Intrinsic Weakness Research Articles

JADES – the Rosetta stone of JWST-discovered AGN: deciphering the intriguing nature of early AGN

ABSTRACT JWST has discovered a large population of active galactic nuclei (AGN) at high redshift, which are weak in the X-rays. Here we present the NIRSpec spectrum of the most extreme of these objects, GN-28074, an AGN at $z=2.26$ with prominent hydrogen and He i broad lines, and with the highest limit on the bolometric to X-ray luminosity ratio among all spectroscopically confirmed AGN in GOODS. This source is also characterized by a mid-IR excess, likely associated with the AGN torus’ hot dust. The high bolometric luminosity and moderate redshift of this AGN allow us to explore its properties more in depth relative to other JWST-discovered AGN. The NIRSpec spectrum reveals prominent, slightly blueshifted absorption of H$\alpha$, H$\beta$, and He i $\lambda$10830. The Balmer absorption lines require gas with densities of $n_{\rm H}\gt 10^8~{\rm cm}^{-3}$, consistent with clouds in the broad-line region (BLR). This finding suggests that part of the X-ray weakness is due to high (Compton-thick) X-ray absorption by clouds in the BLR, or in its outer regions. GN-28074 is also extremely radio-weak. The radio weakness can also be explained in terms of absorption, as the inferred density of the BLR clouds makes them attenuate the radio emission through free–free absorption. Alternatively, the nuclear magnetic field may be underdeveloped, resulting both in intrinsically weak radio emission and lack of hot corona, hence intrinsic X-ray weakness. Finally, we show that recently proposed scenarios, invoking hyper-dense outflows or Raman scattering to explain the broad H$\alpha$, are ruled out.

Evidence for Intrinsic X-Ray Weakness among Red Quasars at Cosmic Noon

Quasar feedback is a key ingredient in shaping galaxy evolution. A rare population of extremely red quasars (ERQs) at z = 2−3 are often associated with high-velocity [O iii]λ5008 outflows and may represent sites of strong feedback. In this paper, we present an X-ray study of 50 ERQs to investigate the link between the X-ray and outflow properties of these intriguing objects. Using hardness ratio analysis, we confirm that the ERQs are heavily obscured systems with gas column density reaching N H = 1023−24 cm−2. We identify 20 X-ray-nondetected ERQs at high mid-infrared (MIR) luminosities of ν L ν,6 μm ≳ 3 × 1046 erg s−1. By stacking the X-ray observations, we find that the nondetected ERQs are on average underluminous in X-rays by a factor of ∼10 for their MIR luminosities. We consider such X-ray weakness to be due to both heavy gas absorption and intrinsic factors. Moreover, we find that the X-ray-weak sources also display higher-velocity outflows. One option to explain this trend is that weaker X-rays facilitate more vigorous line-driven winds, which then accelerate the [O iii]-emitting gas to kiloparsec scales. Alternatively, super-Eddington accretion could also lead to intrinsic X-ray weakness and more powerful continuum-driven outflow.

Respiratory performance in Duchenne muscular dystrophy: Clinical manifestations and lessons from animal models.

Duchenne muscular dystrophy (DMD) is a fatal genetic neuromuscular disease. Lack of dystrophin in skeletal muscles leads to intrinsic weakness, injury, subsequent degeneration and fibrosis, decreasing contractile function. Dystropathology eventually presents in all inspiratory and expiratory muscles of breathing, severely curtailing their critical function. In people with DMD, premature death is caused by respiratory or cardiac failure. There is an urgent need to develop therapies that improve quality of life and extend life expectancy in DMD. Surprisingly, there is a dearth of information on respiratory control in animal models of DMD, and respiratory outcome measures are often limited or absent in clinical trials. Characterization of respiratory performance in murine and canine models has revealed extensive remodelling of the diaphragm, the major muscle of inspiration. However, significant compensation by extradiaphragmatic muscles of breathing is evident in early disease, contributing to preservation of peak respiratory system performance. Loss of compensation afforded by accessory muscles in advanced disease is ultimately associated with compromised respiratory performance. A new and potentially more translatable murine model of DMD, the D2.mdx mouse, has recently been developed. Respiratory performance in D2.mdx mice is yet to be characterized fully. However, based on histopathological features, D2.mdx mice might serve as useful preclinical models, facilitating the testing of new therapeutics that rescue respiratory function. This review summarizes the pathophysiological mechanisms associated with DMD both in humans and in animal models, with a focus on breathing. We consider the translational value of each model to human DMD and highlight the urgent need for comprehensive characterization of breathing in representative preclinical models to better inform human trials.

Glutamate, Gangliosides, and the Synapse: Electrostatics at Work in the Brain.

The synapse is a piece of information transfer machinery replacing the electrical conduction of nerve impulses at the end of the neuron. Like many biological mechanisms, its functioning is heavily affected by time constraints. The solution selected by evolution is based on chemical communication that, in theory, cannot compete with the speed of nerve conduction. Nevertheless, biochemical and biophysical compensation mechanisms mitigate this intrinsic weakness: (i) through the high concentrations of neurotransmitters inside the synaptic vesicles; (ii) through the concentration of neurotransmitter receptors in lipid rafts, which are signaling platforms; indeed, the presence of raft lipids, such as gangliosides and cholesterol, allows a fine tuning of synaptic receptors by these lipids; (iii) through the negative electrical charges of the gangliosides, which generate an attractive (for cationic neurotransmitters, such as serotonin) or repulsive (for anionic neurotransmitters, such as glutamate) electric field. This electric field controls the flow of glutamate in the tripartite synapse involving pre- and post-synaptic neurons and the astrocyte. Changes in the expression of brain gangliosides can disrupt the functioning of the glutamatergic synapse, causing fatal diseases, such as Rett syndrome. In this review, we propose an in-depth analysis of the role of gangliosides in the glutamatergic synapse, highlighting the primordial and generally overlooked role played by the electric field of synaptic gangliosides.

CGG/CCG Repeat Expansions in LOC642361/NUTM2B-AS1 in Thai Patients With Oculopharyngodistal Myopathy.

This study characterizes oculopharyngodistal myopathy in 4 Thai patients from 3 families with CGG/CCG repeat expansion in LOC642361/NUTM2B-AS1. Repeat-primed PCR analyzed CGG/CCG repeat size in LOC642361/NUTM2B-AS1 in 4 Thai patients suspected of oculopharyngodistal myopathy (OPDM). Clinical records were reviewed for clinicopathologic features. All patients exhibited strong somatic instabilities of the expanded CGG/CCG repeats, primarily manifesting as oculopharyngeal weakness. Patient 1 had mild finger extensor and intrinsic hand muscle weakness, and although patient 2 lacked limb weakness, both siblings showed electrophysiologic evidence of distal myopathy, indicative of OPDM. Patient 3, the daughter of a sibling with OPDM reported in 2004, lacked limb weakness or leukoencephalopathy on brain MRI. Patient 4, initially misdiagnosed with refractory myasthenia gravis, had generalized muscle weakness. While initially characterized as oculopharyngeal myopathy with leukoencephalopathy (OPML) in a Japanese family, our study suggests a stronger association between CGG/CCG expansion in LOC642361/NUTM2B-AS1 and oculopharyngodistal myopathy (OPDM) rather than OPML. The variable presence or absence of leukoencephalopathy further supports OPDM as the predominant clinical manifestation linked to CGG/CCG expansion in LOC642361/NUTM2B-AS1.

Supercharge end-to-side nerve transfer from anterior interosseous nerve to augment intrinsic recovery in high ulnar nerve injuries of varying magnitudes

High ulnar nerve injuries result in intrinsic muscle weakness and are inconvenient for patients. Moreover, conventional surgical techniques often fail to achieve satisfactory motor recovery. A potential reconstructive solution in the form of the supercharge end-to-side (SETS) anterior interosseous nerve (AIN) transfer method has emerged. Therefore, this study aims to compare surgical outcomes of patients with transected and in-continuity high ulnar nerve lesions following SETS AIN transfer. Between June 2015 and May 2023, patients with high ulnar palsy in the form of transection injuries or lesion-in-continuity were recruited. The assessment encompassed several objective results, including grip strength, key pinch strength, compound muscle action potential, sensory nerve action potential, and two-point discrimination tests. The muscle power of finger abduction and adduction was also recorded. Additionally, subjective questionnaires were utilized to collect data on patient-reported outcomes. Overall, the patients were followed up for up to 2 years. Patients with transected high ulnar nerve lesions exhibited worse baseline performance than those with lesion-in-continuity, including motor and sensory functions. However, they experienced greater motor improvement but less sensory recovery, resulting in comparable final motor outcomes in both groups. In contrast, the transection group showed worse sensory outcomes. Our findings suggest that SETS AIN transfer benefits patients with high ulnar nerve palsy, regardless of the lesion type. Nonetheless, improvements may be more pronounced in patients with transected lesions.

A probability-exponential method of converting Z-numbers and its systematic applications in multi-attribute decision making

Z-numbers contain fuzzy restrictions, credibility measures, and probability distributions to effectively represent uncertain information. Converting Z-numbers to fuzzy numbers facilitates extensive applications (such as multi-attribute decision-making (MADM)), thus becoming valuable for research purposes. Regarding Z-number conversions, the original method never considers the association probability, while probabilistic strategies offer better informatization. Recently, a probability-driven conversion starts with a linear transformation of the centroid difference between the fuzzy restriction and probabilistic distribution. However, it has the invalidation weakness of edge information due to underlying non-normalization. To improve this probability-linear conversion, a Z-number conversion is proposed by using underlying probability-exponential descriptions, and this new method is further applied to MADM. At first, the current probability-linear conversion is analyzed based on the initial non-probabilistic conversion, and its intrinsic weakness and correctional improvement are revealed. Then, the novel probability-exponential conversion resorts to an exponential characterization of centroid difference between the restriction and distribution, and it gains information enrichment due to underlying normalization. The refined method preserves the inherent characteristics of Z-numbers more effectively, facilitating their application in subsequent engineering practices. This is especially pertinent in decision-making systems based on expert input and initial value problems. The proposed method for converting Z-numbers aims to minimize information loss in transitions between Z-numbers and classical fuzzy numbers. This approach will be further explored in future research. Furthermore, the probability-exponential conversion induces an ExpTODIM algorithm for MADM, called PE-ExpTODIM. Three Z-number conversions (i.e., the non-probabilistic, probability-linear, and probability-exponential types) and three decision algorithms (i.e., ExpTODIM, EDAS, MOORA) are combined to establish a 3 × 3 framework of Z-number-driven MADM. Finally, the systematical 9 algorithms are applied to the problem of site selection of carbon storage. They are validated by criss-cross contrast analyses and statistical significance tests. Thus, PE-ExpTODIM exhibits the desired optimization. The last technology of statistical testing is original, ingenious, and valuable for MADM.

Patients with transobturator tape: a retrospective observational study of ten-year follow-up

Stress urinary incontinence (SUI) may result from intrinsic sphincter weakness or urethral hypermobility brought on by weakened muscles in the pelvic floor that sustain the urethra and bladder. The amount of mid-urethral support is increased by the mid-urethral tape's function to serve as an anchored pubo-urethral neo-ligament. This study's objective is to assess the safety and effectiveness of transobturator tape (TOT) for SUI after a 10-year follow-up period. There were 103 patients included in this retrospective observational single-arm research. Only 95 participants were included in the trial since 8 patients were lost to follow-up. Patients who had TOT between 2010 and 2013 were monitored until December 2022. The effectiveness of the tape was assessed at 10 years for both early and late surgical problems in the patients. Those diagnosed with SUI were 52.27 years old on average (standard deviation ±8.48). 24% of patients (n=21) experienced mixed urinary incontinence (MUI), compared to 79.61% (n=82) of patients who had just pure stress incontinence. At 10 years, the success rate in our research was 97.09%. Demand incontinence was healed in 57.14% (n=12) of the 21 MUI patients. 7.69% of de novo urgency was noted (n=7). There were no significant side effects including mesh erosion, bladder and intestine perforation, or vascular hemorrhage. Excellent patient satisfaction was rated in 43% of cases (n=44), good in 54% of cases (n=56), and low in 3% of cases (n=3). At 10 years, TOT for SUI shows an impressive cure rate and excellent effectiveness. When the treatment is carried out by experienced hands, there are no significant difficulties.

Chapter 6 - Ulnar neuropathy

Ulnar neuropathy at the elbow is the second most common compressive neuropathy. Less common, although similarly disabling, are ulnar neuropathies above the elbow, at the forearm, and the wrist, which can present with different combinations of intrinsic hand muscle weakness and sensory loss. Electrodiagnostic studies are moderately sensitive in diagnosing ulnar neuropathy, although their ability to localize the site of nerve injury is often limited. Nerve imaging with ultrasound can provide greater localization of ulnar injury and identification of specific anatomical pathology causing nerve entrapment. Specifically, imaging can now reliably distinguish ulnar nerve entrapment under the humero-ulnar arcade (cubital tunnel) from nerve injury at the retro-epicondylar groove. Both these pathologies have historically been diagnosed as either "ulnar neuropathy at the elbow," which is non-specific, or "cubital tunnel syndrome," which is often erroneous. Natural history studies are few and limited, although many cases of mild-moderate ulnar neuropathy at the elbow appear to remit spontaneously. Conservative management, perineural steroid injections, and surgical release have all been studied in treating ulnar neuropathy at the elbow. Despite this, questions remain about the most appropriate management for many patients, which is reflected in the absence of management guidelines.

Macroscale ultradurable superlubricity on passivated transition-metal diborides

Superlubricity is a sliding regime with almost vanishing friction sustained under stringent material conditions. This remarkable phenomenon was first found between surfaces with incommensurate lattice structures, and later extended to materials with weak shear, as in many two-dimensional layered materials. Such materials, however, face great challenges that limit their applications, including the difficulty to scale up to meet the needs of many practical implementations and low durability stemming from the intrinsic structural weakness. Overcoming these limitations hinges on new design and fabrication of advanced superlubricating materials. Here, we report on the realization of macroscale ultradurable superlubricity on passivated transition-metal diborides (TMB2) following an unconventional design principle that first construct materials with strong anti-wear ability then create superlubricity via effective surface passivation. TMB2 possess superior mechanical strength and durability, along with the ability to activate in-situ load-induced passivation layers via tribochemical actions at the surface. The resultant passivated TMB2 exhibits characteristic superlubricating and ultradurable friction coefficient (0.002) and wear rate (10−19 m3/N·m). These findings introduce a fresh approach toward rational design and implementation of superlubricating materials, opening a new avenue for versatile applications at large (up to industrial) scales.

On the Subparsec-scale Core Composition of FR 0 Radio Galaxies

Although Fanaroff–Riley type 0 (FR 0) radio galaxies are known to be the most numerous jet population in the local Universe, they are much less explored than the well-established class of FR type I (FR I) and FR type II galaxies due to their intrinsic weakness. Observationally, their nuclear radio, optical, and X-ray properties are comparable to the nuclear environment of FR Is. The recent detection of two FR 0s in the high-energy band suggests that, like in FR Is, charged particles are accelerated there to energies that enable gamma-ray production. Up to now, only the lack of extended radio emission from FR 0s distinguishes them from FR Is. By comparing the spectral energy distribution of FR 0s with that of FR Is and in particular with that of M87 as a well-studied reference source of the FR I population, we find the broadband spectrum of FR 0 s exceptionally close to M87's quiet core emission. Relying on that similarity, we apply a lepto-hadronic jet-accretion flow model to FR 0s. This model is able to explain the broadband spectral energy distribution, with parameters close to particle-field equipartition and matching all observational constraints. In this framework, FR 0s are multimessenger jet sources, with a nature and highly magnetized environment similar to those of the naked quiet core of FR Is.

Selective Analysis of Redox Processes at the Electrode Interface with Time-Resolved Raman Spectroscopy.

Electrochemistry and electrochemical reactions are increasingly important in the transition to a sustainable chemical industry. The electron transfer that drives such reactions takes place within nanometers of the electrode surface, and follow-up chemical reactions take place within the diffusion layer. Hence, understanding electrochemical reactions requires time-, potential-, and spatially resolved analysis. The confocal nature of Raman spectroscopy provides high spatial resolution, in addition to detailed information on molecular structure. The intrinsic weakness of nonresonant Raman scattering, however, is not sensitive enough for relatively minor changes to the solution resulting from reactions at the electrode interface. Indeed, the limit of detection is typically well above the concentrations used in electrochemical studies. Here, we show that surface-enhanced Raman scattering (SERS) and resonance Raman (rR) spectroscopy allow for spatially and time-resolved analysis of solution composition at (<1-2 nm) and near (within 5 μm) the electrode surface, respectively, in a selective manner for species present at low (<1 mM) concentrations. We show changes in concentration of species at the electrode surface, without the need for labels, specific adsorption, or resonance enhancement, using a SERS-active gold electrode prepared readily by electrochemical surface roughening. A combination of smooth and roughened gold electrodes is used to distinguish between surface and resonance enhancement using the well-known redox couples ferrocene and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). We discuss the impact of specific adsorption on the spectral analysis with the ruthenium(II) polypyridyl complex, [Ru(bpy)3]2+. The dual function of the electrode (surface enhancement and electron transfer) in the analysis of solution processes is demonstrated with the reversible oxidation of TMA (4,N,N-trimethylaniline), where transient soluble species are identified in real time, with rapid spectral acquisition, making use of localized enhancement. We anticipate that this approach will find use in elucidating electro(catalytic) reactions at electrode interfaces.

Botulinum Toxins for the Treatment of Raynaud Phenomenon: A Systematic Review With Meta-analysis.

Botulinum toxin (Btx) therapy has emerged as a potential treatment for patients with Raynaud phenomenon (RP) in recent years. This study aimed to investigate the efficacy and safety of Btx treatment for RP. Databases of PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from their inception up to August 2022. Studies that reported Btx use for the treatment of RP were included. A meta-analysis was conducted for the Shortened version of the Disabilities of the Arm, Shoulder, and Hand (Quick DASH) score and visual analog scale pain score using a random-effects model. Thirteen full-text studies were included. The pooled standard mean changes for the visual analog scale pain score and QuickDASH score were -3.82 (95% confidence interval, -6.62 to -1.02) and 0.83 (95% confidence interval, -1.47 to -0.19), respectively. The 2 most common complications were injection site pain and intrinsic hand weakness. The effect of Btx treatment on RP is promising based on current evidence. Nevertheless, more studies and randomized clinical trials with larger sample sizes are needed to confirm the current results.

Solving the Schrödinger equation of a planar model H4 molecule

The Schrödinger equation of a planar model H4 molecule was solved with the free complement (FC) - local Schrödinger equation (LSE) theory using the direct local sampling (DLS) method. Although this molecule is often used to examine the intrinsic weakness of the Hartree-Fock related theory, the present FC-LSE-DLS theory successfully produced accurate solutions of the Schrödinger equation at any geometries of this molecule. We mapped the two-dimensional potential energy surfaces and revealed that the ground state has a dissociation channel to a couple of H2 molecules but the two excited states have local minimums constructing H4 molecule.

Forced Subduction Initiation Near Spreading Centers: Effects of Brittle‐Ductile Damage

AbstractAlthough positive buoyancy of young lithosphere near spreading centers does not favor spontaneous subduction, subduction initiation occurs easily near ridges due to their intrinsic rheological weakness when plate motion reverses from extension to compression. It has also been repeatedly proposed that inherited detachment faults may directly control the nucleation of new subduction zones near ridges subjected to forced compression. However, recent 3D numerical experiments suggested that direct inversion of a single detachment fault does not occur. Here we further investigate this controversy numerically by focusing on the influence of brittle‐ductile damage on the dynamics of near‐ridge subduction initiation. We self‐consistently model the inversion of tectonic patterns formed during oceanic spreading using 3D high‐resolution thermomechanical numerical models with strain weakening of faults and grain size evolution. Numerical results show that forced compression predominantly reactivates and rotates inherited extensional faults, shortening and thickening the weakest near‐ridge region of the oceanic lithosphere, thereby producing ridge swellings. As a result, a new megathrust zone is developed, which accommodates further shortening and subduction initiation. Furthermore, brittle/plastic strain weakening has a key impact on the collapse of the thickened ridge and the onset of near‐ridge subduction initiation. In contrast, grain size evolution of the mantle only slightly enhances the localization of shear zones at the brittle‐ductile transition and thus plays a subordinate role. Compared to the geological record, our numerical results provide new helpful insights into possible physical controls and dynamics of natural near‐ridge subduction initiation processes recorded by the Mirdita ophiolite of Albania.

Robust Vehicle Detection Based on Improved You Look Only Once

Vehicle detection is still challenging for intelligent transportation systems (ITS) to achieve satisfactory performance. The existing methods based on one stage and two-stage have intrinsic weakness in obtaining high vehicle detection performance. Due to advancements in detection technology, deep learning-based methods for vehicle detection have become more popular because of their higher detection accuracy and speed than the existing algorithms. This paper presents a robust vehicle detection technique based on Improved You Look Only Once (RVD-YOLOv5) to enhance vehicle detection accuracy. The proposed method works in three phases; in the first phase, the K-means algorithm performs data clustering on datasets to generate the classes of the objects. Subsequently, in the second phase, the YOLOv5 is applied to create the bounding box, and the Non-Maximum Suppression (NMS) technique is used to eliminate the overlapping of the bounding boxes of the vehicle. Then, the loss function CIoU is employed to obtain the accurate regression bounding box of the vehicle in the third phase. The simulation results show that the proposed method achieves better results when compared with other state-of-art techniques, namely Lightweight Dilated Convolutional Neural Network (LD-CNN), Single Shot Detector (SSD), YOLOv3 and YOLOv4 on the performance metric like precision, recall, mAP and F1-Score. The simulation and analysis are carried out on PASCAL VOC 2007, 2012 and MS COCO 2017 datasets to obtain better performance for vehicle detection. Finally, the RVD-YOLOv5 obtains the results with an mAP of 98.6% and Precision, Recall, and F1-Score are 98%, 96.2% and 97.09%, respectively.

PRIORITIZATION OF IMPROVEMENT ACTIONS IN INDUSTRIAL PRODUCTION: APPLICATION OF THE FITRADEOFF METHOD TO ORDER IMPROVEMENT ACTIONS IDENTIFIED THROUGH THE FAILURES MODES AND EFFECTS ANALYSIS (FMEA)

The Failures Modes and Effects Analysis (FMEA) method is applied to different activities in order to improve production processes. Its operation allows to analyze failure modes, describe their effects, identify causes and design control systems. In addition to assessing these factors, it contributes to the formulation of various improvement actions; however, it has an intrinsic weakness when it comes to prioritizing these actions. Although recent versions acknowledge that it is convenient to regulate the beginning of the proposed actions, the method does not provide indisputable tools to establish priorities and organize action plans due to the fact that the Risk Priority Level traditional indicator has been questioned. In face of this need, this contribution proposes to complement the application of the FMEA with an individual multi-criteria compensatory method that allows actions to be programmed in a participatory manner to improve their management. This proposal provides an example of a real world application. The results and limitations of this work are presented in the conclusion.

Time-resolved enantiomer-exchange probed by using the orbital angular momentum of X-ray light.

Molecular chirality, a geometric property of utmost importance in biochemistry, is now being investigated in the time-domain. Ultrafast chiral techniques can probe the formation or disappearance of stereogenic centers in molecules. The element-sensitivity of X-rays adds the capability to probe chiral nuclear dynamics locally within the molecular system. However, the implementation of ultrafast techniques for measuring transient chirality remains a challenge because of the intrinsic weakness of chiral-sensitive signals based on circularly polarized light. We propose a novel approach for probing the enantiomeric dynamics by using the orbital angular momentum (OAM) of X-ray light, which can directly monitor the real-time chirality of molecules. Our simulations probe the oscillations in excited chiral formamide on different potential energy surfaces and demonstrate that using the X-ray OAM can increase the measured asymmetry ratio. Moreover, combining the OAM and SAM (spin angular momentum) provides stronger dichroic signals than linearly polarized light, and offers a powerful scheme for chiral discrimination.

Abstract 13029: Acute Myocardial Infarction - Mortality Trends in the United States

Introduction: Acute Myocardial Infarction (AMI) contributes to a significant cardiovascular related deaths in the general population. AMI is a life-threatening condition that occurs when the blood supply to the myocardium is abruptly cut-off due to blockage in coronary arteries resulting in tissue infarction. AMI is associated with high morbidity and mortality (up to 34-42%). We hypothesized that with recent advancements in reperfusion therapy and techniques for treating arrhythmias and pump failure, the mortality rates might show downward trends. Methods: In this retrospective observational study, death certificate data was retrieved from the Center for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiological Research (WONDER) database from 2001 to 2020. WONDER database identifies the underlying cause of death. Mortality for AMI including anterior, posterior, inferior wall, or unspecified (ICD-10 121.0; 121.1; 121.2; 121.3; 121.4; 121.9) as an underlying cause of death was queried from 2001 to 2020. This study duration was further divided into five-year periods. Crude mortality rate and age-adjusted mortality rate per 100,000 deaths (with a 95% confidence interval) were calculated for four U.S. census regions to explore regional variations (CR-1 Northeast; CR-2 Midwest; CR-3 South; CR-4 West). Results: The overall age-adjusted mortality rate (AAMR) decreased from 58.0 to 27.1 per 100,000 deaths (53.5%) in the years 2001-2005 to 2016-2020 as illustrated in the figure 1. AAMR showed a comparable downward trend in all 4 U.S. census regions (Figure 1). Conclusions: From 2001 to 2020 AAMR showed a downward trend which may indicate an improvement in AMI patient care with evolving guidelines based therapeutic interventions. Limitations of this study include intrinsic weakness of the WONDER dataset (Changes with ICD-9 to ICD 10 codes, and potential miscoding) which may need further discovery.

The Epigenetic Dimension of Protein Structure Is an Intrinsic Weakness of the AlphaFold Program.

One of the most important lessons we have learned from sequencing the human genome is that not all proteins have a 3D structure. In fact, a large part of the human proteome is made up of intrinsically disordered proteins (IDPs) which can adopt multiple structures, and therefore, multiple functions, depending on the ligands with which they interact. Under these conditions, one can wonder about the value of algorithms developed for predicting the structure of proteins, in particular AlphaFold, an AI which claims to have solved the problem of protein structure. In a recent study, we highlighted a particular weakness of AlphaFold for membrane proteins. Based on this observation, we have proposed a paradigm, referred to as “Epigenetic Dimension of Protein Structure” (EDPS), which takes into account all environmental parameters that control the structure of a protein beyond the amino acid sequence (hence “epigenetic”). In this new study, we compare the reliability of the AlphaFold and Robetta algorithms’ predictions for a new set of membrane proteins involved in human pathologies. We found that Robetta was generally more accurate than AlphaFold for ascribing a membrane-compatible topology. Raft lipids (e.g., gangliosides), which control the structural dynamics of membrane protein structure through chaperone effects, were identified as major actors of the EDPS paradigm. We conclude that the epigenetic dimension of a protein structure is an intrinsic weakness of AI-based protein structure prediction, especially AlphaFold, which warrants further development.