Differential Shift Research Articles

Complexes of Iron(II), Cobalt(II), and Nickel(II) with DOTA-Tetraglycinate for pH and Temperature Imaging Using Hyperfine Shifts of an Amide Moiety.

Paramagnetic complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA4-) derivatives have shown potential for molecular imaging with magnetic resonance. DOTA-tetraglycinate (DOTA-4AmC4-) coordinated with lanthanide metal ions (Ln3+) demonstrates pH/temperature sensing with Biosensor Imaging of Redundant Deviation in Shifts (BIRDS) and Chemical Exchange Saturation Transfer (CEST), respectively, detecting nonexchangeable (e.g., -CHy, where 3 ≥ y ≥ 1) and exchangeable (e.g., -OH or -NHx, where 2 ≥ x ≥ 1) protons. Herein, we report paramagnetic complexes of divalent transition-metal ions (M2+ = Fe2+, Co2+, Ni2+) with DOTA-4AmC4- that endow a unique amide proton (-NH) moiety for pH/temperature sensing. Crystallographic data reveal that DOTA-4AmC4- coordinates with M2+ through oxygen and nitrogen donor atoms, ranging in coordination numbers from 8-coordinate in Fe(II)DOTA-4AmC2-, 7-coordinate in Co(II)DOTA-4AmC2-, and 6-coordinate in Ni(II)DOTA-4AmC2-. The -CHy protons in M(II)DOTA-4AmC2- displayed modest pH/temperature sensitivities, but -NH protons exhibited higher intensity, suggesting prominent BIRDS properties. The pH sensitivity was the highest for Ni(II)DOTA-4AmC2- (1.42 ppm/pH), followed by Co(II)DOTA-4AmC2- (0.21 ppm/pH) and Fe(II)DOTA-4AmC2- (0.16 ppm/pH), whereas temperature sensitivities were comparable (i.e., 0.22, 0.13, and 0.17 ppm/°C, respectively). The CEST image contrast for -NH in M(II)DOTA-4AmC2- was much weaker compared to that of Ln(III)DOTA-4AmC-. Given its high pH sensitivity and low cytotoxicity, Ni(II)DOTA-4AmC2- shows promise for use in preclinical BIRDS-based pH imaging.

Abstract 4138498: Sex Differences in Plasma Acylcarnitines in Patients with STEMI undergoing Primary PCI

Background: Rapid coronary reperfusion using primary PCI is the corner stone therapy for patients presenting with STEMI that restores blood flow and limits infarct size. But paradoxically, the reperfusion process itself can induce additional myocardial injury. Females have increased rates of cardiovascular death compared with males following MI, and it is unclear whether this is related to differences in presentation or reperfusion injury. Given these differences, we aim to better understand the sex differences in the lipidome shift post PCI. METHODS&RESULTS: 126 patients(97 males, 29 females) undergoing PCI for STEMI in a tertiary centre underwent venous blood sampling and semi-targeted Liquid Chromatography Tandem Mass Spectrometry(LC/MS/MS) to determine 291 lipid species. Samples were taken pre-PCI(T0), and 2 hours post PCI(T1) with successful reperfusion. Each lipid class and species were compared between males and females at each time point using statistical analysis, to determine the similarities and differences in plasma lipidome shifts in ACS between sexes. Whilst most lipid classes decrease following reperfusion in STEMI (T0 vs T1), Acylcarnitines increase (20%, adjusted p=0.003) in both sexes. There is a clear sex difference with a greater increase in females (39% increase, adjusted p=0.03), as compared with males (13% increase, adjusted p=0.048). In both sexes this is primarily driven by OctadecanoylCarnitine (C8), which is a medium-chained acylcarnitine. Notably, there was no significant difference in C8 between the sexes in the control group, nor the pre-PCI group(adjusted p=0.48, at T0). At T0, total free fatty acids(FFA) and total phosphatidylinositol were significantly elevated in females compared with males(adjusted p=0.012, p=0.018 respectively). Conclusion: Our analysis suggests there are differences in lipidomics shift between males and females in response to myocardial reperfusion. The higher levels of circulating FFA in ischemic females pre-PCI(T0), followed by a parallel increase of acylcarnitine with reperfusion(T0vsT1), suggest differences between the sexes in myocardial metabolic response to reperfusion injury. C8 has been associated with elevated risk of cardiovascular death in stable CAD, but its clinical impact during reperfusion is still unknown. Detailed understanding of sex specific lipidomics shifts during reperfusion injury will allow us to better understand the mechanistic differences in clinical outcome between males and females.

Structurally Diverse Duclauxins from a Coral-Derived Talaromyces sp. and Insight into Determining the Configuration at C-1 of Heptacyclic Duclauxins by 1H NMR.

A chemical investigation of the coral-derived fungus Talaromyces sp. TJ403-AL05 led to the isolation of 18 duclauxin analogues (1-18), 14 of which, taladuxins A-N (1-14), are new and consist of the first example of duclauxin fused with one 1,6-dioxaspiro[4.5]decan-2-one moiety (1), as well as its biosynthetic product (2), and 12 6/6/6/5/6/6/6 heptacyclic derivatives (3-14). Comprehensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, DP4+ probability analyses, single-crystal X-ray diffraction, and vibrational circular dichroism (VCD) calculations were employed to characterize their structures and revise the published structure of verruculosin B. An efficient 1H NMR method was established to discriminate 1R and 1S configurations at C-1 of 6/6/6/5/6/6/6 heptacyclic duclauxins according to chemical shift differences of diastereotopic methylene H2-11 or H2-12 (ΔδH-11 or ΔδH-12). Compounds 4, 7-8, 13-15, and 18 exhibited moderate inhibition of Arabidopsis thaliana 4-hydroxyphenylpyruvate dioxygenase (AtHPPD), with IC50 values ranging from 17.1 to 71.3 μM.

Evaluation of the interactions between human stratum corneum and liposome formulations using QCM-D

The interactions between human stratum corneum (SC) and two liposomal formulations, azithromycin (AZM)- and nisin-loaded liposomal formulations designed for topical/intradermal application, were investigated using quartz crystal microbalance with dissipation (QCM-D) using. SC isolated from cadaver skin was affixed onto the QCM sensor’s surface. The liposome formulations were prepared using the thin film rehydration method. The particle sizes of the blank liposome, nisin-loaded, AZM-loaded, and combined-loaded liposomes were measured as 90.7 ± 0.58 nm, 100.8 ± 2.5 nm, 136.9 ± 6.5 nm, and 174.3 ± 9.8 nm, respectively. The frequency shifts when blank and drug-loaded liposomes were passed over the gold surface were ∼20 and ∼25 Hz, respectively as a result of the formation of bilayers in a two-step process, adsorption of intact vesicles followed by the formation of the bilayer upon rinsing with water. The frequency shifts for blank and drug-loaded liposomes on SC were ∼8 and ∼15 Hz, respectively. These results show that the liposomes are deposited as bilayers on SC with both the blank and drug-loaded liposomes. The increase in frequency shifts with drug-loaded liposomes indicate the deposition of drug along with lipids onto both the gold and SC surfaces. More significantly, the data showed much slower kinetics of liposome component spreading onto the SC than on gold. The changes in dissipation that accompanies these differences in frequency shifts show transformation of vesicle onto rigid bilayer on gold upon rinsing with water, but direct formation of lipid bilayers on SC. The findings of this study contribute to a better understanding of the interaction between SC and liposomes, such as adsorption, deformation, and rupture of liposomes on different substrates, paving the way for investigating topical and intradermal mechanisms of drug delivery and cosmetic products developed based on liposome formulations.

Measurement of Healthy Adult Brain Temperature Using 1HMagnetic Resonance Spectroscopy Thermometry.

The purpose of this study is to measure the brain temperature (Tbr) by using 1Hmagnetic resonance spectroscopy (1HMRS) thermometry and investigate its age and gender differences in healthy adults. The brain temperature was further compared with the body temperature (Tbo) to investigate the possible existence of brain-body temperature gradient (∆T). Atotal of 80subjects were included in this study. 1HMRS data were collected on a3.0TMR scanner using Point Resolved Selective Spectroscopy (PRESS) sequence. Voxels were positioned in the right frontal (RF) lobe and left frontal (LF) lobe, respectively. The temperature of each voxel was calculated by chemical shift difference (∆δ) between H2O and NAA which was obtained by LCModel software. The average temperature of bilateral frontal lobe voxels was defined as Tbr for each subject. The average forehead temperature was acquired before MR scanning, defined as Tbo, in this study. The difference between Tbr and Tbo, denoted as the brain-body temperature gradient (∆T), was calculated. Age and gender characteristics of Tbr, ∆T and Tbo were analyzed. Tbr (38.51 ± 0.59℃) was higher than Tbo (36.47 ± 0.26℃) (P < 0.05). Negative correlations were observed between Tbr and age (r = -0.49, P < 0.05) and between ∆T and age (r = -0.44, P < 0.05), whereas no correlation existed between Tbo and age (r = -0.03, P = 0.79). Our observation demonstrated that the brain temperature, derived from 1HMRS thermometry, is significantly higher than the body temperature, indicating the existence of abrain-body temperature gradient, and the brain temperature gradually decreases with age.

Large Range Curvature Measurement Using FBGs in Two-Core Fiber with Protective Coating

In this work, we propose a fiber Bragg grating (FBG)-based sensor for curvature measurements. Two gratings are inscribed through the protective coating in a specialty optical fiber using focused femtosecond laser pulses and point-by-point direct writing technology. One grating is inscribed on the central core adjacent to an air channel, while the other is inscribed on the eccentric core. The bending characteristics of the two-core fiber strongly depend on the bending direction due to the asymmetry of the fiber cores. A bending sensitivity of 58 pm/m−1 is achieved by the FBG in the eccentric fiber core over the curvature range of 0–50 m−1 . Temperature and humidity cross-sensitivity could be significantly reduced by analyzing the differences in peak shifts between the two gratings. The sensor features a large sensing range and good robustness due to the presence of its protective buffer coating, which makes it a good candidate for curvature sensing in engineering fields.

STAD: Ship trajectory anomaly detection in ocean with dynamic pattern clustering

With the continuous increase of maritime traffic, developing an efficient and accurate model for ship trajectory anomaly detection has become crucial for ensuring maritime transportation safety. The high complexity and variability of the marine environment lead to diverse ship trajectory patterns, making it challenging to learn effective trajectory representations for accurately identifying anomalies. We thus proposed an unsupervised deep learning model called STAD for ship trajectory anomaly detection in ocean to address this challenge. Concretely, STAD leverages offset reconstruction-based representation learning and a deep Gaussian Mixture Model (GMM) estimation network to learn the underlying complex clustering patterns of ship trajectories and utilize the learned patterns to enhance trajectory anomaly detection. Extensive experiments on multiple AIS datasets indicate that our model significantly outperforms existing methods in detecting multiple representative types of ship trajectory anomalies, including shift deviation, abnormal heading, and abnormal speeding. This study could help closely monitor the status of ship movement and detect abnormal behaviors in advance, thus benefiting maritime safety.

Anionic N-Heterocyclic Carbenes from Mesoionic Imidazolium-4-pyrrolides: The Influence of Substituents, Solvents, and Charge on their 77Se NMR Chemical Shifts.

Mesoionic compounds are the starting material for the synthesis of unique anionic N-heterocyclic carbenes. Herein, mesoionic imidazolium pyrrolides synthesized from pyrrole-2-carbaldehyde via various N-alkyl-4-pyrroyl-imidazoles are described. These were converted into nine new 4-(pyrrol-2-yl)-substituted imidazolium salts and transformed into the mesoionic title compounds using an anion exchange resin. The DFT-calculated (B3LYP/6-311++G**) CREF values indicate a great potential for the formation of anionic N-heterocyclic carbenes by deprotonation, which were generated and reacted with selenium to obtain selenoureas. The 77Se NMR shifts investigated under systematic variation of conditions are dependent on the substitution pattern (ΔδSe = 133 ppm) and the steric demand of the substituents. Solvent dependencies of the 77Se NMR shifts were investigated applying toluene-d8, THF-d8, CDCl3, CD2Cl2, pyridine-d5, acetone-d6, DMSO-d6, CD3CN, AcOD, and MeOD. The influences of the referencing method on the 77Se shifts using external or internal Me2Se or Ph2Se2 and solvent can add up to ΔδSe = ca. 80 ppm. In addition, we observed a temperature dependence of both the selenoureas and the reference reagent Ph2Se2 as well as a 77Se shift difference of the analyte caused by interaction with internally added Ph2Se2. The negative charge of deprotonated selenoureas shifts the values by an additional -20 ppm.

Triantaspirols A-C and Paraphaeolactone Cs from Paraphaeosphaeria sp. KT4192: Sensitivity of CP3 in Distinguishing Close NMR Signals.

Hybridized spirobisnaphthalene derivatives, triantaspirols A-C (1-3) and paraphaeolactones C1 and C2 (4 and 5), were identified from the culture broth of the fungus Paraphaeosphaeria sp. KT4192. The NMR spectra of 2 and 3, as well as 4 and 5, closely resembled each other, indicating that these were pairs of diastereomers. Although this NMR spectral resemblance made it challenging to distinguish their relative configurations, detailed analysis of the electronic circular dichroism (ECD) spectra and NOE correlations allowed us to deduce them. The CP3 metric with the DFT-based NMR chemical shifts was found to distinguish configurations of diastereomers in a highly sensitive and accurate manner that DP4 could not account for because of the very close chemical shift differences in the experimental NMR spectra. The reliability of this method was assessed using 23 published examples which could not be distinguished by DP4 protocol.

Dose-dependent effects of transcranial photobiomodulation on brain temperature in patients with major depressive disorder: a spectroscopy study.

This study aimed to evaluate the dose-dependent brain temperature effects of transcranial photobiomodulation (t-PBM). Thirty adult subjects with major depressive disorder were randomized to three t-PBM sessions with different doses (low: 50 mW/cm2, medium: 300 mW/cm2, high: 850 mW/cm2) and a sham treatment. The low and medium doses were administered in continuous wave mode, while the high dose was administered in pulsed wave mode. A 3T MRI scanner was used to perform proton magnetic resonance spectroscopy (1H-MRS). A voxel with a volume of 30 × 30 × 15 mm3 was placed on the left prefrontal region. Brain temperature (°C) was derived by analyzing 1H-MRS spectrum chemical shift differences between the water (~ 4.7 ppm) and N-acetyl aspartate (NAA) (~ 2.01 ppm) peaks. After quality control of the data, the following group numbers were available for both pre- and post-temperature estimations: sham (n = 10), low (n = 11), medium (n = 10), and high (n = 8). We did not detect significant temperature differences for any t-PBM-active or sham groups post-irradiation (p-value range = 0.105 and 0.781). We also tested for potential differences in the pre-post variability of brain temperature in each group. As for t-PBM active groups, the lowest fluctuation (variance) was observed for the medium dose (σ2 = 0.29), followed by the low dose (σ2 = 0.47), and the highest fluctuation was for the high dose (σ2 = 0.67). t-PBM sham condition showed the overall lowest fluctuation (σ2 = 0.11). Our 1H-MRS thermometry results showed no significant brain temperature elevations during t-PBM administration.

Neural net analysis of NMR spectra from strongly-coupled spin systems

Extracting parameters such as chemical shifts and coupling constants from proton NMR spectra is often a first step in using spectra for compound identification and structure determination. This can become challenging when scalar couplings between protons are comparable in size to chemical shift differences (strongly coupled), as is often the case with low-field (bench top) spectrometers. Here we explore the potential utility of AI methods, in particular neural networks, for extracting parameters from low-field spectra. Rather than seeking large experimental sets of spectra for training a network, we chose quantum mechanical simulation of sets, something that is possible with modern software packages and computer resources. We show that application of a network trained on 2-D J-resolved spectra and applied to a spectrum of iduronic acid, shows some promise, but also meets with some obstacles. We suggest that these may be overcome with improved pulse sequences and more extensive simulations.

Dual-comb source with a reconfigurable repetition frequency difference using intracavity Brillouin lasers

A Brillouin-assisted 80-GHz-spaced dual-comb source with a reconfigurable repetition frequency difference ranging from 48 MHz to 1.486 GHz is demonstrated. Two pairs of dual-pump seeds with an interval offset produce the corresponding dual Brillouin lasers in two fiber loops, and then the Brillouin lasers give rise to dual combs via the cavity-enhanced cascaded four-wave mixing effect. The repetition frequency difference is determined by the interval offset of the dual-pump seeds, which is induced by the Brillouin frequency shift difference between different fibers in a frequency shifter. Each comb provides 22 lasing lines, and the central 10 lines in a 20-dB power deviation feature high optical signal-to-noise ratios exceeding 50 dB. The linewidths of the dual-comb beating signals are less than 300 Hz, and the absolute linewidths of the comb lines are around 1.5 kHz. The dual-comb source enables substantial repetition frequency differences from 48 MHz to 1.486 GHz by changing the pluggable fibers in the frequency shifter.

The essential synergy of MD simulation and NMR in understanding amorphous drug forms.

Molecular dynamics (MD) simulations and chemical shifts from machine learning are used to predict 15N, 13C and 1H chemical shifts for the amorphous form of the drug irbesartan. The local environments are observed to be highly dynamic well below the glass transition, and averaging over the dynamics is essential to understanding the observed NMR shifts. Predicted linewidths are about 2 ppm narrower than observed experimentally, which is hypothesised to largely result from susceptibility effects. Previously observed differences in the 13C shifts associated with the two tetrazole tautomers can be rationalised in terms of differing conformational dynamics associated with the presence of an intramolecular interaction in one tautomer. 1H shifts associated with hydrogen bonding can also be rationalised in terms of differing average frequencies of transient hydrogen bonding interactions.

Semisynthesis, Structure Elucidation and Anti-Mycobacterium marinum Activity of a Series of Marine-Derived 14-Membered Resorcylic Acid Lactones with Interesting Ketal Groups.

The incidence of Mycobacterium marinum infection is on the rise; however, the existing drug treatment cycle is lengthy and often requires multi-drug combination. Therefore, there is a need to develop new and effective anti-M. marinum drugs. Cochliomycin A, a 14-membered resorcylic acid lactone with an acetonide group at C-5' and C-6', exhibits a wide range of antimicrobial, antimalarial, and antifouling activities. To further explore the effect of this structural change at C-5' and C-6' on this compound's activity, we synthesized a series of compounds with a structure similar to that of cochliomycin A, bearing ketal groups at C-5' and C-6'. The R/S configuration of the diastereoisomer at C-13' was further determined through an NOE correlation analysis of CH3 or CH2 at the derivative C-13' position and the H-5' and H-6' by means of a 1D NOE experiment. Further comparative 1H NMR analysis of diastereoisomers showed the difference in the chemical shift (δ) value of the diastereoisomers. The synthetic compounds were screened for their anti-microbial activities in vitro. Compounds 15-24 and 28-35 demonstrated promising activity against M. marinum, with MIC90 values ranging from 70 to 90 μM, closely approaching the MIC90 of isoniazid. The preliminary structure-activity relationships showed that the ketal groups with aromatic rings at C-5' and C-6' could enhance the inhibition of M. marinum. Further study demonstrated that compounds 23, 24, 29, and 30 had significant inhibitory effects on M. marinum and addictive effects with isoniazid and rifampicin. Its effective properties make it an important clue for future drug development toward combatting M. marinum resistance.

Study on the role of alkali halides on the mutarotation and dehydration of d-xylose in aqueous solution

Although the xylose mutarotation and transformation have been investigated largely separately, their relationship has been rarely systematically elaborated. The effect of several factors such as xylose concentration, temperature, and salt concentration, affecting the mutarotation of xylose are discussed. Nine alkali halides (LiCl, NaCl, KCl, LiBr, NaBr, KBr, LiI, NaI, and KI) are used to test salt effects. The relationship between xylose rotation rate constant (kM), specific optical rotation at equilibrium ([α]eqm), α/β ratio, H chemical shift difference (ΔΔδ), Gibbs free energy difference (ΔG), hydrogen ion or hydroxide ion concentration ([H+] or [OH−]), and xylose conversion is discussed. Different salts dissolved in water result in different pH of the solutions, which affect the mutarotation of xylose, with the nature of both cation and anion. Shortly, the smaller the cation radius is and the larger the anion radius is, the greater the mutarotation rate is. In the dehydration of xylose to furfural in salty solutions, xylose conversion is positively correlated to mutarotation rate, H+ or OH− concentration, and the energy difference between α-xylopyranose and β-xylopyranose. Although the [α]eqm of xylose is positively correlated with α/β configuration ratio, there is no obvious correlation with xylose dehydration. The conversion to furfural in chlorides is superior to that in bromines and iodides, which is due to the fact that the pH of chloride salts is smaller than that of the corresponding bromide and iodized salts. Higher H+ concentration prefers to accelerate the formation of furfural. In basic salt solutions, the xylulose selectivity is higher than that of furfural at the initial stage of reaction. The furfural selectivity and carbon balance are better in acidic condition rather than in basic condition. In H2O-MTHF (2-Methyltetrahydrofuran) biphasic system, the optimal furfural selectivity of 81.0 % is achieved at 190 °C in 1 h with the assistance of LiI and a little HCl (0.2 mmol, 8 mmol/L in aqueous phase). A high mutarotation rate represents rapid xylose conversion, but a high furfural selectivity prefers in acidic solutions, which would be perfect if organic solvents were available to form biphasic systems.

Two-dimensional refractive index distribution using polarization phase shifting interferometry and total internal reflection

An effective method to measure the 2-D refractive index distribution of homogeneous liquids: acetic acid and glycerol- water mixture at different concentration and a non- homogeneous mixture of liquids: water, acetic acid, acetone and glycerin but not limited to these liquids is presented. In the present setup a combination of polarization phase shifting interferometry (PPSI) and total internal reflection (TIR) is used. The s-polarized light strikes the boundary of a right angle prism and a tested liquid droplet. When TIR occurs on the interface, the incident light has a phase variation which depends on the refractive index of adhered liquid on prism surface. Two-dimensional index distributions can be easily calculated using the relation among reflection phase shift difference and the liquid index. The results of the tested mixed liquid by proposed technique show the refractive index and its distribution in range 1.433 ± 0.031 to 1.433 ± 0.124.

Highly sensitive intensity-type polarization chiral sensor with reference light.

Optical rotation is a special phenomenon in which the plane of polarization of polarized light is rotated after passing through a chiral medium. This work first, to our knowledge, presents and optimizes a polarization chiral sensor with a reference light on the basis of a weak measurement light path. The influences of phase shift and polarization angle difference on sensitivity were theoretically optimized and verified experimentally. The introduction of a reference light further reduced the impact of light source fluctuations on the detection signal, improving the signal-to-noise ratio and reducing the optical rotation resolution to 2 × 10-5 rad. This method has the characteristics of low cost, high sensitivity, and real-time rapid detection, making it potentially applicable in the field of chemical analysis, such as chiral molecule detection.

Latitudinal Dependence of Variations in the Frequencies of Solar Oscillations Above the Acoustic Cut-Off

At high frequencies beyond the acoustic cut-off, a peak-like structure is visible in the solar power spectrum. Known as the pseudo-modes, their frequencies have been shown to vary in anti-phase with solar magnetic activity. In this work, we determined temporal variations in these frequencies across the solar disc, with the aim of identifying any potential latitudinal dependence of pseudo-mode frequency shifts. We utilised nearly 22 years of spatially resolved GONG data for all azimuthal orders, m\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$\ extit{m}$\\end{document}, for harmonic degrees 0≤l≤200\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$0\\leq l\\leq 200$\\end{document}, and determined shifts using the resampled periodogram method. Periodogram realisations were created from overlapping, successive 216 day-long segments in time, and cropped to 5600 – 6800 μHz. Cross-correlation functions were then repeatedly generated between these realisations to identify any variation in frequency and the uncertainty. We categorised each mode by its latitudinal sensitivity and used this categorisation to produce average frequency shifts for different latitude bands (15∘ and 5∘ in size) which were compared to magnetic proxies, the F10.7\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$F_{\\mathrm{10.7}}$\\end{document} index and GONG synoptic maps. Morphological differences in the pseudo-mode shifts between different latitudes were found, which were most pronounced during the rise to solar maximum where shifts reach their minimum values. At all latitudes, shift behaviour was strongly in anti-correlation with the activity proxy. Additionally, periodicities shorter than the 11-year cycle were observed. Wavelet analysis was used to identify a periodicity of four years at all latitudes.

It is challenging to reproduce both anatomical and functional aspects of anterolateral reconstruction: postoperative 3D-CT analysis of the femoral tunnel position

BackgroundThis study aimed to evaluate the femoral tunnel position and fiber length of the anterolateral ligament (ALL) reconstruction compared with the natural anatomy of the ALL. We also evaluated whether the femoral tunnel position would affect residual pivot shift.MethodsThis study was a retrospective review of 55 knees that underwent ALL reconstruction considering the anatomical and functional aspects, during primary anterior cruciate ligament (ACL) reconstruction in the presence of a high-grade pivot shift or revisional ACL reconstruction. We determined the position of the femoral tunnel and the length of graft using a three-dimensional (3D)-computed tomography (CT) model after ALL reconstruction. We also measured graft excursion during surgery and examined pivot shift 2 years after surgery. We conducted a subgroup analysis of femoral tunnel position, fiber length, isometricity, and residual pivot shift depending on whether the tunnel was anterior or posterior to the lateral epicondyle (LE). We also performed a subgroup analysis depending on whether the ACL reconstruction was primary or revisional.ResultsThe mean femoral tunnel position was 2.04 mm posterior and 14.5 mm proximal from the center of the LE. The mean lengths of the anterior and posterior fibers were 66.6 and 63.4 mm, respectively. The femoral tunnel was positioned more proximally than the anatomical position, and both anterior and posterior ALL fibers were longer than the natural anatomy. The anteroposterior femoral tunnel position was significantly correlated with anterior (p = 0.045) and posterior (p = 0.037) fiber excursion. In the subgroup analysis, there was no significant difference in the residual pivot shift between the posterior and anterior tunnel positions. However, there were significant differences for proximal position (p < 0.001) and fiber length (p = 0.006). There was no significant difference between primary and revisional ACL regarding femoral tunnel position and fiber lengths.ConclusionIt is challenging to reproduce both anatomical and functional aspects of ALL reconstruction in both primary and revision ACL reconstruction. Especially for functional reconstruction, the femoral tunnel tended to be positioned more proximally than the anatomical position. However, the femoral tunnel position did not affect functional clinical outcomes at the 2-year follow-up.Level of evidenceLevel IV Case series.

Distinct chemical degradation pathways of AAV1 and AAV8 under thermal stress conditions revealed by analytical anion exchange chromatography and LC-MS-based peptide mapping

Adeno-associated virus (AAV)-based gene therapy is experiencing a rapid growth in the field of medicine and holds great promise in combating a wide range of human diseases. For successful development of AAV-based products, comprehensive thermal stability studies are often required to establish storage conditions and shelf life. However, as a relatively new modality, limited studies have been reported to elucidate the chemical degradation pathways of AAV products under thermal stress conditions. In this study, we first presented an intriguing difference in charge profile shift between thermally stressed AAV8 and AAV1 capsids when analyzed by anion exchange chromatography. Subsequently, a novel and robust peptide mapping protocol was developed and applied to elucidate the underlying chemical degradation pathways of thermally stressed AAV8 and AAV1. Compared to the conventional therapeutic proteins, the unique structure of AAV capsids also led to some key differences in how modifications at specific sites may impact the overall charge properties. Finally, despite the high sequency identity, the analysis revealed that the opposite charge profile shifts between thermally stressed AAV8 and AAV1 could be mainly attributed to a single modification unique to each serotype.