Soft Restraints Research Articles

SimRNAweb v2.0: a web server for RNA folding simulations and 3D structure modeling, with optional restraints and enhanced analysis of folding trajectories.

Research on ribonucleic acid (RNA) structures and functions benefits from easy-to-use tools for computational prediction and analyses of RNA three-dimensional (3D) structure. The SimRNAweb server version 2.0 offers an enhanced, user-friendly platform for RNA 3D structure prediction and analysis of RNA folding trajectories based on the SimRNA method. SimRNA employs a coarse-grained model, Monte Carlo sampling and statistical potentials to explore RNA conformational space, optionally guided by spatial restraints. Recognized for its accuracy in RNA 3D structure prediction in RNA-Puzzles and CASP competitions, SimRNA is particularly useful for incorporating restraints based on experimental data. The new server version introduces performance optimizations and extends user control over simulations and the processing of results. It allows the application of various hard and soft restraints, accommodating alternative structures involving canonical and noncanonical base pairs and unpaired residues, while also integrating data from chemical probing methods. Enhanced features include an improved analysis of folding trajectories, offering advanced clustering options and multiple analyses of the generated trajectories. These updates provide comprehensive tools for detailed RNA structure analysis. SimRNAweb v2.0 significantly broadens the scope of RNA modeling, emphasizing flexibility and user-defined parameter control. The web server is available at https://genesilico.pl/SimRNAweb.

Navigating Medical Care for a Young Adult with Developmental Disability.

Sam is a 20-year-old young man with intermittent gastritis, autism spectrum disorder, and intellectual disability who was admitted to the hospital because of nutritional concerns. His parents have legal guardianship and report that he has had increasing frequency of refusal to eat, resulting in a 15-pound weight loss over the past 3 months. On admission, a multidisciplinary team including specialists in gastroenterology, nutrition, feeding (behavioral and mechanical), psychiatry, palliative care, and social work was engaged to develop an evaluation and care plan. Sam's nutritional assessment was significant for severe malnutrition. An upper endoscopy was performed and was without abnormalities, including signs of significant gastritis.An upper endoscopy was performed and was without abnormalities, including signs of significant gastritis.A carefully obtained history found that Sam does not have a primary care physician. He was recently hospitalized at another facility because of his weight loss and nutritional concerns but was discharged against medical advice because of parental dissatisfaction with his care. His mother shared that she has tried many strategies to encourage Sam to eat including pushing spoons of food into his mouth, syringe feeding, and verbally pleading with Sam to take a bite, but all of these have been without success.Because of concerns that persistent attempts to verbally and physically coerce Sam to eat may be contributing to his aversion to food/eating, the feeding team provided Sam's parents with education and coaching for utilization of behavioral cues to determine when Sam wanted to eat. Despite parents expressing their understanding of the importance of avoiding physical attempts to "make" Sam eat and the team palliative care physician meeting with Sam's parents to elicit their goals for Sam's care, his nurses reported observing several instances of Sam's mother tapping a loaded spoon on his lips. Because of minimal oral intake, a nasogastric tube was placed for provision of hydration and nutrition. Sam's parents consented to the use of soft restraints and the presence of a bedside patient care assistant because of Sam becoming agitated and pulling at the tube.After 10 days of hospitalization, Sam was taking about 50% of his goal intake by mouth. Unfortunately, Sam removed his NG tube, and his parents refused to allow the tube to be replaced. Sam's parents then discharged him against medical advice, stating that they believed he would recover better at home. What are important considerations in caring for patients like Sam in the hospital setting and beyond?

Self-reported incidence of verbal and physical violence against emergency medical services (EMS) personnel in Singapore

BackgroundWestern studies have highlighted alarmingly high rates of work-related violence experienced by emergency medical services (EMS) staff. As there is a paucity of Asian studies, we aimed to investigate the incidence of physical and verbal violence against the EMS crew in the Singapore Civil Defence Force (SCDF). MethodsThis was a cross-sectional study, utilising an online survey made available to all active paramedics in the SCDF. Paramedics with at least one year of work experience were eligible to participate. All responses were kept anonymous. ResultsThe response rate was 50.9% (n = 246), out of 483 paramedics in service at the time of the study. The respondents consisted of 144 males (58.5%) and 102 females (41.5%). They were between 18 and 55 years old; 160 (65.0%) of them had worked in EMS for less than 6 years. The paramedics experienced high levels of verbal and physical violence, but there was reticence in reporting these incidents. The main risk factor for violence appeared to be alcohol intoxication. ConclusionsParamedics may benefit from security escort for clients with history of alcohol intoxication or violence and more teaching on self-defence and soft restraints. Current training and protocols should be revised to meet these needs.

Synthesis and structural characterization of 3-[1-[4-(2-methylpropyl)phenyl]ethyl]-6-(4-fluorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole

3-[1-[4-(2-Methylpropyl)phenyl]ethyl]-6-(4-fluorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C21H21FN4S) has been synthesized as a member of a series of triazolothiadiazoles having NSAIDs moieties with cytotoxic activity. The crystal structure of this new compound has been solved and refined using conventional laboratory X-ray powder diffraction data and optimized using density functional techniques. The final structure solution was achieved by Rietveld refinement using soft restraints on all non-H atom bond lengths and angles. This compound crystallizes in $P\bar{1}\;$ space group, with the unit cell parameters a = 5.5880(4) Å, b = 9.3074(7) Å, c = 19.497(4) Å, α = 99.311(10)°, β = 91.925(9)°, γ = 98.199(6)°, and V = 988.8(2) Å3. To complement and verify the structure solution of the compound, the density functional theory (DFT) calculations were performed by using the local density approximation and the generalized gradient approximation for exchange-correlation energy. In order to see the effect of the van der Waals interactions on the electronic structure, the relevant structure was also optimized with B3LYP-D2, PBE-D2, and optB88-vdW functionals. The refined crystal structure was confirmed by the DFT calculations. The best agreement with the experimental structure was achieved by optB88-vdW functional.

The crystal structures of 6'-(4-chloro-phen-yl)- and 6'-(4-meth-oxy-phen-yl)-6a'-nitro-6a',6b',7',9',10',12a'-hexa-hydro-2H,6'H,8'H-spiro-[ace-naphthyl-ene-1,12'-chromeno[3,4-a]indolizin]-2-one.

In the title compounds, C32H25ClN2O4 (I) and C33H28N2O5 (II), the six-membered pyran and piperidine rings adopt envelope and chair conformations, respectively. The five-membered pyrrolidine rings adopt twist conformations. Compound (II) crystallizes with two independent mol-ecules (A and B) in the asymmetric unit. In all three mol-ecules there is a C-H⋯O intra-molecular hydrogen bond present enclosing an S(7) ring motif. In (I), both oxygen atoms of the nitro group are disordered, while in (II) the meth-oxy-benzene group is disordered in mol-ecule B. The geometries were regularized by soft restraints. In the crystal of (I), mol-ecules are linked by C-H⋯O hydrogen bonds, forming chains along [010]. The chains are linked by C-H⋯Cl hydrogen bonds, forming layers parallel to (10). Within the layer there are C-H⋯π inter-actions present. In the crystal of (II), the A and B mol-ecules are linked via C-H⋯O hydrogen bonds, forming a square four-membered A-B-A-B unit. These units are linked by a number of C-H⋯π inter-actions, forming a three-dimensional supra-molecular structure.

Challenge in Management of Aggressive Clients in Psychiatric Setting: Development of Four-Point Physical Restraints

Introduction: The use of physical restraints is a very common procedure in psychiatric setting from the beginning of psychiatry as a branch of medicine. Any measure that keep someone under control is called a restraint. Four-point physical restraints are required for managing clients with mental illness. Material and Method: The objective of the project was to develop a safe and secure soft limb restraints for aggressive clients. A set of soft limb restraints (two each for upper and lower limbs) was developed along with user guidelines. High quality narrow woven fabric material was selected for preparing the restraints. The restraints were tested in 5 psychiatric hospitals. A 12 item checklist was developed and validated for assessing the user friendliness of the restraints. Necessary modifications were made based on the feedback given by the nurses who tested it. Results: All the nurses (100%) reported that the developed restraints were easy to apply, easy to remove and met the safety of the clients. Conclusion: The restraints developed was found to be more safe and operable as compared to other commercially available restraints.

Structure determination of phase II of the antifungal drug griseofulvin by powder X-ray diffraction.

Two new crystalline polymorphs of the widely used antifungal drug griseofulvin (phases II and III), which originate from the crystallization of the melt, have been detected recently. The crystal structure of phase II of griseofulvin {systematic name: (2S,6'R)-7-chloro-2',4,6-trimethoxy-6'-methyl-3H,4'H-spiro[1-benzofuran-2,1'-cyclohex-2-ene]-3,4'-dione}, C17H17ClO6, has been solved by powder X-ray diffraction (PXRD). The PXRD pattern of this new phase was recorded at room temperature using synchrotron radiation. The starting structural model was generated by a Monte Carlo simulated annealing method. The final structure was obtained through Rietveld refinement with soft restraints for interatomic bond lengths and angles, except for the aromatic ring, where a rigid-body constraint was applied. The symmetry is orthorhombic (space group P212121) and the asymmetric unit contains two molecules.

Structure determination of two structural analogs, named 3-[1-(2-fluoro-4-biphenyl)ethyl]-6-(4-fluorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C23H16F2N4S) and 3-[1-(2-fluoro-4-biphenyl)ethyl]-6-(4-chlorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C23H16ClFN4S) by synchrotron X-ray powder diffraction

Two novel compounds, 3-[1-(2-fluoro-4-biphenyl)ethyl]-6-(4-fluorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C23H16F2N4S) (1) and 3-[1-(2-fluoro-4-biphenyl)ethyl]-6-(4-chlorophenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole (C23H16ClFN4S) (2), have been designed and synthesized as cytotoxic agents. The compounds were characterized by infrared, proton nuclear magnetic resonance, mass spectral data, elemental analysis and X-ray powder diffraction. The present study comprises spectral data and crystal structures of these novel compounds determined from synchrotron X-ray powder diffraction data. The structure solutions were obtained by simulated annealing. The final structures were achieved by Rietveld refinement using soft restraints for all bond lengths, bond angles, and planar groups. Both compounds crystallize in space group $P\bar 1$, Z = 2, with the unit-cell parameters a = 6.37433(9), b = 11.3641(2), c = 14.09115(19) Å, α = 80.1740(8)°, β = 85.1164(8)°, γ = 80.9831(10)°, V = 991.55(3) Å3 of compound (1) and a = 6.53736(6), b = 11.55725(15), c = 14.01373(13) Å, α = 80.3323(7)°, β = 84.8939(6)°, γ = 79.3954(8)°, V = 1024.08(2) Å3 of compound (2). Structural analyses reveal that the title compounds are isostructural.

Structures of 2 new sulfates, Na2M(SO4)2(M=Co, Ni), with rare SO42-coordination

In this study the structures of two new sulfates, Na2M(SO4)2(M=Co, Ni), were determined via both single crystal diffraction and neutron and laboratory X-ray diffraction data. The structural analysis was initiated with single crystal diffraction of the cobalt analogue and while this elucidated the cation positions the oxygen positions were still elusive. Therefore, combined Rietveld refinements of laboratory and neutron powder diffraction data was performed employing both hard constraints and soft restraints. The 5 K neutron data of both compounds are isostructural with the room temperature data as shown by Rietveld refinements. Refinements show that the transition metal ions are in a pseudo octahedral coordination that is better represented by a trigonal bipyramid, where one of the ligands is an edge of a SO42-tetrahedra. This rare coordination of sulfate tetrahedra was corroborated by spectroscopic techniques: UV-vis, Raman, and infrared. Additionally these compounds adopt large unit cells within the space group C2/c: Na2Co(SO4)2vol=4137.17(1)Å3and Na2Ni(SO4)2vol=4080.17(5) Å3.

Cannonite [Bi2O(SO4)(OH)2] from Alfenza (Crodo, Italy): crystal structure and morphology

AbstractCanonite from Alfenza grows as crowded, radiating, acicular aggregates covering bismuthinite crystals. Individual crystals have a lozenge-shaped habit on {010}, the presumed cleavage plane of cannonite. Crystal structure refinements in the P21/c space group of two single crystals led to the following cell parameters: a = 7.7196(5) Å, b = 13.8856(9), c = 5.6980(4), b = 109.174(1)º (R1 = 0.0424); and a = 7.7100(8), b = 13.8717(14), c = 5.6939(6), b = 109.155(2)º (R1 = 0.0438). Hydrogen atoms were also localized in the density-difference Fourier map and refined with soft restraints on the bond distances. Raman and IR spectroscopy confirm the presence of OH groups and the absence of molecular water, and deliver OH···O geometry wholly comparable with the structure refinement. Electron microprobe analyses revealed no significant levels of elements other than those expected in the ideal formula except fluorine which was present up to 0.14 a.p.f.u. The crystal structure can be described in terms of anion-centred OBi4 edge-sharing tetrahedra forming chains running parallel to z and strongly cemented along x by isolated SO4 tetrahedra. Each OBi4 tetrahedron is further connected along y by OH groups, making walls of composition Bi4O2(SO4)2(OH)4 parallel to (010). These walls are tied to each other along y by fewer Bi–O–S bridges and weaker OH···O bonds.

Structure determination of the crystalline phase ofn-butanol by powder X-ray diffraction and study of intermolecular associations by Raman spectroscopy

X-ray powder diffraction patterns of n-butanol at 110 K and the isothermal transformation above the glass transition temperature of the supercooled liquid into the glacial state were recorded with a laboratory diffractometer. The starting structural model of the crystalline stable phase was found by a Monte-Carlo simulated annealing method. The final structure was obtained through Rietveld refinements with soft restraints on the interatomic bond lengths and angles. The cell is triclinic with space group P1 and contains two molecules. The width of the Bragg peaks is interpreted by a phenomenological microstructural approach in terms of anisotropic strain effects. The study of the hydrogen bonds by Raman spectroscopy shows the existence of two main kinds of hydrogen bonds in the crystal, in agreement with the structure obtained by diffraction. The glacial state resulting from an abortive crystallization is composed of microcrystallites of the stable phase coexisting with non-transformed supercooled liquid. Crystalline features of the glacial state were determined as closely connected to the microstructural description of the crystal, leading to information about the origin of the glacial state.

Structure determination of the crystalline phase ofn-butanol by powder X-ray diffraction and study of intermolecular associations by Raman spectroscopy

X-ray powder diffraction patterns of n-butanol at 110 K and the isothermal transformation above the glass transition temperature of the supercooled liquid into the glacial state were recorded with a laboratory diffractometer. The starting structural model of the crystalline stable phase was found by a Monte-Carlo simulated annealing method. The final structure was obtained through Rietveld refinements with soft restraints on the interatomic bond lengths and angles. The cell is triclinic with space group P1 and contains two molecules. The width of the Bragg peaks is interpreted by a phenomenological microstructural approach in terms of anisotropic strain effects. The study of the hydrogen bonds by Raman spectroscopy shows the existence of two main kinds of hydrogen bonds in the crystal, in agreement with the structure obtained by diffraction. The glacial state resulting from an abortive crystallization is composed of microcrystallites of the stable phase coexisting with non-transformed supercooled liquid. Crystalline features of the glacial state were determined as closely connected to the microstructural description of the crystal, leading to information about the origin of the glacial state.

Structure determination of L-arabinitol by powder X-ray diffraction

Powder X-ray diffraction patterns of the commercial phase of L-arabinitol were recorded with a laboratory diffractometer. The starting structural model was found by a Monte-Carlo simulated annealing method. The final structure was obtained through Rietveld refinements with soft restraints on the interatomic bond lengths and bond angles. H atoms of hydroxyl groups were localized by minimization of the crystalline energy. The cell is triclinic with the space group P1 and contains two molecules. The crystalline cohesion is achieved by an important network of O-H···O hydrogen bonds.

The restrained Rietveld refinement of modulated trivalent metal polyphosphates M(PO3)3

Abstract Room temperature X-ray powder diffraction data were used to investigate modulated crystal structures of two monoclinic polyphosphates of crystal form C, In(PO3)3 and Y(PO3)3, by the Rietveld refinement. The structures were refined with the program JANA2006 in the superspace groups Xc(0β0)0, β = 1/3, for commensurately modulated In(PO3)3, and Cc(0β0)0, β = 0.36564(7), for incommensurately modulated Y(PO3)3. The positional modulations were described with the first-order harmonic functions. The Rietveld refinement was performed with soft restraints on bond lengths and valence angles in PO4 tetrahedra, as well as on angles in MO6 octahedra. No initial information about modulation parameters was used. A good agreement of the observed and calculated intensities of main and satellite reflections was achieved for both compounds. Obtained modulated structures of In(PO3)3 and Y(PO3)3 are close to published single crystal data.

Ab initio structure determination of phase II of racemic ibuprofen by X-ray powder diffraction

Annealing of the quenched ibuprofen at 258 K yielded a new crystalline form, called phase II. Powder X-ray diffraction patterns of this phase II were recorded with a laboratory diffractometer equipped with an INEL G3000 goniometer and a curved position-sensitive detector CPS120. The starting structural model was found by a Monte-Carlo simulated annealing method. The final structure was obtained through Rietveld refinements with rigid-body constraints for the phenyl group and soft restraints on the other interatomic bond lengths and bond angles. The cell volume is 5% larger than that of the conventional phase I at 258 K. It is also shown that the orientation of the propanoic acid group is drastically changed with respect to phase I, leading to strong modifications of the orientation of the O-H...O hydrogen bonds with respect to the chains of dimers. These structural considerations could explain the metastable character of this phase II.

Postoperative Delirium

Postoperative Delirium

An X-ray powder investigation ofcatena-poly[copper(II)-di-μ-chloro-κ41:2Cl-μ-1,5-dimethyl-1H-tetrazole-κ2N3:N4

The crystal structure of the polymeric title complex, [CuCl2(C3H6N4)]n, has been solved from laboratory X-ray powder diffraction data collected at room temperature. The structural model obtained was refined with the Rietveld method using geometric soft restraints. There are two Cu atoms, two Cl atoms and one 1,5-dimethyltetrazole ligand in the asymmetric unit. Both Cu atoms lie on inversion centres and adopt essentially elongated octahedral coordination. Within the octahedra, the elongated axial positions are occupied by Cl atoms, while two Cl and two N atoms (N3 and N4 of the tetrazole ring) are in equatorial sites. Each Cl atom forms an asymmetric bridge between neighbouring Cu atoms, which are also bridged via the N3-N4 bond of the tetrazole ring. These bridges result in the formation of polymeric chains, running along the a axis, with weak C-H...Cl hydrogen bonds crosslinking the chains.

Two isostructural manganese (III) diphosphates, acid α-MnHP2O7 and double MnLiP2O7: crystal structure determination from X-ray powder diffraction data

Summary Ab initio crystal structure determination of the α form of MnHP2O7 and Rietveld refinement of the MnLiP2O7 structure were performed using powder X-ray diffraction data. The final structures have been obtained using soft restraints on interatomic bond lengths and bond angles for the diphosphate group. The two compounds were found to be to a great extent isostructural. They crystallize in the monoclinic space group P21, Z = 2, a = 6.7547(6), b = 8.3160(7), c = 4.8769(5) Å, β = 113.1791(18)°, R p = 0.0283, R wp = 0.0390, R Bragg = 0.0930, R F = 0.0869 for α-MnHP 22O7, and a = 7.0018(5), b = 8.1616(6), c = 4.7267(4)Å, β = 109.404(3)°, R p = 0.0307, R wp = 0.0423, R Bragg = 0.0960, R F = 0.0861 for MnLiP2O7. In both compounds, diphosphate groups adopt nearly eclipsed configuration. Their structures present three-dimensional networks, which have tunnels including the lithium cations or hydrogen atoms. The behaviour of the crystalline forms of MnHP2O7 in H/Li exchange reactions is discussed, vs. their structural aspects.

Protein Folding with a Reduced Model and Inaccurate Short-Range Restraints

Summary: A reduced high-coordination lattice protein model and the Replica Exchange Monte Carlo sampling were employed in de novo folding simulations of a set of representative small proteins. Three distinct situations were analyzed. In the first series of simulations, the folding was controlled purely by the generic force field of the model. In the second, a bias was introduced towards the theoretically predicted secondary structure. Finally, we superimposed soft restraints towards the native-like local conformation of the backbone. The short-range restraints used in these simulations are based on approximate values of ϕ and ψ dihedral angles, which may simulate restraints derived from inaccurate experimental measurements. Incorporating such data into the reduced model required developing a procedure, which transforms the ϕ and ψ coordinates into coordinates of the protein alpha carbon trace. It has been shown that such limited data are sufficient for de novo determination of three-dimensional structures of small and topologically not too complex proteins. Protein folding based on secondary structure prediction and simulated torsion angles data.

A novel strategy forab initiostructure determination using micro-powder X-ray diffraction: structure solution and refinement of 3-bromophenylboronic acid and tris(4-bromophenyl)boroxine

Micro-powder X-ray diffraction patterns of two compounds, namely 3-bromophenylboronic acid and tris(4-bromophenyl)boroxine, were recorded with microgram quantities of sample using a recently developed method employing nylon loops with synchrotron radiation and an image-plate detector. This method, besides using small amount of samples, offers the advantage of recording the powder pattern in the shortest possible time (less than a minute). The structures of the two compounds have been solved byab initiomethods using real-space techniques (simulated annealing and/or parallel tempering) followed by Rietveld refinements with soft restraints on the bond lengths of the rigid bodies. The former compound crystallizes in the monoclinic system [a= 15.7797 (4),b= 5.3085 (2),c= 9.3757 (3) Å, β = 93.357 (3)°; space groupP21/c;Z= 4;Rp= 16.060,Rwp= 10.543,RB= 4.25] with sheets of individual molecules linked through an extended hydrogen-bonding network. Tris(4-bromophenyl)boroxine, displaying molecular disorder, crystallizes in the orthorhombic system [a= 18.9289 (6),b= 21.8872 (6),c= 4.8842 (2) Å; space groupPnma;Z= 4;Rp= 13.270,Rwp= 12.083,RB= 6.06], with discrete molecules held by weak van der Waals forces in a zigzag fashion. It is believed that this is the first time that powder X-ray diffraction patterns using microgram samples have been successfully employed for the structure solution and refinement of molecules with reasonable complexity.