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Drug discovery is a crucial part of human healthcare and has dramatically benefited human lifespan and life quality in recent centuries, however, it is usually time- and effort-consuming. Structural biology has been demonstrated as a powerful tool to accelerate drug development. Among different techniques, cryo-electron microscopy (cryo-EM) is emerging as the mainstream of structure determination of biomacromolecules in the past decade and has received increasing attention from the pharmaceutical industry. Although cryo-EM still has limitations in resolution, speed and throughput, a growing number of innovative drugs are being developed with the help of cryo-EM. Here, we aim to provide an overview of how cryo-EM techniques are applied to facilitate drug discovery. The development and typical workflow of cryo-EM technique will be briefly introduced, followed by its specific applications in structure-based drug design, fragment-based drug discovery, proteolysis targeting chimeras, antibody drug development and drug repurposing. Besides cryo-EM, drug discovery innovation usually involves other state-of-the-art techniques such as artificial intelligence (AI), which is increasingly active in diverse areas. The combination of cryo-EM and AI provides an opportunity to minimize limitations of cryo-EM such as automation, throughput and interpretation of medium-resolution maps, and tends to be the new direction of future development of cryo-EM. The rapid development of cryo-EM will make it as an indispensable part of modern drug discovery.

Objective Acute pancreatitis (AP) is a common and unpredictable disease. Severity stratification and prognostic prediction play an important role in reducing the mortality of AP and improving its prognosis in the early stage. We aimed to establish a clinical prediction model by logistic regression analysis visualized by nomogram. Methods A total of 497 patients with AP in the Nanfang Hospital, Southern Medical University between January 2015 and January 2018 were retrospectively collected. 497 patients were randomly (ratio = 7:3) divided into the training cohort (N = 347) and the validation cohort (N = 147), and both cohorts were divided into non-severe acute pancreatitis (non-SAP) and SAP groups. Univariate and multivariate logistic regression analysis were used to identify the factors associated with the severity of AP. Based on multivariate logistic regression analysis, nomogram was established and validated. The performance, discrimination, and calibration of nomogram were conducted. Decision curve analysis was used to evaluate the net benefits and clinical usefulness of the prediction model. Result Multivariate logistic regression analysis showed that alcohol use, hyperlipidemia, gender, hypertension, ionized serum calcium and serum albumin were independent risk factors for SAP. The individualized nomogram showed good discrimination both in the training cohort (area under the receiver operating characteristic curve [AUC], 0.782) and in the validation cohort (AUC, 0.764) with good calibration. Decision curve analysis demonstrated that in terms of clinical usefulness, the nomogram was found to have some clinical values and can be used in clinical practice. Conclusion The proposed nomogram based on easy-to-obtain features are of high efficacy in predicting SAP patients, which may facilitate clinical decision-making.

Meningioangiomatosis (MA) is a disease that is extremely rarely reported. Sporadic MA is occasionally combined with meningioma or other lesions (identified as non-pure MA). This retrospective study investigated the difference between pure MA and non-pure MA by exploring clinical manifestations, histopathology characteristics, and outcomes of MA after surgery. We reviewed the medical records of 36 histopathologically confirmed MA patients (18 pure MA and 18 non-pure MA) who received surgery at our institution between 2012 and 2021. We compared differences in demographic, clinical, imaging, pathological features, and surgical outcomes between pure MA and non-pure MA through descriptive statistics. Compared to non-pure MA, pure MA presented with a more prominent male predilection (5:1 vs. 1.57:1, P = 0.264), a higher seizure incidence (83.3% vs 50.0%, P = 0.038), a more seizure type of GTCS (14/15 vs 5/9, P = 0.047), a less prominent enhancement on MRI (27.8% vs 88.9%, P 0.001) and a preference of temporal and frontal lobe (100% vs 44.4%, P 0.001). The differences in clinical characteristics between pure MA and non-pure MA demonstrate their disparate biological natures. Pure MA seems to be a non-neoplastic lesion, while non-pure MA is commonly combined with meningioma, which is a neoplastic lesion. A correct differential diagnosis can be achieved via a triad of the type of seizure, the location of lesion and the radiological presentation. MA is curable and the prognosis is excellent as most patients are free of seizure and recurrence after surgical treatment.

In previous studies, pulse signals have been analysed primarily to standardise and objectify pulse diagnosis, but the influence of TCM constitution on pulse signals and disease has been neglected. Our study links the wrist pulse wave signal to TCM constitution to find TCM constitution factors that predispose to disease while improving the accuracy of disease classification. Our specific approach is set out below. A wrist pulse signal sampler based on a piezoelectric sensor was designed and 95 healthy subjects and 20 hypertensive patients were invited to complete the CCMQ (Constitution in the Chinese Medicine Questionnaire), of which 48 completed the pulse wave signal. Meanwhile, we improved the Butterworth filtering algorithm to denoise the pulse wave signals, and after smoothing and period segmentation, we finally extracted 27 time-domain features and 8 wavelet packet energy features. Then, we used the independent sample t-test and binary logistic regression analysis to analyze the correlation between the prevalence of hypertension and TCM constitution and found that the three constitutions of YaD (Yang-deficiency), YiD (Yin-deficiency), and PW (Phlegm-wet) were significantly associated with whether the subjects suffered from hypertension. The final classification results showed that the fusion features after adding the three constitution features with a high correlation with hypertension had a 17.46% higher F-score than the classification model without the constitution features. It can be seen that the incorporation of constitution characteristics into pulse characteristics in this paper has important implications for disease classification. This also provides a basis for studying the correlation between TCM physical characteristics and certain diseases, and patients can adopt targeted TCM management techniques to prevent diseases in advance.

AIM: To observe the changes of serum Adropin protein(AD)and neprilysin(NEP)levels in patients with diabetic retinopathy and to analyse the influencing factors. METHODS: A total of 167 patients with type 2 diabetes were enrolled in this study. They were divided into simple type 2 diabetes group(DM group)with 59 cases and type 2 diabetic retinopathy group(DR group)with 108 cases. Furthermore, the DR group included patients in two periods of non-proliferation diabetic retinopathy(NPDR group)and proliferative diabetic retinopathy(PDR group). There were 45 patients in NPDR group and 63 patients in PDR group, meanwhile, another 57 healthy subjects were selected as the normal control group(NC group). Measuring the hight and weight and calculating body mass index(BMI). Indices of fasting plasma glucose(FPG), systolic blood pressure(SBP), diastolic blood pressure(DBP), total cholesterol(TC), triacylglycerol(TG), alanine aminotransferase(ALT), aspartate aminotransferase(AST)hemoglobin Alc(HbA1c)were be detected, while levels of serum adropin protein(AD)and neprilysin(NEP)were measured by enzyme-linked immunosorbent assay(ELISA). The correlation between AD, NEP and other indicators was analyzed by Pearson correlation analysis. The independent influence factors of both were analyzed by multiple linear regression. RESULTS: Compared with the NC group, the AD level in the DM group, NPDR group, and PDR group decreased gradually, with the lowest level in the PDR group(PPCONCLUSION: In patients with diabetic retinopathy, AD level would be decreased with the progression of DR, and NEP level would be gradually increased, both of which may be involved in the development of DR.

ObjectiveThe brain compensation mechanism in postoperative delirium (POD) has not been reported. We uncovered the mechanism by exploring the association between POD and glioma grades, and the relationship between preoperative brain structural and functional compensation with POD in patients with frontal glioma.MethodsA total of 335 adult patients with glioma were included. The multivariable analysis examined the association between tumor grade and POD. Then, 20 patients with left frontal lobe glioma who had presurgical structural and functional MRI data and Montreal Cognitive Assessment (MoCA) in this cohort were analyzed. We measured the gray matter volume (GMV) and functional connectivity (FC) in patients with (n = 8) and without (n = 12) POD and healthy controls (HCs, n = 29) to detect the correlation between the structural and functional alteration and POD.ResultsThe incidence of POD was 37.3%. Multivariable regression revealed that high-grade glioma had approximately six times the odds of POD. Neuroimaging data showed that compared with HC, the patients with left frontal lobe glioma showed significantly increased GMV of the right dorsal lateral prefrontal cortex (DLPFC) in the non-POD group and decreased GMV of right DLPFC in the POD group, and the POD group exhibited significantly decreased FC of right DLPFC, and the non-POD group showed the increasing tendency. Partial correlation analysis showed that GMV in contralesional DLPFC were positively correlated with preoperative neurocognition, and the GMV and FC in contralesional DLPFC were negatively correlated with POD.ConclusionsOur findings suggested that insufficient compensation for injured brain regions involving cognition might be more vulnerable to suffering from POD.

Background: Our previous study showed that molecular hydrogen could effectively suppress glioblastoma multiforme (GBM) tumor growth via induction of glioblastoma stem cells (GSCs) differentiation. Metabolic reprogramming has been demonstrated to delicately regulate the stemness of cancer stem cells. In the present study, we explored whether metabolic reprogramming is involved in the hydrogen-induced GSCs differentiation. Methods: Immunofluorescence staining was conducted to determine the expression of cell surface markers. Glucose uptake and lactate secretion was determined by spectrophotometric method. Untargeted metabolomics analyses were conducted to investigate the metabolic alteration in GSCs after hydrogen treatment. 13 C-labeled metabolic flux analysis was performed to explore the regulatory effects of molecular hydrogen on the glucose metabolism of GSCs. Results: Immunofluorescence staining showed the up-regulated expression of oligodendroglial markers in hydrogen-treated GSCs. Both glucose uptake and lactate production in GSCs were significantly inhibited by hydrogen treatment. Untargeted metabolomics analyses showed hydrogen-induced promotion of de novo synthesis of nucleotides in GSCs. Metabolic flux analysis showed decreased glucose metabolism in GSCs induced by hydrogen. Conversely, the content of glycerol 3-phosphate, glutamate and glutamine were increased by hydrogen treatment. Conclusions: Results from this study demonstrated that molecular hydrogen could inhibit glucose metabolism and promote de novo synthesis of nucleotides in GSCs, suggesting the involvement of metabolic reprogramming in the hydrogen-induced GSCs differentiation. Our study also provides important new clues to seek the target of molecular hydrogen.

The potential therapeutic effects of molecular hydrogen (H2) have now been confirmed in various human and animal-disease models. However, the effects of H2 on the physiological function in a normal state have been largely neglected. Hydrogen-rich water (HRW) intake and hydrogen inhalation (HI) are the most common used methods for hydrogen administration, the difference in the effects between HRW intake and HI remains elusive. In the present study, the body weight and 13 serum biochemical parameters were monitored during the six-month hydrogen intervention, all these parameters were significantly altered by oral intake of HRW or HI. Among the 13 parameters, the most striking alterations induced by hydrogen treatment were observed in serum myocardial enzymes spectrum. The results also showed that the changes in these parameters occurred at different time points, and the alterations in most of the parameters were much more significant in HI than HRW. The results of this study provides the basic data for the mechanism research and application of molecular hydrogen in the future.

The intrinsic effect of the support microstructure on the catalytic function of VOx/Al2O3 in the oxidative dehydrogenation of propane (ODHP) was studied. The results of characterization indicate that similar vanadia species are supported on Al2O3 with different microstructures, but that the interactions between VOx and alumina are slightly modified. In this case, the microstructure-dependent catalytic function in the ODHP reaction is rigorously revealed. The flower-like morphology with non-compact and non-monolithic particles assembled as nanoribbons exhibits inter-particle stacking pores, which contribute to a severe extra-granular diffusion limitation (EGDL). The sphere-like morphology with compact and monolithic particles assembled as nanosheets possesses both inter-particle and intra-particle pores, which lead to a moderate EGDL. However, neither catalyst exhibits an intra-granular diffusion limitation (IGDL). Conversely, the bulk-like morphology with monolithic particles and without the assembly of secondary granules only exhibits intra-particle pores, which results in a slight EGDL and IGDL. Moreover, these two disturbances of diffusion can be excluded by means of controlling the reaction parameters. A comparison of the apparent and intrinsic kinetics, together with the structure–function relationship, determines that the EGDL might play an important role in influencing the ODHP efficiency. An in situ FT-IR study shows that the adsorption-activation of propane and that of propylene proceed via different initial intermediates and transformation processes. The former initially involves surface propoxide species that will be transformed into aldehydic and ketonic intermediates at the reaction temperature. The latter directly involves π-allyl alkoxidic and σ-allyl aldehydic species, as well as vanadia-carboxylate species with a quasi-anhydride structure at ambient temperatures, at which these intermediates are prone to catalytic combustion.

Adipic acid diselenoester was developed as an efficient cross-linker for covalent protein conjugation with a variety of small molecular haptens, including mono- and disaccharides, peptide, fluorescence dye, and nicotine. Compared to the counterparts of N-hydroxysuccinimide (NHS) and p-nitrophenyl (PNP) linkers, the diselenoester linker demonstrates improved balance between reactivity and stability and coupling of haptens to proteins under mild conditions with high incorporation efficiency.

A large number of polymer materials bearing dynamic bond systems have been reported, while the focus is mainly on the macroscopic properties such as self-healing and shape memory. It is well established that dynamic bonds have significant effect on the performance of polymers. In this article, we report the rational design of 2-ureido-4[1H]-pyrimidinone (UPy) units as reversible crosslinking networks introduced into polyisoprene (PI) chains and special consideration has been devoted to the effect of UPy dimers on relaxation behavior of elastomer. The incorporation of UPy dimers into PI chains is corroborated by Fourier Transform Infrared and thermal measurements. As revealed by synchrotron X-ray, the inhomogeneities of modified PI originate from UPy dimers, which resulted in the increased dielectric strength of segmental motion. An additional relaxation process (new mode) has been observed in the samples with high UPy content by broadband dielectric spectroscopy but cannot be found in neat PI. It is evident that this new mode relaxation process behaves as a thermally activated process. However, the dielectric strength of new mode exhibits the opposite trend, compared with that of segmental motion. This anomalous phenomenon could be rationally attributed to the dissociation process of UPy dimers induced by high temperature.

In order to survive in a mammalian host, Mycobacterium tuberculosis (Mtb) produces aryl-capped siderophores known as the mycobactins for iron acquisition. Salicylic acid is a key building block of the mycobactin core and is synthesized by the bifunctional enzyme MbtI, which converts chorismate into isochorismate via a SN2″ reaction followed by further transformation into salicylate through a [3,3]-sigmatropic rearrangement. MbtI belongs to a family of chorismate-utilizing enzymes (CUEs) that have conserved topology and active site residues. The transition-state inhibitor 1 described by Bartlett, Kozlowski and co-workers is the most potent reported inhibitor to date of CUEs. Herein we disclose a concise asymmetric synthesis and the accompanying biochemical characterization of 1 along with three closely related analogues beginning from bromobenzene cis-1S,2S-dihydrodiol produced through microbial oxidation that features a series of regio- and stereoselective transformations for introduction of the C-4 hydroxy and C-6 amino substituents. The flexible synthesis enables late–stage introduction of the carboxy group and other bioisosteres at the C-1 position as well as installation of the enol-pyruvate side chain at the C-5 position.

A fully synthetic self-adjuvanting cancer vaccine candidate was constructed through covalent conjugation of invariant natural killer T (iNKT) cell ligand α-galactosylceramide (αGalCer) with sialyl Tn (STn), a representative tumor-associated carbohydrate antigen (TACA). This two-component vaccine STn-αGalCer is devoid of antigenic peptide, featuring the well-defined structure with high simplicity. STn-αGalCer showed remarkable efficacy in inducing antibody class switching from IgM to STn-specific IgG. Subtypes of IgG antibody were primarily IgG1 and IgG3.

Extended Influence Diagram (EID) is a graph model for modeling and solving decision problems under uncertainty, extended from the Influence Diagram. Architecture analysis is one of the main contents of architecture lifecycle. This paper introduces the modeling elements and architecture analysis process of EID, specifics probability elicitation procedure of directly controllable node according to DM2, discusses architecture maintainability by EID, finally summarizes this method's advantages and disadvantages.

A new approach is described for preparing carbon foam (CF) through coaxial electrohydrodynamic atomization (EHDA). Using polyacrylonitrile (PAN) and borneol as a carbonaceous precursor and a blowing agent, respectively, hybrid PAN-borneol films were prepared and transferred to a honeycomb PAN membrane through blowing, drying, and pre-oxidation with the CF prepared by carbonization of the PAN film. Scanning electron microscopy observations showed that the CF has a homogeneous structure, having pores with an average diameter of 2.34 ± 0.73 μm. The surface of the CF, which had a thickness of 10 μm, was smooth and compact. The coaxial EHDA process can be exploited for preparing CF with tailored structures.

GalNAc-T14 was identified as a novel IGFBP-3 binding partner in previous studies. Here, we furtherly confirmed the interaction between them by confocal microscopy, and identified the binding domain and probable interaction sites of GalNAc-T14 with IGFBP-3. The result of subcellular localization indicated that GalNAc-T14 was distributed in the cytosol, whereas IGFBP-3 existed in the cytosol and nucleolus. Confocal analyses demonstrated that IGFBP-3 and GalNAc-T14 colocalized in the cytosol. The result from yeast two hybrid assay showed that the C terminus of GalNAc-T14 (408-552aa) was essential for the interaction between GalNAc-T14 and IGFBP-3, especially Tyr(408), Pro(409), and Glu(410) of GalNAc-T14 may play key roles in the interaction with IGFBP-3. In conclusion, these studies demonstrated that IGFBP-3 and GalNAc-T14 are colocalized in MCF-7 cells and confirmed the interaction between IGFBP-3 and GalNAc-T14. This interaction may play an important role in the functional regulation of IGFBP-3.

In the prevention and control of the mine water ，the water level of the dynamic monitoring storehouse play a pivotal role. Mine water warehouse water level measurement and control system which is designed by this paper is by programmable logic devices S7-200 and configuration king Wincc constitute a hardware and software. Between master of the computer and monitoring stations can bus is for data transmission. Laboratory simulation test and Field testing have a good effect, And it can realize the function of Sound and light alarm , dynamic display of water level-the time trend curve and data storage and reports, provide effective basis for coal mine water storehouse safety management and monitoring water-level.

For the support problem of set-up room to be 7.8m wide with thick and broken coal roof in Pangpangta coal mine, the truss cable support system is adopted to control the set-up room surrounding rock. The main support parameters, such as cable length, cable angle and distance between orifice and side of the truss cable support system are simulated and optimally designed by using numerical simulation software FLAC3D, by which the support scheme is designed reasonably. The support scheme is successfully tested at set-up room No. 10101 in Pangpangta mine. The set-up room deformation is small, and the support system is safe and reliable. This kind of support technology can be widely used in the similar set-up rooms.

In this work we have compared and contrasted the pervaporation behaviour (separation factor and flux) of fluorosilicone dense membranes based on poly(trifluoropropylmethylsiloxane) (PTFPMS) with poly(dimethylsiloxane) (PDMS) dense membranes. In particular, pervaporation experiments were carried out at 298 K using lab-made PTFPMS, lab-made PDMS and commercial PDMS membranes in order to remove three different organic liquids pyridine (PY), isopropanol (IPA) and methylethylketone (MEK) from dilute (

Insulin-like growth factor binding protein-3 (IGFBP-3) is a multi-functional protein known to induce apoptosis of various cancer cells in an insulin-like growth factor (IGF)-dependent and IGF-independent manner. In our previous study, we found that IGFBP-3 induced apoptosis through the activation of caspases in 786-O cells. In this study, we further examined that whether IGFBP-3 induced apoptosis through the induction of cell cycle arrest in 786-O, A549 and MCF-7 cells. Our results showed that overexpressed IGFBP-3 resulted in typical apoptotic ultrastructures in A549 cells under transmission electron microscope. The result of flow cytometry analysis indicated that IGFBP-3 arrested the cell cycle at G1-S phase in 786-O, A549 and MCF-7 cells. In A549 cells, quantitative real-time PCR and Western blot analysis showed a significant change in the expression of cell cycle-regulated proteins—a decrease in cyclin E1 expression, an increase in p21 expression. These results indicate a possible mechanism for G1 cell cycle arrest by IGFBP-3. Taken together, cyclin E1 and p21 may play important roles in the IGFBP-3-inducing G1 cell cycle arrest and apoptosis in several human cancer cells.

To get hydrogenated polybutadiene-polymethyl methacrylate (HPB-b-PMMA) block copolymer to be used as a compatibilizer for blends of polyolefin/polar polymer, PB-b-PMMA was synthesized by anionic-free radical mechanism transformation polymerization. Selective extraction, gradient elution thin layer chromatography, and oil-oil emulsion separation techniques were tried to attempt to separate the copolymerization products. Hydrogenation of the PB sequence in PB-b-PMMA yielded HPB-b-PMMA. The compatibilizing function of PB-b-PMMA was shown in blending experiments. © 1993 John Wiley & Sons, Inc.

A new type of evanescent field sensors based on a doubly cladding single mode fiber is proposed. The theoretical analysis shows that the measurable refractive index (RI) ranges for the sensors are limited in the single mode in the fiber becoming leaky and the range is less than the RI difference between the core and the cladding of the fibers. Two temperature sensors and a humidity sensor were fabricated. One temperature sensor showed a good linear response in a range of 60°C, the modulation depth of 40 dB, and the insertion loss of -1.4 dB. The humidity sensors fabricated by agarose gel had a measurable moisture range of 16 ~ 100% of RH. Its optical power variation with humidity is 8.5 dB and insertion loss is 3.9 dB. We confirmed that the DC single mode fiber sensors became a new type of intensity sensors characterized in good linear response, low insertion loss, high modulation depth, and low cost in fabrication.

This paper gives the concept of semi-autonomous Agent firstly and points out the important significance of semi-autonomous Agent communication model. Then study on three parts, semi-autonomous Agent communication mechanism and structure of multi-agents system communication and language of semi-autonomous Agent communication, After that, the paper educes conclusion of semi-autonomous Agent communication model and gives the interior disposal mechanism of semi-autonomous Agent communication and content of extend KQML communication language.

This paper expatiate Swarm which can solve the problem of complex adaptive systems, Weapon equipment systems can be disposed by CAS theory, Because it can use this method to deal with the problem. After that, it designs a multi-Agent/CA model frame of weapon equipment systems, then discuss the critical technology of the model, At last it illuminates the next step of the emulation.

Fiber optical evanescent field sensors provide means of optical power sensitive to temperature. This paper proposed a novel and practicable fiber optical temperature sensor with doubly cladding structure. It worked on the basis of optical attenuation brought about by the outer cladding medium with a large thermooptic coefficient. As the external diameter of the sensing section was less than 1mm, the sensors were sensitive to the temperature of ambient air. The doubly cladding fiber optical sensors with different fabrication characteristics (basically length and the diameter of inner cladding of the sensing section) and external medium were studied experimentally. The sensor obtained by an outer cladding of Dow Corning OE-4110 showed a low insertion loss of -0.7dB, a peak value of power loss of -66dB at 51°C, and a linear dynamic range of -53dB for a temperature interval of 5°C at 1550nm. The sensor obtained by SILRES®Ren60 had the peak value of power loss at about 105°C and a temperature interval of 65°C in a linear dynamic range of -5 dB.

Prisms are involved in many instruments of measurements of refractive indices. The optical feedback effect in a semiconductor laser introduced by the reflection of a prism was applied to the determination of zero incident angle. Without any additional optical components or calibration setups the angular resolution reached 0.00074°. This approach was used in refractometers and prism coupling system. Prisms, water, wintergreen oil and a quartz plate were measured by total internal reflection technique and the optical feedback effect. In the measurement of prism, we proposed that the base angle of a detected prism should be appropriately prepared so as that the refractive index of an isosceles prism made of any material can be precisely measured. The results for a SrTiO 3 prism with a base angle 30.0169 degree was 2.3780 at 659 nm. The measurements of water and wintergreen oil were performed by a reference prism made of SrTiO 3 . We found that the result for a quartz plate wouldn't be influenced by the index matching liquid between the plate and a reference prism, which was intentionally introduced, only if the index of the liquid was larger than that of the quartz. The refractive index of a polymer film was measured accurately and the maximum of deviation from mean was ±0.0001.

A fiber-polymer VOA design for simple frame was proposed. The theory and experiment demonstrated that the range of attenuations can reach about 30 dB if the temperature of device has a change of 5°C.

Mass spectrometry (MS) has previously proved to be very valuable for characterizing the thermal decomposition of poly-(dimethylsiloxane) (PDMS) via pyrolysis-MS. Secondary ion mass spectrometry (SIMS) has also been applied to identify the various fragments characteristic of PDMS and thus give fingerprint'' spectra for identification purposes. This paper describes the characterization of deuterated linear PDMS -[(CD[sub 3])[sub 2]SiO][sub n]- using time-of-flight secondary ion mass spectrometry. The work is part of a program investigating the conformations and interactions of deuterated siloxanes in isotopic blends -[(CD[sub 3])[sub 2]SiO][sub n]-/-[CH[sub 3][sub 2]SiO][sub n]- using small-angle neutron scattering. It is therefore clearly important to demonstrate that no deuterium/hydrogen exchanges occurred during the synthetic methodology used.