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HIV cure has been reported for five individuals who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with cells from CCR5Δ32homozygous donors. By contrast, viral rebound has occurred in other people living with HIV who interrupted antiretroviral treatment after undergoing allo-HSCT, with cells mostly from wild-type CCR5donors. Here we report the case of a male individual who has achieved durable HIV remission following allo-HSCT with cells from an unrelated HLA-matched (9 of 10 matching for HLA-A, HLA-B, HLA-C, HLA-DRB1and HLA-DQB1alleles) wild-type CCR5donor to treat an extramedullary myeloid tumor. To date, plasma viral load has remained undetectable for 32 months after the interruption of antiretroviral treatment. Treatment with ruxolitinib has been maintained during this period to treat chronic graft-versus-host disease. Low levels of proviral DNA were detected sporadically after allo-HSCT, including defective but not intact HIV DNA. No virus could be amplified in cultures of CD4+T cells obtained after antiretroviral treatment interruption, while CD4+T cells remained susceptible to HIV-1 infection in vitro. Declines in HIV antibodies and undetectable HIV-specific T cell responses further corroborate the absence of viral rebound after antiretroviral treatment interruption. These results suggest that HIV remission could be achieved in the context of allo-HSCT with wild-type CCR5.

Introduction: Closed-loop spinal cord stimulation (CL-SCS) is a recently introduced system that records evoked compound action potentials (ECAPs) from the spinal cord elicited by each stimulation pulse and uses this information to automatically adjust the stimulation strength in real time, known as ECAP-controlled SCS. This innovative system compensates for fluctuations in the distance between the epidural leads and the spinal cord by maintaining the neural response (ECAP) at a predetermined target level. This data collection study was designed to assess the performance of the first CL-SCS system in a real-world setting under normal conditions of use in multiple European centers. The study analyzes and presents clinical outcomes and electrophysiological and device data and compares these findings with those reported in earlier pre-market studies of the same system. Methods: This prospective, multicenter, observational study was conducted in 13 European centers and aimed to gather electrophysiological and device data. The study focused on the real-world application of this system in treating chronic pain affecting the trunk and/or limbs, adhering to standard conditions of use. In addition to collecting and analyzing basic demographic information, the study presents data from the inaugural patient cohort permanently implanted at multiple European centers. Results: A significant decrease in pain intensity was observed for overall back or leg pain scores (verbal numerical rating score [VNRS]) between baseline (mean ± standard error of the mean [SEM]; n= 135; 8.2 ± 0.1), 3 months (n= 93; 2.3 ± 0.2), 6 months (n= 82; 2.5 ± 0.3), and 12 months (n= 76; 2.5 ± 0.3). Comparison of overall pain relief (%) to the AVALON and EVOKE studies showed no significant differences at 3 and 12 months between the real-world data release (RWE; 71.3%; 69.6%) and the AVALON (71.2%; 73.6%) and EVOKE (78.1%; 76.7%) studies. Further investigation was undertaken to objectively characterize the physiological parameters of SCS therapy in this cohort using the metrics of percent time above ECAP threshold (%), dose ratio, and dose accuracy (µV), according to previously described methods. Results showed that a median of 90% (40.7–99.2) of stimuli were above the ECAP threshold, with a dose ratio of 1.3 (1.1–1.4) and dose accuracy of 4.4 µV (0.0–7.1), based on data from 236, 230, and 254 patients, respectively. Thus, across all three metrics, the majority of patients had objective therapy metrics corresponding to the highest levels of pain relief in previously reported studies (usage over threshold > 80%, dose ratio > 1.2, and error < 10 µV). Conclusions: In conclusion, this study provides valuable insights into the real-world application of the ECAP-controlled CL-SCS system, highlighting its potential for maintaining effective pain relief and objective neurophysiological therapy metrics at levels seen in randomized control trials, and potential for quantifying patient burden associated with SCS system use via patient–device interaction metrics. Clinical Trial Registration: In the Netherlands, the study is duly registered on the International Clinical Trials Registry Platform (Trial NL7889). In Germany, the study is duly registered as NCT05272137 and in the United Kingdom as ISCRTN27710516 and has been reviewed by the ethics committee in both countries.

ABSTRACTIn the inevitable high-density urbanization process, existing urban green space (UGS) design approaches are ineffective in creating more green areas and combining multidisciplinary design principles to provide balanced sets of ecosystem services (ESs). This paper proposes a systematic framework for UGS design in the context of high-density urban development, results in spatial patterns, a pattern language, that combines specific design principles with a wide range of complementary ESs suitable for high-density environments. Such design approach can create more possibilities for UGS provisioning, deal with the complexity in high-density contexts, and provides consistency at different scale for UGS designs.

This paper describes a gradual transition of charge transport across molecular junctions from coherent to incoherent tunneling by increasing the number and polarizability of halide substituents of phenyl-terminated aliphatic monolayers of the form S(CH2)10OPhXn, X = F, Cl, Br, or I; n= 0, 1, 2, 3, or 5. In contrast to earlier work where incoherent tunneling was induced by introducing redox-active groups or increasing the molecular length, we show that increasing the polarizability, while keeping the organization of the monolayer structure unaltered, results in a gradual change in the mechanism of tunneling of charge carriers where the activation energy increased from 23 meV for n= 0 (associated with coherent tunneling) to 257 meV for n= 5 with X = Br (associated with incoherent tunneling). Interestingly, this increase in incoherent tunneling rate with polarizability resulted in an improved molecular diode performance. Our findings suggest an avenue to improve the electronic function of molecular devices by introducing polarizable atoms.

The “Molar Mass (or Molecular Weight) of a Volatile Liquid” laboratory is a common chemistry experiment performed by many school students, as well as college students. Usually, a “simple” variant of the Dumas bulb method is applied to determine the molar masses of volatile liquids, applying the ideal gas law. The evaluation of this classic experiment starts with a theoretical analysis of the experimental conditions. Shortcomings of the experiment’s underlying model are pointed out. A corrected model is developed targeting to bring achievable experimental results closer to “reality”. A simulation is performed, revealing how severe results deviate when using the classic experiment in the classroom, important information for educators. Experimental data confirming the theoretical considerations and simulations are provided. The results presented provide a tool to handle the common discrepancies associated with the classic Molar Mass experiment and, therefore, present a valuable teaching resource. An important aspect of this publication is to demonstrate that basic and common chemistry experiments provide a variety of science teaching opportunities. Throughout this experiment’s evaluation, instructor targeted suggestions are provided to highlight teaching opportunities at levels ranging from middle school to graduate level chemistry.

Plasmon excitation in molecular tunnel junctions is interesting because the plasmonic properties of the device can be, in principle, controlled by varying the chemical structure of the molecules. The plasmon energy of the excited plasmons usually follows the quantum cutoff law, but frequently overbias plasmon energy has been observed, which can be explained by quantum shot noise, multielectron processes, or hot carrier models. So far, clear correlations between molecular structure and the plasmon energy have not been reported. Here, we introduce halogenated molecules (HS(CH2)12X, with X = H, F, Cl, Br, or I) with polarizable terminal atoms as the tunnel barriers and demonstrate molecular control over both the excited plasmon intensity and energy for a given applied voltage. As the polarizability of the terminal atom increases, the tunnel barrier height decreases, resulting in an increase in the tunneling current and the plasmon intensity without changing the tunneling barrier width. We also show that the plasmon energy is controlled by the electrostatic potential drop at the molecule–electrode interface, which depends on the polarizability of the terminal atom and the metal electrode material (Ag, Au, or Pt). Our results give new insights in the relation between molecular structure, electronic structure of the molecular junction, and the plasmonic properties which are important for the development of molecular scale plasmonic-electronic devices.

The paper gives an overview of the latest magnet design activities at CEA for the EU-DEMO Magnet Systems. It explains the latest changes in design constraints, inputs and definitions, the updates that have been implemented in the design tools, and shows the latest CEA proposed design for the TF magnet. We will discuss the recent updates in the TF and PF design tools which were used in 2022 and 2023. In particular, the tools have evolved to include additional constraints or operating points like possible sub-cooling of the coils or synchronous discharge of the axisymmetric PF/CS system. The electromagnetic coupling of the TF coils with coil case and radial plates is also discussed during a fast safety discharge, along with energy extraction and deposition sharing. Furthermore, a new 2D TF mechanical model is presented that permits to make a fast iteration with design tools and optimize the radial build. Finally, the paper also includes an update on the CEA TF conductor qualification sample, describing in particular the latest results obtained in the Twente Press.

Allogeneic haematopoietic stem-cell transplantation (allo-HSCT) markedly reduces HIV reservoirs, but the mechanisms by which this occurs are only partly understood. In this study, we aimed to describe the dynamics of virological and immunological markers of HIV persistence after allo-HSCT.

The objective of the present study is to assess the rates of acquired tolerance to cow's milk (CM) after 36 months in subjects who consumed amino acid‐based formula with synbiotics (AAF‐S) or amino acid‐based formula without synbiotics (AAF) during a 1‐year intervention period in early life as part of the PRESTO study (Netherlands Trial Register number NTR3725). Differences in CM tolerance development between groups were analysed using a logistic regression model. Results show that the proportion of subjects (mean [±SD] age, 3.8 ± 0.27 years) who developed CM tolerance after 36 months was similar in the group receiving AAF‐S (47/60 [78%]) and in the group receiving AAF (49/66 [74%]) (p= 0.253), that is, figures comparable to natural outgrowth of CM allergy. Our data suggest that the consumption of AAF and absence of exposure to CM peptides do not slow down CM tolerance acquisition. The randomized double‐blind controlled trial PRESTO showed that infants receiving amino acid‐based formula (AAF) with or without synbiotics for 12 months in early life demonstrated effective symptom resolution.After 12 and 24 months, development of tolerance to cow's milk (CM) was in line with natural outgrowth. The randomized double‐blind controlled trial PRESTO showed that infants receiving amino acid‐based formula (AAF) with or without synbiotics for 12 months in early life demonstrated effective symptom resolution. After 12 and 24 months, development of tolerance to cow's milk (CM) was in line with natural outgrowth. This study shows that, 36 months after the start of the intervention, a high proportion of children (about three‐quarters) developed tolerance to CM.These data suggest that the consumption of AAF, with or without synbiotics, and the absence of exposure to CM peptides do not slow down CM tolerance acquisition. This study shows that, 36 months after the start of the intervention, a high proportion of children (about three‐quarters) developed tolerance to CM. These data suggest that the consumption of AAF, with or without synbiotics, and the absence of exposure to CM peptides do not slow down CM tolerance acquisition.

Outcoupling of plasmonic modes excited by inelastic electron tunneling (IET) across plasmonic tunnel junctions (TJs) has attracted significant attention due to low operating voltages and fast excitation rates. Achieving selectivity among various outcoupling channels, however, remains a challenging task. Employing nanoscale antennas to enhance the local density of optical states (LDOS) associated with specific outcoupling channels partially addressed the problem, along with the integration of conducting 2D materials into TJs, improving the outcoupling to guided modes with particular momentum. The disadvantage of such methods is that they often involve complex fabrication steps and lack fine-tuning options. Here, we propose an alternative approach by modifying the dielectric medium surrounding TJs. By employing a simple multilayer substrate with a specific permittivity combination for the TJs under study, we show that it is possible to optimize mode selectivity in outcoupling to a plasmonic or a photonic-like mode characterized by distinct cutoff behaviors and propagation length. Theoretical and experimental results obtained with a SiO2–SiN–glass multilayer substrate demonstrate high relative coupling efficiencies of (62.77 ± 1.74)% and (29.07 ± 0.72)% for plasmonic and photonic-like modes, respectively. The figure-of-merit, which quantifies the tradeoff between mode outcoupling and propagation lengths (tens of μm) for both modes, can reach values as high as 180 and 140. The demonstrated approach allows LDOS engineering and customized TJ device performance, which are seamlessly integrated with standard thin film fabrication protocols. Our experimental device is well-suited for integration with silicon nitride photonics platforms.

Plasmonic tunnel junctions are a unique electroluminescent system in which light emission occurs via an interplay between tunnelling electrons and plasmonic fields instead of electron–hole recombination as in conventional light-emitting diodes. It was previously shown that placing luminescent molecules in the tunneling pathway of nanoscopic tunnel junctions results in peculiar upconversion electroluminescence where the energy of emitted photons exceeds that of excitation electrons. Here we report the observation of upconversion electroluminescence in macroscopic van der Waals plasmonic tunnel junctions comprising gold and few-layer graphene electrodes separated by a ~2-nm-thick hexagonal boron nitride tunnel barrier and a monolayer semiconductor. We find that the semiconductor ground exciton emission is triggered at excitation electron energies lower than the semiconductor optical gap. Interestingly, this upconversion is reached in devices operating at a low conductance (<10−6S) and low power density regime (<102W cm−2), defying explanation through existing proposed mechanisms. By examining the scaling relationship between plasmonic and excitonic emission intensities, we elucidate the role of inelastic electron tunnelling dipoles that induce optically forbidden transitions in the few-layer graphene electrode and ultrafast hot carrier transfer across the van der Waals interface.

Approximately 10% of patients who undergo inguinal hernia repair or Pfannenstiel incision develop chronic (> three months) postsurgical inguinal pain (PSIP). If medication or peripheral nerve blocks fail, a neurectomy is the treatment of choice. However, some patients do not respond to this treatment. In such cases, stimulation of the dorsal root ganglion (DRG) appears to significantly reduce chronic PSIP in selected patients.

For fusion tokamaks, such as International Thermonuclear Experimental Reactor (ITER), the magnet systems are based on superconducting cable-in-conduit conductors (CICCs). Due to the limited production length of the CICCs and the necessary electrical and thermal connections, joints are widely used to connect the CICC units within the magnet coils, as well as the electrical and thermal interfaces outside the magnet. The joints dominate the current redistribution in the coils and, thus, are critical for the magnet stability. In this study, an ITER poloidal field coil joint operating in pulsed mode is chosen to study the current nonuniformity and relevant stability issues. An optimized joint design by applying high resistive polyimide layers, called “masks” to actively block the large induced coupling currents, is tested with the numerical code JackPot-AC/DC. The current nonuniformity, power dissipation, and thermal evolution of the joints with different configurations are quantitatively analyzed.

Introduction: A novel closed-loop spinal cord stimulation (SCS) system has recently been approved for use which records evoked compound action potentials (ECAPs) from the spinal cord and utilizes these recordings to automatically adjust the stimulation strength in real time. It automatically compensates for fluctuations in distance between the epidural leads and the spinal cord by maintaining the neural response (ECAP) at a determined target level. This data collection was principally designed to evaluate the performance of this first closed-loop SCS system in a ‘real-world’ setting under normal conditions of use in a single European center. Methods: In this prospective, single-center observational data collection, 22 patients were recruited at the outpatient pain clinic of the St. Antonius Hospital. All candidates were suffering from chronic pain in the trunk and/or limbs due to PSPS type 2 (persistent spinal pain syndrome). As standard of care, follow-up visits were completed at 3 months, 6 months, and 12 months post-device activation. Patient-reported outcome data (pain intensity, patient satisfaction) and electrophysiological and device data (ECAP amplitude, conduction velocity, current output, pulse width, frequency, usage), and patient interaction with their controller were collected at baseline and during standard of care follow-up visits. Results: Significant decreases in pain intensity for overall back or leg pain scores (verbal numerical rating score = VNRS) were observed between baseline [mean ± SEM (standard error of the mean); n= 22; 8.4 ± 0.2)], 3 months (n= 12; 1.9 ± 0.5), 6 months (n= 16; 2.6 ± 0.5), and 12 months (n= 20; 2.0 ± 0.5), with 85.0% of the patients being satisfied at 12 months. Additionally, no significant differences in average pain relief at 3 months and 12 months between the real-world data (77.2%; 76.8%) and the AVALON (71.2%; 73.6%) and EVOKE (78.1%; 76.7%) studies were observed. Conclusions: These initial ‘real-world’ data on ECAP-controlled, closed-loop SCS in a real-world clinical setting appear to be promising, as they provide novel insights of the beneficial effect of ECAP-controlled, closed-loop SCS in a real-world setting. The presented results demonstrate a noteworthy maintenance of pain relief over 12 months and corroborate the outcomes observed in the AVALON prospective, multicenter, single-arm study and the EVOKE double-blind, multicenter, randomized controlled trial. Trial Registration: The data collection is registered on the International Clinical Trials Registry Platform (Trial NL7889).

State of the art MgB2 is reviewed as a potential material for the poloidal field (PF) coils of the future fusion reactor due to its high critical temperature and low material cost. The heat treatment process is a crucial step in the development of MgB2 magnets. The temperature lag in heat treatment of large magnets can lead to insufficient thermal reaction time. It may be infeasible to control the temperature of a magnet according to the heat treatment scheme recommended for the MgB2 wire. Hence, the heat treatment process of a large magnet needs to be evaluated. Therefore, the dynamic temperature distribution of a MgB2 PF coil is obtained by simulating the heat transfer in heat treatment process. A suitable heat treatment schedule for a large magnet is proposed and the experimental results of a sub-size Cable-In-Conduit Conductor manufactured with MgB2 strand confirmed the feasibility of the newly proposed heat treatment process. The results provide a reference for the heat treatment method of a future larger MgB2 coil.

Abstract:Christian-democratic parties not only constituted the most successful political force in much of Western Europe during most of the twentieth century; their attitudes toward solidaristic welfare reform have arguably also been more diverse than have those of most other major political groupings during this period. Whereas existing studies have mostly attributed this variation to electoral or strategic considerations, this article emphasizes the importance of interest group involvement. It analyzes and compares postwar old-age pension reform in three important Christian-democratic-ruled societies, Belgium, Germany, and the Netherlands, and shows how the very different attitudes of the main Christian-democratic parties toward solidaristic welfare reform in these countries related to the strength and unity of the Christian-democratic labor union movements there.

AbstractChristian-democratic parties not only constituted the most successful political force in much of Western Europe during most of the twentieth century; their attitudes toward solidaristic welfare reform have arguably also been more diverse than have those of most other major political groupings during this period. Whereas existing studies have mostly attributed this variation to electoral or strategic considerations, this article emphasizes the importance of interest group involvement. It analyzes and compares postwar old-age pension reform in three important Christian-democratic-ruled societies, Belgium, Germany, and the Netherlands, and shows how the very different attitudes of the main Christian-democratic parties toward solidaristic welfare reform in these countries related to the strength and unity of the Christian-democratic labor union movements there.

Laser powder-directed energy deposition (LP-DED) is gaining interest in the production of complex large parts at a high production rate compared to conventional machining. Typically, these products are milled out of solid blocks. The aim of this work is to show the whole production chain to manufacture a titanium flaperon rib starting from the process optimisation to production and post-processing of the part itself. First, the process parameters for thin and bulky structures were optimised in LP-DED. Then different characteristic design features of the rib were defined and the manufacturing strategies were optimised. Lastly, all optimised strategies were applied for the production of the full-scale flaperon ribs. In this work, several design guidelines and optimum process conditions were obtained for Ti6Al4V processed by LP-DED. On one hand, the process parameters for thin walls and solid features were obtained. In addition, intersections and overhang structures were studied to achieve stable and high-quality connections. On the other hand, different strategies for reducing the deformations were studied and minimum deformations were obtained for large slender build plates. All developed strategies were implemented to successfully produce a large-sized flaperon rib in Ti6Al4V by powder LP-DED.

This study reports on a survey on project managers' priorities. The survey used ISO 21500 as a scaffold to ask various respondents, like junior, experienced, and senior project managers, project sponsors, and students, to share their perceptions on the priorities for junior project managers. The respondent groups shared similar perceptions. Furthermore, project type and sector had little effect on junior project managers' priorities. Experienced and senior project managers shared their own priorities as well. The perceptions of priorities for junior, experienced, and senior project managers were mostly alike. However, experienced and senior project managers' priorities seemed slightly more affected by project type and sector. A session with experts in project management and teaching project management highlighted that the results for junior project managers could provide accents for introducing project management to students in higher education, provided the entire playing field of project management is also introduced.

Children with a solitary functioning kidney (SFK) have an increased risk of kidney injury. The exact risk of and risk factors for kidney injury remain unknown, which impedes personalized care. Here, we recruited a nationwide multicenter cohort of 944 patients with SFK to get more insight into this by consenting patients born in 1993-2020 and diagnosed with congenital or acquired SFK before adulthood. The median follow-up was 12.8 years and four indications of kidney injury were studied: urine protein-creatinine ratios, blood pressure, estimated glomerular filtration rate and use of anti-hypertensive/proteinuric medication. For each indicator except medication use, separate cut-off values for any injury and severe injury were used. Survival analyses indicated that at 18 years of age, any or severe kidney injury were present in 75% and 39% of patients with congenital SFK, respectively. Risk factors for kidney injury included kidney agenesis as cause of the SFK, anomalies in the SFK, and high body mass index at last follow-up. Kidney agenesis and being overweight were specifically associated with proteinuria and high blood pressure, whereas anomalies in the SFK were associated with reduced estimated glomerular filtration rates. The high prevalence of kidney injury in patients with SFK emphasizes the need for long-term follow-up, in which lifestyle is an important topic to address. More research into the etiological role of risk factors will help to translate our findings into individualized care strategies. Thus, our study shows that a significant proportion of children with SFK will develop kidney injury over time.

Despite scientific evidence originating from two patients published to date that CCR5Δ32/Δ32 hematopoietic stem cell transplantation (HSCT) can cure human immunodeficiency virus type 1 (HIV-1), the knowledge of immunological and virological correlates of cure is limited. Here we characterize a case of long-term HIV-1 remission of a 53-year-old male who was carefully monitored for more than 9 years after allogeneic CCR5Δ32/Δ32 HSCT performed for acute myeloid leukemia. Despite sporadic traces of HIV-1 DNA detected by droplet digital PCR and in situ hybridization assays in peripheral T cell subsets and tissue-derived samples, repeated ex vivo quantitative and in vivo outgrowth assays in humanized mice did not reveal replication-competent virus. Low levels of immune activation and waning HIV-1-specific humoral and cellular immune responses indicated a lack of ongoing antigen production. Four years after analytical treatment interruption, the absence of a viral rebound and the lack of immunological correlates of HIV-1 antigen persistence are strong evidence for HIV-1 cure after CCR5Δ32/Δ32 HSCT.

2-year follow-up data from our randomised controlled trial showed that peroral endoscopic myotomy is associated with a significantly higher efficacy than pneumatic dilation as initial treatment of therapy-naive patients with achalasia. Here we report therapeutic success rates in patients treated with peroral endoscopic myotomy compared with pneumatic dilation at the 5-year follow-up.

The most studied HIV eradication approach is the “shock and kill” strategy, which aims to reactivate the latent reservoir by latency reversing agents (LRAs) and allowing elimination of these cells by immune‐mediated clearance or viral cytopathic effects. The CNS is an anatomic compartment in which (persistent) HIV plays an important role in HIV‐associated neurocognitive disorder. Restriction of the CNS by the blood–brain barrier is important for maintenance of homeostasis of the CNS microenvironment, which includes CNS‐specific cell types, expression of transcription factors, and altered immune surveillance. Within the CNS predominantly myeloid cells such as microglia and perivascular macrophages are thought to be a reservoir of persistent HIV infection. Nevertheless, infection of T cells and astrocytes might also impact HIV infection in the CNS. Genetic adaptation to this microenvironment results in genetically distinct, compartmentalized viral populations with differences in transcription profiles. Because of these differences in transcription profiles, LRAs might have different effects within the CNS as compared with the periphery. Moreover, reactivation of HIV in the brain and elimination of cells within the CNS might be complex and could have detrimental consequences. Finally, independent of activity on latent HIV, LRAs themselves can have adverse neurologic effects. We provide an extensive overview of the current knowledge on compartmentalized (persistent) HIV infection in the CNS and on the “shock and kill” strategy. Subsequently, we reflect on the impact and promise of the “shock and kill” strategy on the elimination of persistent HIV in the CNS. Review on the obstacles and limitations of using the shock and kill strategy to eradicate the HIV CNS reservoir.

Understanding the mechanisms of charge transport (CT) across biomolecules in solid-state devices is imperative to realize biomolecular electronic devices in a predictive manner. Although it is well-accepted that biomolecule–electrode interactions play an essential role, it is often overlooked. This paper reveals the prominent role of graphene interfaces with Fe-storing proteins in the net CT across their tunnel junctions. Here, ferritin (AfFtn-AA) is adsorbed on the graphene by noncovalent amine–graphene interactions confirmed with Raman spectroscopy. In contrast to junctions with metal electrodes, graphene has a vanishing density of states toward its intrinsic Fermi level (“Dirac point”), which increases away from the Fermi level. Therefore, the amount of charge carriers is highly sensitive to temperature and electrostatic charging (induced doping), as deduced from a detailed analysis of CT as a function of temperature and iron loading. Remarkably, the temperature dependence can be fully explained within the coherent tunneling regime due to excitation of hot carriers. Graphene is not only demonstrated as an alternative platform to study CT across biomolecular tunnel junctions, but it also opens rich possibilities in employing interface electrostatics in tuning CT behavior.

After an interpretation trajectory, the Dutch Quality of Healthcare Institute recommended that for five indications, spinal cord stimulation, dorsal root ganglion stimulation, or occipital nerve stimulation, together referred to as neurostimulation, can be considered effective and be reimbursed in the Netherlands. These five indications are the well and largely studied, accepted neurostimulation indications in scientific literature.

Liquid metal droplets, such as eutectic gallium–indium (EGaIn), are important in many research areas, such as soft electronics, catalysis, and energy storage. Droplet contact on solid surfaces is typically achieved without control over the applied force and without optimizing the wetting properties in different environments (e.g., in air or liquid), resulting in poorly defined contact areas. In this work, we demonstrate the direct manipulation of EGaIn microdroplets using an atomic force microscope (AFM) to generate repeated, on-demand making and breaking of contact on self-assembled monolayers (SAMs) of alkanethiols. The nanoscale positional control and feedback loop in an AFM allow us to control the contact force at the nanonewton level and, consequently, tune the droplet contact areas at the micrometer length scale in both air and ethanol. When submerged in ethanol, the droplets are highly nonwetting, resulting in hysteresis-free contact forces and minimal adhesion; as a result, we are able to create reproducible geometric contact areas of 0.8–4.5 μm2with the alkanethiolate SAMs in ethanol. In contrast, there is a larger hysteresis in the contact forces and larger adhesion for the same EGaIn droplet in air, which reduced the control over the contact area (4–12 μm2). We demonstrate the usefulness of the technique and of the gained insights in EGaIn contact mechanics by making well-defined molecular tunneling junctions based on alkanethiolate SAMs with small geometric contact areas of between 4 and 12 μm2in air, 1 to 2 orders of magnitude smaller than previously achieved.

Lassa fever continues to be a major public health burden in West Africa, yet effective therapies or vaccines are lacking. The isolation of protective neutralizing antibodies against the Lassa virus glycoprotein complex (GPC) justifies the development of vaccines that can elicit strong neutralizing antibody responses. However, Lassa vaccine candidates have generally been unsuccessful at doing so, and the associated antibody responses to these vaccines remain poorly characterized. Here, we establish an electron microscopy-based epitope mapping workflow that enables high-resolution structural characterization of polyclonal antibodies to the GPC. By applying this method to rabbits vaccinated with a recombinant GPC vaccine and a GPC-derived virus-like particle, we reveal determinants of neutralization that involve epitopes of the GPC-A competition cluster. Furthermore, by identifying undescribed immunogenic off-target epitopes, we expose the challenges that recombinant GPC vaccines face. By enabling detailed polyclonal antibody characterization, our work ushers in a next generation of more rational Lassa vaccine design.

Deer 255, a mule deer known for her long-distance migration, died during her annual journey from Wyoming to Idaho. At 10 years old, she had successfully navigated obstacles and predators, and had given birth to seven sets of twins. Her story highlights the endurance and vulnerability of migrating mammals like deer, pronghorn, and elk. While Deer 255's herd mates completed their migration, the need for permanent protection of their migration routes remains. [Extracted from the article]

Despite its promising advantages, the application of directed energy deposition (DED) to produce large metal parts is hindered by challenges inherent to the process. Undesired residual stresses, distortions and heterogeneous material properties mainly originate from a part’s thermal history. Fast part-scale thermal models therefore facilitate improved applicability of DED by enabling the prediction and mitigation of these unwanted effects. In this work, the efficiency of a discontinuous Galerkin-based thermal model with heat input by hot element addition, is evaluated and improved to allow such fast simulations. It is found that the model permits the use of a coarse discretization around the heat source, which significantly reduces simulation time while maintaining accurate solutions. It is also shown that the model naturally facilitates the use of local time stepping, which can considerably improve the efficiency of thermal additive manufacturing simulations.

Eutectic gallium–indium (EGaIn) is increasingly employed as an interfacial conductor material in molecular electronics and wearable healthcare devices owing to its ability to be shaped at room temperature, conductivity, and mechanical stability. Despite this emerging usage, the mechanical and physical mechanisms governing EGaIn interactions with surrounding objects─mainly regulated by surface tension and interfacial adhesion─remain poorly understood. Here, using depth-sensing nanoindentation (DSN) on pristine EGaIn/GaOxsurfaces, we uncover how changes in EGaIn/substrate interfacial energies regulate the adhesive and contact mechanic behaviors, notably the evolution of EGaIn capillary bridges with distinct capillary geometries and pressures. Varying the interfacial energy by subjecting EGaIn to different chemical environments and by functionalizing the tip with chemically distinct self-assembled monolayers (SAMs), we show that the adhesion forces between EGaIn and the solid substrate can be increased by up to 2 orders of magnitude, resulting in about a 60-fold increase in the elongation of capillary bridges. Our data reveal that by deploying molecular junctions with SAMs of different terminal groups, the trends of charge transport rates, the resistance of monolayers, and the contact interactions between EGaIn and monolayers from electrical characterizations are governed by the interfacial energies as well. This study provides a key understanding into the role of interfacial energy on geometrical characteristics of EGaIn capillary bridges, offering insights toward the fabrication of EGaIn junctions in a controlled fashion.

AbstractSpatial-visual landscape design vocabulary is important for landscape architects to understand, design, and communicate about landscape spaces. Despite the importance, there is no comprehensive overview available. This article aims to fill this gap by reviewing and categorising the spatial-visual design vocabulary for the field of landscape architecture and to provide a systematic framework for understanding landscape spaces inter-subjectively. Based on the analysis of the vocabulary used in the extensive body of literature available in landscape architecture and related disciplines, four dominant categories are selected in describing spatial and visual organisation. The categories identified and discussed are sequence, orientation, continuity, and complexity. In addition, a landscape design syntax is developed to understand and to describe the visual manifestation of landscape spaces, how space is organised, and what ordering principles play a role from both qualitative and quantitative perspectives.

Robust processes to fabricate densely packed high-aspect-ratio (HAR) vertical semiconductor nanostructures are important for applications in microelectronics, energy storage and conversion. One of the main challenges in manufacturing these nanostructures is pattern collapse, which is the damage induced by capillary forces from numerous solution-based processes used during their fabrication. Here, using an array of vertical silicon (Si) nanopillars as test structures, we demonstrate that pattern collapse can be greatly reduced by a solution-phase deposition method to coat the nanopillars with self-assembled monolayers (SAMs). As the main cause for pattern collapse is strong adhesion between the nanopillars, we systematically evaluated SAMs with different surface energy components and identified H-bonding between the surfaces to have the largest contribution to the adhesion. The advantage of the solution-phase deposition method is that it can be implemented before any drying step, which causes patterns to collapse. Moreover, after drying, these SAMs can be easily removed using a gentle air-plasma treatment right before the next fabrication step, leaving a clean nanopillar surface behind. Therefore, our approach provides a facile and effective method to prevent the drying-induced pattern collapse in micro- and nanofabrication processes.

To realize molecular-scale electrical operations beyond the von Neumann bottleneck, new types of multifunctional switches are needed that mimic self-learning or neuromorphic computing by dynamically toggling between multiple operations that depend on their past. Here, we report a molecule that switches from high to low conductance states with massive negative memristive behaviour that depends on the drive speed and number of past switching events, with all the measurements fully modelled using atomistic and analytical models. This dynamic molecular switch emulates synaptic behavior and Pavlovian learning, all within a 2.4-nm-thick layer that is three orders of magnitude thinner than a neuronal synapse. The dynamic molecular switch provides all the fundamental logic gates necessary for deep learning because of its time-domain and voltage-dependent plasticity. The synapse-mimicking multifunctional dynamic molecular switch represents an adaptable molecular-scale hardware operable in solid-state devices, and opens a pathway to simplify dynamic complex electrical operations encoded within a single ultracompact component.

Deoxyribonucleic acid (DNA) has been hypothesized to act as a molecular wire due to the presence of an extended π-stack between base pairs, but the factors that are detrimental in the mechanism of charge transport (CT) across tunnel junctions with DNA are still unclear. Here we systematically investigate CT across dense DNA monolayers in large-area biomolecular tunnel junctions to determine when intrachain or interchain CT dominates and under which conditions the mechanism of CT becomes thermally activated. In our junctions, double-stranded DNA (dsDNA) is 30-fold more conductive than single-stranded DNA (ssDNA). The main reason for this large change in conductivity is that dsDNA forms ordered monolayers where intrachain tunneling dominates, resulting in high CT rates. By varying the temperature Tand the length of the DNA fragments in the junctions, which determines the tunneling distance, we reveal a complex interplay between T, the length of DNA, and structural order on the mechanism of charge transport. Both the increase in the tunneling distance and the decrease in structural order result in a change in the mechanism of CT from coherent tunneling to incoherent tunneling (hopping). Our results highlight the importance of the interplay between structural order, tunneling distance, and temperature on the CT mechanism across DNA in molecular junctions.

Family-centered care has been implemented in the ICU to meet relatives' needs concerning information, support, participation and shared decision making. This study explores the needs, beliefs, feelings and behaviors of relatives of patients admitted to the ICU regarding participation during physical activity.

Charge transfer (CT) dynamics across metal–molecule interfaces has important implications for performance and function of molecular electronic devices. CT times, on the order of femtoseconds, can be precisely measured using synchrotron-based core-hole clock (CHC) spectroscopy, but little is known about the impact on CT times of the metal work function and the bond dipole created by metals and the anchoring group. To address this, here we measure CT dynamics across self-assembled monolayers bound by thiolate anchoring groups to Ag, Au, and Pt. The molecules have a terminal ferrocene (Fc) group connected by varying numbers of methylene units to a diphenylacetylene (DPA) wire. CT times measured using CHC with resonant photoemission spectroscopy (RPES) show that conjugated DPA wires conduct electricity faster than aliphatic carbon wires of a similar length. Shorter methylene connectors exhibit increased conjugation between Fc and DPA, facilitating CT by providing greater orbital mixing. We find nearly 10-fold increase in the CT time on Pt compared to Ag due to a larger bond dipole generated by partial electron transfer from the metal–sulfur bond to the carbon–sulfur bond, which creates an electrostatic field that impedes CT from the molecules. By fitting the RPES signal, we distinguish electrons coming from the Fe center and from cyclopentadienyl (Cp) rings. The latter shows faster CT rates because of the delocalized Cp orbitals. Our study demonstrates the fine tuning of CT rates across junctions by careful engineering of several parts of the molecule and the molecule–metal interface.

The article discusses the history and impact of the Endangered Species Act (ESA), which was signed into law by President Richard Nixon in 1973. The law was a response to growing public demand for environmental protection, fueled by concerns about wildlife conservation and public health. The ESA has faced criticism and controversy over the years, but it remains one of the most powerful environmental laws in the world. The article also highlights the need for the ESA to adapt to new circumstances and realize its full potential in order to protect species and ecosystems. [Extracted from the article]