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This work reveals that standard quantization toolkits can be abused to activate a backdoor. We demonstrate that a full-precision backdoored model which does not have any backdoor effect in the presence of a trigger—as the backdoor is dormant—can be activated by (i) TensorFlow-Lite (TFLite) quantization, the only product-ready quantization framework to date, and (ii) the beta released PyTorch Mobile framework. In our experiments, we employ three popular model architectures (VGG16, ResNet18, and ResNet50), and train each across three popular datasets: MNIST, CIFAR10 and GTSRB. We ascertain that all trained float-32 backdoored models exhibit no backdoor effect even in the presence of trigger inputs. Particularly, four influential backdoor defenses are evaluated, and they fail to identify a backdoor in the float-32 models. When each of the float-32 models is converted into an int-8 format model through the standard TFLite or PyTorch Mobile framework's post-training quantization, the backdoor is activated in the quantized model, which shows a stable attack success rate close to 100% upon inputs with the trigger, while it usually behaves upon non-trigger inputs. This work highlights that a stealthy security threat occurs when an end-user utilizes the on-device post-training model quantization frameworks, informing security researchers of a cross-platform overhaul of DL models post-quantization even if these models pass security-aware front-end backdoor inspections. Significantly, we have identified Gaussian noise injection into the malicious full-precision model as an easy-to-use preventative defense against the PQ backdoor.

To improve the modeling resilience of silicon strong physical unclonable functions (PUFs), in particular, the APUFs that yield a very large number of challenge-response pairs (CRPs), a number of composited APUF variants, such as XOR-APUF, interpose-PUF (iPUF), feed-forward APUF (FF-APUF), and OAX-APUF, have been devised. When examining their security in terms of modeling resilience, utilizing multiple information sources, such as power side channel information (SCI) or/and reliability SCI, given a challenge is under-explored, which poses a challenge to their supposed modeling resilience in practice. Building upon multilabel/head deep learning (DL) model architecture, this work proposes multilabel multiside-channel-information-enabled DL attacks (MLMSAs) to thoroughly evaluate the modeling resilience of aforementioned APUF variants. Despite its simplicity, MLMSA can successfully break large-scaled APUF variants, which has not previously been achieved. More precisely, the MLMSA breaks 128-stage 30-XOR-APUF, (9, 9)- and (2, 18)-iPUFs, and $(2,2,30)$ -OAX-APUF when CRPs, power SCI, and reliability SCI are concurrently used. It breaks 128-stage 12-XOR-APUF and $(2,2,9)$ -OAX-APUF even when only the easy-to-obtain reliability SCI and CRPs are exploited. The 128-stage six-loop FF-APUF and one-loop 20-XOR-FF-APUF can be broken by simultaneously using reliability SCI and CRPs. All these attacks are normally completed within an hour with a standard personal computer. Therefore, MLMSA is a useful technique for evaluating other existing or any emerging strong PUF designs.

Hypercomplex signal and image processing extends upon conventional methods by using hypercomplex numbers in a unified framework for algebra and geometry. The special issue is divided into two parts and is focused on current advances and applications in computational signal and image processing in the hypercomplex domain. The first part offered well-rounded coverage of the field, with seven articles that focused on overviews of current research, color image processing, signal filtering, and machine learning.

Novel computational signal and image analysis methodologies based on feature-rich mathematical/computational frameworks continue to push the limits of the technological envelope, thus providing optimized and efficient solutions. Hypercomplex signal and image processing is a fascinating field that extends conventional methods by using hypercomplex numbers in a unified framework for algebra and geometry. Methodologies that are developed within this field can lead to more effective and powerful ways to analyze signals and images. Processing audio, video, images, and other types of data in the hypercomplex domain allows for more complex and intuitive representations with algebraic properties that can lead to new insights and optimizations. Applications in image processing, signal filtering, and deep learning (just to name a few) have shown that working in the hypercomplex domain can lead to more efficient and robust outcomes. As research in this field progresses and software tools become more widely available, we can expect to see increasingly sophisticated applications in many areas of research, e.g., computer vision, machine learning, and so on.

Currently, a high demand for on-device deep neural network (DNN) model deployment is limited by the large model size, computing-intensive floating-point operations (FLOPS), and intellectual property (IP) infringements (i.e., easy access to model duplication for the avoidance of license payments). One appealing solution to addressing the first two concerns is model quantization, which reduces the model size and uses integer operations commonly supported by microcontrollers (MCUs usually do not support FLOPS). To this end, a 1-bit quantized DNN model or deep binary neural network (BNN) significantly improves the memory efficiency, where each parameter in a BNN model has only 1 bit. However, BNN cannot directly provide IP protection (in particular, the functionality of the model is locked unless there is a license payment). In this article, we propose a reconfigurable BNN (RBNN) to further amplify the memory efficiency for resource-constrained Internet of Things (IoT) devices while naturally protecting the model IP. Generally, RBNN can be reconfigured on demand to achieve any one of $M$ ( $M>1$ ) distinct tasks with the same parameter set, thus only a single task determines the memory requirements. In other words, the memory utilization is improved by a factor of $M$ . Our extensive experiments corroborate that up to seven commonly used tasks ( $M=7$ , six of these tasks are image related and the last one is audio) can co-exist (the value of $M$ can be larger). These tasks with a varying number of classes have no or negligible accuracy drop-off (i.e., within 1%) on three binarized popular DNN architectures, including VGG, ResNet, and ReActNet. The tasks span across different domains, e.g., computer vision and audio domains validated herein, with the prerequisite that the model architecture can serve those cross-domain tasks. To fulfill the IP protection of an RBNN model, the reconfiguration can be controlled by both a user key and a device-unique root key generated by the intrinsic hardware fingerprint (e.g., SRAM memory power-up pattern). By doing so, an RBNN model can only be used per paid user per authorized device, thus benefiting both the user and the model provider. The source code is released at https://github.com/LearningMaker/RBNN.

Police distributed a photograph, but no one came forward to claim the body. Eyewitnesses reported having seen the man, whom the newspapers dubbed the Somerton Man and who appeared to be in his early 40s, lying on the beach earlier, perhaps at one point moving his arm, and had concluded that he was drunk. The place of death led the police to treat the case as a suicide, despite the apparent lack of a suicide note. The presence of blood in the stomach, a common consequence of poisoning, was noted at the autopsy. Several chemical assays failed to identify any poison; granted, the methods of the day were not up to the task.

Digital realization of neuron models, especially implementation on a field programmable gate array (FPGA), is one of the key objectives of neuromorphic research, because the effective hardware realization of the biological neural networks plays a crucial role in implementing the behaviors of the brain for future applications. In this paper, a hybrid FitzHugh Nagumo-Morris Lecar (FNML) neuron model with electromagnetic flux coupling is considered, and two multiplierless piecewise linear (PWL) models, which have similar behaviors to the biological neuron, are presented. A comparison between digital implementation results of the original FNML and PWL models illustrates that, the PWL1 model provides a 65% speed-up with an overall saving (in FPGA resources) of 66.2%, and the PWL2 model yields a 71% speed-up with an overall saving of 78.2%.

A careful DNA analysis revealed a few differences in the DNA between the brothers. DerekAbbott University of Adelaide, Australia It is possible to determine the genetic difference between identical twins if you target single nucleotide polymorphisms (SNPs) in their DNA rather than the short tandem repeats (STRs) that are used for standard DNA tests. SNP analysis is much more finegrained, as each SNP represents a difference in a single nucleotide, the building block of DNA. [Extracted from the article]

Background: The protein product of the BRCA2 gene mediates repair of double-strand breaks in DNA. Because a number of cancer therapies exert cytotoxic effects via the initiation of double-strand breaks, cancers comprised of cells carrying BRCA2 gene mutations may be more amenable to treatment with agents that cause such breaks. Methods: We identified a human pancreatic adenocarcinoma cell line lacking one copy of the BRCA2 gene and containing a mutation (6174delT) in the remaining copy. In vitro and in vivo experiments were conducted with this cell line and with other carcinoma cell lines matched for similar genetic mutations, similar differentiation status, and/or similar carcinoma type to examine double-strand break repair, sensitivity to drugs that induce double-strand breaks, and radiation sensitivity. Results: BRCA2-defective cells were unable to repair the double-strand DNA breaks induced by ionizing radiation. These cells were also markedly sensitive to mitoxantrone, amsacrine, and etoposide (drugs that induce double-strand breaks) (two-sided P = .002) and to ionizing radiation (two-sided P = .001). Introduction of antisense BRCA2 deoxyribonucleotides into cells possessing normal BRCA2 function led to increased sensitivity to mitoxantrone (two-sided P = .008). Tumors formed by injection of BRCA2-defective cells into nude mice were highly sensitive ([is greater than] 90% tumor size reduction, two-sided P = .002) to both ionizing radiation and mitoxantrone when compared with tumors exhibiting normal BRCA2 function. Histologic analysis of irradiated BRCA2-defective tumors showed a large degree of necrosis compared with that observed for control tumors possessing normal BRCA2 function. Conclusion: BRCA2-defective cancer cells are highly sensitive to agents that cause double-strand breaks in DNA. [J Natl Cancer Inst 1998;90: 978-85]

The reversible insulating-to-conducting phase transition (ICPT) of vanadium dioxide (VO2) makes it a versatile candidate for the implementation of integrated optical devices. In this paper, a bi-functional in-line optical device based on a four-layer stack of PMMA/graphene/VO2/graphene deposited on a side-polished fiber (SPF) is proposed. The structure can be employed as an ultra-compact TE modulator or a TM-pass polarizer, operating at 1.55 μm. We show that the ICPT characteristic can be used for polarization-selective mode shaping (PSMS) to manipulate orthogonal modes separately. On the one hand, as an optical modulator, the PSMS is used to modify mode profiles so that the TE mode attenuation is maximized in the off-state (and IL is minimized in the on-state), while the power carried by the TM mode remains unchanged. As a result, a TE modulator with an ultrahigh extinction ratio (ER) of about ER = 165 dB/mm and a very low insertion loss (IL) of IL = 2.3 dB/mm is achieved. On the other hand, the structure can act as a TM-pass polarizer featuring an extremely high polarization extinction ratio (PER) of about PER = 164 dB/mm and a low TM insertion of IL = 3.86 dB/mm. The three-dimensional heat transfer calculation for the ICPT process reveals that the response time of the modulator is in the order of few nanoseconds. Moreover, the required bias voltage of the proposed device is calculated to be as low as 1.1 V. The presented results are promising a key step towards the realization of an integrated high-performance in-line modulator/polarizer.

In this article, a hollow core antiresonant photonic crystal fiber is analyzed for terahertz applications. A numerical analysis of the proposed fiber is first carried out to minimize coupling between the core and cladding modes. The modeling of the scaled-up and inhibited coupling fiber is carried out by means of a finite element method, which is then demonstrated using a Zeonex filament fiber, fabricated by fused deposition modeling of 3-D printing technology. The simulation is carried out to analyze both the transmission and possibility of refractometric sensing, whereas the experimental analysis is carried out using terahertz time-domain spectroscopy, and supports our numerical findings, illustrating how the proposed fibers can be used for low-loss transmission of terahertz waves. The simplicity of the proposed fiber structures facilitates fabrication for a number of different transmission and sensing applications in the terahertz range.

A mechanism for the cellular effects of the gas H2S, is the oxidative modification of protein cysteine residues. We developed a quantitative proteomics tool to profile protein S-persulfidation in cellular proteomes. We discovered a Redox Thiol Switch of S-glutathioinylation to S- persulfidation of proteins, among them enzymes in cellular energy metabolism. This work allows identification of redox regulation of cysteine residues of proteins in physiological and disease states and can assist design of therapeutics for diseases such cancer and diabetes.

Resisting and tolerating microbes are alternative strategies to survive infection, but little is known about the evolutionary mechanisms controlling this balance. Here genomic analyses of anatomically modern humans, extinct Denisovan hominins and mice revealed a TNFAIP3allelic series with alterations in the encoded immune response inhibitor A20. Each TNFAIP3allele encoded substitutions at non-catalytic residues of the ubiquitin protease OTU domain that diminished IκB kinase-dependent phosphorylation and activation of A20. Two TNFAIP3alleles encoding A20 proteins with partial phosphorylation deficits seemed to be beneficial by increasing immunity without causing spontaneous inflammatory disease: A20 T108A;I207L, originating in Denisovans and introgressed in modern humans throughout Oceania, and A20 I325N, from an N-ethyl-N-nitrosourea (ENU)-mutagenized mouse strain. By contrast, a rare human TNFAIP3allele encoding an A20 protein with 95% loss of phosphorylation, C243Y, caused spontaneous inflammatory disease in humans and mice. Analysis of the partial-phosphorylation A20 I325N allele in mice revealed diminished tolerance of bacterial lipopolysaccharide and poxvirus inoculation as tradeoffs for enhanced immunity.

We propose and numerically characterize an exposed-core photonic crystal fiber for biosensing applications. Surface plasmons are excited within gold (Au) strips, and titanium dioxide is employed to support adhesion of Au with glass. In consideration of ease of fabrication, only four air holes are used to simplify the sensor structure. Simulation results show an improved wavelength and amplitude sensitivity of 34,000 nm/RIU and 1170  RIU^−1, respectively, that comes with a low confinement loss of 0.79 dB/cm. Results also indicate a low full width at half-maximum that contributes to high figure of merit of 310.

As technology continues to advance, the development of novel sensing systems opens new possibilities for low-cost, practical biosensing applications. In this Letter, we demonstrate a localized surface plasmon resonance system that combines both wave-guiding and plasmonic resonance sensing with a single microstructured polymeric structure. Characterizing the sensor using the finite element method simulation shows, to the best of our knowledge, a record wavelength sensitivity (WS) of 111000 nm/refractive index unit (RIU), high amplitude sensitivity (AS) of 2050  RIU^−1, high sensor resolution and limit of detection of 9×10^−7 RIU and 8.12×10^−12  RIU^2/nm, respectively. Furthermore, these sensors have the capability to detect an analyte within the refractive index range of 1.33–1.43 in the visible to mid-IR, therefore being potentially suitable for applications in biomolecular and chemical analyte detection.

Ethanol is widely used in chemical industrial processes as well as in the food and beverage industry. Therefore, methods of detecting alcohol must be accurate, precise, and reliable. In this content, a novel Zeonex-based photonic crystal fiber (PCF) has been modeled and analyzed for ethanol detection in terahertz frequency range. A finite-element-method-based simulation of the PCF sensor shows a high relative sensitivity of 68.87% with negligible confinement loss of 7.79×10^−12  cm^−1 at 1 THz frequency and x-polarization mode. Moreover, the core power fraction, birefringence, effective material loss, dispersion, and numerical aperture are also determined in the terahertz frequency range. Owing to the simple fiber structure, existing fabrication methods are feasible. With the outstanding waveguiding properties, the proposed sensor can potentially be used in ethanol detection, as well as polarization-preserving applications of terahertz waves.

We report on the design, in-depth analysis, and characterization of a novel elliptical array shaped core rectangular shaped cladded photonic crystal fiber (PCF) for multichannel communication and polarization maintaining applications of terahertz waves. The asymmetrical structure of air holes in both core and cladding results in increased birefringence, while a compact geometry and different cladding air hole size makes the dispersion characteristic flat. The modal characteristics of the PCF are calculated using a finite element method. The simulated results show a near-zero dispersion flattened property of ±0.02  ps/THz/cm, high birefringence of 0.063, low effective material loss of 0.06  cm^−1, and negligible confinement loss of 5.45×10^−13  cm^−1 in the terahertz frequency range. Additionally, the core power fraction, effective area, physical attributes, and potential fabrication possibilities of the fiber are discussed.

Ubiquitylation of the TNFR1 signalling complex (TNF-RSC) controls the activation of RIPK1, a kinase critically involved in mediating multiple TNFα-activated deleterious events. However, the molecular mechanism that coordinates different types of ubiquitylation modification to regulate the activation of RIPK1 kinase remains unclear. Here, we show that ABIN-1/NAF-1, a ubiquitin-binding protein, is recruited rapidly into TNF-RSC in a manner dependent on the Met1-ubiquitylating complex LUBAC to regulate the recruitment of A20 to control Lys63 deubiquitylation of RIPK1. ABIN-1 deficiency reduces the recruitment of A20 and licenses cells to die through necroptosis by promoting Lys63 ubiquitylation and activation of RIPK1 with TNFα stimulation under conditions that would otherwise exclusively activate apoptosis in wild-type cells. Inhibition of RIPK1 kinase and RIPK3 deficiency block the embryonic lethality of Abin-1–/–mice. We propose that ABIN-1 provides a critical link between Met1 ubiquitylation mediated by the LUBAC complex and Lys63 deubiquitylation by phospho-A20 to modulate the activation of RIPK1. Dziedzic et al. show that the ubiquitin-binding protein ABIN-1 is recruited into TNFR1 signalling complex in a manner dependent on Met1 -ubiquitinating complex LUBAC to regulate K63 de-ubiquitination to activate RIPK1.

Wireless sensors are increasingly penetrating every domain of our lives through integration with Internet of Things, e.g., such devices are widely incorporated into smart buildings and for monitoring critical industrial infrastructure. Sensing, collecting and communication of sensor data, however, are under threat from various attacks due to the difficulty in implementing proper protection mechanisms and limited computational resources available in these cost-sensitive devices. This paper expands on recent research on physical unclonable function (PUF) sensors to secure sensing by taking the advantage of inherent physical randomness. In particular, PUF unreliability originates from its sensitivity to ambient parameter variations that is usually undesirable for elementary PUF applications—such as authentication and key generation—is exploited to guarantee the veracity of the sensed value. In this paper, a PUF naturally acting as a sensor or a PUF explicitly integrated with a sensor is called a PUF sensor. Security of sensing in a PUF sensor is attributed to the natural merging of cryptography and sensing to eschew the need for a standalone crypto module. Thus, the PUF sensor is appealing for low-cost applications. To obtain the sensed value, we develop an authenticated sensing protocol that is robust against eavesdropping, also capable of detecting man-in-the-middle manipulation of the sensed value. Compared to initial investigations of PUF sensors, we avoid the stringent requirements of a strong PUF. We validate the feasibility of the proposed authenticated sensing protocol based on an experimental implementation of a ring oscillator PUF sensor. To improve the sensing capability, we present an efficient approach to select sensitive responses and only employ them for sensing. Significantly improved efficacy is validated through comprehensive experimental results. [ABSTRACT FROM PUBLISHER]

We demonstrate a terahertz flat lens based on tri-layer metasurfaces allowing for broadband linear polarization conversion, where the phase can be tuned through a full 2π range by tailoring the geometry of the subwavelength resonators. The lens functionality is realized by arranging these resonators to create a parabolic spatial phase profile. The fabricated 124-μm-thick device is characterized by scanning the beam profile and cross section, showing diffraction-limited focusing and ∼68% overall efficiency at the operating frequency of 400 GHz. This device has potential for applications in terahertz imaging and communications, as well as beam control in general.

In this paper, we present the design and analysis of a novel hybrid porous core octagonal lattice photonic crystal fiber for terahertz (THz) wave guidance. The numerical analysis is performed using a full-vector finite element method (FEM) that shows that 80% of bulk absorption material loss of cyclic olefin copolymer (COC), commercially known as TOPAS can be reduced at a core diameter of 350 μm. The obtained effective material loss (EML) is as low as 0.04  cm^−1 at an operating frequency of 1 THz with a core porosity of 81%. Moreover, the proposed photonic crystal fiber also exhibits comparatively higher core power fraction, lower confinement loss, higher effective mode area, and an ultra-flattened dispersion profile with single mode propagation. This fiber can be readily fabricated using capillary stacking and sol-gel techniques, and it can be used for broadband terahertz applications.

This paper presents an approach to classification of substances based on their terahertz spectra. We use geometric algebra to provide a concise mathematical means for attacking the classification problem in a coordinate-free form. For the first time, this allows us to perform classification independently of dispersion and, hence, independently of the transmission path length through the sample. Finally, we validate the approach with experimental data. In principle, the coordinate-free transformation can be extended to all types of pulsed signals, such as pulsed microwaves or even acoustic signals in the field of seismology. Our source code for classification based on geometric algebra is publicly available at: https://github.com/swuzhousl/Shengling-zhou/blob/geometric-algebra-classifier/GAclassifier/.

Although a clear association has been established between IL-33 and inflammatory bowel disease, mechanistic studies to date, primarily using acute murine models of colitis, have yielded contradicting results, demonstrating both pathogenic and protective roles. We used a well-characterized, spontaneous model of inflammatory bowel disease [ie, SAMP1/YitFc (SAMP) mice] to investigate the role of IL-33 during chronic intestinal inflammation. Our results showed marked eosinophil infiltration into the gut mucosa with increased levels of eotaxins and type 2 helper T-cell (Th2) cytokines as disease progressed and became more severe, which could be reversed upon either eosinophil depletion or blockade of IL-33 signaling. Exogenous IL-33 administration recapitulated these effects in ilea of uninflamed (parental) control AKR/J mice. Human data supported these findings, showing colocalization and up-regulation of IL-33 and eosinophils in the colonic mucosa of inflammatory bowel disease patients versus noninflamed controls. Finally, colonization of commensal flora by fecal material transplantation into germ-free SAMP and the presence of the gut microbiome induced IL-33, subsequent eosinophil infiltration, and mounting of Th2 immune responses, leading to exacerbation of chronic intestinal inflammation characteristic of SAMP mice. These data demonstrate a pathogenic role for IL-33–mediated eosinophilia and activation of Th2 immunity in chronic intestinal inflammation that is dependent on the gut microbiome. Targeting IL-33 may represent a novel therapeutic approach to treat patients with inflammatory bowel disease.

Pyroptosis is a mechanism of programmed, necrotic cell death mediated by gasdermins, a family of pore-forming proteins. Caspase-1 activates gasdermin D (GSDMD) under inflammatory conditions, whereas caspase-3 activates GSDME under apoptotic conditions, such as those induced by chemotherapy. These pathways are thought to be separate. However, we found that they are part of an integrated network of gatekeepers that enables pyroptotic cell death. We observed that GSDMD was the primary pyroptotic mediator in cultured blood cells in response to doxorubicin and etoposide, two common chemotherapies for hematopoietic malignancies. Upon treatment, the channel protein pannexin-1 (PANX1), which is stimulated by the initiation of apoptosis, increased membrane permeability to induce K+efflux-driven activation of the NLRP3 inflammasome and GSDMD. However, either PANX1 or GSDME could also be the primary mediator of chemotherapy-induced pyroptosis when present at higher amounts. The most abundant pore-forming protein in acute myeloid leukemias from patients predicted the cell death pathway in response to chemotherapy. This interconnected network, a multistep switch that converts apoptosis to pyroptosis, could be clinically titratated to modulate cell death with regard to antitumor immunity or tumor lysis syndrome in patients.

The problems facing the Kent Architecture Centre reflect the challenges regional design centres face (News April 13). In an increasingly centralised era of design policy-making--via the ODPM--it's vital to support [...]

Partially unfolded proteins can self-assemble to form insoluble protein fibrils with diameters in the nanometer scale. These are of particular interest in healthcare because of their presence in diseases such as Alzheimer's disease and type-II diabetes. Tracking the formation of protein fibrils has far-reaching benefits for research into treatment of these diseases. Current optical techniques that track fibrillation either limit samples to their aqueous form or are slow to conduct. We present in this work terahertz and far-infrared (FIR) spectroscopic analyses of fibrils made from three globular proteins. We track the fibrillation process over an extended period to show that mature fibrils have distinct absorbance properties that are not solely caused by scattering. Results also show that FIR spectroscopy can provide information about fibril structures that is otherwise missed by optical techniques.

In this paper, a second-order frequency selective surface (FSS) made of miniaturized elements is proposed and designed for terahertz applications. The FSS is composed of two layers of metallic arrays separated from each other by a polymer dielectric spacer. The unit cells on the front and back layers are smaller than $\lambda _{0}/5$ , where $\lambda _{0}$ is the free space wavelength. The operation principle of the proposed FSS is described through a circuit model, and a synthesis procedure is presented for designing a desired filtering response. A prototype of the FSS is synthesized to operate at a center frequency of 0.42 THz with 45% fractional bandwidth. The designed FSS is fabricated by using microfabrication process. The performance is evaluated by using terahertz time-domain spectroscopy. Measurement results show a low sensitivity of the FSS response to oblique angles of incidence for both of the TE and TM polarizations.

Loss of NF-κB signaling causes immunodeficiency, whereas inhibition of NF-κB can be efficacious in treating chronic inflammatory disease. Inflammatory NF-κB signaling must therefore be tightly regulated, and although many mechanisms to downregulate NF-κB have been elucidated, there have only been limited studies demonstrating positive feedforward regulation of NF-κB signaling. In this work, we use a bioinformatic and proteomic approach to discover that the IKK family of proteins can phosphorylate the E3 ubiquitin ligase ITCH, a critical downregulator of TNF-mediated NF-κB activation. Phosphorylation of ITCH by IKKs leads to impaired ITCH E3 ubiquitin ligase activity and prolongs NF-κB signaling and pro-inflammatory cytokine release. Since genetic loss of ITCH mirrors IKK-induced ITCH phosphorylation, we further show that the ITCH−/−mouse’s spontaneous lung inflammation and subsequent death can be delayed when TNF signaling is genetically deleted. This work identifies a new positive feedforward regulation of NF-κB activation that drives inflammatory disease.

Modeling and implementation of biological neural networks are significant objectives of the neuromorphic research field. In this field, neuronal synchronization plays a significant role in the processing of biological information. This paper presents a set of piecewise linear (MLPWL1) and multiplierless piecewise linear (MLPWL2) neuron models, which mimic behaviors of different types of neurons, similar to the biological behavior of conductance-based neurons. Both simulations and a low-cost digital implementation are carried out to compare the proposed models to a single ML neuron and two coupled ML neurons, demonstrating the required range of dynamics with a more efficient implementation. Hardware implementations on a field-programmable gate array (FPGA) show that the modified models mimic the biological behavior of different types of neurons with higher performance and significantly lower implementation costs compared to the previous realizations of the ML model. The mean normalized root mean square errors (NRMSEs) of the MLPWL1 and MLPWL2 models are 3.70% and 4.89%, respectively, as compared to the original ML model. [ABSTRACT FROM AUTHOR]

The mammalian auditory system is able to process sounds over an extraordinarily large dynamic range, which makes it possible to extract information from very small changes both in sound amplitude and frequency. Evidently, response of the cochlea is essentially nonlinear, where it operates within Hopf bifurcation boundaries to maximize tuning and amplification. This paper presents a set of piecewise linear (PWL) and multiplierless piecewise linear (MLPWL1 and MLPWL2) active cochlear models, which mimic a range of behaviors, similar to the biological cochlea. These proposed models show similar dynamical characteristics of the Hopf equation for the active nonlinear artificial cochlea. Accordingly, a compact model structure is proposed upon which a 2-D cochlea is developed. The proposed models are investigated, in terms of their digital realization and hardware cost, targeting large scale implementation. Hardware synthesis and physical implementation on a FPGA show that the proposed models can reproduce precise active cochlea behaviors with higher performance and considerably lower computational costs in comparison with the original model. Results indicate that the MLPWL1 model has a lower computational overhead, precision, and hardware cost, while the PWL model has a higher precision and dynamically tracks the original model. On the other hand, the MLPWL2 model outperforms the others in terms of accuracy, dynamical tracking of the original model and implementation cost. The gain variations of the original, PWL, MLPWL1, and MLPWL2 models are 230, 100, 105, and 230 dB, respectively. The mean normalized root mean square errors (NRMSEs) of the PWL, MLPWL1, and MLPWL2 models are 0.11%, 11.97%, and 0.34%, respectively, as compared to the original cochlear model. [ABSTRACT FROM AUTHOR]

Derek Abbott, Sittingbourne, Kent Folkestone's proposed high-density beach housing provokes both comment and pertinent questions. Although deep-bore piles etc may achieve structural stability, what protection will lower-floor residents have against [...]

Apropos the insurance problems with housing in the Thames Gateway (News February 13), surely a radical review of the whole Thames Gateway project is long overdue. Enshrined by both Tory [...]

This paper presents a modified astrocyte model that allows a convenient digital implementation. This model is aimed at reproducing relevant biological astrocyte behaviors, which provide appropriate feedback control in regulating neuronal activities in the central nervous system. Accordingly, we investigate the feasibility of a digital implementation for a single astrocyte and a biological neuronal network model constructed by connecting two limit-cycle Hopf oscillators to an implementation of the proposed astrocyte model using oscillator–astrocyte interactions with weak coupling. Hardware synthesis, physical implementation on field-programmable gate array, and theoretical analysis confirm that the proposed astrocyte model, with considerably low hardware overhead, can mimic biological astrocyte model behaviors, resulting in desynchronization of the two coupled limit-cycle oscillators. [ABSTRACT FROM AUTHOR]

Review on the role that the NOD2:RIP2 complex plays in inflammatory disease, with an emphasis on its inhibition as a future drug target. The role of NOD2 and RIP2 in inflammatory disease has been paradoxical. Whereas loss‐of‐function NOD2 polymorphisms cause CD, a granulomatous disease of the gastrointestinal tract, gain‐of‐function mutations cause EOS—a granulomatous disease primarily affecting the skin, joints, and eyes. Thus, gain‐of‐function mutations and loss‐of‐function polymorphisms cause granulomatous inflammatory disease, only in different anatomic locations. The situation is complicated further by the fact that WT NOD2 and WT RIP2 activity has been implicated in diseases such as asthma, inflammatory arthritis and MS. This article reviews the role that the NOD2:RIP2 complex plays in inflammatory disease, with an emphasis on the inhibition of this signaling pathway as a novel pharmaceutical target in inflammatory disease.

This paper is focused on the application of split ring resonators (SRRs) to the design of compact bandpass filters for terahertz surface waves on single-wire waveguides, the so-called planar Goubau lines (PGLs). Through equivalent circuit models, electromagnetic simulations, and experiments, it is shown that, while a pair of SRRs coupled to a PGL inhibits the propagation of surface waves along the line, introducing a capacitive gap to the PGL switches the bandstop behavior to a bandpass behavior. In order to highlight the potential application of the proposed structure to the design of practical higher order terahertz bandpass filters, two types of compact bandpass filters are designed and fabricated: 1) third-order periodic bandpass filters based on SRR/gap-loaded PGL and 2) coupled-resonator bandpass filters. It is shown that, while the frequency response of the both filter types can be controlled by altering the physical dimensions of the structure, a wider bandwidth can be achieved from the coupled-resonator filters. The design concept and simulation results are validated through experiments.

While the I kappa kinase (IKK) scaffolding protein NF-κB essential modulator (NEMO) binds to polyubiquitin chains to transmit inflammatory signals, NEMO itself is also ubiquitinated in response to a variety of inflammatory agonists. Although there have been hints that polyubiquitination of NEMO is essential for avoiding inflammatory disorders, the in vivo physiologic role of NEMO ubiquitination is unknown. In this work, we knock in a NEMOallele in which two major inflammatory agonist-induced ubiquitination sites cannot be ubiquitinated. We show that mice with a nonubiquitinatable NEMOallele display embryonic lethality. Heterozygous females develop inflammatory skin lesions, decreased B cell numbers, and hypercellular spleens. Embryonic lethality can be complemented by mating onto a TNFR1−/−background, at the cost of severe steatohepatitis and early mortality, and we also show that NEMO ubiquitination is required for optimal innate immune signaling responses. These findings suggest that NEMO ubiquitination is crucial for NF-κB activity in response to innate immune agonists.

Could nuclear power be rapidly expanded on a global scale? There are a number of practical limiting factors, including site availability and acceptability, nuclear waste disposal issues, and the risks of accidents and proliferation. But there are also a variety of resource limitations. One particular resource limitation that has not been clearly articulated in the nuclear debate thus far is the availability of the relatively scarce metals used in the construction of the reactor vessel and core. While this scarcity is not of immediate concern, it would present a hard limit to the ultimate expansion of nuclear power. This limit appears to be a harder one than the supply of uranium fuel. An increased demand for rare metals—such as hafnium, beryllium, zirconium, and niobium, for example—would also increase their price volatility and limit their rate of uptake in nuclear power stations. Metals used in the nuclear vessel eventually become radioactive and, on decommissioning, those with long half-lives cannot be recycled on timescales useful to human civilization. Thus, a large-scale expansion of nuclear power would reduce “elemental diversity” by depleting the world’s supply of some elements and making them unavailable to future generations.

We present the hygroscopicity of polymer and copolymer materials in the low terahertz (THz) frequency range using a linear absorption model. We identify COC 6013 and COC 5013 as optimal THz window materials, possessing both low hygroscopicity and high transmission in the THz regime. The correct choice of window material is of significance for transmission THz spectroscopy and of particular interest for THz liquid spectroscopy.

To determine OSA-related changes in variability of QT interval duration and in heart rate variability (HRV), and to evaluate the relationship of these parameters to disease severity.

Measurements of optical constants at terahertz—or T-ray—frequencies have been performed extensively using terahertz time-domain spectroscopy (THz-TDS). Spectrometers, together with physical models explaining the interaction between a sample and T-ray radiation, are progressively being developed. Nevertheless, measurement errors in the optical constants, so far, have not been systematically analyzed. This situation calls for a comprehensive analysis of measurement uncertainty in THz-TDS systems. The sources of error existing in a terahertz spectrometer and throughout the parameter estimation process are identified. The analysis herein quantifies the impact of each source on the output optical constants. The resulting analytical model is evaluated against experimental THz-TDS data.

Abstract: Fuel ethanol production from plant biomass hydrolysates by Saccharomyces cerevisiae is of great economic and environmental significance. This paper reviews the current status with respect to alcoholic fermentation of the main plant biomass-derived monosaccharides by this yeast. Wild-type S. cerevisiae strains readily ferment glucose, mannose and fructose via the Embden–Meyerhof pathway of glycolysis, while galactose is fermented via the Leloir pathway. Construction of yeast strains that efficiently convert other potentially fermentable substrates in plant biomass hydrolysates into ethanol is a major challenge in metabolic engineering. The most abundant of these compounds is xylose. Recent metabolic and evolutionary engineering studies on S. cerevisiae strains that express a fungal xylose isomerase have enabled the rapid and efficient␣anaerobic fermentation of this pentose. l-Arabinose fermentation, based on the expression of a prokaryotic pathway in S. cerevisiae, has also been established, but needs further optimization before it can be considered for industrial implementation. In addition to these already investigated strategies, possible approaches for metabolic engineering of galacturonic acid and rhamnose fermentation by S. cerevisiae are discussed. An emerging and major challenge is to achieve the rapid transition from proof-of-principle experiments under ‘academic’ conditions (synthetic media, single substrates or simple substrate mixtures, absence of toxic inhibitors) towards efficient conversion of complex industrial substrate mixtures that contain synergistically acting inhibitors.

Scaling analysis of heart rate time series has emerged as a useful tool for the assessment of autonomic cardiac control. We investigate the heart rate time series of ten athletes (five males and five females), by applying detrended fluctuation analysis (DFA). High resolution ECGs are recorded under standardized resting conditions over 30 min and subsequently heart rate time series are extracted and artifacts filtered. We find three distinct regions of scale invariance, which correspond to the well-known VLF, LF and HF bands in the power spectra of heart rate variability. The scaling exponents ? are ?HF: 1.15 [0.96-1.22], ?LF: 0.68 [0.57-0.84], ?VLF: 0.83[0.82-0.99], p< 10?5). In conclusion, DFA scaling exponents of heart rate time series should be fitted to the VLF, LF and HF ranges, respectively.

We study a general 2 × 2 symmetric entangled quantum game. When one player has access only to classical strategies, while the other can use the full range of quantum strategies, there are ‘miracle’ moves available to the quantum player that can direct the game towards the quantum player's preferred result regardless of the classical player's strategy. The advantage pertaining to the quantum player is dependent on the degree of entanglement. Below a critical level, dependent on the pay–offs in the game, the miracle move is of no advantage.

This review is an introduction to solid state quantum computation and its applications for engineers with little or no quantum physics background. Some current classical limits of computation are briefly described, and examples of quantum algorithms are presented to show why quantum computation may be a way of overcoming these limitations. In this review, we have focused on one quantum computer proposal, the Kane proposal. It is a solid-state proposal in silicon doped with 31P atoms. However, significant technological advances will be required in smart electronics, nanotechnology and solid state devices if we are to see a useful solid state quantum computer.

Multi-beam approaches using beamforming antenna array architectures have been identified as one solution for overcoming the limited fields-of-view provided by highly directional mm-wave sensors. They are also ideal front end systems for collision avoidance devices. Rotman lenses offer a compact, rugged and reliable alternative to electronically scanned antenna technologies but architectures that operate at frequencies <20GHzperform poorly at higher frequencies on account of greater losses and dispersion. This paper outlines the design process for providing Rotman-based lenses, examining various levels of simulation that are needed for designs that function at K and W-band frequencies. The impact of using microstrip structures is demonstrated. A key advantage of our approach is that it is compatible with monolithic fabrication, leading the way towards smart collision avoidance sensors.

We introduce Parrondo's paradox that involves games of chance. We consider two fair games, A and B, both of which can be made to lose by changing a biasing parameter. An apparently paradoxical situation arises when the two games are played in any alternating order. A winning expectation is produced, even though both games A and B are losing when we play them individually. We develop an explanation of the phenomenon in terms of a Brownian ratchet model, and also develop a mathematical analysis using discrete–time Markov chains. From the analysis we investigate the range of parameter values for which Parrondo's paradox exists.

Finkel-Biskis-Reilly (FBR) osteosarcoma virus v-Fos causes tumors of mesenchymal origin, including osteosarcomas, rhabdomyosarcomas, chondrosarcomas, and liposarcomas. Because the cell of origin in all these tumors is a pluripotent mesenchymal cell, the variety of tumors seen in mice which express FBR v-Fos implies that FBR v-Fos inhibits multiple differentiation pathways. To study the mechanism of FBR v-Fos' inhibition of mesenchymal differentiation, we utilized an in vitromodel of adipocyte differentiation. We show by both morphological and biochemical means that FBR v-Fos inhibits adipocyte differentiation in vitro. This inhibition is due to FBR v-Fos' inhibition of the growth arrest characteristic of terminal differentiation and FBR v-Fos' inhibition of the expression and activity of a key regulator of this growth arrest, C/EBPα. The in vitroinhibition of adipogenesis by FBR v-Fos has in vivosignificance as immunostaining of FBR v-Fos-induced tumors shows no CCAAT/enhancer binding protein (EBP)-α expression. These data implicate C/EBPα as a protein involved in the generation of liposarcomas.

DNA damage is recognized as a central component of carcinogenesis. DNA-damaging agents activate a number of signal transduction pathways that lead to repair of the DNA, apoptosis, or cell cycle arrest. It is reasoned that a cell deficient in DNA repair is more likely to acquire other cancer-promoting mutations. Despite the recent interest in the link between DNA damage and carcinogenesis, retroviral oncogenes have not yet been shown to affect the DNA damage-signaling pathway. In this report, we show that Finkel-Biskis-Reilly mouse osteosarcoma virus (FBR) v-fos, the retroviral homologue of the c-fosproto-oncogene, inhibits the cellular response to ionizing radiation. Cells that express FBR v-Fos show a decreased ability to repair DNA damage caused by ionizing radiation, and these cells show decreased survival in response to ionizing radiation. In addition, FBR v-Fos inhibits DNA-dependent protein kinase, a kinase specifically activated upon exposure to ionizing radiation. These effects were specific to ionizing radiation, as no effect of FBR v-Fos on the UV light signaling pathway was seen. Last, these effects were dependent on a lipid modification required for FBR v-Fos tumorigenesis, that of myristoylation of FBR v-Fos. A non-myristoylated mutant FBR v-Fos caused none of these effects. This study suggests that a retroviral oncogene can lead to an increased genomic instability, which can ultimately increase the carcinogenic potential of a cell.

Cellular inflammasome activation causes caspase-1 cleavage of the pore-forming protein gasdermin D (GSDMD) with subsequent pyroptotic cell death and cytokine release. Here, we clarify the ambiguous role of the related family member gasdermin E (GSDME) in this process. Inflammasome stimulation in GSDMD-deficient cells led to apoptotic caspase cleavage of GSDME. Endogenous GSDME activation permitted sublytic, continuous interleukin-1β (IL-1β) release and membrane leakage, even in GSDMD-sufficient cells, whereas ectopic expression led to pyroptosis with GSDME oligomerization and complete liberation of IL-1β akin to GSDMD pyroptosis. We find that NLRP3 and NLRP1 inflammasomes ultimately rely concurrently on both gasdermins for IL-1β processing and release separately from their ability to induce cell lysis. Our study thus identifies GSDME as a conduit for IL-1β release independent of its ability to cause cell death.