Enhancing the Electricity Generation and Nitrate Removal of Microbial Fuel Cells With a Novel Denitrifying Exoelectrogenic Strain EB-1

Microbial fuel cells (MFCs) have been tentatively applied for wastewater treatment, but the presence of nitrogen, especially nitrate, induces performance instability by changing the composition of functional biofilms. A novel denitrifying exoelectrogenic strain EB-1, capable of simultaneous denitrification and electricity generation and affiliated with Mycobacterium sp., was isolated from the anodic biofilm of MFCs fed with nitrate containing medium. Polarization curves and cyclic voltammetry showed that strain EB-1 could generate electricity through a direct electron transfer mechanism with a maximum power density of 0.84 ± 0.05 W m−2. Additionally, anodic denitrification, as a concurrent metabolism, was demonstrated with an efficient removal rate of 0.66 ± 0.01 kg N m−3 d−1 at a COD/N ratio of 3.5 ± 0.3. Importantly, voltage output was not negatively influenced by nitrate, indicating that the concurrent process of nitrate removal and electricity generation was a limitation of the electron donor rather than an inhibition of the system. Furthermore, various organic materials were successfully utilized as anode donors for strain EB-1, and demonstrated the exciting performances in terms of simultaneous denitrification and electricity generation. Mycobacterium sp. EB-1 thus expands the diversity of exoelectrogens and contributes to the potential applications of MFC for simultaneous energy recovery and wastewater treatment

Low Correlation Interference OFDM-NLFM Waveform Design for MIMO Radar Based on Alternating Optimization.

The OFDM chirp signal is suitable for MIMO radar applications due to its large time-bandwidth product, constant time-domain, and almost constant frequency-domain modulus. Particularly, by introducing the time-frequency structure of the non-linear frequency modulation (NLFM) signal into the design of an OFDM chirp waveform, a new OFDM-NLFM waveform with low peak auto-correlation sidelobe ratio (PASR) and peak cross-correlation ratio (PCCR) is obtained. IN-OFDM is the OFDM-NLFM waveform set currently with the lowest PASR and PCCR. Here we construct the optimization model of the OFDM-NLFM waveform set with the objective function being the maximum of the PASR and PCCR. Further, this paper proposes an OFDM-NLFM waveform set design algorithm inspired by alternating optimization. We implement the proposed algorithm by the alternate execution of two sub-algorithms. First, we keep both the sub-chirp sequence code matrix and sub-chirp rate plus and minus (PM) code matrix unchanged and use the particle swarm optimization (PSO) algorithm to obtain the optimal parameters of the NLFM signal's time-frequency structure (NLFM parameters). Next, we keep current optimal NLFM parameters unchanged, and optimize the sub-chirp sequence code matrix and sub-chirp rate PM code matrix using the block coordinate descent (BCD) algorithm. The above two sub-algorithms are alternately executed until the objective function converges to the optimal solution. The results show that the PASR and PCCR of the obtained OFDM-NLFM waveform set are about 5 dB lower than that of the IN-OFDM

Product quality control strategy development for non-mAb complex modalities by using combinatorial cell engineering and OMICS screening tools

Product quality control without compromising productivity has been a major goal in biotherapeutics process development. The challenge is further increased for new modalities using complex and hybrid protein structures, such as nanobodies and bispecific antibodies. New product-related impurities and unique product quality attribute (PQA) species have been found to accompany these new protein scaffolds, which usually don’t exist in standard mAb production. Undesired attributes include unique patterns of glycosylation, conformation heterogeneity, mis-pairing, and partial molecules. Many of these PQAs are related to protein folding and assembly efficiency inside the cell, which impact post-translational modifications such as disulfide bond formation and glycosylation processes, directly or indirectly. We have identified multiple intracellular causal factors that link some PQAs directly to host cell lineage. To improve understanding and increase options in developing a successful production cell line with desired product quality profile, we have used this information to develop diversified CHO host lineages using both conditioned-culture adaptation and CRISPR genome editing approaches. The resulting CHO hosts showed significant differences in cell growth and recombinant protein production, including productivity and quality attribute profiles. Furthermore, the hosts respond differently to changes in medium components and process conditions. These differences were more significant for complex/ hybrid proteins such as nanobodies and bispecific antibodies. OMICS tools were systematically utilized to identify the evolutionarily significance of genetic and epigenetic variability of individual host cell lineages, which determine the specific PQA profile of the expressed recombinant protein. Overall, our presentation will illustrate the importance of selecting the appropriate host cell line through screening and/or engineering, as part of quality control strategy to obtain the desired recombinant protein PQA profile.

MoNet: A Fast Payment Channel Network for Scriptless Cryptocurrency Monero

We propose MoNet, the first bi-directional payment channel network with unlimited lifetime for Monero. It is fully compatible with Monero without requiring any modification of the current Monero blockchain. MoNet preserves transaction fungibility, i.e., transactions over MoNet and Monero are indistinguishable, and guarantees anonymity of Monero and MoNet users by avoiding any potential privacy leakage introduced by the new payment channel network. We also propose a new crypto primitive, named Verifiable Consecutive One-way Function (VCOF). It allows one to generate a sequence of statement-witness pairs in a consecutive and verifiable way, and these statement-witness pairs are one-way, namely it is easy to compute a statement-witness pair by knowing any of the pre-generated pairs, but hard in an opposite flow. By using VCOF, a signer can produce a series of consecutive adaptor signatures CAS. We further propose the generic construction of consecutive adaptor signature as an important building block of MoNet. We develop a proof-of-concept implementation for MoNet, and our evaluation shows that MoNet can reach the same transaction throughput as Lightning Network, the payment channel network for Bitcoin. Moreover, we provide a security analysis of MoNet under the Universal Composable (UC) security framework

Fact and Fiction: Challenging the Honest Majority Assumption of Permissionless Blockchains

Honest majority is the key security assumption of Proof-of-Work (PoW) based blockchains. However, the recent 51% attacks render this assumption unrealistic in practice. In this paper, we challenge this assumption against rational miners in the PoW-based blockchains in reality. In particular, we show that the current incentive mechanism may encourage rational miners to launch 51% attacks in two cases. In the first case, we consider a miner of a stronger blockchain launches 51% attacks on a weaker blockchain, where the two blockchains share the same mining algorithm. In the second case, we consider a miner rents mining power from cloud mining services to launch 51% attacks. As 51% attacks lead to double-spending, the miner can profit from these two attacks. If such double-spending is more profitable than mining, miners are more intended to launch 51% attacks rather than mine honestly. We formally model such behaviours as a series of actions through a Markov Decision Process. Our results show that, for most mainstream PoW-based blockchains, 51% attacks are feasible and profitable, so profit-driven miners are incentivised to launch 51% attacks to gain extra profit. In addition, we leverage our model to investigate the recent 51% attack on Ethereum Classic (on 07/01/2019), which is suspected to be an incident of 51% attacks. We provide insights on the attacker strategy and expected revenue, and show that the attacker’s strategy is near-optimal

AuxChannel: Enabling Efficient Bi-Directional Channel for Scriptless Blockchains

Payment channels have been a promising solution to blockchain scalability. While payment channels for script-empowered blockchains (such as Bitcoin and Ethereum) have been well studied, developing payment channels for scriptless blockchains (such as Monero) is considered challenging. In particular, enabling bidirectional payment on scriptless blockchains remains an open challenge. This work closes this gap by providing AuxChannel, the first bi-directional payment channel protocol for scriptless blockchains, meaning that building payment channels only requires the support of verifiably encrypted signature (aka adaptor signature) on the underlying blockchain. AuxChannel leverages verifiably encrypted signature to create a commitment for each off-chain payment and deploys a verifiable decentralised key escrow service to resolve dispute. To enable efficient construction of AuxChannel, we introduce a new cryptographic primitive, named Consecutive Verifiably Encrypted Signature (CVES), as a core building block and it can also be of independent interest for other applications. We provide and implement a provably secure instantiation on Schnorr-based CVES. We also provide a formal security analysis on the security of the proposed AuxChannel

How do different Industry 4.0 technologies support certain Circular Economy practices?

Purpose: Uncovering the relationship between Industry 4.0 (I4.0) technologies and circular economy (CE) practices is critical not only for implementing CE but also for leveraging I4.0 to achieve sustainable development goals. However, the potential connection between them – especially how different I4.0 technologies may influence various CE practices – remains inadequately researched. The purpose of this study was to quantitatively explore the impacts of various I4.0 technologies on CE practices. Design/methodology/approach: A mixed method consisting of a systematic literature review, content analysis, and social network analysis was adopted. First, 266 articles were selected and mined for contents of I4.0 technologies and CE practices; 27 I4.0 technologies and 21 CE practices were identified. Second, 62 articles were found that prove the positive influence of I4.0 technologies on CE practices, and 124 relationships wereidentified. Third, based on evidence supporting the link between I4.0 technologies and CE practices, a two-mode network and two one-mode networks were constructed, and their network density and degree centrality indicators were analyzed. Findings: I4.0 technologies have a low application scope and degree for promoting CE. The adoption of a single I4.0 technology has limited effect on CE practices, and wider benefits can be realized through integrating I4.0 technologies. The Internet of Things (IoT), additive manufacturing, big data and analytics, and artificial intelligence (AI) are among the top technologies promoting CE implementation and reduction and recycling were identified as the main mechanism. The integration of these technologies is the most popular and effective. Twelve CE practices were identified to be the most widely implemented and supported by I4.0 technologies. Research limitations/implications: First, only journal articles, reviews, and online publications written in English were selected, excluding articles published in other languages. Therefore, the results obtained only represent a specific group of scholars, which may be fragmented to a certain extent. Second, because the extraction of the impact of I4.0 on CE mainly relies on a manual literature review, this paper only provides the statistics of the number of publications involving relationships, while lacking the weight measurement of relationships. Originality/value: A comprehensive, quantitative, and visual analysis method was employed to unveil the current implementation levels of I4.0 technologies and CE practices. Further, it was explored how different I4.0 technologies can affect various CE aspects, how different I4.0 technologies are integrated to promote CE realization, and how various CE practices are implemented simultaneously by I4.0 technologies

Cost-Effectiveness of Primary versus Secondary Prophylaxis with Pegfilgrastim in Women with Early-Stage Breast Cancer Receiving Chemotherapy

AbstractObjectiveProphylaxis with granulocyte colony-stimulating factor (G-CSF) reduces the risk of febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy. We estimated the incremental cost-effectiveness of G-CSF pegfilgrastim primary (starting in cycle 1 and continuing in subsequent cycles of chemotherapy) versus secondary (only after an FN event) prophylaxis in women with early-stage breast cancer receiving myelosuppressive chemotherapy with a ≥20% FN risk.MethodsA decision-analytic model was constructed from a health insurer's perspective with a lifetime study horizon. The model considers direct medical costs and outcomes related to reduced FN and potential survival benefits because of reduced FN-related mortality. Inputs for the model were obtained from the medical literature. Sensitivity analyses were conducted across plausible ranges in parameter values.ResultsThe incremental cost-effectiveness ratio (ICER) of pegfilgrastim as primary versus secondary prophylaxis was $48,000/FN episode avoided. Adding survival benefit from avoiding FN mortality yielded an ICER of$110,000/life-year gained (LYG) or $116,000/quality-adjusted life-year (QALY) gained. The most influential factors included FN case-fatality, FN relative risk reduction from primary prophylaxis, and age at diagnosis.ConclusionsCompared with secondary prophylaxis, the cost-effectiveness of pegfilgrastim as primary prophylaxis may be equivalent or superior to other commonly used supportive care interventions for women with breast cancer. Further assessment of the direct impact of G-CSF on short- and long-term survival is needed to substantiate these findings

Spinal myeloid sarcoma presenting as initial symptom in acute promyelocytic leukemia with a rare cryptic PLZF::RARα fusion gene: a case report and literature review

BackgroundAcute promyelocytic leukemia (APL) is rarely caused by the PLZF::RARα fusion gene. While APL patients with PLZF::RARα fusion commonly exhibit diverse hematologic symptoms, the presentation of myeloid sarcoma (MS) as an initial manifestation is infrequent.Case presentationA 61-year-old patient was referred to our hospital with 6-month history of low back pain and difficulty walking. Before this admission, spine magnetic resonance imaging (MRI) conducted at another hospital revealed multiple abnormal signals in the left iliac bone and vertebral bodies spanning the thoracic (T11-T12), lumbar (L1-L4), and sacral (S1/S3) regions. This led to a provisional diagnosis of bone tumors with an unknown cause. On admission, complete blood count (CBC) test and peripheral blood smear revealed a slightly increased counts of monocytes. Immunohistochemical staining of both spinal and bone marrow (BM) biopsy revealed positive expression for CD117, myeloperoxidase (MPO), and lysozyme. BM aspirate showed a significant elevation in the percentage of promyelocytes (21%), which were morphologically characterized by round nuclei and hypergranular cytoplasm. Multiparameter flow cytometry of BM aspirate revealed that blasts were positive for CD13, CD33, CD117, and MPO. Through the integrated application of chromosome analysis, fluorescence in situ hybridization (FISH), reverse transcriptase polymerase chain reaction (RT-PCR), and Sanger sequencing, it was determined that the patient possessed a normal karyotype and a rare cryptic PLZF::RARα fusion gene, confirming the diagnosis of APL.ConclusionIn the present study, we report the clinical features and outcome of a rare APL patient characterized by a cryptic PLZF::RARα fusion and spinal myeloid sarcoma (MS) as the initial presenting symptom. Our study not only offers valuable insights into the heterogeneity of APL clinical manifestations but also emphasizes the crucial need to promptly consider the potential link between APL and MS for ensuring a timely diagnosis and personalized treatments

Cinical, Metabolic, and Genetic Analysis and Follow-Up of Eight Patients With HIBCH Mutations Presenting With Leigh/Leigh-Like Syndrome

3-Hydroxyisobutyryl-CoA hydrolase (HIBCH, NM_014362.3) gene mutation can cause HIBCH deficiency, leading to Leigh/Leigh-like disease. To date, few case series have investigated the relationship between metabolites and clinical phenotypes or the effects of treatment, although 34 patients with HIBCH mutations from 27 families have been reported. The purpose of this study was to analyze the phenotypic spectrum, follow-up results, metabolites, and genotypes of patients with HIBCH deficiency presenting with Leigh/Leigh-like syndrome and explore specific metabolites related to disease diagnosis and prognosis through retrospective and longitudinal studies. Applying next-generation sequencing, we identified eight patients with HIBCH mutations from our cohort of 181 cases of genetically diagnosed Leigh/Leigh-like syndrome. Six novel HIBCH mutations were identified: c.977T>G [p.Leu326Arg], c.1036G>T [p.Val346Phe], c.750+1G>A, c.810-2A>C, c.469C>T [p.Arg157*], and c.236delC [p.Pro79Leufs*5]. The Newcastle Pediatric Mitochondrial Disease Scale (NPMDS) was employed to assess disease progression and clinical outcomes. The non-invasive approach of metabolite analysis showed that levels of some were associated with clinical phenotype severity. Five (5/7) patients presented with elevated C4-OH in dried blood spots, and the level was probably correlated with the NPMDS scores during the peak disease phase. 2,3-Dihydroxy-2-methylbutyrate in urine was elevated in six (6/7) patients and elevated S-(2-caboxypropyl)cysteamine in urine was found in three patients (3/3). The median age at initial presentation was 13 months (8–18 months), and the median follow-up was 2.3 years (range 1.3–7.2 years). We summarized and compared with all reported patients with HIBCH mutations. The most prominent clinical manifestations were developmental regression/delay, hypotonia, encephalopathy, and feeding difficulties. We administered drug and dietary treatment. During follow-up, five patients responded positively to treatment with a significant decrease in NPMDS scores. Our research is the largest case series of patients with HIBCH mutations