Structural Analysis of Single-Atom Catalysts by X-ray Absorption Spectroscopy.

ConspectusMetal nanoparticles (NPs) are one of the most frequently used heterogeneous catalysts. However, only the surface atoms in the NPs can participate in catalytic reactions. To maximize the atomic efficiency, the active sites can be reduced to single atoms. Generally, catalysts that have isolated metal atoms on the surface of a support are called single-atom catalysts (SACs). Many techniques have been developed and applied to probe the structures of SACs. Nevertheless, the structural characterization of SACs is still challenging as it requires the analysis of their structure and properties with atomic and sometimes even subatomic resolution. X-ray absorption spectroscopy (XAS) is a powerful tool in investigating the local coordination environment of SACs since it is element-specific and can provide accurate structural information at the subatomic level (∼0.01 Å).In this Account, we present our perspectives on the structural analysis of SACs from some unique features in the X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure (EXAFS). We first highlight the importance of the XANES peak features in the sensitive analysis of SAC structures. Such analysis is illustrated to be even more useful in the joint applications of experimental and theoretical XAS. The inspection of the metal-metal (M-M) peak in Fourier transformed EXAFS (FT-EXAFS) spectra is a widely used method to identify the single-atom structure, but this method is not always reliable. Thus, we point out the importance of fitting EXAFS and the thorough interpretation of structural parameters such as coordination numbers (CNs, the number of neighboring atoms next to a chosen atom), bond distances, and the Debye-Waller factor (σ2). The small FT-EXAFS peak for the M-M shell is often ignored in the structural analysis of SACs. Here, it is demonstrated that a careful analysis of these small peaks could help more reliably analyze the SAC structure, and it would be particularly useful in the analysis of a single-atom alloy (SAA). Next, the usefulness of bond distance and σ2 analysis is highlighted, and such analysis is shown to be particularly helpful for the analysis of SAAs, which is rarely discussed in the literature. Given the advantage that XAS data can be collected under various conditions, we show that in situ XAS can provide important information about the catalytic mechanism of the SAC catalyst. In particular, we emphasize the significance of using an advanced in situ technique to extract detailed structural information that is difficult to obtain from regular XAS experiments. Finally, we highlight the importance of jointly using XAS with other complementary methods in a more complete understanding of the structure and properties of SACs. It is anticipated that with further development of XAS techniques and improved data analysis, XAS will become even more powerful in providing insights into the structure-property relationships of SACs, which can advance their practical applications.

Utility of Spectral Filtering to Improve the Reliability of Marine Fauna Detections from Drone-Based Monitoring.

Monitoring marine fauna is essential for mitigating the effects of disturbances in the marine environment, as well as reducing the risk of negative interactions between humans and marine life. Drone-based aerial surveys have become popular for detecting and estimating the abundance of large marine fauna. However, sightability errors, which affect detection reliability, are still apparent. This study tested the utility of spectral filtering for improving the reliability of marine fauna detections from drone-based monitoring. A series of drone-based survey flights were conducted using three identical RGB (red-green-blue channel) cameras with treatments: (i) control (RGB), (ii) spectrally filtered with a narrow 'green' bandpass filter (transmission between 525 and 550 nm), and, (iii) spectrally filtered with a polarising filter. Video data from nine flights comprising dolphin groups were analysed using a machine learning approach, whereby ground-truth detections were manually created and compared to AI-generated detections. The results showed that spectral filtering decreased the reliability of detecting submerged fauna compared to standard unfiltered RGB cameras. Although the majority of visible contrast between a submerged marine animal and surrounding seawater (in our study, sites along coastal beaches in eastern Australia) is known to occur between 515-554 nm, isolating the colour input to an RGB sensor does not improve detection reliability due to a decrease in the signal to noise ratio, which affects the reliability of detections.

Management of Incidentally Detected Gallbladder Polyps: Society of Radiologists in Ultrasound Consensus Conference Recommendations.

Gallbladder polyps (also known as polypoid lesions of the gallbladder) are a common incidental finding. The vast majority of gallbladder polyps smaller than 10 mm are not true neoplastic polyps but are benign cholesterol polyps with no inherent risk of malignancy. In addition, recent studies have shown that the overall risk of gallbladder cancer is not increased in patients with small gallbladder polyps, calling into question the rationale for frequent and prolonged follow-up of these common lesions. In 2021, a Society of Radiologists in Ultrasound, or SRU, consensus conference was convened to provide recommendations for the management of incidentally detected gallbladder polyps at US. See also the editorial by Sidhu and Rafailidis in this issue.

Longitudinal Ultrasound Assessment of Changes in Size and Number of Incidentally Detected Gallbladder Polyps.

BACKGROUND. Previous European multisociety guidelines recommend routine follow-up imaging of gallbladder polyps (including polyps < 6 mm in patients without risk factors) and cholecystectomy for polyp size changes of 2 mm or more. OBJECTIVE. The purpose of this study was to assess longitudinal changes in the number and size of gallbladder polyps on serial ultrasound examinations. METHODS. This retrospective study included patients who underwent at least one ultrasound examination between January 1, 2010, and December 31, 2020 (as part of a hepatocellular carcinoma screening and surveillance program) that showed a gallbladder polyp. Number of polyps and size of largest polyp were recorded based primarily on review of examination reports. Longitudinal changes on serial examinations were summarized. Pathologic findings from cholecystectomy were reviewed. RESULTS. Among 9683 patients, 759 (8%) had at least one ultrasound examination showing a polyp. Of these, 434 patients (248 men, 186 women; mean age, 50.6 years) had multiple examinations (range, 2-19 examinations; mean, 4.8 examinations per patient; mean interval between first and last examinations, 3.6 ± 3.1 [SD] years; maximum interval, 11.0 years). Among these 434 patients, 257 had one polyp, 40 had two polyps, and 137 had more than two polyps. Polyp size was 6 mm or less in 368 patients, 7-9 mm in 52 patients, and 10 mm or more in 14 patients. Number of polyps increased in 9% of patients, decreased in 14%, both increased and decreased on serial examinations in 22%, and showed no change in 55%. Polyp size increased in 10% of patients, decreased in 16%, both increased and decreased on serial examinations in 18%, and showed no change in 56%. In 9% of patients, gallbladder polyps were not detected on follow-up imaging; in 6% of patients, gallbladder polyps were not detected on a follow-up examination but were then detected on later studies. No gallbladder carcinoma was identified in 19 patients who underwent cholecystectomy. CONCLUSION. Gallbladder polyps fluctuate in size, number, and visibility over serial examinations. Using a 2-mm threshold for growth, 10% increased in size. No carcinoma was identified. CLINICAL IMPACT. European multisociety guidelines that propose surveillance of essentially all polyps and a 2-mm size change as the basis for cholecystectomy are likely too conservative for clinical application.

Single-atom alloy catalysts: structural analysis, electronic properties and catalytic activities.

Monometallic catalysts, in particular those containing noble metals, are frequently used in heterogeneous catalysis, but they are expensive, rare and the ability to tailor their structures and properties remains limited. Traditionally, alloy catalysts have been used instead that feature enhanced electronic and chemical properties at a reduced cost. Furthermore, the introduction of single metal atoms anchored onto supports provided another effective strategy to increase both the atomic efficiency and the chance of tailoring the properties. Most recently, single-atom alloy catalysts have been developed in which one metal is atomically dispersed throughout the catalyst via alloy bonding; such catalysts combine the traditional advantages of alloy catalysts with the new feature of tailoring properties achievable with single atom catalysts. This review will first outline the atomic scale structural analysis on single-atom alloys using microscopy and spectroscopy tools, such as high-angle annular dark field imaging-scanning transmission electron microscopy and extended X-ray absorption fine structure spectroscopy. Next, progress in research to understand the electronic properties of single-atom alloys using X-ray spectroscopy techniques and quantum calculations will be presented. The catalytic activities of single-atom alloys in a few representative reactions will be further discussed to demonstrate their structure-property relationships. Finally, future perspectives for single-atom alloy catalysts from the structural, electronic and reactivity aspects will be proposed.

Site-Specific Electronic Properties of [Ag25 (SR)18 ]- Nanoclusters by X-Ray Spectroscopy.

Silver nanoclusters (NCs) are of significant interest owing to their interesting structural, electronic, and catalytic properties. Among these NCs, Ag25 (SR)18 is particularly attractive due to its identical geometry as its Au counterpart, Au25 (SR)18 . Herein, the site-specific electronic properties of Ag25 (SR)18 and Au25 (SR)18 using X-ray spectroscopy experiments and quantum simulations are presented. To overcome the final state effect observed in X-ray photoelectron spectroscopy (XPS), a unique method is developed to reliably analyze the charge transfer behavior of the NCs. Density functional theory calculations are combined with XPS to provide more insight into the electronic properties of the NCs. The differences in the XPS valence bands of these two NCs are further compared and interpreted using the relativistic effect. The first derivative of the X-ray absorption near-edge structure (XANES) spectrum is further used as a tool to sensitively probe the bonding properties of Ag25 (SR)18 . By combining the experimental XANES data and their site-specific quantum simulations, the large impact of the staple motif on the bonding properties of the NC is demonstrated. These findings highlight the unique electronic properties of each atomic site in Ag25 (SR)18 ; the effective X-ray analysis techniques developed here can offer new opportunities for the site-specific study of other NCs.

Lack of cortical or Ia-afferent spinal pathway involvement in muscle force loss after passive static stretching.

This study investigated whether modulation of corticospinal-motoneuronal excitability and/or synaptic transmission of the Ia afferent spinal reflex contributes to decreases in voluntary activation and muscular force after an acute bout of prolonged static muscle stretching. Fifteen men performed five 60-s constant-torque stretches (15-s rest intervals; total duration 5 min) of the plantar flexors on an isokinetic dynamometer and a nonstretching control condition in random order on 2 separate days. Maximum isometric plantar flexor torque and triceps surae muscle electromyographic activity (normalized to M wave; EMG/M) were simultaneously recorded immediately before and after each condition. Motor-evoked potentials (using transcranial magnetic stimulation) and H-reflexes were recorded from soleus during EMG-controlled submaximal contractions (23.4 ± 6.9% EMG maximum). No changes were detected in the control condition. After stretching, however, peak torque (mean ± SD; -14.3 ± 7.0%) and soleus EMG/M (-17.8 ± 6.2%) decreased, and these changes were highly correlated (r = 0.83). No changes were observed after stretching in soleus MEP or H-reflex amplitudes measured during submaximal contractions, and interindividual variability of changes was not correlated with changes in EMG activity or maximum torque. During EMG-controlled submaximal contractions, torque production was significantly decreased after stretching (-22.7 ± 15.0%), indicating a compromised muscular output. These data provide support that changes in the excitability of the corticospinal-motoneuronal and Ia afferent spinal reflex pathways do not contribute to poststretch neural impairment.NEW & NOTEWORTHY This study is the first to specifically examine potential sites underlying the decreases in neural activation of muscle and force production after a bout of muscle stretching. However, no changes were found in either the H-reflex or motor-evoked potential amplitude during submaximal contractions.

Jordanian Nursing Student and Instructor Perceptions of the Clinical Learning Environment.

Background Training within clinical areas is a vital part of nursing education. In order to effectively modify and facilitate such training, it is important to understand the perceptions of nursing educators and students about what constitutes effective practices. OBJECTIVE: This study explores perceptions of Jordanian nursing students and clinical instructors related to clinical training and the learning environment. DESIGN: Interpretative phenomenological qualitative approach was used in this study. METHOD: semi-structured focus group interviews in two Jordanian Universities Results: The study identified four themes focused on the experiences of these participants. Themes were attributes of clinical training placement, attributes of clinical instructors, attributes of clinical nursing curriculum and student's attributes. The first theme had two subthemes "Structure and nature of clinical placement" and "Nurses' collaboration". CONCLUSION: The study recommendations are: nursing schools should plan students' clinical experience taking into consideration the challenges associated with these attributes.

Modeling covalent-modifier drugs.

In this review, we present a summary of how computer modeling has been used in the development of covalent-modifier drugs. Covalent-modifier drugs bind by forming a chemical bond with their target. This covalent binding can improve the selectivity of the drug for a target with complementary reactivity and result in increased binding affinities due to the strength of the covalent bond formed. In some cases, this results in irreversible inhibition of the target, but some targeted covalent inhibitor (TCI) drugs bind covalently but reversibly. Computer modeling is widely used in drug discovery, but different computational methods must be used to model covalent modifiers because of the chemical bonds formed. Structural and bioinformatic analysis has identified sites of modification that could yield selectivity for a chosen target. Docking methods, which are used to rank binding poses of large sets of inhibitors, have been augmented to support the formation of protein-ligand bonds and are now capable of predicting the binding pose of covalent modifiers accurately. The pKa's of amino acids can be calculated in order to assess their reactivity towards electrophiles. QM/MM methods have been used to model the reaction mechanisms of covalent modification. The continued development of these tools will allow computation to aid in the development of new covalent-modifier drugs. This article is part of a Special Issue entitled: Biophysics in Canada, edited by Lewis Kay, John Baenziger, Albert Berghuis and Peter Tieleman.

Validation of quantitative susceptibility mapping with Perls' iron staining for subcortical gray matter.

Quantitative susceptibility mapping (QSM) measures bulk susceptibilities in the brain, which can arise from many sources. In iron-rich subcortical gray matter (GM), non-heme iron is a dominant susceptibility source. We evaluated the use of QSM for iron mapping in subcortical GM by direct comparison to tissue iron staining. We performed in situ or in vivo QSM at 4.7 T combined with Perls' ferric iron staining on the corresponding extracted subcortical GM regions. This histochemical process enabled examination of ferric iron in complete slices that could be related to susceptibility measurements. Correlation analyses were performed on an individual-by-individual basis and high linear correlations between susceptibility and Perls' iron stain were found for the three multiple sclerosis (MS) subjects studied (R(2) = 0.75, 0.62, 0.86). In addition, high linear correlations between susceptibility and transverse relaxation rate (R2*) were found (R(2) = 0.88, 0.88, 0.87) which matched in vivo healthy subjects (R(2) = 0.87). This work validates the accuracy of QSM for brain iron mapping and also confirms ferric iron as the dominant susceptibility source in subcortical GM, by demonstrating high linear correlation of QSM to Perls' ferric iron staining.

Subcortical gray matter segmentation and voxel-based analysis using transverse relaxation and quantitative susceptibility mapping with application to multiple sclerosis.

PURPOSE: To investigate subcortical gray matter segmentation using transverse relaxation rate (R2 *) and quantitative susceptibility mapping (QSM) and apply it to voxel-based analysis in multiple sclerosis (MS). MATERIALS AND METHODS: Voxel-based variation in R2 * and QSM within deep gray matter was examined and compared to standard whole-structure analysis using 37 MS subjects and 37 matched controls. Deep gray matter nuclei (caudate, putamen, globus pallidus, and thalamus) were automatically segmented and morphed onto a custom atlas based on QSM and standard T1 -weighted images. Segmentation accuracy and scan-rescan reliability were tested. RESULTS: When considering only significant regions as returned by the multivariate voxel-based analysis, increased R2 * and QSM was found in MS subjects compared to controls in portions of all four nuclei studied (P < 0.002). For R2 *, regional analysis yielded at least 66-fold improved P-value significance in all nuclei over standard whole-structure analysis, while for QSM only thalamus benefited, with 5-fold improvement in significance. Improved segmentation over standard methods, particularly for globus pallidus (2.8 times higher Dice score), was achieved by incorporating high-contrast QSM into the atlas. Voxel-based reliability was highest for QSM (<1% variation). CONCLUSION: Automatic segmentation of iron-rich deep gray matter can be improved by incorporating QSM. Voxel-based evaluation yielded increased R2 * and QSM in MS subjects in all four nuclei studied with R2 *, benefiting the most from localized analysis over whole-structure measures.

Identification of Conserved and Novel MicroRNAs during Tail Regeneration in the Mexican Axolotl.

The Mexican axolotl salamander (Ambystoma mexicanum) is one member of a select group of vertebrate animals that have retained the amazing ability to regenerate multiple body parts. In addition to being an important model system for regeneration, the axolotl has also contributed extensively to studies of basic development. While many genes known to play key roles during development have now been implicated in various forms of regeneration, much of the regulatory apparatus controlling the underlying molecular circuitry remains unknown. In recent years, microRNAs have been identified as key regulators of gene expression during development, in many diseases and also, increasingly, in regeneration. Here, we have used deep sequencing combined with qRT-PCR to undertake a comprehensive identification of microRNAs involved in regulating regeneration in the axolotl. Specifically, among the microRNAs that we have found to be expressed in axolotl tissues, we have identified 4564 microRNA families known to be widely conserved among vertebrates, as well as 59,811 reads of putative novel microRNAs. These findings support the hypothesis that microRNAs play key roles in managing the precise spatial and temporal patterns of gene expression that ensures the correct regeneration of missing tissues.

Longitudinal MR imaging of iron in multiple sclerosis: an imaging marker of disease.

PURPOSE: To investigate the relationship between magnetic resonance (MR) imaging markers of iron content and disease severity in patients with multiple sclerosis (MS) over a 2-year period. MATERIALS AND METHODS: This prospective study was approved by the local ethics committee, and written informed consent was obtained from all participants. Seventeen patients with MS and 17 control subjects were examined twice, 2 years apart, by using phase imaging and transverse relaxation (R2*) mapping at 4.7 T. Quantitative differences in iron content in deep gray matter between patients and control subjects were evaluated with repeated-measures multivariate analysis of variance separately for R2* mapping and phase imaging. Multiple regression analysis was used to evaluate correlations of MR imaging measures, both 2-year-difference and single-time measurements, to baseline disease severity. RESULTS: R2* mapping using 2-year-difference measurements had the highest correlation to disease severity (r = 0.905, P < .001) compared with R2* mapping using single-time measurements (r = 0.560, P = .019) and phase imaging by using either single-time (r = 0.539, P = .026) or 2-year-difference (r = 0.644, P = .005) measurements. Significant increases in R2* occur during 2 years in the substantia nigra (P < .001) and globus pallidus (P = .035), which are both predictors of disease in regression analysis, in patients compared with control subjects. There were group differences in the substantia nigra, globus pallidus, pulvinar thalamus, thalamus, and caudate nucleus, compared with control subjects with R2* mapping (P < .05), and group differences in the caudate nucleus and pulvinar thalamus, compared with control subjects with phase imaging (P < .05). CONCLUSION: There are significant changes in deep gray matter iron content in MS during 2 years measured with MR imaging, changes that are strongly related to physical disability. Longitudinal measurements may produce a higher correlation to disease severity compared with single-time measurements because baseline iron content of deep gray matter is variable among subjects.

Patterns of Rising HIV Positivity in Northern Madagascar: Evidence of an Urgent Public Health Concern.

Despite over two decades of progress against HIV/AIDS in adjacent sub-Saharan Africa, HIV rates and deaths due to AIDS are exponentially rising in Madagascar. Furthermore, a growing body of evidence suggests that, due to a scarcity of general-population screening data, even the startling increase demonstrated by official models vastly underestimates the true population prevalence of HIV. We aimed to implement a real-world HIV screening and treatment protocol to serve a general population stemming from across northern Madagascar. In collaboration with the Malagasy Ministry of Health, we provided point-of-care HIV screening and confirmatory testing for over 1000 participants from 73 towns, villages, and cities. We recorded an overall HIV prevalence of 2.94%. Notably, we observed a 13.1% HIV prevalence rate among urban populations and showed that proximity to a major route of travel was significantly associated with HIV risk. We also observed a link between HIV risk and various occupations, including those associated with increased mobility (such as mining). Importantly, all HIV-positive individuals were initiated on antiretroviral therapy in concordance with local health authorities. To our knowledge, this study marks the largest primary test data-based HIV study to date among Madagascar's general population, showing a greatly higher HIV prevalence (2.9%) than previously reported modeling-based figures (0.4%). Our rates aligned with the pattern of higher prevalence demonstrated in smaller general-population screening studies occurring more commonly prior to political strife in the mid-2000s. These findings demonstrate evidence of a growing HIV epidemic in northern Madagascar and underscore the need for future investment into more comprehensive HIV screening and control initiatives in Madagascar.

Management of incidentally detected gallbladder polyps: a review of clinical scenarios using the 2022 SRU gallbladder polyp consensus guidelines.

Gallbladder (GB) polyps are a common incidental finding on sonography, but only a small fraction of polyps become GB cancer. The Society of Radiologists in Ultrasound (SRU) consensus committee recently performed an extensive literature review and published guidelines for GB polyp follow-up/management to provide clarity among the many heterogeneous recommendations that are available to clinicians. As these guidelines have become adopted into clinical practice, challenging clinical scenarios have arisen including GB polyps in primary sclerosing cholangitis (PSC), high risk geographic/genetic patient populations, shrinking polyps, pedunculated vs sessile polyps, thin vs thick stalked polyps, vascular polyps and multiple polyps. According to the SRU guidelines, clinicians should refer to gastroenterology guidelines when managing GB polyps in patients with known PSC. If patients at high geographic/genetic risk develop GB polyps, 'extremely low risk' polyps may be managed as 'low risk' and 10-14 mm 'extremely low risk' or '7-14 mm' low risk polyps that decrease in size by ≥ 4 mm require no follow-up. Thin-stalked or pedunculated polyps are 'extremely low risk' and thick-stalked pedunculated polyps are 'low risk'. Sessile polyps are 'low risk' but should receive immediate specialist referral if features suggestive of GB cancer are present. Neither polyp multiplicity nor vascularity impact risk of GB cancer and follow up should be based on morphology alone.

Multiple sclerosis: validation of MR imaging for quantification and detection of iron.

PURPOSE: To investigate the relationship between iron staining and magnetic resonance (MR) imaging measurements in postmortem subjects with multiple sclerosis (MS). MATERIALS AND METHODS: Institutional ethical approval was obtained, and informed consent was obtained from the subjects and/or their families. Four MR imaging methods based on transverse relaxation (T2 weighting, R2 mapping, and R2* mapping) and phase imaging were performed by using a 4.7-T system in three in situ postmortem patients with MS less than 28 hours after death and in one in vivo patient 1 year before death. Iron staining with the Perls iron reaction was performed after brain extraction. Region-of-interest measurements from six subcortical gray matter structures were obtained from MR imaging and then correlated with corresponding locations on photographs of iron-stained pathologic slices by using a separate linear least-squares regression in each subject. Iron status of white matter lesions, as determined by staining, was compared with appearance on MR images. RESULTS: R2* mapping had the highest intrasubject correlations with iron in subcortical gray matter (R(2) = 0.857, 0.628, and 0.685; all P < .001), while R2 mapping (R(2) = 0.807, 0.615, 0.628, and 0.489; P < .001 and P = .001, .034, and .001, respectively), phase imaging (R(2) = 0.672, 0.441, 0.596, 0.548; all P ≤ .001), and T2-weighted imaging (R(2) = 0.463, 0.582, 0.650, and 0.551; all P < .001) had lower but still strong correlations. Within lesions, hypointense areas on phase images did not always represent iron. A hyperintense rim surrounding lesions on R2* maps was only present with iron staining, yet not all iron-staining lesions had R2* rim hyperintensity. CONCLUSION: All four MR imaging methods had significant linear correlations with iron and could potentially be used to determine iron status of subcortical gray matter structures in MS, with R2* mapping being preferred. A reliable method of determining iron status within MS lesions was not established.

CRISPRi screening identifies CASP8AP2 as an essential viability factor in lung cancer controlling tumor cell death via the AP-1 pathway.

Since lung cancer remains the leading cause of cancer death globally, there is an urgent demand for novel therapeutic targets. We carried out a CRISPR interference (CRISPRi) loss-of-function screen for human lung adenocarcinoma (LUAD) targeting 2098 deregulated genes using a customized algorithm to comprehensively probe the functionality of every resolvable transcriptional start site (TSS). CASP8AP2 was identified as the only hit that significantly affected the viability of all eight screened LUAD cell lines while the viability of non-transformed lung cells was only moderately impacted. Knockdown (KD) of CASP8AP2 induced both autophagy and apoptotic cell death pathways. Systematic expression profiling linked the AP-1 transcription factor to the CASP8AP2 KD-induced cancer cell death. Furthermore, inhibition of AP-1 reverted the CASP8AP2 silencing-induced phenotype. Overall, the tailored CRISPRi screen profiled the impact of over 2000 genes on the survival of eight LUAD cell lines and identified the CASP8AP2 - AP-1 axis mediating lung cancer viability.

CD8+ T cell escape mutations in simian immunodeficiency virus SIVmac239 cause fitness defects in vivo, and many revert after transmission.

Virus-specific CD8(+) T lymphocytes select for escape mutations in human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). To assess the effects of these mutations on viral fitness, we introduced escape mutations into 30 epitopes (bound by five major histocompatibility complex class I [MHC-I] molecules) in three different viruses. Two of these MHC-I alleles are associated with elite control. Two of the three viruses demonstrated reduced fitness in vivo, and 27% of the introduced mutations reverted. These findings suggest that T cell epitope diversity may not be such a daunting problem for the development of an HIV vaccine.

Susceptibility phase imaging with improved image contrast using moving window phase gradient fitting and minimal filtering.

PURPOSE: To enhance image contrast in susceptibility phase imaging using a new method of background phase removal. MATERIALS AND METHODS: A background phase removal method is proposed that uses the spatial gradient of the raw phase image to perform a moving window third-order local polynomial estimation and correction of the raw phase image followed by minimal high pass filtering. The method is demonstrated in simulation, 10 healthy volunteers, and 5 multiple sclerosis patients in comparison to a standard phase filtering approach. RESULTS: Compared to standard phase filtering, the new method increased phase contrast with local background tissue in subcortical gray matter, cortical gray matter, and multiple sclerosis lesions by 67% ± 33%, 13% ± 7%, and 48% ± 19%, respectively (95% confidence interval). In addition, the new method removed more phase wraps in areas of rapidly changing background phase. CONCLUSION: Local phase gradient fitting combined with minimal high pass filtering provides better tissue depiction and more accurate phase quantification than standard filtering.