Light Distribution in 3D-Printed Thermoplastics.

Daylight distribution is an essential performance parameter for building facades that aim to maximize user comfort while maintaining energy efficiency. This study investigates the feasibility of using 3D-printed thermoplastic to improve daylight distribution and transmission. To identify how geometry influences light distribution and transmission, 12 samples with various patterns were robotically fabricated. In a physical simulation of spring, summer, and winter, a robotic arm was used to direct light onto the samples in both the vertical and horizontal print pattern directions. In addition, three samples of conventional facade materials, including a polycarbonate panel, a polycarbonate sheet, and a single sheet of glass, were compared with the 3D-printed samples. All samples were examined and compared using high dynamic range imaging to qualitatively characterize luminance. The data analysis demonstrated that 3D-printed geometry can successfully generate customizable diffusive light distribution based on the needs of the user. Furthermore, the results showed that the vertical pattern direction had higher light transmission values than the horizontal pattern direction.

A framework for robotic excavation and dry stone construction using on-site materials.

Automated building processes that enable efficient in situ resource utilization can facilitate construction in remote locations while simultaneously offering a carbon-reducing alternative to commonplace building practices. Toward these ends, we present a robotic construction pipeline that is capable of planning and building freeform stone walls and landscapes from highly heterogeneous local materials using a robotic excavator equipped with a shovel and gripper. Our system learns from real and simulated data to facilitate the online detection and segmentation of stone instances in spatial maps, enabling robotic grasping and textured 3D scanning of individual stones and rubble elements. Given a limited inventory of these digitized stones, our geometric planning algorithm uses a combination of constrained registration and signed-distance-field classification to determine how these should be positioned toward the formation of stable and explicitly shaped structures. We present a holistic approach for the robotic manipulation of complex objects toward dry stone construction and use the same hardware and mapping to facilitate autonomous terrain-shaping on a single construction site. Our process is demonstrated with the construction of a freestanding stone wall (10 meters by 1.7 meters by 4 meters) and a permanent retaining wall (65.5 meters by 1.8 meters by 6 meters) that is integrated with robotically contoured terraces (665 square meters). The work illustrates the potential of autonomous heavy construction vehicles to build adaptively with highly irregular, abundant, and sustainable materials that require little to no transportation and preprocessing.

The Bcm rule allows a spinal cord model to learn rhythmic movements.

Currently, it is accepted that animal locomotion is controlled by a central pattern generator in the spinal cord. Experiments and models show that rhythm generating neurons and genetically determined network properties could sustain oscillatory output activity suitable for locomotion. However, current central pattern generator models do not explain how a spinal cord circuitry, which has the same basic genetic plan across species, can adapt to control the different biomechanical properties and locomotion patterns existing in these species. Here we demonstrate that rhythmic and alternating movements in pendulum models can be learned by a monolayer spinal cord circuitry model using the Bienenstock-Cooper-Munro learning rule, which has been previously proposed to explain learning in the visual cortex. These results provide an alternative theory to central pattern generator models, because rhythm generating neurons and genetically defined connectivity are not required in our model. Though our results are not in contradiction to current models, as existing neural mechanism and structures, not used in our model, can be expected to facilitate the kind of learning demonstrated here. Therefore, our model could be used to augment existing models.

Eggshell Pavilion: a reinforced concrete structure fabricated using robotically 3D printed formwork.

This paper discusses the design, fabrication, and assembly of the 'Eggshell Pavilion', a reinforced concrete structure fabricated using 3D printed thin shell formwork. Formworks for columns and slabs were printed from recycled plastic using a pellet extruder mounted to a robotic arm. The formworks were cast and demoulded, and the finished elements were assembled into a pavilion, showcasing the architectural potential of 3D printed formwork. The Eggshell Pavilion was designed and fabricated within the scope of a design studio at ETH Zurich. The structure was designed using a fully parametric design workflow that allowed for incorporating changes into the design until the fabrication. The pavilion consists of four columns and floor slabs. Each column and floor slab is reinforced with conventional reinforcing bars. Two different methods are used for casting the columns and floor slabs. The columns are cast using 'Digital casting systems', a method for the digitally controlled casting of fast-hardening concrete. Digital casting reduces the hydrostatic pressure exerted on the formwork to a minimum, thereby enabling the casting of tall structures with thin formwork. The floor slabs are cast with a commercially available concrete mix, as the pressure exerted on the formwork walls is lower than for the columns. In this research, 3D printed formwork is combined with traditional reinforcing, casting, and assembly methods, bringing the technology closer to an industrial application. Supplementary Information: The online version contains supplementary material available at 10.1007/s41693-023-00090-x.

Additive Digital Casting: From Lab to Industry.

Concrete construction harms our environment, making it urgent to develop new methods for building with less materials. Structurally efficient shapes are, however, often expensive to produce, because they require non-standard formworks, thus, standard structures, which use more material than is often needed, remain cheaper. Digital fabrication has the potential to change this paradigm. One method is Digital Casting Systems (DCS), where the hydration of self-compacting concrete is controlled on the fly during production, shortening the required setting time and reducing hydrostatic pressure on the formwork to a minimum. This enables a productivity increase for standard concrete production. More importantly, though, it enables a rethinking of formworks, as the process requires only cheap thin formworks, thus, unlocking the possibility to produce optimised structural members with less bulk material and lower environmental cost. While DCS has already proven effective in building structural members, this process faces the challenge of moving into industry. This paper covers the next steps in doing so. First, we present the benchmark and expectations set by the industry. Second, we consider how we comply with these requirements and convert our fast-setting self-compacting mortar mix into a coarser one. Third, we present the next generation of our digital processing system, which moves closer to the industrial requirements in terms of size and the control system. Finally, two prototypes demonstrate how DSC: (a) increases standard bulk production by 50% and (b) can be cast into ultra-thin formworks. We discuss the results and the short-term industrial concerns for efficiency and robustness, which must be addressed for such a system to be fully implemented in industry.

Diversified physiological sensory input connectivity questions the existence of distinct classes of spinal interneurons.

The spinal cord is engaged in all forms of motor performance but its functions are far from understood. Because network connectivity defines function, we explored the connectivity of muscular, tendon, and tactile sensory inputs among a wide population of spinal interneurons in the lower cervical segments. Using low noise intracellular whole cell recordings in the decerebrated, non-anesthetized cat in vivo, we could define mono-, di-, and trisynaptic inputs as well as the weights of each input. Whereas each neuron had a highly specific input, and each indirect input could moreover be explained by inputs in other recorded neurons, we unexpectedly also found the input connectivity of the spinal interneuron population to form a continuum. Our data hence contrasts with the currently widespread notion of distinct classes of interneurons. We argue that this suggested diversified physiological connectivity, which likely requires a major component of circuitry learning, implies a more flexible functionality.

Robotic Plaster Spraying: Crafting Surfaces with Adaptive Thin-Layer Printing.

Embedded in a long tradition of craftsmanship, inside or outside building surfaces, is often treated with plaster, which plays both functional and ornamental roles. Today, plasterwork is predominantly produced through rationalized, time-, and cost-efficient processes, used for standardized building elements. These processes have also gained interest in the construction robotics field, and while such approaches target the direct automation of standardized plasterwork, they estrange themselves from the inherent qualities of this malleable material that are well known from the past. This research investigates the design potentials of robotic plaster spraying, proposing an adaptive, thin-layer vertical printing method for plasterwork that aims to introduce a digital craft through additive manufacturing. The presented work is an explorative study of a digitally controlled process that can be applied to broaden the design possibilities for the surfaces of building structures. It involves the spraying of multiple thin layers of plaster onto a vertical surface to create volumetric formations or patterns, without the use of any formwork or support structures. This article describes the experimental setup and the initial results of the data collection method involving systematic studies with physical testing, allowing to develop means to predict and visualize the complex-to-simulate material behavior, which might eventually enable to design with the plasticity of this material in a digital design tool.

Impact Printing.

This article introduces the concept of Impact Printing, a new additive manufacturing (AM) method that aggregates malleable discrete elements (or soft particles) by a robotic shooting process. The bonding between the soft particles stems from the transformation of kinetic energy, gained during the acceleration phase, into plastic deformation upon impact. Hence, no additional binding material is needed between the soft particles; the cohesion and self-interlocking capacities of the material itself acts as the primary binding agent. Shooting, and consequent impacting, forces can be modulated and result in distinct compaction ratios. By linearly shooting material, we decouple the deposition apparatus from the produced parts and provide flexibility to the deposition process to potentially build in any directions or onto uncontrolled surfaces. Impact Printing produces parts with formal characteristics standing between brick laying-assembly of discrete building blocks-and 3D Printing-computer-controlled depositioning or solidifying of material. It brings forward a novel digital fabrication method and an alternative to the conventional continuous AM process. This article validates the Impact Printing approach with a series of prototypical experiments, conducted with a robotic fabrication setup consisting of a six-axis robotic arm mounted with a material shooting apparatus, that forms, orients, and projects the soft particles. We will explain and demonstrate its principles and define the fabrication parameters, such as shooting force, shooting distance, and the resulting aggregations' characteristics.

A Non-spiking Neuron Model With Dynamic Leak to Avoid Instability in Recurrent Networks.

Recurrent circuitry components are distributed widely within the brain, including both excitatory and inhibitory synaptic connections. Recurrent neuronal networks have potential stability problems, perhaps a predisposition to epilepsy. More generally, instability risks making internal representations of information unreliable. To assess the inherent stability properties of such recurrent networks, we tested a linear summation, non-spiking neuron model with and without a "dynamic leak", corresponding to the low-pass filtering of synaptic input current by the RC circuit of the biological membrane. We first show that the output of this neuron model, in either of its two forms, follows its input at a higher fidelity than a wide range of spiking neuron models across a range of input frequencies. Then we constructed fully connected recurrent networks with equal numbers of excitatory and inhibitory neurons and randomly distributed weights across all synapses. When the networks were driven by pseudorandom sensory inputs with varying frequency, the recurrent network activity tended to induce high frequency self-amplifying components, sometimes evident as distinct transients, which were not present in the input data. The addition of a dynamic leak based on known membrane properties consistently removed such spurious high frequency noise across all networks. Furthermore, we found that the neuron model with dynamic leak imparts a network stability that seamlessly scales with the size of the network, conduction delays, the input density of the sensory signal and a wide range of synaptic weight distributions. Our findings suggest that neuronal dynamic leak serves the beneficial function of protecting recurrent neuronal circuitry from the self-induction of spurious high frequency signals, thereby permitting the brain to utilize this architectural circuitry component regardless of network size or recurrency.

Biological data questions the support of the self inhibition required for pattern generation in the half center model.

Locomotion control in mammals has been hypothesized to be governed by a central pattern generator (CPG) located in the circuitry of the spinal cord. The most common model of the CPG is the half center model, where two pools of neurons generate alternating, oscillatory activity. In this model, the pools reciprocally inhibit each other ensuring alternating activity. There is experimental support for reciprocal inhibition. However another crucial part of the half center model is a self inhibitory mechanism which prevents the neurons of each individual pool from infinite firing. Self-inhibition is hence necessary to obtain alternating activity. But critical parts of the experimental bases for the proposed mechanisms for self-inhibition were obtained in vitro, in preparations of juvenile animals. The commonly used adaptation of spike firing does not appear to be present in adult animals in vivo. We therefore modeled several possible self inhibitory mechanisms for locomotor control. Based on currently published data, previously proposed hypotheses of the self inhibitory mechanism, necessary to support the CPG hypothesis, seems to be put into question by functional evaluation tests or by in vivo data. This opens for alternative explanations of how locomotion activity patterns in the adult mammal could be generated.

Mastering Yield Stress Evolution and Formwork Friction for Smart Dynamic Casting.

The construction industry is a slow adopter of new technologies and materials. However, interdisciplinary research efforts in digital fabrication methods with concrete aim to make a real impact on the way we build by showing faster production, higher quality and enlarged freedom of design. In this paper, the potential and constraints of a specific digital slip-forming process, smart dynamic casting (SDC), are investigated with a material-focused approach in the complex task of producing thin folded structures. Firstly, the workability and the strength evolution of different material compositions are studied to achieve the constant processing rate for SDC. Secondly, friction between the formwork walls and the concrete, a key aspect in slip-casting, is studied with a simplified experimental setup to identify if any of these mixes would provide an advantage for processing. Finally, a theoretical framework is constructed to link the material properties, the process conditions and the designed geometry. This framework introduces the 'SDC number' as a simplified approach to formulate the process window, the suitable conditions for slip-forming. The experimental results prove the assumption of the model that friction is proportional to yield stress for all base compositions and acceleration methods regardless of the filling history. The results are evaluated in the context of the narrow process window of thin folded structures as well as the wider process window of columns. The necessity of consistent strength evolution is underlined for narrow windows. Further, friction is shown to be the highest initially, thus with both narrow and wide process windows, after a successful start-up the continuation of slipping is less prone to failure. The proposed theoretical model could provide material and geometry-specific slipping strategy for start time and slipping rate during production.

Does a Train-the-Trainer Approach for Enhancing Healthcare Professionals' Skills in Patient Education during Inpatient Medical Rehabilitation Improve Patient Outcomes?

This study is aimed at identifying the impact of a team-based train-the-trainer program (TTT-P) to enhance healthcare professional (HCP) skills in patient education during medical rehabilitation. Focusing on patient-reported outcomes, a prospective, sequential two-cohort study was conducted in the fields of psychosomatic and oncological rehabilitation. Two hundred fifteen patients were evaluated before (Cohort 1) and 196 post implementation of TTT-P (Cohort 2). Patients of both cohorts completed validated questionnaires on self-management (heiQ®), general self-efficacy (GSE scale), and quality of life (WHOQOL-Bref) at the beginning, at the end, and at the 6-month follow-up to analyze short- and intermediate-term effects. Analyses were conducted separately for the psychosomatic and oncological setting. Results showed that TTT-P had no impact on patient outcomes in both rehabilitation settings. Patients did report positive outcomes as a result of the whole inpatient rehabilitation programs, though effects at follow-up were mostly small to medium size. Concerning self-management competencies, cancer patients gained less benefit during rehabilitation than psychosomatic patients. In conclusion, TTT-P did not result in measurable improvements at the patient level, likely because of the limited nature of the intervention. However, these populations of rehabilitants took benefit from participating in a multimodal rehabilitation program, of which patient education is one part.

Rethinking drug design in the artificial intelligence era.

Artificial intelligence (AI) tools are increasingly being applied in drug discovery. While some protagonists point to vast opportunities potentially offered by such tools, others remain sceptical, waiting for a clear impact to be shown in drug discovery projects. The reality is probably somewhere in-between these extremes, yet it is clear that AI is providing new challenges not only for the scientists involved but also for the biopharma industry and its established processes for discovering and developing new medicines. This article presents the views of a diverse group of international experts on the 'grand challenges' in small-molecule drug discovery with AI and the approaches to address them.

Gamma-spectrometric analysis of high salinity fluids: how to analyze radionuclides of the thorium decay chain far from radioactive equilibrium?

Highly saline brines from a geothermal plant in Neustadt-Glewe, Germany, were investigated with respect to their radionuclide concentrations. The natural decay series in these fluids are far from radioactive equilibrium with main activity contributions from the radium isotopes (226)Ra, (228)Ra and (224)Ra. A general mathematical formulation for the coupled radionuclide activities within one decay chain is applied on the system (228)Ra…(212)Pb and tested on real samples in order to evaluate several radionuclide concentrations at the moment of sampling.

Importin α7 is essential for zygotic genome activation and early mouse development.

Importin α is involved in the nuclear import of proteins. It also contributes to spindle assembly and nuclear membrane formation, however, the underlying mechanisms are poorly understood. Here, we studied the function of importin α7 by gene targeting in mice and show that it is essential for early embryonic development. Embryos lacking importin α7 display a reduced ability for the first cleavage and arrest completely at the two-cell stage. We show that the zygotic genome activation is severely disturbed in these embryos. Our findings indicate that importin α7 is a new member of the small group of maternal effect genes.

Importin alpha3 interacts with HIV-1 integrase and contributes to HIV-1 nuclear import and replication.

HIV-1 employs the cellular nuclear import machinery to actively transport its preintegration complex (PIC) into the nucleus for integration of the viral DNA. Several viral karyophilic proteins and cellular import factors have been suggested to contribute to HIV-1 PIC nuclear import and replication. However, how HIV interacts with different cellular machineries to ensure efficient nuclear import of its preintegration complex in dividing and nondividing cells is still not fully understood. In this study, we have investigated different importin alpha (Impalpha) family members for their impacts on HIV-1 replication, and we demonstrate that short hairpin RNA (shRNA)-mediated Impalpha3 knockdown (KD) significantly impaired HIV infection in HeLa cells, CD4(+) C8166 T cells, and primary macrophages. Moreover, quantitative real-time PCR analysis revealed that Impalpha3-KD resulted in significantly reduced levels of viral 2-long-terminal repeat (2-LTR) circles but had no effect on HIV reverse transcription. All of these data indicate an important role for Impalpha3 in HIV nuclear import. In an attempt to understand how Impalpha3 participates in HIV nuclear import and replication, we first demonstrated that the HIV-1 karyophilic protein integrase (IN) was able to interact with Impalpha3 both in a 293T cell expression system and in HIV-infected CD4(+) C8166 T cells. Deletion analysis suggested that a region (amino acids [aa] 250 to 270) in the C-terminal domain of IN is involved in this viral-cellular protein interaction. Overall, this study demonstrates for the first time that Impalpha3 is an HIV integrase-interacting cofactor that is required for efficient HIV-1 nuclear import and replication in both dividing and nondividing cells.

Notch1 signaling is mediated by importins alpha 3, 4, and 7.

The Notch signaling pathway is an important regulation system for the development and self-renewal of different tissues. A specific feature of this signaling cascade is the function of Notch as a surface receptor and regulator of gene expression. Hence, Notch activation and signal transduction requires the proteolytic release of the Notch intracellular domain (NICD), which activates the transcription of cell-specific genes after its transport into the nucleus. To date, little is known about the mechanisms that mediate NICD nuclear import. We here show that transport of NICD into the nucleus is mediated by the canonical importin alpha/beta1 pathway. GST pull-down experiments revealed that NICD binds via one of its four potential nuclear localization signals to importins alpha3, alpha4, and alpha7, but not to alpha1 and alpha5. siRNA-mediated knockdown experiments showed that importins alpha3, alpha4 (and to a lesser extent, alpha7) mediate nuclear import of NICD and thus are directly involved in Notch signaling.

Cellular oxygen sensing: Importins and exportins are mediators of intracellular localisation of prolyl-4-hydroxylases PHD1 and PHD2.

Hypoxia-inducible factors are crucial in the regulatory process of oxygen homeostasis of vertebrate cells. Inhibition of prolyl hydroxylation of HIF-alpha subunits by prolyl-hydroxylases (PHD1, PHD2 and PHD3) leads to transcription of a greater number of hypoxia responsive genes. We have investigated the subcellular distribution and the molecular mechanisms regulating the intracellular allocation of PHD1 and PHD2. As reported earlier we find PHD1 located exclusively in the nucleus. We demonstrate that nuclear import of PHD1 occurs importin alpha/beta dependently and relies on a nuclear localisation signal (NLS). By contrast PHD2 is cycling between nucleus and cytoplasm, and nuclear import seems to be independent of "classical" importin alpha/beta receptors. Furthermore, we reveal that the exit of PHD2 from the nucleus requires CRM1 and the N-terminal 100 amino acids of the protein. Our findings provide new insights into the mechanisms of the regulation of the oxygen sensor cascade of PHDs in different cellular compartments.

Seizures increase importin-beta1 expression in NG2+ cells in the rat hippocampus.

Importins, also called karyopherins, belong to a large family of proteins involved in cytoplasm-to-nucleus transport. Transport machinery generally involves a complex formed by two different importin subtypes (alpha and beta). Both alpha and beta importins are expressed in the brain, and their expression and localization is regulated by physiological neuronal activity. Little is known about regulation of importin expression in brain pathological conditions. Here we studied the expression of importin beta1 (imp beta 1) in the rat hippocampus after acute and chronic seizures induced by the glutamate agonist kainic acid (KA). The overall content of imp beta 1 mRNA and protein did not change after acute KA seizures. However, acute KA seizures rapidly induced the translocation of imp beta 1 protein from the cytoplasm to the nucleus in pyramidal CA1 neurons. KA-induced imp beta 1 translocation was prevented by the NMDA (N-methyl-D-aspartic acid) receptor blocker MK-801. After chronic seizures, the overall levels of imp beta 1 mRNA and protein did not change in the whole hippocampus. Immunohistochemistry revealed a massive loss of imp beta 1-positive neurons in pyramidal layers (that degenerated after KA), whereas an increased number of imp beta 1-positive cells was detected in the stratum radiatum of rats with chronic seizures compared with control animals. Double-labeling experiments identified these cells as glial cells expressing the chondroitin sulfate proteoglycan NG2 (neuron/glial antigen 2), a glial subtype recently shown to regulate hippocampal neuron excitability. These data show a differential regulation of imp beta 1 expression after acute and chronic seizure activity in the rat hippocampus.

Nuclear translocation of hypoxia-inducible factors (HIFs): involvement of the classical importin alpha/beta pathway.

Hypoxia-inducible factors are the key elements in the essential process of oxygen homeostasis of vertebrate cells. Stabilisation and subsequent nuclear localisation of HIF-alpha subunits results in the activation of target genes such as vegf, epo and glut1. The passage of transcription factors e.g. HIF-1alpha into the nucleus through the nuclear pore complex is regulated by nuclear transport receptors. Therefore nucleocytoplasmic shuttling can regulate transcriptional activity by facilitating the cellular traffic of transcription factors between both compartments. Here, we report on the identification of specific interactions of hypoxia-inducible factors with nuclear transport receptors importin alpha/beta. HIF-1alpha, -1beta, and HIF-2alpha are binding to importin alpha1, alpha3, alpha5, and alpha7. The direct interaction of HIF-1alpha to alpha importins is dependent on a functional nuclear localisation signal within the C-terminal region of the protein. In contrast, the supposed N-terminal NLS is not effective. Our findings provide new insight into the mechanism of the regulation of nuclear transport of hypoxia-inducible factors.