Miracle-dz/UniFAR-FTUs huggingface dataset:
Generation of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) Using Directed Molecular Evolution

G protein–coupled receptors (GPCRs) and their signal transductions are important for both physiological and pathological processes in neuron systems. Neuronal GPCRs activated by synthetic ligands have been created by designed mutagenesis for studying their functions and signal pathways. However, these engineered GPCRs have problems, such as their high constitutive activity. To overcome this drawback, a new generation of receptors termed designer receptors exclusively activated by designer drugs (DREADDs), have been designed. DREADDs are exclusively activated by synthetic ligands, but are insensitive to their endogenous ligand and have no constitutive activity, which provides the ability to selectively modulate signal transduction of certain GPCRs in vitro and in vivo. This protocol provides detailed instructions for creating DREADDs using directed molecular evolution. The procedures to generate DREADDS include GPCR functional expression in yeast, mutant GPCR library generation, and high‐throughput yeast screening. These methods are general and suitable for any GPCRs that can be functionally expressed in yeast. Curr. Protoc. Neurosci. 50:4.33. 1‐4.33. 25. © 2010 by John Wiley & Sons, Inc.
Routing and Ad-hoc Retrieval with the TREC-3 Collection in a Distributed Loosely Federated Environment

In this paper, we investigate retrieval methods for loosely coupled IR systems. In such an environment, each IR system operates independently on its own document collection. For query processing, an agent takes the query and sends it to the different IR systems. From the answers received from these servers, it forms a single ranking and sends it back to the user. In the work presented here, we examine different methods for performing routing and had hoc queries in such a environment. For experiments, we use the TREC-3 collection and the SMART retrieval system.
A 1.5 GHz 90 nm embedded microprocessor core

A 90 nm ARM/spl trade/ V5TE compatible microprocessor core intended for high performance and low power embedded applications is described. The core includes an ECC protected 2 level 512 MB cache, high-bandwidth single-cycle L1 cache line fill and evict, and cache coherency. Circuit design for high speed and low power are described, as well as their impact on the micro-architecture. Features to support low standby power modes and embedded test are also described.
A cross-vocoder study of speaker independent synthetic speech detection using phase information

Current speaker verification systems are vulnerable to advanced speech manipulation techniques such as voice conversion and speaker adaptation for TTS systems. Effective anti-spoofing systems that allow the discrimination between human and synthetic impostors have been developed. However, many of them still present two main drawbacks: speaker dependency and, more importantly, counterfeiting technique dependency. Thus, getting a universal synthetic speech detector (SSD) remains an open issue. This paper explores the feasibility of such a system using a statistical classifier for human and synthetic speech. Provided the great diversity of counterfeiting techniques, we have chosen to model a variety of state-of-the-art minimum-phase vocoders, creating imposter synthetic signals by copy-synthesis. Two speech parameter sets are used: MFCCs as a canonical baseline and relative phase shift (RPS) based parameterization. Phase related parameters allow synthetic speech detection based on the presumably different phase structures of the human and synthetic signals due to the fact that most speech synthesis and conversion techniques disregard phase information. The results of the experiments show that speaker independent classifiers perform very well for every vocoder. Cross-vocoder experiments show that the system is highly dependent on the type of vocoder, and that RPS parameterization performs better than MFCC for multi-vocoder models.
Carbohydrate bioavailability

There is consensus that carbohydrate foods, in the form of fruit, vegetables and whole-grain products, are beneficial to health. However, there are strong indications that highly processed, fibre-depleted, and consequently rapidly digestible, energy-dense carbohydrate food products can lead to over-consumption and obesity-related diseases. Greater attention needs to be given to carbohydrate bioavailability, which is determined by the chemical identity and physical form of food. The objective of the present concept article is to provide a rational basis for the nutritional characterisation of dietary carbohydrates. Based on the properties of carbohydrate foods identified to be of specific relevance to health, we propose a classification and measurement scheme that divides dietary carbohydrates into glycaemic carbohydrates (digested and absorbed in the small intestine) and non-glycaemic carbohydrates (enter the large intestine). The glycaemic carbohydrates are characterised by sugar type, and by the likely rate of digestion described by in vitro measurements for rapidly available glucose and slowly available glucose. The main type of non-glycaemic carbohydrates is the plant cell-wall NSP, which is a marker of the natural fibre-rich diet recognised as beneficial to health. Other non-glycaemic carbohydrates include resistant starch and the resistant short-chain carbohydrates (non-digestible oligosaccharides), which should be measured and researched in their own right. The proposed classification and measurement scheme is complementary to the dietary fibre and glycaemic index concepts in the promotion of healthy diets with low energy density required for combating obesity-related diseases.
Activity of the TonEBP/OREBP transactivation domain varies directly with extracellular NaCl concentration

Hypertonicity-induced binding of the transcription factor TonEBP/OREBP to its cognate DNA element, ORE/TonE, is associated with increased transcription of several osmotically regulated genes. Previously, it was found that hypertonicity rapidly causes nuclear translocation and phosphorylation of TonEBP/OREBP and, more slowly, increases TonEBP/OREBP abundance. Also, the C terminus of TonEBP/OREBP was found to contain a transactivation domain (TAD). We have now tested for tonicity dependence of the TAD activity of the 983 C-terminal amino acids of TonEBP/OREBP. HepG2 cells were cotransfected with a reporter construct and one of several TAD expression vector constructs. The reporter construct contained GAL4 DNA binding elements, a minimal promoter, and the Photinus luciferase gene. TAD expression vectors generate chimeras comprised of the GAL4 DNA binding domain fused to (i) the 983 C-terminal amino acids of TonEBP/OREBP, (ii) 17 glutamine residues, (iii) the TAD of c-Jun, or (iv) no TAD. All TAD-containing chimeras were functional at normal extracellular osmolality (300 mosmol/kg), but the activity only of the chimera containing the 983 C-terminal amino acids of TonEBP/OREBP varied with extracellular NaCl concentration, decreasing by >80% at 200 mosmol/kg and increasing 8-fold at 500 mosmol/kg. The chimera containing the 983 C-terminal amino acids of TonEBP/OREBP was constitutively localized to the nucleus and showed tonicity-dependent posttranslational modification consistent with phosphorylation. The activity at 500 mosmol/kg was reduced by herbimycin, a tyrosine kinase inhibitor and by 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole, a protein kinase CK2 inhibitor. Thus, the 983 C-terminal amino acids of TonEBP/OREBP contain a TAD that is regulated osmotically, apparently by tonicity-dependent phosphorylation.
Lipidomics of Mesenchymal Stromal Cells: Understanding the Adaptation of Phospholipid Profile in Response to Pro‐Inflammatory Cytokines

Mesenchymal stromal cells (MSCs) present anti‐inflammatory properties and are being used with great success as treatment for inflammatory and autoimmune diseases. In clinical applications MSCs are subjected to a strong pro‐inflammatory environment, essential to their immunosuppressive action. Despite the wide clinical use of these cells, how MSCs exert their effect remains unclear. Several lipids are known to be involved in cell's signaling and modulation of cellular functions. The aim of this paper is to examine the variation in lipid profile of MSCs under pro‐inflammatory environment, induced by the presence of tumor necrosis factor alpha (TNF‐α) and interferon gamma (IFN‐γ), using the most modern lipidomic approach. Major changes in lipid molecular profile of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), lysoPC (LPC), and sphingomyelin (SM) classes were found. No changes were observed in the phosphatidylinositol (PI) profile. The levels of PC species with shorter fatty acids (FAs), mainly C16:0, decreased under pro‐inflammatory stimuli. The level of PC(40:6) also decreased, which may be correlated with enhanced levels of LPC(18:0), which is known to be an anti‐inflammatory LPC, observed in MSCs subjected to TNF‐α and IFN‐γ. Simultaneously, the relative amounts of PC(36:1) and PC(38:4) increased. TNF‐α and IFN‐γ also enhanced the levels of PE(40:6) and decreased the levels of PE(O‐38:6). Higher expression of PS(36:1) and SM(34:0) along with a decrease in PS(38:6) levels were observed. These results indicate that lipid metabolism and signaling are modulated during MSCs activation, which suggests that lipids may be involved in MSCs functional and anti‐inflammatory activities. J. Cell. Physiol. 231: 1024–1032, 2016. © 2015 Wiley Periodicals, Inc.
Pathogenesis and progression of chronic myeloid leukemia

We reassessed the prevalence of TT viral DNA in Italian blood donors by using primers derived from a highly conserved non-coding region of the viral genome. Our previous underestimation of the prevalence of TTV is proved by the new figure obtained: 85% vs 5%. Again, we observed no difference with respect to a group of potential donors with elevated alanine aminotransferase levels.
Circulating tumor cells: silent predictors of metastasis

Circulating tumor cells (CTCs) were added to the arsenal of clinical testing in 2004 for three cancer types: metastatic breast, prostate, and colorectal cancer. CTCs were found to be an independent prognostic indicator of survival for these three diseases. Multiple enrichment/isolation strategies have been developed and numerous assay applications have been performed using both single and pooled captured/enriched CTCs. We have reviewed the isolation techniques and touched on many analyses. The true utility of a CTC is that it acts as a “silent” predictor of metastatic disease. The mere presence of a single CTC is an indication that disease has spread from the primary site. Comments and suggestions have been set forth for CTCs and cell-free DNA to be used as a screening panel for the early detection of disease recurrence and metastatic spread, providing the opportunity for early intervention with curative intent to treat metastatic disease.
Surface plasmon resonance waveguide biosensor by bipolarization wavelength interrogation

A new surface-plasmon-resonance (SPR) waveguide biosensor with the capability of bipolarization wavelength interrogation is presented. In the conventional SPR biosensors, only the transverse magnetic (TM)-polarized lightwave can couple with the surface plasma wave. The proposed SPR biosensor can make both the TM- and the transverse electric (TE)-polarized lightwave to produce the SPR. Therefore, two kinds of biomaterials can be separately detected by the signals from the TM- and the TE-polarized modes, and the number of detectable materials in a single chip can be doubled. Human serum albumin is coated on the device to sense the concentration of beta-blocker. Experimental results show that the concentration of beta-blocker is related to the SPR wavelength shift at a rate of 0.08 and 0.027 nm/ppm for the TM- and the TE-polarized modes, respectively.
Exploring Opportunities for Heterogeneous-ISA Core Architectures in High-Performance Mobile SoCs

High-performance processors use more transistors to deliver better performance. This comes at a cost of higher power consumption, often lowering energy efficiency. Conventional approaches mitigate this problem by adding heterogeneous energy-efficient cores for matching tasks. However, reducing high-performance components, such as caches or out-oforder processing capabilities, broadly affects performance. In this paper, we instead explore opportunities to increase energy efficiency by providing cores with restricted functionality, but without necessarily impacting performance. We aim to achieve this by removing support for complex but less frequently executed instructions. Since instruction mixes used by real-world workloads are often heavily biased, the potential to remove unused or less frequently used instructions is relatively high. To explore such opportunities, we investigate which instructions are worthwhile to remove, how frequently they are used, and how much performance degradation is expected after removing direct hardware support. We analyze a subset of instructions in the ARM ISA and their corresponding logic burden in the microarchitecture. Furthermore, we present instruction profiling results and show performance degradation when candidate instructions are removed. Experimental results show that removing most of the identified complex instructions has negligible impact on performance except for NEON instructions, which result in large performance degradations for floating-point-oriented workloads. We further propose a heterogeneous-ISA system to achieve energy efficiency without performance degradation using a system architecture that combines both fulland reducedISA cores. Results show that by providing the flexibility of heterogeneous-ISA cores, the proposed system can improve energy efficiency by 12% on average and up to 15% for applications that do not require NEON support, all without performance overhead.
Coral physiology and microbiome dynamics under combined warming and ocean acidification

Rising seawater temperature and ocean acidification threaten the survival of coral reefs. The relationship between coral physiology and its microbiome may reveal why some corals are more resilient to these global change conditions. Here, we conducted the first experiment to simultaneously investigate changes in the coral microbiome and coral physiology in response to the dual stress of elevated seawater temperature and ocean acidification expected by the end of this century. Two species of corals, Acropora millepora containing the thermally sensitive endosymbiont C21a and Turbinaria reniformis containing the thermally tolerant endosymbiont Symbiodinium trenchi, were exposed to control (26.5°C and pCO2 of 364 μatm) and treatment (29.0°C and pCO2 of 750 μatm) conditions for 24 days, after which we measured the microbial community composition. These microbial findings were interpreted within the context of previously published physiological measurements from the exact same corals in this study (calcification, organic carbon flux, ratio of photosynthesis to respiration, photosystem II maximal efficiency, total lipids, soluble animal protein, soluble animal carbohydrates, soluble algal protein, soluble algal carbohydrate, biomass, endosymbiotic algal density, and chlorophyll a). Overall, dually stressed A. millepora had reduced microbial diversity, experienced large changes in microbial community composition, and experienced dramatic physiological declines in calcification, photosystem II maximal efficiency, and algal carbohydrates. In contrast, the dually stressed coral T. reniformis experienced a stable and more diverse microbiome community with minimal physiological decline, coupled with very high total energy reserves and particulate organic carbon release rates. Thus, the microbiome changed and microbial diversity decreased in the physiologically sensitive coral with the thermally sensitive endosymbiotic algae but not in the physiologically tolerant coral with the thermally tolerant endosymbiont. Our results confirm recent findings that temperature-stress tolerant corals have a more stable microbiome, and demonstrate for the first time that this is also the case under the dual stresses of ocean warming and acidification. We propose that coral with a stable microbiome are also more physiologically resilient and thus more likely to persist in the future, and shape the coral species diversity of future reef ecosystems.
Parametric study on conical log-spiral antenna

The paper investigates conical shapes of log-spiral antenna in the radiation pattern and the frequency independences of gain and axial ratio. Parametric study is based on numerical modelling using FEKO simulator. Unidirectional radiation pattern appears only at the lowest working frequency for a wider cone angle or appears wideband for the cone angle lower than 20°. The 3dB beamwidth strongly depends on a cone angle and a rate of wrap, and ranges from 80 to 200°.
Isolation of rotavirus from asymptomatic dogs in Brazil

Rotaviruses (Reoviridae: Rotavirus), the causative agents of acute diarrhea in mammals, including man and birds, possess a nonenveloped triple-layered icosahedral capsid about 75nm diameter, with a characteristic 11segmented genome of double-stranded RNA (dsRNA) (Estes and Cohen, 1989). The genus Rotavirus is subdivided both serologically, based on the inner capsid VP6 protein, and electropherotypically, based on the arrangement of the 11 dsRNA segments, into seven groups (A to G). Groups A, B, and C are found in both humans and animals, whereas groups D, E, F, and G have been found only in animals to date. In most cases, the electrophoretic pattern of the genome of group A rotaviruses is composed of four high-molecular-weight dsRNA segments (numbered 1 to 4), two middle-sized segments (5 and 6), a distinctive triplet of segments (7 to 9), and two smaller segments (10 and 11) (Estes and Kapikian, 2007).
Objective determination of benzodiazepine use and abuse in alcoholics.

Summary The extent of concurrent use and abuse of benzodiazepines and alcohol in chronic alcoholics is not known. Prospective data collected on 216 consecutive outpatient referrals between 1 June and 31 July 1981 (age range, 16 to 70 years, 75 per cent men) showed that benzodiazepines were detected in the urine of 33 per cent of patients undergoing medical assessment. Other drugs identified in urine were ethanol (5.0 %), codeine (1.99 %) and barbiturates (1.5 %). According to patient histories, the predictive value of benzodiazepine allegation was high for positive and negative allegation (0.87 and 0.83, respectively), indicating that patients reliably report benzodiazepine use if questioned. However, only one patient considered himself to be a benzodiazepine abuser. The proportion of women with a positive test for benzodiazepines (48%) was significantly higher than that of men (28%: X – 7.7; p 2700 mg of diazepam or equivalent and a positive urine test). These results · indicate that benzodiazepines are very commonly used and abused by alcoholics. Treatment programmes for alcoholics should identify such patients, consider directing treatment toward control of benzodiazepine use, and monitor changes in benzodiazepine use during and after treatment.
Optimizing Strategic Safety Stock Placement in Supply Chains with Clusters of Commonality

Multiechelon inventory optimization is increasingly being applied by business users as new tools expand the class of network topologies that can be optimized. In this paper, we formalize a topology that we call networks with clusters of commonality (CoC), which captures a large class of real-world supply chains that contain component commonality. Viewed as a modified network, a CoC network is a spanning tree where the nodes in the modified network are themselves maximal bipartite subgraphs in the original network. We first present algorithms to identify these networks and then present a single-state-variable dynamic program for optimizing safety stock levels and locations. We next present two reformulations of the dynamic program that significantly reduce computational complexity while preserving the optimality of the resulting solution. This work both incorporates arbitrary safety stock cost functions and makes possible optimizing a large class of practically useful but previously intractable networks. It has been successfully applied at several Fortune 500 companies, including the recent Edelman finalist project at Hewlett Packard described in detail in Billington et al. (2004).
Introduction of protein kinase recognition sites into proteins: a review of their preparation, advantages, and applications.

Labeled proteins are used in a variety of applications. This review focuses on methods that utilize genetic engineering to introduce protein kinase recognition sites into proteins. Many protein kinase recognition sites can be introduced into proteins and serve as useful tags for a variety of purposes. The introduction of protein kinase recognition sites into proteins can be achieved without modifying the essential structure or function of the proteins. Because proteins modified by these procedures retain their activity after phosphorylation, they can be used in many applications. The phosphorylatable proteins can be labeled easily to high specific activity with radioisotopes ((32)P, (33)P, or (35)S), or the nonradioactive (31)P can be used. The use of these radioisotopes provides a convenient and safe method for radiolabeling proteins. Moreover, the use of the nonradioactive (31)P with protein tyrosine kinase recognition sites permits the tagging of proteins and their detection with the many anti-phosphotyrosine antibodies available. Overall, the procedure represents a convenient, safe, and efficient method to label proteins for a variety of applications.
Measuring P700 Absorbance Changes around 830 nm with a New Type of Pulse Modulation System

Abstract A new measuring system for monitoring absorbance changes around 830 n m is described, which was developed by modification of a commercially available pulse modulation fluorometer. All modifications concern the emitter-detector unit of the fluorometer, such that only this unit needs to be exchanged when changing from fluorescence to absorbance measurements and vice versa. The new system is shown to be well-suited for measuring redox changes of P700, the reaction center of photosystem I, in intact leaves and isolated chloroplasts. The observed kinetic changes at 830 nm in response to single turnover or multiple turnover saturating flashes are practically identical to those previously measured around 700 nm . The signal/noise ratio is sufficiently high to give well-resolved kinetics without signal averaging. W h e n P700 is oxidized by far-red background light, valuable information on the state of the intersystem electron transport chain is given by the re-reduction kinetics induced by single or multiple turnover saturating flashes. Such measurements are facilitated by the use of poly-furcated fiberoptics. With intact leaves, almost identical responses are found when measuring through the leaf (transmission mode) or from the leaf surface (remission mode). Modulated chlorophyll fluorescence can be measured in parallel; application of saturation pulses for fluorescence quenching analysis produces transient P700 oxidation without oversaturating the measuring system. The information on the P700 redox state complements that obtained from fluorescence measurements, yielding a new practical tool in plant physiological research.