Swiss Federal Institute of Technology in Lausanne

This study explores the chemical activity of isolated metal atoms confined in graphene on Ni(111), using carbon monoxide as a probe molecule. At room temperature, CO stably adsorbs on Co but not on Ni. Electronic descriptors clarify this behavior, offering valuable insights for designing graphene‐based single‐atom catalysts. image

Transient receptor potential (TRP) melastatin 4 (TRPM4) protein is a calcium-activated monovalent cation channel associated with various genetic and cardiovascular disorders. The anthranilic acid derivative NBA is a potent and specific TRPM4 inhibitor, but its binding site in TRPM4 has been unknown, although this information is crucial for drug development targeting TRPM4. We determine three cryo-EM structures of full-length human TRPM4 embedded in native lipid nanodiscs without inhibitor, bound to NBA, and an anthranilic acid derivative, IBA. We found that the small molecules NBA and IBA were bound in a pocket formed between the S3, S4, and TRP helices and the S4-S5 linker of TRPM4. Our structural data and results from patch clamp experiments enable validation of a binding site for small molecule inhibitors, paving the way for further drug development targeting TRPM4.

Aims/Purpose: Cataract, i.e., an opacification of the natural intraocular lens, is one of the leading causes of visual impairments worldwide. Cataract surgery, which involves the removal of the opaque lens and implantation of an artificial intraocular lens, is one of the most cost‐efficient interventions in all of health care to improve visual impairments. However, it remains unclear how exactly visual performance changes after surgery, which we aim to investigate in our study. Methods: We tested 30 older adults undergoing cataract surgery longitudinally with a battery of visual tests. Participants were tested a total of four times: before surgery, after surgery on one eye, after surgery on the second eye, and a few weeks after surgery when vision was fully stabilized. The battery tested various visual abilities and included the following tests: visual acuity, contrast sensitivity, coherent motion, orientation discrimination, reaction time, and visual search. All tests were performed binocularly, and a subset of tests was repeated monocularly. Results: Results suggest that visual acuity and orientation discrimination performance increase after each surgery. Performance in contrast sensitivity and coherent motion significantly increases after the surgery on the first eye but not between the second and third tests. Thus, monocular surgery is sufficient to improve performance in these tests. On the other side, visual search and reaction time performance do not seem to benefit from cataract surgery. For all tests, the level of performance after surgery is maintained in the last testing. Conclusions: Our study shows that cataract surgery leads to improved perceptual functions in most, but not all, tests. Future analysis will determine whether the level of performance change depends on baseline performance, and whether predictions about surgery success can be made based on performance in the tests.

Aims/Purpose: Cataract, i.e., an opacification of the natural intraocular lens, is one of the leading causes of visual impairments worldwide. Cataract surgery, which involves the removal of the opaque lens and implantation of an artificial intraocular lens, is one of the most cost‐efficient interventions in all of health care to improve visual impairments. However, it remains unclear how exactly visual performance changes after surgery, which we aim to investigate in our study. Methods: We tested 30 older adults undergoing cataract surgery longitudinally with a battery of visual tests. Participants were tested a total of four times: before surgery, after surgery on one eye, after surgery on the second eye, and a few weeks after surgery when vision was fully stabilized. The battery tested various visual abilities and included the following tests: visual acuity, contrast sensitivity, coherent motion, orientation discrimination, reaction time, and visual search. All tests were performed binocularly, and a subset of tests was repeated monocularly. Results: Results suggest that visual acuity and orientation discrimination performance increase after each surgery. Performance in contrast sensitivity and coherent motion significantly increases after the surgery on the first eye but not between the second and third tests. Thus, monocular surgery is sufficient to improve performance in these tests. On the other side, visual search and reaction time performance do not seem to benefit from cataract surgery. For all tests, the level of performance after surgery is maintained in the last testing. Conclusions: Our study shows that cataract surgery leads to improved perceptual functions in most, but not all, tests. Future analysis will determine whether the level of performance change depends on baseline performance, and whether predictions about surgery success can be made based on performance in the tests.

Making sense of a musical excerpt is an acquired skill that depends on previous musical experience. Having acquired familiarity with different types of chords, a listener can distinguish tones in a musical texture that outline these chords (i.e., chord tones) from ornamental tones such as neighbor or passing notes that elaborate the chord tones. However, music-theoretical definitions of chord types usually only mention chord tones, excluding typical figurations. The aim of this project is to investigate (i) how knowledge about (chord-specific) figurations can be incorporated into characterizations of chord types and (ii) how these characterizations can be acquired by the listener. To this end, we develop a computational model of chord types that distinguishes chord tones and “figuration tones” and can be learned using Bayesian inference following methods in computational cognitive science. This model is trained on two datasets using Bayesian variational inference, comprising scores of Western classical and popular music, respectively, and containing harmonic annotations as well as heuristically determined note-type labels. We find that the proposed characterization of chords is indeed learnable and the specific inferred profiles match previous music-theoretic accounts. In addition, we can observe patterns in the use of figuration, such as the distribution of figuration tones being related to the diatonic contexts in which chords appear and chord types differing in their predisposition to generate non-chord tones. Moreover, the differences in figuration distributions between the two corpora indicate style-specific peculiarities in the role and usage of figurations. The different patterns of typical figuration tones for specific chord types indicate that harmony and figuration are not independent.

Mobile devices with limited resources are prevalent as they have a relatively low price. Providing a good user experience with limited resources has been a big challenge. This paper found that foreground applications are often unexpectedly interfered by background applications’ memory activities. Improving user experience on resource-limited mobile devices calls for a strong collaboration between memory and process management. This paper proposes a framework, Ice, to optimize the user experience on resource-limited mobile devices. With Ice, processes that will cause frequent refaults in the background are identified and frozen accordingly. The frozen application will be thawed when memory condition allows. Based on the proposed Ice, this paper shows that the refault can be further reduced by revisiting the LRU lists in the original kernel with app-freezing awareness (called Ice ⁺ ). Evaluation of resource-limited mobile devices demonstrates that the user experience is effectively improved with Ice. Specifically, Ice boosts the frame rate by 1.57x on average over the state-of-the-art. The frame rate is further enhanced by 5.14% on average with Ice ⁺ .

Over the past 3 decades, phononic crystals experienced revolutionary development for understanding and utilizing mechanical waves by exploring interaction between mechanical waves and structures. With the significant advances in manufacture technologies from nanoscale to macroscale, phononic crystals attract researchers from diverse disciplines to study abundant directions such as bandgaps, dispersion engineering, novel modes, reconfigurable control, efficient design algorithms and so on. The aim of this roadmap is to present the current state of the art, an overview of properties, functions and applications of phononic crystals, opinions on the challenges and opportunities. The various perspectives cover wide topics on basic property, homogenization, machine learning assisted design, topological, non-Hermitian, nonreciprocal, nanoscale, chiral, nonlocal, active, spatiotemporal, hyperuniform properties of phononic crystals, and applications in underwater acoustics, seismic wave protection, vibration and noise control, thermal transport, sensing, acoustic tweezers, written by over 40 renown experts. It is also intended to guide researchers, funding agencies and industry in identifying new prospects for phononic crystals in the upcoming years.

Amyloid self‐assembly of α‐synuclein (αSyn) is linked to the pathogenesis of Parkinson’s disease (PD). Type 2 diabetes (T2D) has recently emerged as a risk factor for PD. Cross‐interactions between their amyloidogenic proteins may act as molecular links. In fact, fibrils of islet amyloid polypeptide (IAPP) (T2D) can cross‐seed αSyn amyloidogenesis and αSyn and IAPP colocalize in PD brains. Inhibition of both self‐ and IAPP‐cross‐seeded αSyn amyloidogenesis could thus interfere with PD pathogenesis. Here we show that macrocyclic peptides, designed to mimic IAPP self‐/cross‐interaction sites and previously found to inhibit amyloidogenesis of IAPP and/or Alzheimer’s disease (AD) amyloid‐β peptide Aβ40(42), are nanomolar inhibitors of both self‐ and IAPP‐cross‐seeded amyloid self‐assembly of αSyn. Anti‐amyloid function is mediated by nanomolar affinity interactions with αSyn via three αSyn regions which are identified as key sites of both αSyn self‐assembly and its cross‐interactions with IAPP. We also show that the peptides block Aβ42‐mediated cross‐seeding of αSyn as well. Based on their broad spectrum anti‐amyloid function and additional drug‐like features, these peptides are leads for multifunctional anti‐amyloid drugs in PD, T2D, AD, and their comorbidities, while the identified αSyn key segments are valuable targets for novel, multi‐site targeting amyloid inhibitors in PD and related synucleinopathies.

Human enteric viruses can remain infective in surface waters for extended periods of time, posing a public health risk. Microbial activity contributes to the inactivation of waterborne enteric viruses, but while individual bacteria–virus interactions have been characterized, the importance of microbial diversity remains unknown. Here, we experimentally manipulated the diversity of bacterial communities from Lake Geneva across three seasons using a dilution-to-extinction approach and monitored the inactivation and genome decay of echovirus 11, a member of the Enterovirus genus. Long-read sequencing of the 16S rRNA gene revealed diversity gradients ranging between 373 and 2,722 bacterial species. Compared to sterile controls, echovirus 11 inactivation was enhanced by the presence of active bacteria and depended both on season and sample dilution. Throughout all seasons, the highest inactivation (between 3.0 and 7.9 log 10 fold reduction in infectivity over 96 h) was observed in the least diluted incubations (i.e., the highest bacterial richness). Genome decay exhibited a 24-h lag and was less pronounced than the corresponding infectivity loss (ranging between 2.3 and 3.8 log 10 fold over 96 h), indicating that microbial inactivation primarily targets the echovirus 11 capsid. We found a positive-saturating relationship between bacterial species richness and viral inactivation, suggesting functional redundancy and pointing toward the importance of rare species for viral inactivation. Biomarker analysis revealed several clades of bacteria, particularly members of Chitinophagaceae , to be significantly associated with echovirus 11 inactivation. Overall, these findings suggest that high microbial diversity enhances the capacity of surface waters to rid themselves of contamination by enteric viruses and hence protects public health. IMPORTANCE Human enteric viruses in natural waterbodies pose a public health risk. Microorganisms, particularly bacteria, contribute to the inactivation of enteroviruses, thereby mitigating this risk. We use experimental manipulations of lake water bacterial diversity to unravel the importance of diversity for the inactivation of echovirus 11, a model human pathogen. Our findings suggest that bacterial diversity is important for echovirus 11 inactivation and that specific, but numerically rare, bacteria present in the surface water of Lake Geneva across different seasons contribute to viral inactivation. These findings contribute to our understanding of the inactivation of human enteric viruses in natural waterbodies—a hitherto understudied ecosystem service.

Amyloid self‐assembly of α‐synuclein (αSyn) is linked to the pathogenesis of Parkinson’s disease (PD). Type 2 diabetes (T2D) has recently emerged as a risk factor for PD. Cross‐interactions between their amyloidogenic proteins may act as molecular links. In fact, fibrils of islet amyloid polypeptide (IAPP) (T2D) can cross‐seed αSyn amyloidogenesis and αSyn and IAPP colocalize in PD brains. Inhibition of both self‐ and IAPP‐cross‐seeded αSyn amyloidogenesis could thus interfere with PD pathogenesis. Here we show that macrocyclic peptides, designed to mimic IAPP self‐/cross‐interaction sites and previously found to inhibit amyloidogenesis of IAPP and/or Alzheimer’s disease (AD) amyloid‐β peptide Aβ40(42), are nanomolar inhibitors of both self‐ and IAPP‐cross‐seeded amyloid self‐assembly of αSyn. Anti‐amyloid function is mediated by nanomolar affinity interactions with αSyn via three αSyn regions which are identified as key sites of both αSyn self‐assembly and its cross‐interactions with IAPP. We also show that the peptides block Aβ42‐mediated cross‐seeding of αSyn as well. Based on their broad spectrum anti‐amyloid function and additional drug‐like features, these peptides are leads for multifunctional anti‐amyloid drugs in PD, T2D, AD, and their comorbidities, while the identified αSyn key segments are valuable targets for novel, multi‐site targeting amyloid inhibitors in PD and related synucleinopathies.

Vaccination strategies against HIV-1 aim to elicit broadly neutralizing antibodies (bnAbs) using prime-boost regimens with HIV envelope (Env) immunogens. Epitope mapping has shown that early antibody responses are directed to easily accessible nonneutralizing epitopes on Env instead of bnAb epitopes. Autologously neutralizing antibody responses appear upon boosting, once immunodominant epitopes are saturated. Here, we use electron microscopy–based polyclonal epitope mapping (EMPEM) to elucidate how repeated immunization with HIV Env SOSIP immunogens results in the generation of Ab2α anti-idiotypic antibodies in rabbits and rhesus macaques. We present the structures of six anti–immune complex antibodies and find that they target idiotopes composed of framework regions of antibodies bound to Env. Examination of cryo–electron microscopy density enabled prediction of sequences for an anti–immune complex antibody, the paratope of which is enriched with aromatic amino acids. This work sheds light on current vaccine development efforts for HIV, as well as for other pathogens in which repeated exposure to antigen is required.

Hormones control normal breast development and function. They also impinge on breast cancer (BC) development and disease progression in direct and indirect ways. The major ovarian hormones, estrogens and progesterone, have long been established as key regulators of mammary gland development in rodents and linked to human disease. However, their roles have been difficult to disentangle because they act on multiple tissues and can act directly and indirectly on different cell types in the breast, and their receptors interact at different levels within the target cell. Estrogens are well-recognized drivers of estrogen receptor-positive (ER+) breast cancers, and the ER is successfully targeted in ER+ disease. The role of progesterone receptor (PR) as a potential target to be activated or inhibited is debated, and androgen receptor (AR) signaling has emerged as a potentially interesting pathway to target on the stage. In this chapter, we discuss hormone signaling in normal breast development and in cancer, with a specific focus on the key sex hormones: estrogen, progesterone, and testosterone. We will highlight the complexities of endocrine control mechanisms at the organismal, tissue, cellular, and molecular levels. As we delve into the mechanisms of action of hormone receptors, their interplay and their context-dependent roles in breast cancer will be discussed. Drawing insights from new preclinical models, we will describe the lessons learned and the current challenges in understanding hormone action in breast cancer.

Accurate reconstruction of the right heart geometry and motion from time‐resolved medical images is crucial for diagnostic enhancement and computational analysis of cardiac blood dynamics. Commonly used segmentation and/or reconstruction techniques, exclusively relying on short‐axis cine‐MRI, lack precision in critical regions of the right heart, such as the ventricular base and the outflow tract, due to its unique morphology and motion. Furthermore, the reconstruction procedure is time‐consuming and necessitates significant manual intervention for generating computational domains. This study introduces an end‐to‐end hybrid reconstruction method specifically designed for computational simulations. Integrating information from various cine‐MRI series (short/long‐axis and 2/3/4 chambers views) with minimal user contribution, our method leverages registration‐ and morphing‐based algorithms to accurately reconstruct crucial cardiac features and complete cardiac motion. The reconstructed data enable the creation of patient‐specific computational fluid dynamics models, facilitating the analysis of the hemodynamics in healthy and clinically relevant scenarios. We assessed the accuracy of our reconstruction method against ground truth and a standard method. We also evaluated volumetric clinical parameters and compared them with the literature values. The method's adaptability was investigated by reducing the number of cine‐MRI views, highlighting its robustness with varying imaging data. Numerical findings supported the reliability of the approach for simulating hemodynamics. Combining registration‐ and morphing‐based algorithms, our method offers accurate reconstructions of the right heart chambers' morphology and motion. These reconstructions can serve as valuable tools as domain and boundary conditions for computational fluid dynamics simulations, ensuring seamless and effective analysis.

Carbon perovskite solar cells (C‐PSCs) represent a promising photovoltaic technology that addresses the long‐term operating stability needed to compete with commercial Si solar cells. However, the poor interface contacts between the carbon electrode and the perovskite result in a gap between C‐PSC's performances and state‐of‐the‐art PSCs based on metallic back electrodes. In this work, Cu (II) phthalocyanine (CuPc) was rediscovered as an effective hole‐transporting material (HTM) to be coupled with carbon electrodes. In particular, based on computional studies and VASP calculations, it is found that the tetragonal structure of CuPc could efficiently coordinated to perovskite layer via N and Cu atoms to Pb and I atoms, respectively. By systematically optimizing the concentration of the CuPc HTL solution, and screening the coupling of CuPc HTL with two types of carbon electrodes, based on carbon black:graphite mixture and reduced graphene oxide, respectively, a maximum power conversion efficiency of 21.4% has been achieved. In addition, our cells demonstrate satisfactory stability under thermal ageing at 85°C; 20% PCE loss after more than 200 h and shelf‐life ageing 20 days with 1.3% PCE loss in ambient conditions (ISOS‐D‐1). These findings are interesting in developing commercially competitive C‐PSCs, as they combine both high PCE and stability.

Carbon perovskite solar cells (C‐PSCs) represent a promising photovoltaic technology that addresses the long‐term operating stability needed to compete with commercial Si solar cells. However, the poor interface contacts between the carbon electrode and the perovskite result in a gap between C‐PSC's performances and state‐of‐the‐art PSCs based on metallic back electrodes. In this work, Cu (II) phthalocyanine (CuPc) was rediscovered as an effective hole‐transporting material (HTM) to be coupled with carbon electrodes. In particular, based on computional studies and VASP calculations, it is found that the tetragonal structure of CuPc could efficiently coordinated to perovskite layer via N and Cu atoms to Pb and I atoms, respectively. By systematically optimizing the concentration of the CuPc HTL solution, and screening the coupling of CuPc HTL with two types of carbon electrodes, based on carbon black:graphite mixture and reduced graphene oxide, respectively, a maximum power conversion efficiency of 21.4% has been achieved. In addition, our cells demonstrate satisfactory stability under thermal ageing at 85°C; 20% PCE loss after more than 200 h and shelf‐life ageing 20 days with 1.3% PCE loss in ambient conditions (ISOS‐D‐1). These findings are interesting in developing commercially competitive C‐PSCs, as they combine both high PCE and stability.

Li‐TFSI/t‐BP is the most widely utilized p‐dopant for hole‐transporting materials (HTMs) in state‐of‐the‐art perovskite solar cells (PSCs). However, its nonuniformity of doping, along with the hygroscopicity and migration of dopants, results in the devices exhibiting limited stability and performance. This study reports on the utilization of a spherical anion derived from the p‐dopant, regulated by its radius and shape, as an alternative to the linear TFSI⁻ anion. The theoretical and experimental results reveal that the spherical anion significantly increases the doping effect of HTMs due to an enhanced electron transfer from larger dipole moments. The enhanced transfer leads to a shift in the Pb‐6p defect orbitals, resulting in shallower trap states. Moreover, compared to the linear structure of the TFSI⁻ anion, the anion of sodium tetrakis[3,5‐bis(trifluoro methyl)phenyl]borate (Na‐TFPB) with a larger van der Waals radius and spherical shape offers increased hydrophobicity and migration barriers, which can protect the perovskite crystal and facilitate stable p‐doping of HTMs. The use of Na‐TFPB results in enhanced thermal and ambient stability of PSCs. The devices fabricated with the shape‐ and radius‐regulated p‐dopant achieve remarkable efficiencies of 24.49 % and 24.31 % for CJ‐01 and spiro‐OMeTAD, respectively, representing the highest efficiency values for organic dopants to date. This study underscores the ingenious design of spherical anions of p‐dopants in contrast to the conventional linear anions.

Post-traumatic stress disorder (PTSD) is a psychiatric condition triggered by experiencing or witnessing traumatic events, such as death, serious injury, or threats to oneself or others. Affecting 5-10 % of the population, PTSD is often underreported due to the reluctance of individuals to disclose personal traumatic experiences. This study explore the effectiveness of a digital (electronic mental health and psychosocial support) and psychologist-led intervention in mitigating PTSD symptoms. A randomized control trial was conducted, comparing the effects of human and digital intervention (conditions 1 and 2), and no intervention (control group) on PTSD symptoms induced by a traumatic film excerpt. Participants were randomly assigned to one of the three conditions. Emotional responses were measured using various scales, and flashbacks were recorded over a week following the intervention. Results demonstrated that both human and digital interventions significantly reduced negative emotions and flashbacks compared to the control group. The psychologist-led intervention was the most effective, followed by the digital intervention. This study highlights the potential of digital intervention to provide accessible, anonymous, and effective support for trauma victims, suggesting a promising avenue for future mental health interventions.

Heat transfer differs in the regions where the flow is developed and developing thermally. These regions can be differentiated by using the thermal entry length. Many researchers have presented correlations to determine the thermal entry length for natural and forced convection. In this study, heat transfer in the entrance region of a concentric annuli is investigated. It is accepted that beginning from the inlet of annuli the flow is developed hydrodynamically and it is developing thermally. Heat transfer is investigated where the internal or external surfaces of the annuli are at constant but different heat fluxes. The fluid velocity is assumed to be constant or radially variable. Due to thermal boundary conditions, one thermal boundary layer appears on the outer cylinder surface, another on the inner cylinder surface. The edge of two boundary layers will be adiabatic and naturally, the temperature of fluid between the two edges will be equal to free stream temperature. Transformation, Separation of Variables method, eigenvalue problem, Sturm‐Liouville system, Bessel differential equation and properties of orthogonal functions are used in solution of the problem. Exact and analytical solutions of the momentum and energy equations are presented. Velocity and temperature distributions, local Nusselt numbers and convection heat transfer coefficients are calculated for the internal and external surfaces of annuli.

Our motivation in this paper is twofold. First, we study the geometry of a class of exploration sets, called exit sets, which are naturally associated with a 2D vector-valued Gaussian Free Field : $\phi : \mathbb {Z}^2 \rightarrow \mathbb {R}^N, N\ge 1$. We prove that, somewhat surprisingly, these sets are a.s. degenerate as long as $N\ge 2$, while they are conjectured to be macroscopic and fractal when N=1. This analysis allows us, when $N\ge 2$, to understand the percolation properties of the level sets of $\{ \Vert \phi (x)\Vert _{{2}}, x\in \mathbb {Z}^2\}$ and leads us to our second main motivation in this work: if one projects a spin O(N+1) model (the case N=2 corresponds to the classical Heisenberg model) down to a spin O(N) model, we end up with a spin O(N) in a quenched disorder given by random conductances on $\mathbb {Z}^2$. Using the exit sets of the N-vector-valued GFF, we obtain a local and geometric description of this random disorder in the limit $\beta \rightarrow \infty$. This allows us in particular to revisit a series of celebrated works by Patrascioiu and Seiler (J Stat Phys 69(3):573–595, 1992, Nucl Phys B Proc Suppl 30:184–191, 1993, J Stat Phys 106(3):811–826, 2002) which argued against Polyakov’s prediction that spin O(N+1) model is massive at all temperatures as long as $N\ge 2$ (Polyakov in Phys Lett B 59(1):79–81, 1975). We make part of their arguments rigorous and more importantly we provide the following counter-example: we build ergodic environments of (arbitrary) high conductances with (arbitrary) small and disconnected regions of low conductances in which, despite the predominance of high conductances, the XY model remains massive. Of independent interest, we prove that at high $\beta$, the fluctuations of a classical Heisenberg model near a north pointing spin are given by a N=2 vectorial GFF. This is implicit for example in Polyakov (1975) but we give here the first (non-trivial) rigorous proof. Also, independently of the recent work Dubédat and Falconet (Random clusters in the villain and xy models, arXiv preprint arXiv:2210.03620, 2022), we show that two-point correlation functions of the spin O(N) model can be given in terms of certain percolation events in the cable graph for any $N\ge 1$.