Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficient Cocaine Degradation by Cocaine Esterase-Loaded Red Blood Cells

Recombinant bacterial cocaine esterase (CocE) represents a potential protein therapeutic for cocaine use disorder treatment. Unfortunately, the native enzyme was highly unstable and the corresponding mutagenized derivatives, RBP-8000 and E196-301, although improving in vitro thermo-stability and in vivo half-life, were a partial solution to the problem. For cocaine use disorder treatment, an efficient cocaine-metabolizing enzyme with a longer residence time in circulation would be needed. We investigated in vitro the possibility of developing red blood cells (RBCs) loaded with RBP-8000 and E196-301 as a biocompatible system to metabolize cocaine for a longer period of time. RBP 8000 stability within human RBCs is limited (approximately 50% residual activity after 1 h at 37°C) and not different as for the free enzyme, while both free and encapsulated E196-301 showed a greater thermo-stability. By reducing cellular glutathione content during the loading procedure, in order to preserve the disulfide bonds opportunely created to stabilize the enzyme dimer structure, it was possible to produce an encapsulated protein maintaining 100% stability at least after 4 h at 37°C. Moreover, E196-301-loaded RBCs were efficiently able to degrade cocaine in a time- and concentration-dependent manner. The same stability results were obtained when murine RBCs were used paving the way to preclinical investigations. Thus, our in vitro data show that E196-301-loaded RBCs could act as efficient bioreactors in degrading cocaine to non-toxic metabolites to be possibly considered in substance-use disorder treatments. This approach should now be investigated in a preclinical model of cocaine use disorder to evaluate if further protein modifications are needed to further improve long term enzyme stability.
Squamous cell carcinoma of the head and neck: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up.

Squamous cell carcinoma of the head and neck: EHNS–ESMO–ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up V. Grégoire, J.-L. Lefebvre, L. Licitra & E. Felip On behalf of the EHNS–ESMO–ESTRO Guidelines Working Group* Department of Radiation Oncology, St-Luc University Hospital, Brussels, Belgium; Department of Head and Neck Surgery, Centre Oscar Lambret, Lille, France; Medical Oncology Head and Neck Unit, Istituto Nazionale dei Tumori, Milan, Italy; Medical Oncology Service, Vall d’Hebron University Hospital, Barcelona, Spain
A Comparison of Deaf and Hearing Children's Reading Comprehension Profiles

Purpose: Although deaf children typically exhibit severe delays in reading achievement, there is a paucity of research looking at their text-level comprehension skills. We present a comparison of deaf and normally hearing readers' profiles on a commonly used reading comprehension assessment: the Neale Analysis of Reading Ability II. Methods: Comprehension questions were coded into 3 types: literal questions; local cohesion questions; and global coherence questions. Deaf children were matched to 3 groups of hearing children: chronological age-matched controls; reading-age-matched controls; and a group of poor comprehenders. Results: Deaf children had significantly weaker reading comprehension skills than both chronological age- and reading-age-matched controls, but their skills were commensurate with poor comprehenders. All groups found it easier to make inferences to establish local cohesion than those required to establish global coherence. Discussion/Conclusions: These results suggest that deaf children's reading comprehension profiles are remarkably similar to those of poor comprehenders. These findings are discussed in light of the potential differences in underlying causes of reading difficulties in these 2 groups.
Preventing Familial Breast and Ovarian Cancer: Major Research Advances with Little Implication

ovarian cancer. Although mutation carriers face a very high lifetime risk, personalized accurate and age-adjusted timely prediction still remains elusive, whereas even women with negative genetic testing, but strong family history, have an increased risk of developing breast and ovar-ian cancer. Multiple questions on an optimal preventive or therapeutic approach are raised by both positive and negative
COVID-19 and Oral Fluids

The coronavirus disease 2019 (COVID-19) is an acute infectious disease that has led to a global pandemic. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for this infection. This virus enters the body through the mucous membranes (oral, nasal, or conjunctival ocular) or the skin and replicates in the respiratory system (nasal cavity, throat, and the lung) but may cause damage to other systems and organs. Main transmission is through saliva droplets and oral fluids (OF) including saliva and non-salivary elements that contain infective viral loads of the virus. SARS-Cov-2 enters cells via receptor angiotensin-converting enzyme II (ACE2) and the action of an enzyme (furin) that cleaves the viral envelope and enhances the infection of the host cells. Although the origin, mechanism, and dynamics of SARS-CoV-2 in OF remain to be elucidated, its presence in OF is now established. Therefore, OF might be a diagnostic or monitoring tool for COVID-19 either alone or in combination with other tests in addition to the clinical examination. Moreover, the presence of SARS-CoV-2 in OF raises the question of the management of the infectious risk for dental practice. There is an urgent need to inform the dental community and ensure measures to protect dentists and dental staff from the new SARS-CoV-2. This comprehensive review of COVID-19 and oral health depicts the roles of OF in the transmission dynamics of SARS-CoV-2 and discusses the value of OF as a diagnostic tool and focuses on the management of risk transmission related to OF in dental practice.
Efficiency optimization of an automotive multi-phase bi-directional DC-DC converter

The paper proposes methods to improve the efficiency of a bi-directional, multi-phase buck+boost DC-DC converter for application in Hybrid Electrical Vehicles (HEV) or Fuel Cell Vehicles (FCV). Thereto, the modulation strategy for a highly-compact, 30kW/Liter, constant-frequency soft-switching converter is optimized based on a converter loss model that includes the losses in the power semiconductors and the buck+boost inductor. An algorithm for numerical calculation of the optimum switching times is given, whereas the values for the loss-optimized operation of the converter are stored in a lookup-table that is accessed by the digital controller. In addition, a novel method and control concept to ensure a Zero Voltage Switching (ZVS) of all semiconductor switches by determination of a zero voltage across the MOSFET switches with analog comparators is proposed that results in the lowest inductor RMS currents for ZVS operation at the same time. Furthermore, at low output power an absolute efficiency gain of over 2.8% is achieved by partial operation of the six interleaved converter phases. A detailed description on the control concept that determines the optimum number of activated phases for the current operating point of the converter is given and verified by experimental results. The measurements prove the capability to instantaneously switch the number of active phases during operation without a overshoot or drop in the converter output voltage.
Dynamic Simulation of Surge Corona With Time-Dependent Upwind Difference Method

This paper presents a new algorithm to simulate the surge corona of power transmission lines in two dimension. The charge simulation method and the finite element method are applied to calculate the electric field, while a time-dependent upwind difference algorithm is applied to calculate the migration of the space charges. The implementation of boundary conditions and the choice of mesh size and time step are discussed to ensure the stability of the proposed algorithm. The Q-V (charge-voltage) curves of impulses applying on single conductor and bundle conductors in a cage having a square cross section are calculated. The simulation results are supported by the published experiments.
RNN Models for Dynamic Matrix Inversion: A Control-Theoretical Perspective

In this paper, the existing recurrent neural network (RNN) models for solving zero-finding (e.g., matrix inversion) with time-varying parameters are revisited from the perspective of control and unified into a control-theoretical framework. Then, limitations on the activated functions of existing RNN models are pointed out and remedied with the aid of control-theoretical techniques. In addition, gradient-based RNNs, as the classical method for zero-finding, have been remolded to solve dynamic problems in manners free of errors and matrix inversions. Finally, computer simulations are conducted and analyzed to illustrate the efficacy and superiority of the modified RNN models designed from the perspective of control. The main contribution of this paper lies in the removal of the convex restriction and the elimination of the matrix inversion in existing RNN models for the dynamic matrix inversion. This work provides a systematic approach on exploiting control techniques to design RNN models for robustly and accurately solving algebraic equations.
Fermentation of Shrimp Biowaste under Different Salt Concentrations with Amylolytic and Non-Amylolytic Lactobacillus Strains for Chitin Production

Fermentation of shrimp biowaste was conducted with two Lactobacillus plantarum strains at pH=6.0 under various salt concentrations. The non-amylolytic strain L. plantarum 541 and amylolytic strain L. plantarum A6 showed to possess reasonable growth in biowaste with the addition of salt as high as 6 %. Fermentation carried with 10 % inoculum, 5 % glucose, with initial reduction of pH to 6.0 using acetic acid, showed that there was no spoilage of the biowaste. Growth trends in shrimp waste, in terms of CFU/mL developed on MRS-agar plates, changes in pH and lactic acid production (in g/L) were determined. The deproteination and demineralization efficiency with strain 541 was better than with strain A6. A maximum of 81.4 % demineralization and 59.8 % deproteination under 2 % salt conditions occurred with strain 541, whereas with strain A6, a demineralization of 65.5 % and deproteination of 52.2 % was observed.
TRADING RESTRICTIONS AND STOCK PRICES *

Firms can manipulate their stock price by limiting the ability of their investors to sell. I examine a series of corporate events in Japan in which firms actively reduced their float – the fraction of shares available to trade – for periods of one to three months, locking investors into their long positions. Theory predicts that the greater are the restrictions, the greater is the impact of trading on price. Particularly severe restrictions are associated with returns of over 30 percent, most of which are reversed when the restrictions are removed. Firms are more likely to issue equity or redeem convertible debt during the restricted period, suggesting strong incentives for manipulation. * I thank Malcolm Baker, Chris Malloy, Ken Froot, Hideki Hanaeda, Seki Obata, David Scharfstein, Mike Schor, Erik Stafford, Tuomo Vuolteenaho, Josh Coval, and seminar participants at the University of Connecticut, the University of Massachusetts, Harvard, and the Adam Smith Asset Pricing Conference for useful discussions. I also thank James Zeitler for help with Datastream, Mako Egawa and Chisato Toyama for help in Japan, and Andrew Campbell, Hae Mi Choi, and Mike Schor for research assistance.
Iron deficiency in a male with multiple myeloma

A 58-year-old man with long standing unexplained iron deficiency anaemia presented with severe hypercalcaemia and was subsequently diagnosed with multiple myeloma. Anaemia in multiple myeloma is usually normochromic and normocytic.1 To our knowledge, there are no reported cases in the English literature of true iron deficiency associated with multiple myeloma. Our case highlights the importance of pursuing the aetiology of iron deficiency, especially in a middle aged male. It also reinforces the fact that severe hypercalcaemia usually has a malignant aetiology.
Tissue-specific organelle DNA degradation mediated by DPD1 exonuclease

Organelle DNA in plastids and mitochondria is present in multiple copies and undergoes degradation developmentally. For example, organelle DNA that is detectable cytologically using DNA-fluorescent dye disappears during pollen development. Nevertheless, nucleases involved in this degradation process remain unknown. Our recent study identified the organelle nuclease, DPD1, which has Mg2+-dependent exonuclease activity in vitro. The discovery of DPD1 emerged from Arabidopsis mutant screening and concomitant isolation of dpd1 mutants that retain organelle DNA in mature pollen. DPD1 is conserved only in angiosperms: not in other photosynthetic organisms. Despite these findings, the physiological significance of organelle DNA degradation during pollen development remains unclear because dpd1 exhibits no apparent defects in pollen viability or in the maternal inheritance of organelle DNA. We discuss a possible role of organelle DNA degradation mediated by DPD1, based on a DPD1 expression profile studied using in silico analyses.
Multilevel LDPC Lattices With Efficient Encoding and Decoding and a Generalization of Construction $\text{D}'$

Lattice codes are elegant and powerful structures that not only achieve the capacity of the additive white Gaussian noise (AWGN) channel but are also a key ingredient to many multiterminal schemes that exploit linearity properties. However, constructing lattice codes that can realize these benefits with low complexity is still a challenging problem. In this paper, efficient encoding and decoding algorithms are proposed for multilevel binary low-density parity-check (LDPC) lattices constructed via Construction <inline-formula> <tex-math notation="LaTeX">$\text{D}'$ </tex-math></inline-formula> whose complexity is linear in the total number of coded bits. Moreover, a generalization of Construction <inline-formula> <tex-math notation="LaTeX">$\text{D}'$ </tex-math></inline-formula> is proposed, which relaxes some of the nesting constraints on the parity-check matrices of the component codes, leading to a simpler and improved design. Based on this construction, low-complexity multilevel LDPC lattices are designed whose performance under multistage decoding is comparable to that of polar lattices and close to that of low-density lattice codes on the power-unconstrained AWGN channel.
Design of connected array loaded with artificial dielectric at 60 GHz

In this contribution, we present a 60 GHz design of a connected array of slots combined with artificial dielectric layers (ADLs). The antenna array consists of 2×8 connected-slot elements, fed coherently with a corporate feeding network. The array is loaded with an artificial dielectric slab with high permittivity, which has the advantage of enhancing the forward radiation without supporting surface waves. The ohmic losses introduced by the metallic inclusions of the ADLs are very low due to the non-resonant nature of the electrically small patches. Simulated results are presented, showing desired fan-beam radiation characteristics and a relative bandwidth of 33%.
34 th Annual Precise Time and Time Interval ( PTTI ) Meeting FFT-BASED METHODS FOR SIMULATING FLICKER FM

Four algorithms for simulating flicker FM phase noise (f−3 spectrum) are given, two old and two new. Their Allan deviation and mean square time interval error (MSTIE) are examined. The MSTIE shows that one of the old algorithms has deficient long-term phase deviations on average. The Allan deviation does not reveal this deficiency.
Alcohol outlets and problem drinking among adults in California.

OBJECTIVE The purpose of the study was to examine the relationship between alcohol environments and problem drinking, including excessive alcohol consumption, heavy episodic drinking, driving after drinking, and riding with a drinking driver. METHOD We merged geo-coded individual-level data from the California Health Interview Survey and Los Angeles County Health Survey with alcohol license data from the California Department of Alcoholic Beverage Control, distinguishing off-sale retails from on-sale establishments and, among on-sales, eating places from bars and taverns as well as minor-unrestricted establishments from minor-restricted establishments (i.e., youth below age 21 not allowed on business premises). The primary explanatory variable was alcohol outlets within various distances from an individual's residence or census tract. Multivariate logistic regression and simulation were run for men and women separately. RESULTS On-sale establishments, particularly minor-restricted establishments, were significantly associated with excessive alcohol consumption and heavy episodic drinking, after controlling for individual and neighborhood sociodemographics. The effect was limited to outlets located within proximity, roughly 1 mile from residential homes. Off-sale retails were not found to be related to problem drinking. If the number of minor-restricted establishments increases from median to 90th percentile of their distribution, heavy episodic drinking would increase from 11.1% to 14.3% among women and from 19.6% to 22.0% among men. CONCLUSIONS Certain types of alcohol retailers in neighborhoods were associated with problem drinking. Moratorium of new licenses based on number of licenses per capita at county level is not effective because only a subgroup of licenses matters, and alcohol is more available in terms of distance, travel time, or search costs in densely populated cities.
D^over: An Optimal On-Line Scheduling Algorithm for Overloaded Uniprocessor Real-Time Systems

Consider a real-time system in which every task has a value that it obtains only if it completes by its deadline. The problem is to design an on-line scheduling algorithm (i.e., the scheduler has no knowledge of a task until it is released) that maximizes the guaranteed value obtained by the system. When such a system is underloaded (i.e., there exists a schedule for which all tasks meet their deadlines), Dertouzos [Proceedings IFIF Congress, 1974, pp.\ 807--813] showed that the earliest deadline first algorithm will achieve 100% of the possible value. Locke [Ph. D. thesis, Computer Science Dept., Carnegie-Mellon Univ., Pittsburgh, PA] showed that earliest deadline first performs very badly, however, when the system is overloaded, and he proposed heuristics to deal with overload. This paper presents an optimal on-line scheduling algorithm for overloaded uniprocessor systems. It is optimal in the sense that it gives the best competitive ratio possible relative to an off-line scheduler.
4-Hydroxy-2-nonenal induces endothelial cell injury via PKCdelta and biphasic JNK activation

Hydroxy-2-nonenal (4-HNE), a major product generated during oxidative stress, exhibits cytotoxic effects; however, the mechanisms of 4-HNE-induced endothelial cell injury are not well defined. To explore this issue, we examined how 4-HNE damages human umbilical vein endothelial cells (HUVECs) and found that 4-HNE induced biphasic activation of c-Jun N-terminal kinase (JNK). Both pre- and post-treatment of HUVECs with SP600125, a spe- cific JNK inhibitor, significantly suppressed the cytotoxic effects of 4-HNE. Inhibition of protein kinase Cδ (PKCδ), which was also phosphorylated by 4-HNE, reduced endothelial cell injury as well as late-phase JNK phosphorylation elicited by 4-HNE. Inversely, pre-treatment of HUVECs with SP600125 suppressed PKCδ activation. Taken together, these results support the concept that 4-HNE induces vascular endothelial cell injury by the interac- tion between biphasic JNK activation and the PKCδ pathway.
A lanthanide-gallium complex stabilized by the N-heterocyclic carbene group.

The complex [Nd(L‘){Ga(NArCH)2}(N‘ ‘)(THF)], which exhibits the first f-element−gallium bond, is formed from the reaction between the N-heterocyclic carbene-supported neodymium complex [Nd(L‘)(N‘ ‘)(I)] (L‘ = ButNCH2CH2{C(NCSiMe3 CHNBut)}; N‘ ‘ = N(SiMe3)2) and the anionic gallium(I) heterocycle [Ga(NArCH)2][K(tmeda)] (Ar = 2,6-Pri2C6H3). The Nd−Ga bond energy is calculated to be 386 kJ mol-1.
VESICULAR OCULAR DRUG DELIVERY SYSTEM: PRECLINICAL AND CLINICAL PERSPECTIVE OF DRUGS DELIVERED VIA NIOSOMES

An eye is the most precious and easily accessible organ of the body. It possesses easy route to local drug delivery and is a way to non-invasive clinical treatment of ocular diseases. Ocular delivery in spite of possessing various advantages has the limitation of poor bioavailability and low permeability across the cornea thus, limiting the efficacy of drugs. Therefore, various carrier systems have been developed to overcome these limitations. Most recently, niosomes have been developed as efficient vesicular carrier for ophthalmic drug delivery. Large numbers of drugs of various therapeutic categories have been incorporated in these vesicles. These systems exhibited enhanced permeability required for the treatment of ocular diseases, initiating a new era in vesicular research for ocular delivery. Various reports show promising future of niosomes for topical, transdermal, ocular delivery of various therapeutically active agents more effectively and providing better in vivo data thus suggesting the need of the clinical testing of these carriers for their widespread utility. So, to evaluate its safety and efficacy, various preclinical and clinical studies were conducted. The present review focuses on the preclinical and clinical perspective of delivery of various drugs through niosomal vesicular carriers illustrating enhanced safety and efficacy by designing these carriers.
A versatile ankle-mounted fall detection device based on attitude heading systems

In this paper we propose a wireless wearable device for real-time fall detection attached to the ankle user. This device can also be embedded inside the footwear with similar performance and a lower invasiveness of use. It contains a 3-axis accelerometer, a 3-axis gyroscope and a 3-axis magnetometer realizing an Attitude Heading Reference System (AHRS). The AHRS provides the correct 3D orientation through an implemented data fusion algorithm. On sensor board is also implemented the automatic fall detection algorithm handling the orientation data from AHRS and the acceleration data from the triaxial accelerometer. The fall is a critical event that can cause physical and psychological effects particularly among older people. The elderly timely assistance after a fall could prevent serious health care consequences. For this reason the alarms generated by fall detection algorithm are sent to a smartphone via the Bluetooth module integrated into the device. In the smartphone runs a background application that sends sms alert to preset phone numbers or makes prerecorded phone calls after receiving alarms from the sensor node. In order to evaluate the performance of the proposed fall detection system, the developed device has been tested according to an experimental protocol in which volunteers perform simulated falls, simulated falls with recovery and activities of daily living (ADL). Our ankle-mounted devise shows a significant improvement in performance compared to other devices proposed in literature. In fact, the results of the experimental protocol show a sensitivity of 97% and a specificity of 100%.