Diamagnetic Substances Research Articles

Internal Cerebral Vein in Susceptibility-Weighted Imaging: A Reliable Tool to Differentiate Among Calcification, Microbleed, and Gross Hemorrhage in Brain Tumors.

Background and objective Susceptibility-weighted imaging (SWI) sequence is crucial for brain MRI examinations, as it is equipped with a high sensitivity to detect calcification, microbleed, and gross hemorrhage. Intracranial venous structures such as the superior sagittal sinus (SSS) and cortical veins are used as reference structures in phase image SWI to differentiate diamagnetic and paramagnetic substances. Our study focuses on the internal cerebral vein (ICV) as another reliable reference structure. We aimed to analyze the diagnostic accuracy and detectability of calcification and hemorrhagic components in brain tumors using ICV, cortical veins, and SSS as references on phase image SWI, with CT scans for comparison. Material and methods A retrospective review of calcification and hemorrhagic components in brain tumors was conducted using MRI and CT from January 2017 to June 2023. Results The study included a total of 192 patients with brain tumors. For calcification components (63 cases), ICV and cortical veins as reference structures showed excellent sensitivity (96.8%), specificity (100%), and accuracy (98.9%). SSS demonstrated slightly lower detectability but maintained high sensitivity (96.5%), specificity (100%), and accuracy (98.8%) levels. No statistical differences were noted among these reference structures (p>0.05) and excellent interobserver agreement (Cohen's Kappa of 1) was observed. Conclusions The ICV is located in the central image, is large, without any nearby arteries, and is easy to identify using SWI phase images. Using the ICV as a reference to characterize intratumoral calcification, microbleed, and hemorrhage demonstrates high accuracy and detectability. With its findings of excellent interobserver agreement, our study will be of immense benefit to radiologists.

SUSCEPTIBILITY WEIGHTED IMAGING TECHNIQUE UTILITY IN DIVERSE NEUROLOGICAL ENTITIES

Background: Susceptibility Weighted Imaging (SWI) is a novel modality based upon GE (Gradient Echo) sequences that employ differences in susceptibility of various paramagnetic as well as diamagnetic substances that aid in the better diagnosis of various neurological entities such as intracranial tumors, vascular malformations, arterial stroke, venous hemorrhagic infarcts. Objective:To assess utility of SWI in various neurological diseases. Methods: The retrospective observational study was held in a tertiary care medical center in India in 2021. Multiple neurological diseases on SWI were analyzed in 100 patients with neurological complaints. The inclusion criteria included patient of all age group who presented with neurological signs and symptoms. The exclusion criteria included presence of post-operative non-compatible orthopedic hardware and patients with cardiac pacemakers, cochlear implants in situ. Results: The majority were males and > 60 years (23%) in age. Among 100 patients, most had tumors (18%), followed by trauma (16%), arterial stroke (15%), and hemorrhage (14%). Most of 14 patients with hemorrhage have intraparenchymal hemorrhage 9 (64.29%). There were10 patients with venous sinuses thrombosis and 15 cases with arterial stroke amongst whom most had middle cerebral artery thrombosis (46.66%). Most 13 patients with vascular pathologies had amyloid angiopathy 4 (30.77%). The majority of tumors were primary 15 (83.33%) with 10 (66.67%) newly diagnosed tumors, 11 (61.11%) tumors had a hemorrhage, 3 (16.67%) presented with calcification, and 4 (22.22%) had both hemorrhage and calcification. According to SWI grading of the tumor by intratumoral susceptibility score (ITSS), the majority were in grade III. On the correlation of SWI grading with MR Spectroscopy (MRS) and MR perfusion (MRP) study, 6 (100%) grade III patients showed hyperperfusion on MRP with raised choline/Creatinine ratio. SWI was better than CT (P<0.05) in detecting trauma, hemorrhage, cerebral venous sinus thrombosis, vascular pathologies, and tumors. Conclusion: SWI is a helpful imaging tool in neuroradiological practice and should be incorporated into standard procedures. It is beneficial in identifying hemorrhages, low-flow vascular abnormalities, diffuse axonal injury, and neurodegenerative illnesses. In addition, it is a supplementary sequence in the stroke by distinguishing calcium from hemorrhage in the brain and categorizing brain tumors.

Intracranial Lesion Detection and Artifact Characterization: Comparative Study of Susceptibility and T2*-Weighted Imaging in Dogs and Cats.

Susceptibility-weighted imaging (SWI), an MRI sequence for the detection of hemorrhage, allows differentiation of paramagnetic and diamagnetic substances based on tissue magnetic susceptibility differences. The three aims of this retrospective study included a comparison of the number of areas of signal void (ASV) between SWI and T2*-weighted imaging (T2*WI), differentiation of hemorrhage and calcification, and investigation of image deterioration by artifacts. Two hundred twelve brain MRIs, 160 dogs and 52 cats, were included. The sequences were randomized and evaluated for presence/absence and numbers of ASV and extent of artifacts causing image deterioration by a single, blinded observer. In cases with a CT scan differentiation of paramagnetic (hemorrhagic) and diamagnetic (calcification) lesions was made, SWI was performed to test correct assignment using the Hounsfield Units. Non-parametric tests were performed to compare both sequences regarding detection of ASV and the effect of artifacts on image quality. The presence of ASV was found in 37 SWI sequences and 34 T2*WI sequences with a significant increase in ASV only in dogs >5 and ≤ 15 kg in SWI. The remaining weight categories showed no significance. CT examination was available in 11 cases in which 81 ASV were found. With the use of phase images, 77 were classified as paramagnetic and none as diamagnetic. A classification was not possible in four cases. At the level of the frontal sinus, significantly more severe artifacts occurred in cats and dogs (dogs, p < 0.001; cats, p = 0.001) in SWI. The frontal sinus artifact was significantly less severe in brachycephalic than non-brachycephalic dogs in both sequences (SWI, p < 0.001; T2*WI, p < 0.001). In conclusion, with the advantages of better detection of ASV in SWI compared with T2*WI and the opportunity to differentiate between paramagnetic and diamagnetic origin in most cases, SWI is generally recommended for dogs. Frontal sinus conformation appears to be a limiting factor in image interpretation.

Density Functional Theory modeling of the magnetic susceptibility of heme derivatives

Susceptibility-weighted imaging (SWI) is a magnetic resonance imaging (MRI) technique which magnetic susceptibility differences between tissues can be used as a new type of contrast in MRI. SWI is sensitive to both paramagnetic and diamagnetic substances. Accurate estimations of the magnetic properties of the heme derivatives is essential for the development of the SWI technique.In this paper, we study structural and magnetic properties of the heme derivatives from Density Functional Theory calculations. By applying the Stoner model we obtained the magnetic susceptibility of the heme derivatives.We find that the paramagnetic phase of heme, deoxyhemoglobin and aquomethemoglobin to be more stable than the diamagnetic phase as expected from experimentation but the diamagnetic phase of the oxyhemoglobin and hemichrome is more stable. Our results show that the response of the heme to the external magnetic field is changed by the presence of ligand (imidazole or water) molecule.

Axisymmetric scalable magneto-gravitational trap for diamagnetic particle levitation.

We report on the design, construction, and use of axisymmetric magnetic traps for levitating diamagnetic particles. The magnetic traps each consist of two pole pieces passively driven by a neodymium iron boron (NdFeB) permanent magnet. The magnetic field configuration between the pole pieces combined with the earth's gravitational field forms a 3D confining potential capable of levitating a range of diamagnetic substances, e.g., graphite powder, silica microspheres, and gallium nitride (GaN) powder and nanowires. Particles trap stably at atmosphere and in high-vacuum for periods up to weeks with lifetimes largely determined by choices made to actively destabilize the trap. We describe the principles of operation, finite element design, approximate closed-form results for design rules, and examples of operation of such traps.

Differentiation of Brain Metastases and Gliomas Based on Color Map of Phase Difference Enhanced Imaging.

Background and objective: Phase difference enhanced imaging (PADRE), a new phase-related MRI technique, can enhance both paramagnetic and diamagnetic substances, and select which phases to be enhanced. Utilizing these characteristics, we developed color map of PADRE (Color PADRE), which enables simultaneous visualization of myelin-rich structures and veins. Our aim was to determine whether Color PADRE is sufficient to delineate the characteristics of non-gadolinium-enhancing T2-hyperintense regions related with metastatic tumors (MTs), diffuse astrocytomas (DAs) and glioblastomas (GBs), and whether it can contribute to the differentiation of MTs from GBs.Methods: Color PADRE images of 11 patients with MTs, nine with DAs and 17 with GBs were created by combining tissue-enhanced, vessel-enhanced and magnitude images of PADRE, and then retrospectively reviewed. First, predominant visibility of superficial white matter and deep medullary veins within non-gadolinium-enhancing T2-hyperintense regions were compared among the three groups. Then, the discriminatory power to differentiate MTs from GBs was assessed using receiver operating characteristic analysis.Results: The degree of visibility of superficial white matter was significantly better in MTs than in GBs (p = 0.017), better in GBs than in DAs (p = 0.014), and better in MTs than in DAs (p = 0.0021). On the contrary, the difference in the visibility of deep medullary veins was not significant (p = 0.065). The area under the receiver operating characteristic curve to discriminate MTs from GBs was 0.76 with a sensitivity of 80% and specificity of 64%.Conclusion: Visibility of superficial white matter on Color PADRE reflects inferred differences in the proportion of vasogenic edema and tumoral infiltration within non-gadolinium-enhancing T2-hyperintense regions of MTs, DAs and GBs. Evaluation of peritumoral areas on Color PADRE can help to distinguish MTs from GBs.

Even Liquids Are Magnetic: Observation of the Moses Effect and the Inverse Moses Effect

In our everyday life, it seems that magnetic phenomena are restricted to ferromagnetic materials or electromagnetism caused by electric currents. From a physics point of view, we know that this everyday experience is contrary to the nature of magnetic phenomena. If one regards the magnetic properties of the elements of the periodic table in their natural appearance, there are just a few ferromagnetic (3) but a variety of diamagnetic (34) and paramagnetic (51) substances under standard conditions. Using strong neodymium magnets, it is possible to demonstrate the specific properties of diamagnetism and paramagnetism in the classroom for solids and, unexpectedly, as well for liquids because every piece of matter possesses magnetic properties.

Stabilization of non-controlled magnetic levitation motor utilizing the diamagnetic magnetic force of PG disk and rotating torque measurement

It can be widely applied if it can stably levitate and rotate the floating rotor without using automatic control or superconducting material. The diamagnetic magnetic force generated by diamagnetic substances is very small. The author found that a heavy floating rotor can be levitated by a combination of magnetic force between floating rotor magnet and radially arranged permanent magnets, and diamagnetic magnetic force between fixed magnet group and PG disk. In this paper, I will explain how to levitate the floating rotor. In addition, I show the calculation method necessary for levitation analysis and describe the usefulness of surface current method used for analysis.

Determining magnetic susceptibilities of everyday materials using an electronic balance

The magnetic properties of an object and its interaction with an external magnetic field can be described through the magnetic (volume) susceptibility χV, which divides nearly all kinds of matter into diamagnetic, paramagnetic, and ferromagnetic substances. Quantitative measurements of χV are usually technically sophisticated or require the investigation of substances with high values of χV to reveal meaningful results. Here, we show that both diamagnetic and paramagnetic effects in everyday materials can be measured using only an electronic balance and a neodymium magnet, both of which are within the reach of typical introductory college and high school physics classrooms. The experimental results match related literature values remarkably well.

The Sterilization Effect of Solenoid Magnetic Field Direction on Heterotrophic Bacteria in Circulating Cooling Water

Compared to the chemical treatment of industrial circulating cooling water in the field of industrial water treatment, electromagnetic pulse sterilization technology, an advanced technology, is widely used because of its special characteristics--low energy consumption, nonpoisonous and environmentally friendly. In order to get a better cooling water sterilization effect under the premise of not polluting the environment, some experiments about sterilization of heterotrophic bacteria in industrial circulating cooling water by low frequency square wave pulsed magnetic field were carried out. The comparison experiment on the sterilization effect of low frequency square wave pulsed magnetic field on heterotrophic bacteria in industrial circulating cooling water was carried out by change relative flow direction of solenoid magnetic field and water. The bacterial inhibiting effect was 7.22%∼20.35% higher when the direction of flow of water was in parallel with the magnetic field than in anti-parallel. This study analyzed this phenomenon from the perspective of the diamagnetism of the bacteria cells and the electric dipole moment of proteins. Since the bacterium cell membrane contains diamagnetic substances, when a bacterium cell moves in parallel with the magnetic field, it would be slowed down and stay longer in the field than moving in anti-parallel, so the bacterial inhibiting effect would be stronger. Results of this study have important guiding significance for future application of magnetic field sterilization.

Use of (77)Se and (125)Te NMR Spectroscopy to Probe Covalency of the Actinide-Chalcogen Bonding in [Th(En){N(SiMe3)2}3](-) (E = Se, Te; n = 1, 2) and Their Oxo-Uranium(VI) Congeners.

Reaction of [Th(I)(NR2)3] (R = SiMe3) (1) with 1 equiv of either [K(18-crown-6)]2[Se4] or [K(18-crown-6)]2[Te2] affords the thorium dichalcogenides, [K(18-crown-6)][Th(η(2)-E2)(NR2)3] (E = Se, 2; E = Te, 3), respectively. Removal of one chalcogen atom via reaction with Et3P, or Et3P and Hg, affords the monoselenide and monotelluride complexes of thorium, [K(18-crown-6)][Th(E)(NR2)3] (E = Se, 4; E = Te, 5), respectively. Both 4 and 5 were characterized by X-ray crystallography and were found to feature the shortest known Th-Se and Th-Te bond distances. The electronic structure and nature of the actinide-chalcogen bonds were investigated with (77)Se and (125)Te NMR spectroscopy accompanied by detailed quantum-chemical analysis. We also recorded the (77)Se NMR shift for a U(VI) oxo-selenido complex, [U(O)(Se)(NR2)3](-) (δ((77)Se) = 4905 ppm), which features the highest frequency (77)Se NMR shift yet reported, and expands the known (77)Se chemical shift range for diamagnetic substances from ∼3300 ppm to almost 6000 ppm. Both (77)Se and (125)Te NMR chemical shifts of given chalcogenide ligands were identified as quantitative measures of the An-E bond covalency within an isoelectronic series and supported significant 5f-orbital participation in actinide-ligand bonding for uranium(VI) complexes in contrast to those involving thorium(IV). Moreover, X-ray diffraction studies together with NMR spectroscopic data and density functional theory (DFT) calculations provide convincing evidence for the actinide-chalcogen multiple bonding in the title complexes. Larger An-E covalency is observed in the [U(O)(E)(NR2)3](-) series, which decreases as the chalcogen atom becomes heavier.

回転変調磁場を用いた希土類系高温超伝導体の3次元結晶配向

Modulated rotating magnetic field (MRF) enables bi-axial grain arrangement of substances with tri-axial magnetic anisotropy. Even feeble magnetic (paramagnetic and diamagnetic) substances become target materials for the magnetic grain alignment by using a 10 telsa-class strong magnet. In this review article, the authors introduce high potential of the magnetic alignment technique using MRF as a fabrication process of bi-axially grain-oriented rare-earth(RE)-based cuprate superconductors. In the former topic, the bi-axial magnetic alignment of RE-based cuprate superconductors without twin microstructures at room temperature are reported for the clarification of RE-dependent magnetization axes and tri-axial magnetic anisotropies. In the latter topic, the authors show the bi-axial magnetic alignment of practical RE-based superconductors, REBa2Cu3Oy (RE123), with twin microstructures. The inplane orientation degrees in RE123 were lowered compared with those in RE-based cuprates without twin microstructures; however, bi-axial magnetic alignment has been successfully achieved even in RE123 with twin microstructures.

Effect of external magnetic field on attenuation coefficient for magnetic substances

The measurement of attenuation coefficient of some magnetic substances, to include diamagnetic: Cu, Zn, Ag, Te, Au, Pb, and Perspex; paramagnetic: Al, Ti, Mo, Dy, Ho, and Pt and ferromagnetic substances: Fe, Co, Ni, Gd, FeO, NiO, FeS, and Fe2O3, both in the presence and absence of an external magnetic field has been carried out using narrow beam transmission geometry by using gamma ray photons of incident energy 59.54keV from 100mCi, 241Am point source. It was observed very keenly that the value of linear attenuation coefficient of various substances mentioned above decreased remarkably. It varied in the range of 1–2%, 2–6% and 6–9% for diamagnetic, paramagnetic and ferromagnetic substances respectively in the presence of an external magnetic field. Measured results elucidated it very clearly that linear attenuation coefficient at H=0T, 0.6T and 1.2T continued to decrease with a regular increase of magnetic field. It is also manifested that measurements of linear attenuation coefficient is not affected with the change in thickness of the given substance. Within error limits (1–3%) variations are observed with increases of thickness along with magnetic field. Further to it the obtained results of linear attenuation coefficient without magnetic field (H=0T) were compared with theoretical data tables of FFAST and WinXCOM. It was established that values obtained are well within the experimental errors. To the best of our knowledge no other study in relation to the effect of linear attenuation coefficient in the presence of magnetic field available as precedence.

Susceptibility-weighted imaging and quantitative susceptibility mapping in the brain.

Susceptibility-weighted imaging (SWI) is a magnetic resonance imaging (MRI) technique that enhances image contrast by using the susceptibility differences between tissues. It is created by combining both magnitude and phase in the gradient echo data. SWI is sensitive to both paramagnetic and diamagnetic substances which generate different phase shift in MRI data. SWI images can be displayed as a minimum intensity projection that provides high resolution delineation of the cerebral venous architecture, a feature that is not available in other MRI techniques. As such, SWI has been widely applied to diagnose various venous abnormalities. SWI is especially sensitive to deoxygenated blood and intracranial mineral deposition and, for that reason, has been applied to image various pathologies including intracranial hemorrhage, traumatic brain injury, stroke, neoplasm, and multiple sclerosis. SWI, however, does not provide quantitative measures of magnetic susceptibility. This limitation is currently being addressed with the development of quantitative susceptibility mapping (QSM) and susceptibility tensor imaging (STI). While QSM treats susceptibility as isotropic, STI treats susceptibility as generally anisotropic characterized by a tensor quantity. This article reviews the basic principles of SWI, its clinical and research applications, the mechanisms governing brain susceptibility properties, and its practical implementation, with a focus on brain imaging.

Fundamental Study of Plastic Separation Utilizing Magnetic Force

In order to recycle the plastics, a new method to separate polyethylene (PE) and polypropylene (PP) by the magnetic separation using superconducting magnet was developed. Magnetic separation method is superior to other methods in continuous and high-speed processing. Most of the plastics are diamagnetic, which makes it difficult to separate using traditional magnetic separation method. Therefore, we used magnetic force in horizontal direction and magneto-Archimedes method, which can be applicable to paramagnetic or diamagnetic substances. We designed an apparatus to separate the plastics, and succeeded in separating PP selectively from the mixture of PP and PE, by levitating and moving in a horizontal direction by the magnetic force. We determined appropriate magnetic field source and the concentration of medium by calculation. We confirmed the possibility of magnetic separation of PP and PE by trajectory calculation and demonstrated the separation experiment. As the result, PP and PE were selectively separated by moving PP to the sidewall of the vessel while levitating.

Paramagnetic lanthanides as magnetic resonance thermo-sensors and probes of molecular dynamics: Holmium-DOTA complex

Investigation of lanthanide (Ln) сhelates and their paramagnetic properties with NMR spectroscopy is an established area of research. However, respective data for coordination compounds of holmium (Ho) are scarce. To fill this gap, the present work focuses on detailed determination of intramolecular dynamics and paramagnetic properties for holmium complexes. 1H NMR measurements are reported for D2O solutions of paramagnetic [Ho(H2O)(DOTA)]− (I) complex in the 273–348K temperature range. Diamagnetic complex [Lu(H2O)(DOTA)]− (II) was used as a reference compound. The spectra obtained have been analyzed using band-shape analysis technique in the framework of dynamic NMR (D NMR). Temperature dependences of lanthanide-induced shifts (LIS) were taken into consideration, too. Сonformational dynamic process has been found. The dynamics is caused by an interconversion of square-anti-prismatic (SAP) and twisted-square-anti-prismatic (TSAP) conformers (the estimated activation free energy ΔG‡(298K) is 65±3kJmol−1). Thermodynamics of equilibrium between SAP and TSAP conformers of I was investigated too. The results obtained are found to be consistent with those collected for other Ln-DOTA complexes. In accordance with literature reviewed, the fulfilled experimental study is the first example of intramolecular dynamics determination for holmium complexes. Taking Ho3+ as an example, the methodology of paramagnetic 4f-element probe applications for the study of free-energy changes in chemical exchange processes is discussed. The advantages of this method, compared to D NMR studies of diamagnetic substances are illustrated. Among them is an extension of the range of NMR-accessible rate constants for paramagnetic 4f-element complexes, compared to diamagnetic ones. And last, usage of coordination compounds investigated as a new type of thermometric NMR sensors and lanthanide paramagnetic probes for in situ temperature control in solutions is demonstrated. The investigated coordination compounds are suggested to apply as thermo-sensing contrast reagent for MRI diagnostics of cancer and inflammation.

ChemInform Abstract: Solid‐State NMR of Inorganic Semiconductors

AbstractReview: 380 refs.

Lanthanides as NMR Probes of Fast Molecular Dynamics at High Magnetic Fields and Temperature Sensors: Conformational Interconversion of Erbium Ethylenediaminetetraacetate Complexes

(1)H NMR measurements are reported for D2O solutions of paramagnetic complex [Er(H2O)(EDTA(4-))](-) (I) for temperature interval 273-319 K. Diamagnetic complex [Lu(H2O)(EDTA(4-))](-) (II) was used as an NMR reference compound. The spectra obtained have been analyzed using a band-shape analysis technique in the framework of dynamic NMR (DNMR) taking into account the temperature dependence of lanthanide-induced shifts. Intramolecular dynamics in I was assigned to the interconversion of Δ-λE-δδδδ and Δ-δE-δδδδ conformers with estimated activation free energy ΔG(‡)(298 K) = 50 ± 4 kJ/mol. The methodology of paramagnetic 4f-element probe applications on the example of Er(3+) for the study of free-energy changes in chemical exchange processes, as well as the advantages of this method in comparison with DNMR studies of diamagnetic substances, is discussed. In accordance with the literature reviewed, the fulfilled experimental study is the first example of intramolecular dynamics determination for erbium complexes. An additional advantage of the investigation is in the approach proposed which extends the range of measurement of the NMR rate constants for paramagnetic 4f-element complexes compared to diamagnetic ones. Coordination compounds investigated represent a new type of thermometric NMR sensors and lanthanide paramagnetic probes for in situ temperature control in solutions.

β-Diketiminato Nickel Imides in Catalytic Nitrene Transfer to Isocyanides

The β-diketiminato nickel(I) species [Me3NN]Ni(2-picoline) (1) serves as an efficient catalyst for carbodiimide (RN═C═NR′) formation in the reactions of a range of organoazides N3R with isocyanides R′NC. [Me3NN]Ni(CNR)2 (R = tBu, Ar (Ar = 2,6-Me2C6H3)) species provide carbodiimides RN═C═NAr′ upon reaction with Ar′N3 (Ar′ = 3,5-Me2C6H3). Nitrene transfer takes place via the intermediacy of nickel imides. Reaction of [MexNN]Ni(2-picoline) (x = 2 or 3) with Ar′N3 gives the new dinickel imides {[MexNN]Ni}2(μ-NAr′) (4 (x = 3) and 5 (x = 2)) as deep purple, diamagnetic substances. The X-ray structure of {[Me2NN]Ni}2(μ-NAr′) (5) features short Ni–Nimide distances of 1.747(2) and 1.755(2) A along with a short Ni–Ni distance of 2.7210(3) A. These dinickel imides 4 and 5 react stoichiometrically with tBuNC to provide the corresponding carbodiimides tBuN═C═NAr′ in good yield. Azide transfer takes place upon reaction of 1 with TMS-N3 to give the square planar nickel(II) azide [Me3NN]Ni(N3)(2-picoline) (7). Stoichiome...

Gaussian Filtering Effects on Brain Tissue-masked Susceptibility Weighted Images to Optimize Voxel-based Analysis

A three-dimensional (3D) fully flow-compensated gradient-echo sequence is usually used to acquire both magnitude and phase images. The phase images are especially useful in revealing magnetic susceptibility, since the phase images after a high-pass filter illustrate small anatomic structures that may not be vividly displayed in magnitude images (1). The phase mask is conducted to suppress unwanted phase signals and enhance those from paramagnetic and diamagnetic substances. Paramagnetic substances such as iron, deoxyhemoglobin, methemoglobin, hemosiderin and ferritin cause a positive phase shift, while diamagnetic substances such as calcium show a negative phase shift (2). To increase image contrasts of small veins and INTRODUCTION