative status, nonesterified fatty acid levels at IAT, and haptoglobin concentrations at 6 and 24 h after transportation than transported/non-ESe-administered heifers. Transported/ESe-administered heifers had greater total antioxidative status levels at 48 h after transportation than transported/non-ESe-administered heifers. No ESe administration effects were observed for white blood cell number and neutrophil and lymphocyte percentages and lying time. In conclusion, road transportation caused temporary oxidative stress. Administrating ESe partially alleviated the stress, suggesting that ESe administration could be a viable strategy to reduce stress in transported pregnant heifers, providing a novel role of vitamin E and selenium for improving animal welfare.

Punctuated growth of InAs quantum dashes-in-a-well for enhanced 2-µm emission.

InAs quantum dashes (Qdash) engineered to emit near 2 µm are envisioned to be promising quantum emitters for next-generation technologies in sensing and communications. In this study, we explore the effect of punctuated growth (PG) on the structure and optical properties of InP-based InAs Qdashes emitting near the 2-µm wavelength. Morphological analysis revealed that PG led to an improvement in in-plane size uniformity and increases in average height and height distribution. A 2 × boost in photoluminescence intensity was observed, which we attribute to improved lateral dimensions and structural stabilization. PG encouraged formation of taller Qdashes while photoluminescence measurements revealed a blue-shift in the peak wavelength. We proposed that the blue-shift originates from the thinner quantum well cap and decreased distance between the Qdash and InAlGaAs barrier. This study on the punctuated growth of large InAs Qdashes is a step toward realizing bright, tunable, and broadband sources for 2-µm communications, spectroscopy, and sensing.

Effects of genomic estimated breeding value and dietary energy to protein ratio on growth performance, carcass trait, and lipogenic gene expression in Hanwoo steer.

"Genome-based precision feeding" is a concept that involves the application of customised diets to different genetic groups of cattle. We investigated the effects of the genomic estimated breeding value (gEBV) and dietary energy to protein ratio (DEP) on growth performance, carcass traits, and lipogenic gene expression in Hanwoo (Korean cattle) steers. Forty-four Hanwoo steers (BW = 636 kg, age = 26.9 months) were genotyped using the Illumina Bovine 50 K BeadChip. The gEBV was calculated using genomic best linear unbiased prediction. Animals were separated into high gEBV of marbling score or low-gMS groups based on the upper and lower 50% groupings of the reference population, respectively. Animals were assigned to one of four groups in a 2 × 2 factorial arrangement: high gMS/high DEP (0.084 MJ/g), high gMS/low DEP (0.079 MJ/g), low gMS/high DEP, and low gMS/low DEP. Steers were fed concentrate with a high or low DEP for 31 weeks. The BW tended to be higher (0.05 < P < 0.1) in the high-gMS groups compared to the low-gMS groups at 0, 4, 8, 12, and 20 weeks. The average daily gain (ADG) tended to be lower (P = 0.08) in the high-gMS group than in the low-gMS group. Final BW and measured carcass weight (CW) were positively correlated with the gEBV of carcass weight (gCW). The DEP did not affect ADG. Neither the gMS nor the DEP affected the MS and beef quality grade. The intramuscular fat (IMF) content in the longissimus thoracis (LT) tended to be higher (P = 0.08) in the high-gMS groups than in the low-gMS groups. The mRNA levels of lipogenic acetyl-CoA carboxylase and fatty acid binding protein 4 genes in the LT were higher (P < 0.05) in the high-gMS group than in the low-gMS group. Overall, the IMF content tended to be affected by the gMS, and the genetic potential (i.e., gMS) was associated with the functional activity of lipogenic gene expression. The gCW was associated with the measured BW and CW. The results demonstrated that the gMS and the gCW may be used as early prediction indexes for meat quality and growth potential of beef cattle.

Novel modification of Marcy operation for indirect inguinal hernia reconstituting deep inguinal ring shutter action.

PURPOSE: The two most frequent and significant complications after inguinal hernia repair are hernia recurrence and post-herniorrhaphy chronic pain. To add anatomic and physiologic strength to the tissue repair, especially in indirect inguinal herniorrhaphy, we devised a modification of Marcy operation that can reconstitute inguinal shutter action more efficiently by changing the direction of the sutures vertical to horizontal. METHODS: During 36 months from 1st Jan. 2019, 148cases of 140 patients were operated for Indirect inguinal hernia or Pantaloon hernia (11 cases). 145 indirect inguinal herniorrhaphy were performed exclusively with author's modification of Marcy operation. Hernia recurrence during the follow-up period (3 months-36 months), and postoperative chronic pain at 3 months after herniorrhaphy were analyzed. RESULTS: 104 cases among the 145 indirect inguinal hernia (71.7%) were operated with only deep inguinal ring (DIR) reconstruction as author modified. In 41 cases (28.3%), posterior wall reconstruction was done simultaneously. There was no recurrence or reoperation case during the follow-up period. The incidence of postoperative chronic pain at postoperative 3 months of VAS greater than 3.0 was 2.2% (3 cases). CONCLUSIONS: Author's modification of Marcy operation was feasible anatomically in all indirect inguinal hernia repair, which is theoretically superior to classic Marcy operation in that repositioning the DIR more laterally and securing the obliquity and shutter action of the DIR. Result is at least not inferior in the aspect of short-term recurrence and chronic post-herniorrhaphy pain.

MXene Based Nanocomposites for Recent Solar Energy Technologies.

This article discusses the design and preparation of a modified MXene-based nanocomposite for increasing the power conversion efficiency and long-term stability of perovskite solar cells. The MXene family of materials among 2D nanomaterials has shown considerable promise in enhancing solar cell performance because of their remarkable surface-enhanced characteristics. Firstly, there are a variety of approaches to making MXene-reinforced composites, from solution mixing to powder metallurgy. In addition, their outstanding features, including high electrical conductivity, Young's modulus, and distinctive shape, make them very advantageous for composite synthesis. In contrast, its excellent chemical stability, electronic conductivity, tunable band gaps, and ion intercalation make it a promising contender for various applications. Photovoltaic devices, which turn sunlight into electricity, are an exciting new area of research for sustainable power. Based on an analysis of recent articles, the hydro-thermal method has been widely used for synthesizing MXene-based nano-composites because of the easiness of fabrication and low cost. Finally, we identify new perspectives for adjusting the performance of MXene for various nanocomposites by controlling the composition of the two-dimensional transition metal MXene phase.

Stabilized Radiation Pressure Acceleration and Neutron Generation in Ultrathin Deuterated Foils.

Premature relativistic transparency of ultrathin, laser-irradiated targets is recognized as an obstacle to achieving a stable radiation pressure acceleration in the "light sail" (LS) mode. Experimental data, corroborated by 2D PIC simulations, show that a few-nm thick overcoat surface layer of high Z material significantly improves ion bunching at high energies during the acceleration. This is diagnosed by simultaneous ion and neutron spectroscopy following irradiation of deuterated plastic targets. In particular, copious and directional neutron production (significantly larger than for other in-target schemes) arises, under optimal parameters, as a signature of plasma layer integrity during the acceleration.

Absolute calibration of Fujifilm BAS-TR image plate response to laser driven protons up to 40 MeV.

Image plates (IPs) are a popular detector in the field of laser driven ion acceleration, owing to their high dynamic range and reusability. An absolute calibration of these detectors to laser-driven protons in the routinely produced tens of MeV energy range is, therefore, essential. In this paper, the response of Fujifilm BAS-TR IPs to 1-40 MeV protons is calibrated by employing the detectors in high resolution Thomson parabola spectrometers in conjunction with a CR-39 nuclear track detector to determine absolute proton numbers. While CR-39 was placed in front of the image plate for lower energy protons, it was placed behind the image plate for energies above 10 MeV using suitable metal filters sandwiched between the image plate and CR-39 to select specific energies. The measured response agrees well with previously reported calibrations as well as standard models of IP response, providing, for the first time, an absolute calibration over a large range of proton energies of relevance to current experiments.

A Brief Review of the Role of 2D Mxene Nanosheets toward Solar Cells Efficiency Improvement.

This article discusses the application of two-dimensional metal MXenes in solar cells (SCs), which has attracted a lot of interest due to their outstanding transparency, metallic electrical conductivity, and mechanical characteristics. In addition, some application examples of MXenes as an electrode, additive, and electron/hole transport layer in perovskite solar cells are described individually, with essential research issues highlighted. Firstly, it is imperative to comprehend the conversion efficiency of solar cells and the difficulties of effectively incorporating metal MXenes into the building blocks of solar cells to improve stability and operational performance. Based on the analysis of new articles, several ideas have been generated to advance the exploration of the potential of MXene in SCs. In addition, research into other relevant MXene suitable in perovskite solar cells (PSCs) is required to enhance the relevant work. Therefore, we identify new perspectives to achieve solar cell power conversion efficiency with an excellent quality-cost ratio.

Probing sedimentation non-ideality of particulate systems using analytical centrifugation.

Analytical centrifugation is a versatile technique for the quantitative characterization of colloidal systems including colloidal stability. The recent developments in data acquisition and evaluation allow the accurate determination of particle size, shape anisotropy and particle density. High precision analytical centrifugation is in particular suited for the study of particle interactions and concentration-dependent sedimentation coefficients. We present a holistic approach for the quantitative determination of sedimentation non-ideality via analytical centrifugation for polydisperse, plain and amino-functionalized silica particles spanning over one order of magnitude in particle size between 100 nm and 1200 nm. These systems typically behave as neutral hard spheres as predicted by auxiliary lattice Boltzmann simulations. The extent of electrostatic interactions and their impact on sedimentation non-ideality can be quantified by the repulsion range, which is the ratio of the Debye length and the average interparticle distance. Experimental access to the repulsion range is provided through conductivity measurements. With the experimental repulsion range at hand, we estimate the effect of polydispersity on concentration-dependent sedimentation properties through a combination of lattice Boltzmann and Brownian dynamics simulations. Finally, we determine the concentration-dependent sedimentation properties of charge-stabilized, fluorescently-labeled silica particles with a nominal particle size of 30 nm and reduced interparticle distance, hence an elevated repulsion range. Overall, our results demonstrate how the influence of hard-sphere type and electrostatic interactions can be quantified when probing sedimentation non-ideality of particulate systems using analytical centrifugation even for systems exhibiting moderate sample heterogeneity and complex interactions.

A preliminary evaluation of the circulating leptin/adiponectin ratio in dogs with pituitary-dependent hyperadrenocorticism and concurrent diabetes mellitus.

Leptin and adiponectin are thought to modulate insulin sensitivity and pancreatic ß-cell function, but there is limited information regarding the adipokine status of hyperglycemic dogs with hyperadrenocorticism. This study aimed to determine whether alterations in the leptin/adiponectin ratio, insulin sensitivity, and/or pancreatic ß-cell function are associated with diabetes mellitus (DM) in dogs with pituitary-dependent hyperadrenocorticism (PDH). A total of 48 client-owned dogs were included in this prospective observational study: 20 dogs with PDH (10 normoglycemic and 10 with DM), 15 dogs with DM, and 13 healthy dogs. The serum concentrations of leptin, adiponectin, resistin, interleukin (IL)-1ß, IL-6, IL-10, IL-18, and tumor necrosis factor (TNF)-α were measured, and homeostatic model assessment indices (HOMAs) were calculated and compared among the groups. Serum leptin was significantly higher in PDH dogs with and without DM than in healthy and DM dogs, and it was lower in DM dogs than in PDH dogs without DM. Serum adiponectin was significantly lower in PDH dogs with DM than in healthy and PDH dogs, and it was significantly lower in DM dogs than in healthy dogs. Serum IL-10 was significantly higher in PDH dogs with DM than in healthy and PDH dogs without DM. The leptin/adiponectin ratio was significantly higher in PDH dogs with DM than in normoglycemic PDH dogs. Serum IL-6 concentrations were significantly higher in DM dogs than in healthy dogs. Serum IL-1ß concentration was significantly higher in DM dogs than in healthy dogs and PDH dogs with DM and without DM. Serum TNF-α and IL-18 concentrations were not different among groups. The HOMAß-cell function was significantly lower in PDH dogs with DM than in normoglycemic PDH dogs, while HOMAinsulin sensitivity was significantly lower in PDH dogs with DM than in healthy dogs. These results suggest that adipokine dysregulation, a reduction in insulin sensitivity, and a further impairment in pancreatic ß-cell function might predispose PDH dogs to DM. Further longitudinal study will be necessary to confirm this result.

Search for Sub-eV Sterile Neutrinos at RENO.

We report a search result for a light sterile neutrino oscillation with roughly 2200 live days of data in the RENO experiment. The search is performed by electron antineutrino (ν[over ¯]_{e}) disappearance taking place between six 2.8 GW_{th} reactors and two identical detectors located at 294 m (near) and 1383 m (far) from the center of the reactor array. A spectral comparison between near and far detectors can explore reactor ν[over ¯]_{e} oscillations to a light sterile neutrino. An observed spectral difference is found to be consistent with that of the three-flavor oscillation model. This yields limits on sin^{2}2θ_{14} in the 10^{-4}≲|Δm_{41}^{2}|≲0.5 eV^{2} region, free from reactor ν[over ¯]_{e} flux and spectrum uncertainties. The RENO result provides the most stringent limits on sterile neutrino mixing at |Δm_{41}^{2}|≲0.002 eV^{2} using the ν[over ¯]_{e} disappearance channel.

Predicting patient outcomes in psychiatric hospitals with routine data: a machine learning approach.

BACKGROUND: A common problem in machine learning applications is availability of data at the point of decision making. The aim of the present study was to use routine data readily available at admission to predict aspects relevant to the organization of psychiatric hospital care. A further aim was to compare the results of a machine learning approach with those obtained through a traditional method and those obtained through a naive baseline classifier. METHODS: The study included consecutively discharged patients between 1st of January 2017 and 31st of December 2018 from nine psychiatric hospitals in Hesse, Germany. We compared the predictive performance achieved by stochastic gradient boosting (GBM) with multiple logistic regression and a naive baseline classifier. We tested the performance of our final models on unseen patients from another calendar year and from different hospitals. RESULTS: The study included 45,388 inpatient episodes. The models' performance, as measured by the area under the Receiver Operating Characteristic curve, varied strongly between the predicted outcomes, with relatively high performance in the prediction of coercive treatment (area under the curve: 0.83) and 1:1 observations (0.80) and relatively poor performance in the prediction of short length of stay (0.69) and non-response to treatment (0.65). The GBM performed slightly better than logistic regression. Both approaches were substantially better than a naive prediction based solely on basic diagnostic grouping. CONCLUSION: The present study has shown that administrative routine data can be used to predict aspects relevant to the organisation of psychiatric hospital care. Future research should investigate the predictive performance that is necessary to provide effective assistance in clinical practice for the benefit of both staff and patients.

The Impact of Rate Formulations on Stochastic Molecular Motor Dynamics.

Cells are complex structures which require considerable amounts of organization via transport of large intracellular cargo. While passive diffusion is often sufficiently fast for the transport of smaller cargo, active transport is necessary to organize large structures on the short timescales necessary for biological function. The main mechanism of this transport is by cargo attachment to motors which walk in a directed fashion along intracellular filaments. There are a number of models which seek to describe the motion of motors with attached cargo, from detailed microscopic to coarse phenomenological descriptions. We focus on the intermediate-detailed discrete stochastic hopping models, and explore how cargo transport changes depending on the number of motors, motor interaction, system constraints and rate formulations, which are derived from common thermodynamic assumptions. We find that, despite obeying the same detailed balance constraint, the choice of rate formulation considerably affects the characteristics of the overall motion of the system, with one rate formulation exhibiting novel behavior of loaded motor groups moving faster than a single unloaded motor.

Nod-like receptors are critical for gut-brain axis signalling in mice.

KEY POINTS: •Nucleotide binding oligomerization domain (Nod)-like receptors regulate cognition, anxiety and hypothalamic-pituitary-adrenal axis activation. •Nod-like receptors regulate central and peripheral serotonergic biology. •Nod-like receptors are important for maintenance of gastrointestinal physiology. •Intestinal epithelial cell expression of Nod1 receptors regulate behaviour. ABSTRACT: Gut-brain axis signalling is critical for maintaining health and homeostasis. Stressful life events can impact gut-brain signalling, leading to altered mood, cognition and intestinal dysfunction. In the present study, we identified nucleotide binding oligomerization domain (Nod)-like receptors (NLR), Nod1 and Nod2, as novel regulators for gut-brain signalling. NLR are innate immune pattern recognition receptors expressed in the gut and brain, and are important in the regulation of gastrointestinal physiology. We found that mice deficient in both Nod1 and Nod2 (NodDKO) demonstrate signs of stress-induced anxiety, cognitive impairment and depression in the context of a hyperactive hypothalamic-pituitary-adrenal axis. These deficits were coupled with impairments in the serotonergic pathway in the brain, decreased hippocampal cell proliferation and immature neurons, as well as reduced neural activation. In addition, NodDKO mice had increased gastrointestinal permeability and altered serotonin signalling in the gut following exposure to acute stress. Administration of the selective serotonin reuptake inhibitor, fluoxetine, abrogated behavioural impairments and restored serotonin signalling. We also identified that intestinal epithelial cell-specific deletion of Nod1 (VilCre+ Nod1f/f ), but not Nod2, increased susceptibility to stress-induced anxiety-like behaviour and cognitive impairment following exposure to stress. Together, these data suggest that intestinal epithelial NLR are novel modulators of gut-brain communication and may serve as potential novel therapeutic targets for the treatment of gut-brain disorders.

Fuel-Composition Dependent Reactor Antineutrino Yield at RENO.

We report a fuel-dependent reactor electron antineutrino (ν[over ¯]_{e}) yield using six 2.8 GW_{th} reactors in the Hanbit nuclear power plant complex, Yonggwang, Korea. The analysis uses 850 666 ν[over ¯]_{e} candidate events with a background fraction of 2.0% acquired through inverse beta decay (IBD) interactions in the near detector for 1807.9 live days from August 2011 to February 2018. Based on multiple fuel cycles, we observe a fuel ^{235}U dependent variation of measured IBD yields with a slope of (1.51±0.23)×10^{-43} cm^{2}/fission and measure a total average IBD yield of (5.84±0.13)×10^{-43} cm^{2}/fission. The hypothesis of no fuel-dependent IBD yield is ruled out at 6.6σ. The observed IBD yield variation over ^{235}U isotope fraction does not show significant deviation from the Huber-Mueller (HM) prediction at 1.3 σ. The measured fuel-dependent variation determines IBD yields of (6.15±0.19)×10^{-43} and (4.18±0.26)×10^{-43} cm^{2}/fission for two dominant fuel isotopes ^{235}U and ^{239}Pu, respectively. The measured IBD yield per ^{235}U fission shows the largest deficit relative to the HM prediction. Reevaluation of the ^{235}U IBD yield per fission may mostly solve the reactor antineutrino anomaly (RAA) while ^{239}Pu is not completely ruled out as a possible contributor to the anomaly. We also report a 2.9 σ correlation between the fractional change of the 5 MeV excess and the reactor fuel isotope fraction of ^{235}U.

Measurement of Reactor Antineutrino Oscillation Amplitude and Frequency at RENO.

The RENO experiment reports more precisely measured values of θ_{13} and |Δm_{ee}^{2}| using ∼2200 live days of data. The amplitude and frequency of reactor electron antineutrino (ν[over ¯]_{e}) oscillation are measured by comparing the prompt signal spectra obtained from two identical near and far detectors. In the period between August 2011 and February 2018, the far (near) detector observed 103 212 (850 666) ν[over ¯]_{e} candidate events with a background fraction of 4.8% (2.0%). A clear energy and baseline dependent disappearance of reactor ν[over ¯]_{e} is observed in the deficit of the measured number of ν[over ¯]_{e}. Based on the measured far-to-near ratio of prompt spectra, we obtain sin^{2}2θ_{13}=0.0896±0.0048(stat)±0.0047(syst) and |Δm_{ee}^{2}|=[2.68±0.12(stat)±0.07(syst)]×10^{-3} eV^{2}.

Effect of prolonged inspiratory time on gas exchange during robot-assisted laparoscopic urologic surgery.

BACKGROUND: Gas exchange disturbance may develop during urologic robotic laparoscopic surgery with the patient in a steep Trendelenburg position. This study investigated whether prolonged inspiratory time could mitigate gas exchange disturbances including hypercapnia. METHODS: In this randomized cross-over trial, 32 patients scheduled for robot-assisted urologic surgery were randomized to receive an inspiratory to expiratory time ratio (I:E) of 1:1 for the first hour of pneumoperitoneum followed by 1:2 for last period of surgery (group A, n = 17) or I:E of 1:2 followed by 1:1 (group B, n = 15). Arterial blood gas analysis, airway pressure and hemodynamic variables were assessed at four time points (T1: 10 min after induction of general anesthesia, T2: 1 h after the initiation of pneumoperitoneum, T3: 1 h after T2 and T4: at skin closure). The carry over effect of initial I:E was also evaluated over the next hour through arterial blood gas analysis. RESULTS: There was a significant decrease in partial pressure of oxygen in arterial blood (PaO2) for both groups at T2 and T3 compared to T1 but in group B the PaO2 at T4 was not decreased from the baseline. Partial pressure of carbon dioxide in arterial blood (PaCO2) increased with I:E of 1:2 but did not significantly increase with I:E of 1:1; however, there were no differences in PaO2 and PaCO2 between the groups. CONCLUSION: Decreased oxygenation by pneumoperitoneum was improved and PaCO2 did not increase after 1 h of I:E of 1:1; however, the effect of equal ratio ventilation longer than 1 h remains to be determined. There was no carryover effect of the two different I:E ratios.