Search Results (125)

Background/Objectives: Cows produce antibodies with ultralong CDRH3 segments (ulCABs) that contain a disulfide-stabilized knob domain. This domain is connected to the globular core of the antibody by a β-strand stalk. In the crystal structures, the stalk protrudes from the core in an extended conformation and presents the knob at its distal end. However, the rigidity of this topology has been questioned due to the extensive crystal packing present in most ulCAB crystal structures. To gain more insight into the dynamics of ultralong CDRH3s, we performed a comparative molecular dynamics (MD) study of 19 unique ulCABs. Methods: For all 19 systems, one-microsecond MD simulations were performed in explicit solvent. The analyses included an investigation of the systems’ conformational stability and the dynamics of the knob domain as well as an energetic analysis of the intramolecular knob interactions. Results: The simulations show that the extended stalk–knob conformation observed in the crystal structures is not preserved in solution. There are significant differences in the degree of knob dynamics, the orientations of the knobs, the number of flexible stalk residues, and the frequency of the motions. Furthermore, interactions between the knob and the light chain (LC) of the ulCABs were observed in about half of the systems. Conclusions: The study reveals that pronounced knob dynamics is a general feature of ulCABs rather than an exception. The magnitude of knob motions depends on the system, thus reflecting the high sequence diversity of the CDRH3s in ulCABs. The observed knob–LC interactions might play a role in stabilizing distinct knob orientations. The MD simulations of ulCABs could also help to identify suitable knob fragments as mini-antibodies by suggesting appropriate truncation points based on flexible sites in the stalks. Full article

Transcranial direct current stimulation (tDCS) can modulate cortical excitability in a polarity-specific manner, yet identical protocols often produce inconsistent outcomes across sessions or individuals. This narrative review proposes that much of this variability arises from the brain’s intrinsic temporal landscape. Integrating evidence from chronobiology, sleep research, and non-invasive brain stimulation, we argue that tDCS produces reliable, polarity-specific after-effects only within a circadian–homeostatic “window of efficacy”. On the circadian (Process C) axis, intrinsic alertness, membrane depolarisation, and glutamatergic gain rise in the late biological morning and early evening, whereas pre-dawn phases are marked by reduced excitability and heightened inhibition. On the homeostatic (Process S) axis, consolidated sleep renormalises synaptic weights, widening the capacity for further potentiation, whereas prolonged wakefulness saturates plasticity and can even reverse the usual anodal/cathodal polarity rules. Human stimulation studies mirror this two-process fingerprint: sleep deprivation abolishes anodal long-term-potentiation-like effects and converts cathodal inhibition into facilitation, while stimulating at each participant’s chronotype-aligned (phase-aligned) peak time amplifies and prolongs after-effects even under equal sleep pressure. From these observations we derive practical recommendations: (i) schedule excitatory tDCS after restorative sleep and near the individual wake-maintenance zone; (ii) avoid sessions at high sleep pressure or circadian troughs; (iii) log melatonin phase, chronotype, recent sleep and, where feasible, core temperature; and (iv) consider mild pre-heating or time-restricted feeding as physiological primers. By viewing Borbély’s two-process model and allied metabolic clocks as adjustable knobs for plasticity engineering, this review provides a conceptual scaffold for personalised, time-sensitive tDCS protocols that could improve reproducibility in research and therapeutic gain in the clinic. Full article

Manufacturing processes are collecting a wealth of data on how operational knobs affect process efficiency and product quality. Yet, optimizing the adjustment of these knobs using artificial intelligence remains a challenge. We propose a simple open-loop control method for optimizing a manufacturing process, with pharmaceutical applications in mind, using artificial intelligence. The first step involves fitting a simple supervised learning model to manufacturing data—typically an artificial neural network with universal approximation guarantees—so that operational knobs (such as concentrations and temperatures) can be used to predict process efficiency (e.g., time-to-product) and/or product quality (e.g., yield or quality score). Assuming the supervised learning model works well, we can perform typical optimization procedures, like gradient ascent, to increase efficiency and product quality. We test this on a publicly available dataset for wine and suggest new values for wine parameters that should produce a higher-quality wine with a greater probability. The result is a setting for the manufacturing knobs that optimizes the product using basic artificial intelligence. This method can be further enhanced by incorporating more advanced and recent AI applications for anomaly and defect detection in manufacturing processes. Full article

Background: Treating psychiatric illnesses or influencing mental states with neurofeedback is challenging, likely due to the limited spatial specificity of EEG and the complications arising from the inadequate signal-to-noise ratio reduction of single-trial EEG. Objective: This pilot study aimed to investigate the feasibility of employing a binaural pulse mode-modulation (BPM) device to reduce anxiety by self-regulation. We desired to determine whether anxiety could be significantly reduced or regulated using BPM-type systems. Methods: Sixty adult participants were examined with self-reported anxiety tests (COVID Stress Scale, Generalized Anxiety Disorder 7, Beck Depression Inventory-II), which were completed before treatment, after four weeks, and after 12 weeks post-treatment. This BPM device produced two frequencies which combined to create a binaural pulse through differential auditory tone presentations. The participant calibrated the suitable target tone for optimal treatment efficacy. Each participant adjusted the binaural pulse to enhance the emotional intensity felt when envisioning an experience with comparable emotional significance or while performing a cognitive task while concurrently listening to music. The “treatment” relied on the individual’s regulation of binaural pulses to obtain the desired state. The training concentrated on particular facets of their psychological challenges while listening to an auditory tone, adjusting a knob until the sound amplified the intended emotional state. Another knob was turned to intensify the emotional state associated with distress reduction. Results: On the self-reported measures, the BPM treatment group was significantly better than the sham treatment (control) groups (p < 0.01). These findings indicate that over the four-week intervention period, BPM was similarly effective. On the GAD-7, the significant difference over time was noted before treatment and at the end of treatment for the experimental group, with the average GAD-7 score at the end of treatment being significantly lower (p < 0.01). Conclusions: BPM seems to induce a short-term alteration in self-reported distress levels during therapy. This study’s limitations are examined, and recommendations for future research are provided. Full article

Oncolytic adenoviruses derived from human serotype 5 (Ad5) are being developed to treat cancer. Treatment efficacy could be affected by pre-existing or induced neutralizing antibodies (NAbs), in particular in repeat administration strategies. Several oncolytic adenoviruses that are currently in clinical development have modified fiber proteins to increase their infectivity. One example is Ad5-∆24.RGD, which carries a cyclic RGD peptide insert in the fiber protein to allow cell entry via integrins. The effect of anti-Ad5 NAbs on anticancer efficacy could be different for oncolytic adenoviruses with RGD-modified fibers than for unmodified Ad5-based viruses. Here, we determine pre-existing and elicited NAb titers in the serum of patients with glioblastoma who were treated by delivering Ad5-∆24.RGD to the tumor and to the surrounding tumor-infiltrated brain. We show that intracranial infusion of Ad5-∆24.RGD induced mainly neutralization of adenovirus native tropism. Infection of cells with RGD-modified virus was significantly less affected. In cerebrospinal fluid, neutralizing activity against RGD-mediated infection remained very low. Thus, the RGD-mediated alternative cell entry route allowed to bypass pre-existing and induced anti-Ad5 neutralization. Interestingly, in the course of these experiments, we discovered that the serum of most humans promotes the uptake of RGD-modified adenovirus in human cells. The until now unidentified infection-stimulating factor seems distinct from serum proteins known to promote Ad5 infection. Together, our work supports the utility of RGD-modified oncolytic adenoviruses for the treatment of cancer in humans. Since these viruses hardly induced neutralization, they seem particularly suitable for repeat administration treatments. Full article

Background: Dibothriocephalus nihonkaiense (previously known as Diphyllobothrium nihonkaiense) infection is not common in Hong Kong. D. nihonkaiense is a fish-borne cestode parasite that infects humans after consuming raw or insufficiently cooked fish containing plerocercoids. Case presentation: We reported a case of D. nihonkaiense infection in a 40-year-old woman who presented with a complaint of epigastric pain and diarrhea. A curvilinear opacity was seen at the upper quadrant of the abdomen via abdominal X-ray. An incomplete 80 cm long strobila of D. nihonkaiense without a scolex and neck was found in her feces. A grayish-brown oval egg with an inconspicuous operculum and small knob at the abopercular end was also found. Species-level identification was performed using Nanopore sequencing. Complete blood count and serum vitamin B12 level were tested to check for megaloblastic anemia and vitamin B12 deficiency, respectively. Laboratory investigations demonstrated an elevated percentage of monocytes in peripheral blood. A single oral dose of praziquantel (25 mg/kg) was prescribed to the patient. There was no evidence of relapse after the treatment. Conclusions: We reported a case of D. nihonkaiense infection using Oxford Nanopore NGS as a tool for accurate parasite identification. Full article

Kitchen appliance control panels come in various designs, each with different parameter values. Of these design parameters, the panel angle is a key factor that impacts both usability and user preference. This study empirically investigates the effects of panel angles on the usability of knob panels in kitchen appliances. The research focused on identifying the optimal panel angles for visibility, physical comfort, and user preference. Six different panel angles (0°, 15°, 30°, 45°, 60°, and 90°) were tested through an experimental setup simulating a typical kitchen environment. Twenty participants, with experience in operating kitchen appliances, provided subjective ratings on the three usability factors using a 7-point Likert scale. The results demonstrated significant impacts of panel angle on all three measures, with angles between 45° and 60° showing the highest usability scores. The study highlights that the appropriate panel angle for knob panels should fall between 30° and 90°, with 45° to 60° being the optimal range. The results of this study could contribute to the ergonomic design of kitchen appliances, enhancing usability and minimizing human errors and response times during emergencies. Full article

In light of the significant impact of climate change, it is imperative to identify effective solutions to reduce the environmental burdens of industrial production and to promote recycling strategies also for thermosetting polymers. In this work, the mechanical recycling of phenolic resins, obtained from industrial production scrap of plastic knobs for household appliances, was optimized. The feasibility of a partial substitution of virgin materials with recycled ones was investigated both at a laboratory and industrial scale. Finally, the environmental benefits arising from the use of recycled material were quantified through a life cycle assessment (LCA). The results of laboratory characterization demonstrated that the thermal properties of the phenolic resins were not influenced by the presence of recycled material, and the mechanical performances were not significantly impaired up to a recycled content of 30 wt%. The industrial production trials demonstrated the feasibility of replacing up to 15 wt% of virgin material without any influence on the aesthetical features of the produced components. Finally, LCA of industrially produced knobs highlighted a limited benefit of virgin material substitution in the case of novolac chromium-plated samples, while an overall environmental impact reduction of around 7–10% was detected in the case of resol-based materials. Full article

Microscopic evidence demonstrated a strictly biotrophic lifestyle of the scab fungus Venturia inaequalis on growing apple leaves and characterised its hemibiotrophy as the combination of biotrophy and saprotrophy not described before. The pathogen–host interface was characterised by the formation of knob-like structures of the fungal stroma appressed to epidermal cells as early as 1 day after host penetration, very thin fan-shaped cells covering large parts of the host cell lumen, and enzymatic cuticle penetration from the subcuticular space limited to the protruding conidiophores. The V. inaequalis cell wall had numerous orifices, facilitating intimate contact with the host tissue. Pathogen-induced modifications of host cells included partial degradation of the cell wall, transition of epidermal cells into transfer cells, modification of epidermal pit fields to manipulate the flow of nutrients and other compounds, and formation of globular protuberances of mesophyll cells without contact with the pathogen. The non-haustorial biotrophy was characterised by enlarged areas of intimate contact with host cells, often mediated by a matrix between the pathogen and plant structures. The new microscopic evidence and information on the pathogens’ biochemistry and secretome from the literature gave rise to a model of the lifestyle of V. inaequalis, lacking a necrotrophic stage that covers and explains its holomorphic development. Full article

This paper examined how rotary force feedback in knobs can enhance control over musical techniques, focusing on both performance and user experience. To support our study, we developed the Bend-aid system, a web-based sequencer with pre-designed haptic modes for pitch modulation, integrated with TorqueTuner, a rotary haptic device that controls pitch through programmable haptic effects. Then, twenty musically trained participants evaluated three haptic modes (No-force feedback (No-FF), Spring, and Detent) by performing a vibrato mimicry task, rating their experience on a Likert scale, and providing qualitative feedback in post-experiment interviews. The study assessed objective performance metrics (Pitch Error and Pitch Deviation) and subjective user experience ratings (Comfort, Ease of Control, and Helpfulness) of each haptic mode. User experience results showed that participants found force feedback helpful. Performance results showed that the Detent mode significantly improved pitch accuracy and vibrato stability compared to No-FF, while the Spring mode did not show a similar improvement. Post-experiment interviews showed that preferences for Spring and Detent modes varied, and the applicants provided suggestions for future knob designs. These findings suggest that force feedback may enhance both control and the experience of control in rotary knobs, with potential applications for more nuanced control in DMIs. Full article

Controlling the balance between piezoelectric and flexoelectric effects is crucial for tailoring the electromechanical responses of a material. In twisted graphene, it is found that the electromechanical response near the domain walls (DWs) is dominated by either the flexoelectric effect as in twisted bilayer graphene (tBLG) or the piezoelectric effect as in twisted monolayer–bilayer graphene (tMBG). The codominance of both effects in a single system is rare. Here, utilizing lateral piezoresponse force microscopy (LPFM), we show that piezoelectric and flexoelectric effects can coexist and are equally important in twisted double bilayer graphene (tDBG), termed as the piezo-flexoelectric effect. Unlike tBLG and tMBG, distinctive two-step LPFM spatial profiles are captured across the moiré DWs of tDBG. By decomposing the LPFM signal into axisymmetric and antisymmetric components, we find that the angular dependence of both components satisfies sinusoidal relations. Quantitatively, the in-plane piezoelectric coefficient of DWs in tDBG is determined to be 0.15 pm/V by dual AC resonance tracking (DART) LPFM measurement. The conclusion is further supported by continuum mechanics simulations. Our results demonstrate that the stacking configuration serves as a powerful tuning knob for modulating the electromechanical responses of twisted van der Waals materials. Full article

Fowl adenovirus serotype 4 (FAdV-4) outbreaks have caused significant economic losses in the Chinese poultry industry since 2015. The relationships among viral structural proteins in infected hosts are relatively unknown. To explore the role of different parts of the fiber-1 protein in FAdV-4-infected hosts, we truncated fiber-1 into fiber-1-Δ1 (73–205 aa) and fiber-1-Δ2 (211–412 aa), constructed pEF1α-HA-fiber-1-Δ1 and pEF1α-HA-fiber-1-Δ2 and then transfected them into leghorn male hepatocyte (LMH) cells. After FAdV-4 infection, the roles of fiber-1-Δ1 and fiber-1-Δ2 in the replication of FAdV-4 were investigated, and transcriptome sequencing was performed. The results showed that the fiber-1-Δ1 and fiber-1-Δ2 proteins were the shaft and knob domains, respectively, of fiber-1, with molecular weights of 21.4 kDa and 29.6 kDa, respectively. The fiber-1-Δ1 and fiber-1-Δ2 proteins were mainly localized in the cytoplasm of LMH cells. Fiber-1-Δ2 has a greater ability to inhibit FAdV-4 replication than fiber-1-Δ1, and 933 differentially expressed genes (DEGs) were detected between the fiber-1-Δ1 and fiber-1-Δ2 groups. Functional analysis revealed these DEGs in a variety of biological functions and pathways, such as the phosphoinositide 3-kinase–protein kinase b (PI3K–Akt) signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, cytokine–cytokine receptor interactions, Toll-like receptors (TLRs), the Janus tyrosine kinase–signal transducer and activator of transcription (Jak–STAT) signaling pathway, the nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) signaling pathway, and other innate immune pathways. The mRNA expression levels of type I interferons (IFN-α and INF-β) and proinflammatory cytokines (IL-1β, IL-6 and IL-8) were significantly increased in cells overexpressing the fiber-1-Δ2 protein. These results demonstrate the role of the knob domain of the fiber-1 (fiber-1-Δ2) protein in FAdV-4 infection and provide a theoretical basis for analyzing the function of the fiber-1 protein of FAdV-4. Full article

Security grids consisting of High-Definition (HD) Internet of Things (IoT) cameras are gaining popularity for organizational perimeter surveillance and security monitoring. Transmitting HD video data to cloud infrastructure requires high bandwidth and more storage space than text, audio, and image data. It becomes more challenging for large-scale organizations with massive security grids to minimize cloud network bandwidth and storage costs. This paper presents an application of Machine Vision at the IoT Edge (Mez) technology in association with a novel Grid Sensing (GRS) algorithm to optimize cloud Infrastructure as a Service (IaaS) resource allocation, leading to cost minimization. Experimental results demonstrated a 31.29% reduction in bandwidth and a 22.43% reduction in storage requirements. The Mez technology offers a network latency feedback module with knobs for transforming video frames to adjust to the latency sensitivity. The association of the GRS algorithm introduces its compatibility in the IoT camera-driven security grid by automatically ranking the existing bandwidth requirements by different IoT nodes. As a result, the proposed system minimizes the entire grid’s throughput, contributing to significant cloud resource optimization. Full article

During a survey of marine biodiversity in the deep sea off northeastern Guam, two marine desmoscolecid nematodes belonging to the subgenus Tricoma were discovered. Tricoma (Tricoma) disparseta sp. nov. was described based on specimens collected from sponge and starfish habitats on a seamount at depths ranging from 1300 to 1500 m. Tricoma (Tricoma) disparseta sp. nov. is distinguished by having 59 to 62 main rings, 9 to 10 subdorsal setae, and 14 to 18 subventral setae on each side. Notable features include the differentiation in length and insertion between the subdorsal and subventral setae, as well as the amphid extending to the second or third main ring. Additionally, the spicules have a relatively small capitulum at the proximal end, while the gubernaculum is bent into a hooked shape. The specimen of T. (T.) longirostris observed in this study closely resembles previously reported specimens, characterized by 78 main rings, a long and narrow head shape, eight to nine subdorsal setae, 14 to 15 subventral setae, and a gubernaculum with a knobbed apophysis. Two Tricoma species from the Northwest Pacific Ocean are described in detail, and pictorial keys and comparative tables for species identification are provided for groups with 50 to 64 main rings. Full article

Human–machine interaction (HMI) is becoming increasingly important, especially in the automotive industry, where advancements in automated driving and driver assistance systems are key to enhancing driver safety and convenience. Among the many HMI interfaces, tactile sensing has been widely used in automotive applications as it enables instant and direct interactions with drivers. An area that remains underexplored among the tactile HMI interfaces is the application of haptic feedback to gear shifter modules. Therefore, this study investigates the design optimization of a dial gear shifter by analyzing the vibrations transmitted to the knob surface from an integrated haptic actuator. Specifically, we first tuned the mechanical properties of the haptic actuator (in terms of the resonance frequency and vibration level) in a simulation model by referring to experimental results. Next, a numerical model of a dial gear shifter was constructed, integrated with a haptic actuator, and tuned with the experimental results. The model was further optimized based on the design of the experiment and sensitivity analyses. The optimized design yielded a 24.5% improvement in the vibration level compared with the reference design, exceeding the minimum threshold (>~2.5 m/s² at 200 Hz) required for tactile sensing. The vibration enhancement (>22.x%) was also confirmed under the simulated hand-grabbing condition. This study is technically significant as it demonstrates that the haptic vibration in a dial gear shifter can be efficiently optimized through numerical analyses. This research will be used for the actual prototyping of a dial gear shifter to provide a safe driving experience for drivers. Full article