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In the title compound, C24H23FN4O4S·0.25H2O, the dihydropyrimidine ring is distinctly non-planar, with the flap C atom deviating by 0.297 (2) Å from the least-squares plane. In the crystal, zigzag chains are formed by N—H...N hydrogen bonds parallel to [010] and are connected into layers parallel to (100) by O—H...O, O—H...F, C—H...O, C—H...F and C—H...N hydrogen bonds. Additional C—H...O hydrogen bonds connect the layers into a three-dimensional network. A Hirshfeld surface analysis indicates that the most significant contributions to the crystal packing are from H...H (42.6%), O...H/H...O (16.8%) and C...H/H...C (15.5%) contacts.

The central cyclohexane ring of the title compound, C32H28N2O4, adopts a chair conformation, with puckering parameters Q T = 0.618 (2) Å, θ = 176.72 (19)° and φ = 290 (3)°. In the crystal, molecules are linked by O—H...O, C—H...O and C—H...N hydrogen bonds, forming layers parallel to (100). These layers are linked by weak C—H...π interactions and van der Waals forces. A Hirshfeld surface analysis indicates that the contributions from the most prevalent interactions are H...H (41.2% contribution), C...H/H...C (20.3%), O...H/H...O (17.8%) and N...H/H...N (10.6%).

Molecular design based on generative models, such as variational autoencoders (VAEs), has become increasingly popular in recent years due to its efficiency for exploring high-dimensional molecular space to identify molecules with desired properties. While the efficacy of the initial model strongly depends on the training data, the sampling efficiency of the model for suggesting novel molecules with enhanced properties can be further enhanced via latent space optimization. In this paper, we propose a multi-objective latent space optimization (LSO) method that can significantly enhance the performance of generative molecular design (GMD). The proposed method adopts an iterative weighted retraining approach, where the respective weights of the molecules in the training data are determined by their Pareto efficiency. We demonstrate that our multi-objective GMD LSO method can significantly improve the performance of GMD for jointly optimizing multiple molecular properties., Comment: 13 pages, 6 figures

Supplemental material, sj-docx-1-cix-10.1177_11769351221139491 for TULIP: An RNA-seq-based Primary Tumor Type Prediction Tool Using Convolutional Neural Networks by Sara Jones, Matthew Beyers, Maulik Shukla, Fangfang Xia, Thomas Brettin, Rick Stevens, M Ryan Weil and Satishkumar Ranganathan Ganakammal in Cancer Informatics

Electrolytes for lithium-ion batteries (LiBs) have been put aside for too long because few new solvents have been designed to match electrolyte specifications. Conversely, more attention has been paid to synthesize new electrode materials, and more especially positive electrodes. Particularly, most of the studies dedicated to the investigation of electrolytes for LiBs have been focused on mixing different molecules. Nowadays, the development of high-voltage materials for LiBs stimulates the synthesis of new solvents and new salts more stable against oxidation. Despite the challenges, only few teams are active in this field in developing a rational approach combining physicochemistry, electrochemistry and modelling from the molecular to the macromolecular levels. After assembling a critical collection of physicochemical and electrochemical data from the literature, this paper highlights the main trends between the chemical structure of organic dipolar aprotic solvents and their physicochemical and electrochemical properties in order to provide a guide for the chemists to design new electrolytes for LiBs. This guide also includes indicators to take into account the environmental impact of solvent production by including the life cycle assessment of eight different solvents.

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The semiconductor field-effect platform represents a powerful tool for detecting the adsorption and binding of charged macromolecules with direct electrical readout. In this work, a capacitive electrolyte-insulator-semiconductor (EIS) field-effect sensor consisting of an Al-p-Si-SiO2 structure has been applied for real-time in situ electrical monitoring of the layer-by-layer formation of polyelectrolyte (PE) multilayers (PEM). The PEMs were deposited directly onto the SiO2 surface without any precursor layer or drying procedures. Anionic poly(sodium 4-styrene sulfonate) and cationic weak polyelectrolyte poly(allylamine hydrochloride) have been chosen as a model system. The effect of the ionic strength of the solution, polyelectrolyte concentration, number and polarity of the PE layers on the characteristics of the PEM-modified EIS sensors have been studied by means of capacitance-voltage and constant-capacitance methods. In addition, the thickness, surface morphology, roughness and wettabilityof the PE mono- and multilayers have been characterised by ellipsometry, atomic force microscopy and water contact-angle methods, respectively. To explain potential oscillations on the gate surface and signal behaviour of the capacitive field-effect EIS sensor modified with a PEM, a simplified electrostatic model that takes into account the reduced electrostatic screening of PE charges by mobile ions within the PEM has been proposed and discussed.

Myelin basic protein undergoes a phase transition from a cytoplasmic soluble pool into a cohesive functional amyloid-like assembly; this may be one mechanism of myelin membrane biogenesis., Rapid conduction of nerve impulses requires coating of axons by myelin. To function as an electrical insulator, myelin is generated as a tightly packed, lipid-rich multilayered membrane sheath. Knowledge about the mechanisms that govern myelin membrane biogenesis is required to understand myelin disassembly as it occurs in diseases such as multiple sclerosis. Here, we show that myelin basic protein drives myelin biogenesis using weak forces arising from its inherent capacity to phase separate. The association of myelin basic protein molecules to the inner leaflet of the membrane bilayer induces a phase transition into a cohesive mesh-like protein network. The formation of this protein network shares features with amyloid fibril formation. The process is driven by phenylalanine-mediated hydrophobic and amyloid-like interactions that provide the molecular basis for protein extrusion and myelin membrane zippering. These findings uncover a physicochemical mechanism of how a cytosolic protein regulates the morphology of a complex membrane architecture. These results provide a key mechanism in myelin membrane biogenesis with implications for disabling demyelinating diseases of the central nervous system., Author Summary Myelin is a specialized membrane that covers axons and serves as an insulator to enable the fast conduction of the action potentials. The importance of myelin membrane is highlighted in demyelinating diseases such as multiple sclerosis, which lead to severe neurological disability. Here, we describe a physicochemical mechanism of how myelin is generated and assembled. We find that myelin basic protein (MBP) molecules undergo a phase transition into a cohesive meshwork at the membrane interface, which drives structural changes in the membranes. We provide evidence that the interaction of myelin basic proteins with the inner leaflet of the myelin bilayer results in charge neutralization and triggers self-association of the protein into larger polymers. Interactions between MBP molecules are mediated by hydrophobic phenylalanine residues and amyloid-like association. We propose that phase transition of MBP from a cytoplasmic soluble pool into a cohesive functional amyloid-like assembly is one of the key mechanisms in myelin membrane biogenesis.

In this work we study the interplay between the crystal structure and magnetism of the pyroarsenate \alpha-Cu_2As_2O_7 by means of magnetization, heat capacity, electron spin resonance and nuclear magnetic resonance measurements as well as density functional theory (DFT) calculations and quantum Monte Carlo (QMC) simulations. The data reveal that the magnetic Cu-O chains in the crystal structure represent a realization of a quasi-one dimensional (1D) coupled alternating spin-1/2 Heisenberg chain model with relevant pathways through non-magnetic AsO_4 tetrahedra. Owing to residual 3D interactions antiferromagnetic long range ordering at T_N\simeq10K takes place. Application of external magnetic field B along the magnetically easy axis induces the transition to a spin-flop phase at B_{SF}~1.7T (2K). The experimental data suggest that substantial quantum spin fluctuations take place at low magnetic fields in the ordered state. DFT calculations confirm the quasi-one-dimensional nature of the spin lattice, with the leading coupling J_1 within the structural dimers. QMC fits to the magnetic susceptibility evaluate J_1=164K, the weaker intrachain coupling J'_1/J_1 = 0.55, and the effective interchain coupling J_{ic1}/J_1 = 0.20., Comment: Accepted for publication in Physical Review B

In this work we study the interplay between the crystal structure and magnetism of the pyroarsenate ��-Cu_2As_2O_7 by means of magnetization, heat capacity, electron spin resonance and nuclear magnetic resonance measurements as well as density functional theory (DFT) calculations and quantum Monte Carlo (QMC) simulations. The data reveal that the magnetic Cu-O chains in the crystal structure represent a realization of a quasi-one dimensional (1D) coupled alternating spin-1/2 Heisenberg chain model with relevant pathways through non-magnetic AsO_4 tetrahedra. Owing to residual 3D interactions antiferromagnetic long range ordering at T_N\simeq10K takes place. Application of external magnetic field B along the magnetically easy axis induces the transition to a spin-flop phase at B_{SF}~1.7T (2K). The experimental data suggest that substantial quantum spin fluctuations take place at low magnetic fields in the ordered state. DFT calculations confirm the quasi-one-dimensional nature of the spin lattice, with the leading coupling J_1 within the structural dimers. QMC fits to the magnetic susceptibility evaluate J_1=164K, the weaker intrachain coupling J'_1/J_1 = 0.55, and the effective interchain coupling J_{ic1}/J_1 = 0.20., Accepted for publication in Physical Review B

The magnetic and electrical properties of Co$_3$TeO$_6$ single-crystals with corundum related structure reveal a magnetic-field induced polarization below 21 K. A sharp peak in the specific heat at \approx 18 K indicates a reconstructive-type first-order phase transition. From second-harmonic generation (SHG) measurements breaking of inversion symmetry is evident and the point-group symmetry was determined as m. The temperature and magnetic-field dependence of the magnetic and electrical polarizations are discussed in the light of the SHG results., Comment: 5 pages, 5 figures

We investigate the influence of the cooling epoch on the formation of galaxies in a cold dark matter dominated universe. Isolated haloes, with circular speeds typical of spiral galaxies, have been selected from a low resolution numerical simulation for re-simulation at higher resolution with dark matter and gas components. The initial conditions are evolved with two smoothed particle hydrodynamics codes, TREESPH and GRAPESPH. In previous SPH simulations, strong outward transport of angular momentum has led to the formation of disc-like systems with much smaller angular momenta than observed in real disc galaxies. Here we investigate whether this problem can be circumvented if feedback processes prevent disc formation until late epochs. The results of varying the cooling epoch for each of five different haloes are analysed. When cooling and star formation occur at early times, stellar discs are destroyed during merger events and we observe similar catastrophic transport of angular momentum as seen in previous work. With cooling suppressed until z=1, discs can form by the present day with angular momenta comparable to those of observed disc galaxies. We conclude that feedback processes, which prevent gas from collapsing until late epochs, are an essential ingredient in disc galaxy formation., Comment: 19 pages, LaTeX, MNRAS format, 14 inlined and 2 external Postscript figures. Submitted to MNRAS

We present high resolution (7 arcsec), high sensitivity HI images of the shell galaxy NGC 1210. The neutral hydrogen forms a continous loop which appears in projection as an off-centered ring. Some remarkable aspects are the large HI mass, ( 8 x 10(9) Msun), the sharpness of some of its features (

By using ultrustructural and cytochemical techniques, monocytic precursors and granulocytic precursors can now be identified, and it is possible to isolate “pure acute monoblastic leukemia” [1]. In this study based on a retrospective study of 88 cases, we report the distinctive clinical and biologic features of acute monoblastic leukemia (AMol), which represents about 3.5% of all acute leukemias [2]. Described as a very acute leukemia in 1969 [3], AMol always has a very poor prognosis, despite progress in chemotherapy.

Diaziquone, a new alkylating agent which crosses the blood brain barrier, has shown a 20% response rate in phase II studies in heavily pretreated patients. We have treated 23 patients at our institution as part of a multicentric phase II European trial of diaziquone. All had histologically proven malignant glioma unequivocally progressing on CT scan. Prior therapy had consisted of surgical excision (13 patients), cobalt radiotherapy to CNS (13 patients), and chemotherapy with nitrosourea derivatives (11 patients). Six patients had no prior therapy. Median age was 42 years (range 22-69) and performance status was 3+ or better. They were treated with monthly courses of diaziquone 5.5 mg/m2 I.V. (10 min.) X 5 days. Dosage adjustments were made according to leucocyte and platelet nadirs. Thrombocytopenia was the dose limiting toxicity. Very mild gastrointestinal toxicity was observed. One patient developed hemolytic anemia. One complete response (clinical and CT scan), 7 partial clinical responses (3: greater than 50%, 4: 25-50%), and 1 disease stabilization (less than 25%) were documented. The longest response has now lasted over 26 months. These preliminary results show that chemotherapy with diaziquone can achieve a response rate as high as 35% in malignant glioma even in patients previously treated with a chemotherapy regimen including a nitrosourea (four of the seven objective responses were seen in such patients). Diaziquone is well tolerated and deserves further study in the management of malignant glioma.

Infection is the most common complication in acute leukemia; management of infections has a direct influence on the results of chemotherapy, especially in acute granulocytic leukemia. We report here our experience with white blood cell (WBC) transfusions.

We compared two regimens with respect to their ability to prolong disease-free survival in 506 children and adolescents with acute lymphocytic leukemia. All responders to induction therapy were randomized to treatment with 2400 rad of cranial irradiation plus intrathecal methotrexate or to treatment with intermediate-dose methotrexate plus intrathecal methotrexate, as prophylaxis for involvement of the central nervous system and other "sanctuary" areas. Patients were then treated with a standard maintenance regimen. Complete responders were stratified into either standard-risk or increased-risk groups on the basis of age and white-cell count at presentation. Among patients with standard risk, hematologic relapses occurred in 9 of 117 given methotrexate and 24 of 120 given irradiation (P less than 0.01). The rate of central-nervous-system relapse was higher in the methotrexate group (23 of 117) than in the irradiation group (8 of 120) (P = 0.01). Among patients with increased risk, radiation offered greater protection to the central nervous system than methotrexate (P = 0.03); there was no difference in the rate of hematologic relapse. In both risk strata the frequency of testicular relapse was significantly lower in the methotrexate group (1 patient) than the radiation group (10 patients) (P = 0.01). Methotrexate offered better protection against systemic relapse in standard-risk patients and better protection against testicular relapse overall, but it offered less protection against relapses in the central nervous system than cranial irradiation.

The development of new batteries has historically been achieved through discovery and development cycles based on the intuition of the researcher, followed by experimental trial and error—often helped along by serendipitous breakthroughs. Meanwhile, it is evident that new strategies are needed to master the ever-growing complexity in the development of battery systems, and to fast-track the transfer of findings from the laboratory into commercially viable products. This review gives an overview over the future needs and the current state-of-the art of five research pillars of the European Large-Scale Research Initiative BATTERY 2030+, namely 1) Battery Interface Genome in combination with a Materials Acceleration Platform (BIG-MAP), progress toward the development of 2) self-healing battery materials, and methods for operando, 3) sensing to monitor battery health. These subjects are complemented by an overview over current and up-coming strategies to optimize 4) manufacturability of batteries and efforts toward development of a circular battery economy through implementation of 5) recyclability aspects in the design of the battery.

This paper describes a multimembership Bayesian index of severity calculated by MEDAS (the Medical Emergency Decision Assistance System). This severity index measures the likelihood that the patient will die without immediate intervention. The MEDAS inference engine operates on binary features representing signs, symptoms, and laboratory results. As a basis for calculation of the severity index, severity weights, ranging from 0 to 9 were assigned to each feature by an expert physician in order to form a severity pattern.

Acta crystallographica / Section E 76(5), 715 - 719 (2020). doi:10.1107/S2056989020005411, The crystal structure of MgCO$_3$-II has long been discussed in the literature where DFT-based model calculations predict a pressure-induced transition of the carbon atom from the sp$^2$ to the sp$^3$ type of bonding. We have now determined the crystal structure of iron-bearing MgCO$_3$-II based on single-crystal X-ray diffraction measurements using synchrotron radiation. We laser-heated a synthetic (Mg$_{0.85}$Fe$_{0.15}$)CO$_3$ single crystal at 2500 K and 98 GPa and observed the formation of a monoclinic phase with composition (Mg$_{2.53}$Fe$_{0.47}$)C$_3$O$_9$ in the space group C2/m that contains tetra­hedrally coordinated carbon, where CO$_4$$^{4-}$ tetra­hedra are linked by corner-sharing oxygen atoms to form three-membered C$_3$O$_3$$^{6-}$ ring anions. The crystal structure of (Mg$_{0.85}$Fe$_{0.15}$)CO$_3$ (magnesium iron carbonate) at 98 GPa and 300 K is reported here as well. In comparison with previous structure-prediction calculations and powder X-ray diffraction data, our structural data provide reliable information from experiments regarding atomic positions, bond lengths, and bond angles., Published by National Center for Biotechnology Information, U.S. National Library of Medicine15046, Bethesda, MD

The reaction kinetics and mechanism of geopolymers are studied. The dissolved silicate concentration decreases from the beginning of the reaction. A characteristic time 'to,vit' for the setting of the reaction mixture is derived from isothermal Dynamic Mechanical Analysis experiments. 'to,vit' increases with SiO2/R2O but goes through a minimum for increasing water content. The reaction is slower for K compared to Na-silicate based systems. 29Si and 27Al solution NMR are used to probe the molecular changes. 27Al NMR and FTIR reveal that an 'intermediate aluminosilicate species' (IAS) is formed from the start of the reaction. The concentration decrease of OH- during low-temperature reaction is related to the formation of IAS. The rate law of this process seems to be obeyed by a total reaction order of 5/3, with a partial order of 1 for OH- and 0 for Na+ in the silicate solution.