Miracle-dz/UniFAR-FTUs huggingface dataset:
Hope and recovery: a scoping review

Purpose – Hope is regarded as central to recovery processes. The phenomenon along with its implications for research and practice has, however, gained limited attention within the fields of mental health and substance use. The purpose of this paper is to explore how hope, and what may inspire it, is described within the literature by persons experiencing co-occurring mental health and substance use problems. Design/methodology/approach – The method chosen when conducting this literature review was a scoping study. This allows for a broad approach, aiming to examine research activity and identifying potential gaps within existing literature. Searches were conducted in EMBASE Ovid, PsychINFO Ovid, MEDLINE Ovid, CINAHL Ebsco, SveMed+ and Brithish Nursing Index. Findings – The authors included five articles and one book. None of these presented first-hand experiences of hope and there appears to be a gap in the literature. All included material underlined the importance of the phenomenon to those experiencing.
Massively Parallel Validation of High-Speed Serial Interfaces using Compact Instrument Modules

An extremely dense high-speed serial interface validation tester is presented. By relying on parallelism and on efficient measurement techniques, the proposed tester significantly reduces the time to validate the key parameters for serdes interfaces such as the bit error rate, receiver sensitivity, receiver jitter tolerance, and transmit jitter generation. Key timing specifications include periodic jitter injection with less than 5 psec edge-placement resolution and jitter measurement with 160 fsec sampling delay resolution
Adaptación al castellano y validación psicométrica del cuestionario ID-Pain© para la detección de dolor neuropático

Fundamento y objetivo: El proposito del estudio ha sido realizar la adaptacion cultural al castellano de la escala autoadministrada ID-Pain© y analizar sus propiedades psicometricas como instrumento de deteccion de dolor neuropatico. Material y metodo: Se ha realizado un estudio transversal en 2 fases (adaptacion cultural al castellano y fase de validacion psicometrica), en el que se incluyo consecutivamente a pacientes de ambos sexos mayores de 18 anos, con dolor cronico (> 6 meses) con componente neuropatico (DN) o nociceptivo (DNN). Se valoraron la factibilidad, fiabilidad y validez de la escala con el diagnostico de referencia y con el diagnostico clinico de la escala LANSS (Leeds Assessment of Neuropathic Symptoms and Signs). Se realizaron analisis factorial, curvas de eficacia diagnostica y pruebas de concordancia con el diagnostico de referencia. Se determinaron la sensibilidad, la especificidad y los valores predictivos positivo y negativo. Resultados: Se incluyo en el estudio a 283 pacientes (un 64,4% mujeres), con una edad media (desviacion estandar) de 59,1 (14,9) anos, de los cuales 145 (51,2%) presentaban DN y 138 (48,8%), DNN. El tiempo medio de administracion de la escala fue de 4,2 (3,0) min y solo un 15% de los pacientes necesito ayuda para responder. La escala mostro una unica dimension en el analisis factorial (variancia explicada del 37,5%) y una alta estabilidad en el test-retest (r = 0,98; p < 0,0005). La puntuacion media diferencio claramente entre los pacientes con DN y con DNN: 3,5 (1,2) frente a 1,2 (1,4) puntos (p < 0,0005). El punto de corte optimo se fijo en $ 3 puntos (area bajo la curva = 0,89; p < 0,0005; sensibilidad: 0,81; especificidad: 0,84; kappa = 0,65, con el diagnostico de referencia). La escala mostro una buena validez concurrente con el diagnostico realizado con la escala LANSS (kappa = 0,61; p < 0,0005). Conclusiones: La version adaptada al castellano del ID-Pain© muestra propiedades psicometricas adecuadas como instrumento autoadministrado de deteccion de dolor con componente neuropatico.
The Development of a High-Content Screening Binding Assay for the Smoothened Receptor

In this study, the development of an image-based high-content screening (HCS) binding assay for the seven-transmembrane (7TM) receptor Smoothened (Smo) is described. Using BacMam-based gene delivery of Smo, BODIPY-cyclopamine as a fluorescent probe, and a confocal imaging system, a robust 384-well assay that could be used for high-throughput compound profiling activities was developed. The statistically robust HCS binding assay was developed through optimization of multiple parameters, including cell transduction conditions, Smo expression levels, the image analysis algorithm, and staining procedures. Evaluation of structurally diverse compounds, including functional Smo activators, inhibitors, and related analogs, demonstrated good compound potency correlations between high-content imaging binding, membrane fluorescence polarization binding, and gene reporter assays. Statistical analysis of data from a screening test set of compounds at a single 10-µM concentration suggested that the high-content imaging Smo binding assay is amenable for use in hit identification. The 384-well HCS assay was rapidly developed and met statistical assay performance targets, thus demonstrating its utility as a fluorescent whole-cell binding assay suitable for compound screening and profiling.
Use of Escin as a Perforating Agent on the IonWorks Quattro Automated Electrophysiology Platform

The automated electrophysiology platform IonWorks has facilitated the medium-throughput study of ion channel biology and pharmacology. Electrical and chemical access to the cell is by perforated patch, afforded by amphotericin. Permeation of the amphotericin pore is limited to monovalent cations. We describe here the use of the saponin escin as an alternative perforating agent. With respect to the number and robustness of seals formed across a variety of cell and ion channel types, the performance of escin is equal to that of amphotericin. Escin also permits the permeation of larger molecules through its pore. These include nucleotides, important intracellular modulators of ion channel activity that can be used to prevent ion channel rundown of, for instance, CaV1.2. Furthermore, pharmacologic agents such as QX314 can also permeate and be used for mechanistic studies. Escin, in combination with IonWorks, increases the scope of ion channel screening and can facilitate the assay of previously difficult-to-assay targets.
Dual-Point Competition Association Assay

The concept of ligand-receptor binding kinetics is emerging as an important parameter in the early phase of drug discovery. Since the currently used kinetic assays are laborious and low throughput, we developed a method that enables fast and large format screening. It is a so-called dual-point competition association assay, which measures radioligand binding at two different time points in the absence or presence of unlabeled competitors. Specifically, this assay yields the kinetic rate index (KRI), which is a measure for the binding kinetics of the unlabeled ligands screened. As a prototypical drug target, the adenosine A1 receptor (A1R) was chosen for assay validation and optimization. A screen with 35 high-affinity A1R antagonists yielded seven compounds with a KRI value above 1.0, which indicated a relatively slow dissociation from the target. All other compounds had a KRI value below or equal to 1.0, predicting a relatively fast dissociation rate. Several compounds were selected for follow-up kinetic quantifications in classical kinetic assays and were shown to have kinetic rates that corresponded to their KRI values. The dual-point assay and KRI value may have general applicability at other G-protein-coupled receptors, as well as at drug targets from other protein families.
A low-cost ATE phase signal generation technique for test applications

In this article, an accurate and low-cost clock delay generation system integrated in an automated test equipment (ATE) environment is presented. The input to this system is entirely digital and is driven by a single clock, which can be programmed from the ATE High Speed Digital (HSD) unit. Moreover, the digital input patterns can easily be generated in software off-line; hence, making this system ideal for automated test routines. The system is first discussed and characterized in Matlab under static and dynamic operating conditions. For the static behavior, the impact of the various design tradeoffs on the time resolution is investigated. With regards to the dynamic behavior, the linearity is assessed spectrally with a sinusoidal input and statistically using a Gaussian noise signal. A discrete prototype board is built to validate the correct operation of the system mounted on an ATE to function as a whole. With proper compensation and calibration, a delay resolution of 15 ps was achieved over an 8.4 ns range using a low-speed reference clock running at 16.67 MHz. It is shown through clock scaling that this resolution can improve in direct proportion to increases in the clock frequency.
A Multiplexed Fluorescent Assay for Independent Second-Messenger Systems

There is a growing need in drug discovery and basic research to measure multiple second-messenger components of cell signaling pathways in real time and in relevant tissues and cell types. Many G-protein–coupled receptors activate the heterotrimeric protein, Gq, which in turn activates phospholipase C (PLC). PLC cleaves phosphatidylinositol 4,5-bisphosphate (PIP2) to produce two second messengers: diacylglycerol (DAG), which remains in the plasma membrane, and inositol triphosphate (IP3), which diffuses through the cytosol to release stores of intracellular calcium ions (Ca2+). Our goal was to create a series of multiplex sensors that would make it possible to simultaneously measure two different components of the Gq pathway in living cells. Here we describe new fluorescent sensors for DAG and PIP2 that produce robust changes in green or red fluorescence and can be combined with one another, or with existing Ca2+ sensors, in a live-cell assay. These assays can detect multiple components of Gq signaling, simultaneously in real time, on standard fluorescent plate readers or live-cell imaging systems.
Performance of frequency-hopping multicarrier CDMA on an uplink with correlated Rayleigh fading

This paper examines the bit error rate (BER) performance of a frequency-hopping multicarrier code division multiple-access (FH-MC-CDMA) system in frequency-selective slow fading channels. The performance of FH-MC-CDMA is compared to that of MC-CDMA on an uplink with a tapped delay line (TDL) correlated channel model. FH-MC-CDMA with performance enhancement techniques is proposed as an access technique for future generation broadband wireless networks. It is found that FH-MC-CDMA generally has a much better performance than conventional frequency hopping. In addition, the performance of FH-MC-CDMA with a much smaller number of subcarriers may outperform that of MC-CDMA.
Investigation into voltage and process variation-aware manufacturing test

Traditional test methods that use abstract fault models potentially results in low defect coverage and test escapes for ICs with multiple supply voltage (Vdd) settings for adaptive power management, and in the presence of process variation. In this paper, we address two important defect types, resistive bridge defects and full open defects, and present foundational work on variation-aware test methods. To test ICs with multiple Vdds, Multi-Vdd Test Generation (MVTG) produces Vdd-specific test sets, such that tests are applied using the most effective Vdd. For Process Variation-aware Test Generation (PVTG), we target the most significant test escapes, guided by a novel process variation-aware metric for test quality, called test robustness. We implemented our test methods, and integrated them into a flow of commercial EDA tools. Experimental results on benchmark designs and realistic defects, extracted from layout, show that our test methods achieve high defect coverage while keeping the test sets size low. This serves as proof-of-concept for variation-aware test.
The Nexus of Aβ, Aging, and Sleep

Roh et al. report a positive feedback loop between sleep-wake irregularities and aggregation of β-amyloid (Aβ) peptide, suggesting that sleep alterations could be an early event in Alzheimer’s disease (AD). Roh et al. report a positive feedback loop between sleep-wake irregularities and aggregation of β-amyloid peptide, suggesting that sleep alterations could be an early event in Alzheimer’s disease.
Nonconjugated Polyelectrolyte as Efficient Fluorescence Quencher and Their Applications as Biosensors: Polymer-Polymer Interaction

A simple fluorescence quenching method for the quantitation in serum of an acute phase reactant, C-reactive protein (CRP), which can differentiate between viral and bacterial infections, is described, where material and reagent costs are minimal. The study harnesses a fluorescence quenching between a nonfluorescent polyelectrolyte containing a ligand (O-phosphorylethanolamine, PEA) and fluorophore (fluorescamine isomer 1) containing polyelectrolyte. The quenching was attributed due to strong polymer-polymer interaction through intermolecular hydrogen bonding. The nonlinear behaviour of Stern-Volmer plot indicates a binding induced quenching, that is, static quenching. However, fluorescence was found to increase in presence of C-reactive protein, due to the specific molecular recognition occurring between CRP and PEA, thereby excluding fluorophore containing chain. A definite correlation was found between concentration of CRP and fluorescence intensity and the method exhibited a linear relationship in the range of 40–360 ng/mL with a detection limit of 30 ± 2 ng/mL. The antibody free method was successfully applied for the analysis of CRP in human serum samples and the method showed good correlation with hospital measurements . Thus the fluorescence based polyelectrolyte biosensor is a potential system for rapid, and antibody free platform for CRP detection.
Mucosal Imprinting of Vaccine-Induced CD8+ T Cells Is Crucial to Inhibit the Growth of Mucosal Tumors

Mucosal vaccination induces targeted CD8+ T cell homing to inhibit mucosal tumors. The Nose Knows “Life is a journey, not a destination. ” (Ralph Waldo Emerson) And yet, in the most literal sense, life can depend on both the journey and the destination. The science behind cancer vaccination presupposes that if you can build a sufficient immune response against a tumor, the immune system can be used to attack cancer cells. But what if tumor-targeting cells can’t actually get to the tumor? Sandoval et al. now provide an answer to that question in the context of mucosal tumors. There is a disconnect between successful vaccination of mucosal tumors in animal models and the failure of similar vaccinations in clinical trials. Sandoval et al. hypothesized that the preclinical model systems used—subcutaneous tumors—may provide a partial explanation. Systemically delivered (intramuscular) vaccines successfully inhibited subcutaneous tumors but not those found in the mucosa. The authors then overcame this difficulty by taking a page from infectious disease vaccinology—intranasal immunization. The same vaccine delivered to the mucosa induced tumor-specific CD8+ T cells that inhibited tumor growth in mucosal tumors. These CD8+ T cells expressed CD49a, which correlated to their homing to the mucosa. In this case, although the destination is critical, how you get there is equally important. Although many human cancers are located in mucosal sites, most cancer vaccines are tested against subcutaneous tumors in preclinical models. We therefore wondered whether mucosa-specific homing instructions to the immune system might influence mucosal tumor outgrowth. We showed that the growth of orthotopic head and neck or lung cancers was inhibited when a cancer vaccine was delivered by the intranasal mucosal route but not the intramuscular route. This antitumor effect was dependent on CD8+ T cells. Indeed, only intranasal vaccination elicited mucosal-specific CD8+ T cells expressing the mucosal integrin CD49a. Blockade of CD49a decreased intratumoral CD8+ T cell infiltration and the efficacy of cancer vaccine on mucosal tumor. We then showed that after intranasal vaccination, dendritic cells from lung parenchyma, but not those from spleen, induced the expression of CD49a on cocultured specific CD8+ T cells. Tumor-infiltrating lymphocytes from human mucosal lung cancer also expressed CD49a, which supports the relevance and possible extrapolation of these results in humans. We thus identified a link between the route of vaccination and the induction of a mucosal homing program on induced CD8+ T cells that controlled their trafficking. Immunization route directly affected the efficacy of the cancer vaccine to control mucosal tumors.
Protein − Substrate Adhesion in Microcontact Printing Regulates Cell Behavior

: Microcontact printing ( μ CP) is widely used to create patterns of biomolecules essential for studies of cell mechanics, migration, and tissue engineering. However, di ﬀ erent types of μ CPs may create micropatterns with varied protein − substrate adhesion, which may change cell behaviors and pose uncertainty in result interpretation. Here, we characterize two μ CP methods for coating extracellular matrix (ECM) proteins (stamp-o ﬀ and covalent bond) and demonstrate for the ﬁ rst time the important role of protein − substrate adhesion in determining cell behavior. We found that, as compared to cells with weaker traction force (e.g., endothelial cells), cells with strong traction force (e.g., vascular smooth muscle cells) may delaminate the ECM patterns, which reduced cell viability as a result. Importantly, such ECM delamination was observed on patterns by stamp-o ﬀ but not on the patterns by covalent bonds. Further comparisons of the displacement of the ECM patterns between the normal VSMCs and the force-reduced VSMCs suggested that the cell traction force plays an essential role in this ECM delamination. Together, our results indicated that μ CPs with insu ﬃ cient adhesion may lead to ECM delamination and cause cell death, providing new insight for micropatterning in cell − biomaterial interaction on biointerfaces.
The Fluorescent Two-Hybrid Assay to Screen for Protein–Protein Interaction Inhibitors in Live Cells

Protein–protein interactions (PPIs) are attractive but challenging targets for drug discovery. To overcome numerous limitations of the currently available cell-based PPI assays, we have recently established a fully reversible microscopy-assisted fluorescent two-hybrid (F2H) assay. The F2H assay offers a fast and straightforward readout: an interaction-dependent co-localization of two distinguishable fluorescent signals at a defined spot in the nucleus of mammalian cells. We developed two reversible F2H assays for the interactions between the tumor suppressor p53 and its negative regulators, Mdm2 and Mdm4. We then performed a pilot F2H screen with a subset of compounds, including small molecules (such as Nutlin-3) and stapled peptides. We identified five cell-penetrating compounds as potent p53–Mdm2 inhibitors. However, none exhibited intracellular activity on p53–Mdm4. Live cell data generated by the F2H assays enable the characterization of stapled peptides based on their ability to penetrate cells and disrupt p53–Mdm2 interaction as well as p53–Mdm4 interaction. Here, we show that the F2H assays enable side-by-side analysis of substances’ dual Mdm2–Mdm4 activity. In addition, they are suitable for testing various types of compounds (e.g., small molecules and peptidic inhibitors) and concurrently provide initial data on cellular toxicity. Furthermore, F2H assays readily allow real-time visualization of PPI dynamics in living cells.
SEC-TID

Bioactive small molecules are an invaluable source of therapeutics and chemical probes for exploring biological pathways. Yet, significant hurdles in drug discovery often come from lacking a comprehensive view of the target(s) for both early tool molecules and even late-stage drugs. To address this challenge, a method is provided that allows for assessing the interactions of small molecules with thousands of targets without any need to modify the small molecule of interest or attach any component to a surface. We describe size-exclusion chromatography for target identification (SEC-TID), a method for accurately and reproducibly detecting ligand-macromolecular interactions for small molecules targeting nucleic acid and several protein classes. We report the use of SEC-TID, with a library consisting of approximately 1000 purified proteins derived from the protein databank (PDB), to identify the efficacy targets tankyrase 1 and 2 for the Wnt inhibitor XAV939. In addition, we report novel interactions for the tumor-vascular disrupting agent vadimezan/ASA404 (interacting with farnesyl pyrophosphate synthase) and the diuretic mefruside (interacting with carbonic anhydrase XIII). We believe this method can dramatically enhance our understanding of the mechanism of action and potential liabilities for small molecules in drug discovery pipelines through comprehensive profiling of candidate druggable targets.
Cross-layer approaches for an aging-aware design of nanoscale microprocessors: Dissertation summary: IEEE TTTC E.J. McCluskey doctoral thesis award competition finalist

As CMOS technologies enter nanometer scales, maintaining the microprocessor reliability becomes a major design challenge. In particular, accelerated transistor aging is a serious reliability concern, as it considerably reduces the operational microprocessor lifetime. To address this issue, in this work cross-layer solutions for aging modeling and simulation as well as mitigation are investigated and proposed, to be able to co-optimize reliability together with the traditional design constraints such as power, performance, and cost. Therefore, the knowledge from several abstraction layers, ranging from circuit to architecture-level, are exploited for cost-effective aging-aware micro-architecture design. The detailed simulations and experimental analysis performed in this work show the benefits of this approach over state-of-the-art single-layer solutions.
On the performance improvement through the use of parallel interference cancellation in channel estimation for multipath CDMA systems

A decoupled maximum likelihood (DEML) estimator is employed to estimate the multipath delays and channel coefficients of all users. This estimator starts with a training mode then reverts to a decision-directed mode. In the training mode, the initial values of multipath delays and channel coefficients of all users are estimated. These initial parameters are used for parallel multiuser interference cancellation. Once the multiuser interference is cancelled, the signal is fed back to the estimator for fine estimation of delays and channel coefficients of all users. These fine estimates are used for the next symbol interval. This process continues in the decision-directed modes. The performance of channel estimation with interference cancellation has shown considerable improvement under multipath environments compared to the one without interference cancellation. Conclusively, the proposed scheme removes the intersymbol interference (ISI) resulting from multipath propagation and obtains more accurate channel estimates for further data detection. Finally, analysis is done to justify the simulation results.