Miracle-dz/UniFAR-FTUs huggingface dataset:
Simplifying system-on-chip design through architecture and system cad tools

Historically designers created computing systems by combining Integrated Circuits (ICs) on Printed Circuit Boards (PCBs), whereas now they are able to form complete Systems-on-Chip (SoCs). For the purpose of this study, SoCs are defined as a collection of functional units on one chip that interact to perform a desired operation. These modules are typically of a coarse granularity to promote reuse of previously designed Intellectual Property (IP). The decreasing size of process technologies enables designers to implement increasingly complex SoCs using both Application Specific Integrated Circuits (ASICs) and Field Programmable Gate Arrays (FPGAs). The impact of increasing design complexity is increased design time and costs for electronics. Therefore, this research investigates methods to facilitate the design of SoCs through both architecture and CAD tools. This thesis has two main contributions. The first is an architectural framework for SoCs, wherein they are modelled as Systems Integrating Modules with Predefined Physical Links (SIMPPL). The strength of the model is the Computing Element (CE) abstraction that separates the module's datapath from system-level control and communications to facilitate design reuse. Although SIMPPL can be used to build SoCs for ASICs or FPGAs, using an FPGA provides designers with a reprogrammable implementation platform. Thus, our second contribution is to develop a design infrastructure that leverages the advantages of reconfigurability.
Representing an ensemble of NMR-derived protein structures by a single structure

The usefulness of representing an ensemble of NMR-derived protein structures by a single structure has been investigated. Two stereochemical properties have been used to assess how a single structure relates to the ensemble from which it was derived, namely the distribution of +$ torsion angles and the distribution of x1 torsion angles. The results show that the minimized average structure derived from the ensemble (a total of 11 ensembles from the Brookhaven Protein Data Bank were analyzed) does not always correspond well with this ensemble, particularly for those ensembles generated with a smaller number of experimentally derived restraints per residue. An alternative method that selects the member of the ensemble which is closest to the “average” of the ensemble has been investigated (a total of 23 ensembles from the Brookhaven Protein Data Bank were analyzed). Although this method selected a structure that on the whole corresponded more closely to the ensemble than did the minimized average structure, this is still not a totally reliable means of selecting a single structure to represent the ensemble. This suggests that it is advisable to study the ensemble as a whole. A study has also been made of the practice of selecting the “best” rather than the most representative member of the ensemble. This too suggests that the ensemble should be studied as a whole. A study of the conformational space occupied by the ensemble also suggests the need to consider the ensemble as a whole, particularly for those ensembles generated with a smaller number of experimentally derived restraints per residue.
Clothoid spline based path planning

Path planning for long vehicles plays an important role in safe and efficient operation, especially for those with very large lateral and longitudinal sizes driving in narrow spaces. To address this issue, we start with generalizing a kinematic bicycle model to represent different types of vehicles, based on which a path planning framework composed of a local path planner and a global path planner is developed. During the local planning phase, feasible path primitives are generated subject to kinematic constraints of the curvature maxima and the angular acceleration upper bound. By designing a family of path primitives with clothoid arcs involved which can be efficiently configured according to the given environment and reference points in physical space referred to as waypoints, we are able to obtain a near-optimal solution without numerically solving the two point boundary value problem to generate a feasible path connecting two states under differential constraints. During the global planning phase, the local path planner can be conveniently integrated with sampling based frameworks like the rapidly exploring random tree, which complies with the kinematic constraints when sampling the new states and expanding towards unexplored space. Meanwhile, an efficient clothoid approximation method is presented based on the minimization of curvature profile difference. Quintic Bézier curves are used to ensure higher order geometric continuity with smaller approximation error, and the data is stored in a lookup table to reduce the computing time. The developed methodology is novel and effective, which is capable of addressing a class of nonholonomic planning problems successfully subject to curvature and angular acceleration constraints.
ERYTHROCYTE MEMBRANE-SKELETAL COHESION AND ITS CONTROL OF SPECTRIN SELF-ASSOCIATION †

Spectrin tetramer is the major structural member of the membrane-associated skeletal network of red cells. We show here that disruption of the spectrin-ankyrin-band 3 link to the membrane leads to dissociation of a large proportion of the tetramers into dimers. Non-covalent perturbation of the linkage was induced by a peptide containing the ankyrin-binding site of the spectrin β -chain, and covalent perturbation by treatment with the thiol reagent, N-ethylmaleimide (NEM). This reagent left the intrinsic self-association capacity of the spectrin dimers unaffected, and affected only the ankyrin-band 3 interaction. The dissociation of spectrin tetramers on the membrane into functional dimers was confirmed by the binding of a spectrin peptide directed against the self-association sites. Dissociation of the tetramers resulted, we infer, from detachment of the proximal ends of the constituent dimers from the membrane, thereby reducing their proximity to one another and thus their association. The measured affinity of the interaction of the peptides with the free dimer ends on the membrane permits an estimate of the equilibrium between intact and dissociated tetramers on the native membrane. This indicates that in the physiological state the equilibrium proportion of the dissociated tetramers may be as high as 5-10%. These findings enabled us to identify an additional important functional role for spectrin-ankyrin-band 3 link in regulating spectrin self-association in the red cell membrane. the need for a re-examination of the structural basis of spectrin self-association and its relation to membrane elasticity.
Multi Transporters Generation for High Density Molecule Transportation via Optical Communication

We propose a novel system of a quantum-molecular cryptography using the op- tical tweezers, whereas the transportation of molecules in the communication system can be performed. The molecule transportation states can be identifled by using a single photon state of the transporter, which can be formed in the transmission line. The proposed fabricated ma- terial used is InGaAsP/InP, which can provide the required output signals. The design system consists of a nonlinear microring/nanoring resonator system incorporating an add/drop fllter and a quantum signal processor. The transporter can be formed by the dark soliton, where the optical transporter is tuned and attenuated to be a single photon by the bright soliton control and transmitted into the link. In applications, the use of the proposed system incorporating a quantum processor can be performed the secured molecular communication. 1. INTRODUCTION Recently, several research works have shown that use of dark and bright soliton in various ap- plications can be realized (1{6), where one of them has shown that the secured signals in the communication link can be retrieved by using a suitable an add/drop fllter that is connected into the transmission line. The other promising application of a dark soliton signal (7) is for the large guard band of two difierent frequencies which can be achieved by using a dark soliton generation scheme and trapping a dark soliton pulse within a nanoring resonator (8). Furthermore, the dark soliton pulse shows a more stable behavior than the bright solitons with respect to the perturba- tions such as amplifler noise, flber losses, and intra-pulse stimulated Raman scattering (9). It is found that the dark soliton pulses propagation in a lossy flber, spreads in time at approximately half the rate of bright solitons. Recently, the localized dark solitons in the add/drop fllter has been reported (10). In this paper, the use of dark and bright solitons propagating within the pro- posed ring resonator systems is investigated and described, where the use of suitable parameters based on the realistic device is discussed. The potential of using the generated dark soliton signals for single photon tweezer and molecular transporter, especially, for the hybrid quantum-molecular communication and transportation in the communication network, which is described in details. Bright and dark soliton pulses are introduced into the multi-stage nanoring resonators as shown in Fig. 1, the input time dependent optical fleld (Ein) of the bright and dark soliton pulses input are given by an Equations (1) and (2) (8), respectively.
Functional Analysis of Phenylalanine Residues in the Active Site of CYP2C9 †

The two published crystal structures of CYP2C9, complexed with (S)- warfarin or flurbiprofen, implicate a cluster of three active-site phenylalanine residues (F100, F114, F476) in ligand binding. However, these three residues appear to interact differently with these two ligands based on the static crystal structures. To elucidate the importance of CYP2C9’s active site phenylalanines on substrate binding, orientation and catalytic turnover, a series of leucine and tryptophan mutants was constructed and their interactions with (S)- warfarin and (S)- flurbiprofen examined. The F100 → L mutation had minor effects on substrate binding and metabolism of each substrate. In contrast, the F114L and F476L mutants exhibited substantially reduced (S)- warfarin metabolism and altered hydroxy metabolite profiles, but only modestly decreased NSAID turnover, while maintaining product regioselectivity. The F114 → W and F476 → W mutations also had opposing effects on (S)-warfarin versus NSAID turnover. Notably, the F476W mutant increased the efficiency of (S)-warfarin metabolism 5-fold, yet decreased the efficiency of (S)- flurbiprofen turnover 20-fold. 1 H-NMR T 1 relaxation studies suggested a slightly closer positioning of (S)- warfarin to the heme in the F476W mutant relative to the wild-type enzyme, and stoichiometry studies indicated enhanced coupling of reducing equivalents to product formation for (S)- warfarin, again in contrast to effects observed with (S)- flurbiprofen. These data demonstrate that F114 and F476, but not F100, influence (S)- warfarin’s or tryptophan, to modulate steric bulk and aromaticity, respectively, in order to investigate the effects on spectral binding, steady-state turnover kinetics and metabolite profiles. These studies indicate that the F476 residue, in particular, interacts differentially with (S)- warfarin and (S)- flurbiprofen. 1 H-NMR T 1 relaxation and stoichiometry studies were performed in order to evaluate the mechanism of the gain of function observed for (S)- warfarin metabolism by the F476W mutant.
Large and Small Animal Models of Heart Failure With Reduced Ejection Fraction

Heart failure (HF) describes a heterogenous complex spectrum of pathological conditions that results in structural and functional remodeling leading to subsequent impairment of cardiac function, including either systolic dysfunction, diastolic dysfunction, or both. Several factors chronically lead to HF, including cardiac volume and pressure overload that may result from hypertension, valvular lesions, acute, or chronic ischemic injuries. Major forms of HF include hypertrophic, dilated, and restrictive cardiomyopathy. The severity of cardiomyopathy can be impacted by other comorbidities such as diabetes or obesity and external stress factors. Age is another major contributor, and the number of patients with HF is rising worldwide in part due to an increase in the aged population. HF can occur with reduced ejection fraction (HF with reduced ejection fraction), that is, the overall cardiac function is compromised, and typically the left ventricular ejection fraction is lower than 40%. In some cases of HF, the ejection fraction is preserved (HF with preserved ejection fraction). Animal models play a critical role in facilitating the understanding of molecular mechanisms of how hearts fail. This review aims to summarize and describe the strengths, limitations, and outcomes of both small and large animal models of HF with reduced ejection fraction that are currently used in basic and translational research. The driving defect is a failure of the heart to adequately supply the tissues with blood due to impaired filling or pumping. An accurate model of HF with reduced ejection fraction would encompass the symptoms (fatigue, dyspnea, exercise intolerance, and edema) along with the pathology (collagen fibrosis, ventricular hypertrophy) and ultimately exhibit a decrease in cardiac output. Although countless experimental studies have been published, no model completely recapitulates the full human disease. Therefore, it is critical to evaluate the strength and weakness of each animal model to allow better selection of what animal models to use to address the scientific question proposed.
Lymphatic filariasis: diagnosis and pathogenesis*

Detection of parasites. The parasitological methods available for detection of microfilariae, such as the use of the thick blood film, counting chamber, Knott's concentration technique, membrane filtration techniques and the DEC (diethylcarbamazine) provocative test are described in detail in the WHO manual Control of lymphatic filariasis (1) and in the fourth report of the WHO Expert Committee on Filariasis (2). In addition, a test for detection of microfilariae in preserved blood using membrane filters has recently been developed (3); the preservation of blood samples in a mixture of formalin and anionic detergent makes it possible to utilize the convenience and sensitivity of membrane filtration while eliminating the need to perform tests immediately after blood is collected.
Citalopram for continuation therapy following repetitive transcranial magnetic stimulation (rTMS) in vascular depression

Objectives— We previously reported that repetitive transcranial magnetic stimulation (rTMS) produced a response rate of 39.4% among 62 patients with treatment resistant vascular depression. The current study was undertaken to assess the outcome of continuation therapy to prevent relapse among these patients during 9 weeks after completion of rTMS. Design— Patients were randomly assigned to 18,000 pulses of rTMS given over 3 weeks or sham treatment using double blind methods. Following rTMS, all patients were given 20 mg per day of citalopram for 9 weeks and reevaluated at 3, 6 and 9 weeks. Setting— Outpatient continuation treatment trial. Participants— Patients with vascular depression (n=62), as determined by MRI hyperintensities and/or 3 or more clinical risk factors for vascular disease without other major medical illness, were recruited. They had onset of major depression after age 50 and failed at least one trial of antidepressants. Intervention— Following rTMS or sham treatment, all treatment responders were given citalopram for 9 weeks. Results— Among the 33 patients given rTMS, 13 responded (i.e. >50% decline in Hamilton Depression Scale score). Of these 13, all completed the 9 weeks of continuation treatment. There were 9 patients who continued to be responders and 4 who had a relapse of depression. Conclusion— More effective methods are needed to treat elderly patients with treatment resistant vascular depression and to prevent relapse among treatment responders.
Crystallization and preliminary X-ray crystallographic properties of Hsc20, a J-motif co-chaperone protein from Escherichia coZi

: Hsc20 is a 20-kDa auxiliary protein that functions with the molecular chaperone Hsc66 in Escherichia coli. Crystals of Hsc20 suitable for X-ray diffraction analysis were grown using the hanging drop vapor diffusion technique in polyethylene glycol 400 containing dioxane as an additive to slow growth. The crystals are monoclinic and belong to the space group C2 with unit cell dimensions u = 125.4 A, b = 71.9 A, c = 68.8 A, and p = 97.0". The crystals diffract to a minimum d-spacing of -2.5 A resolution, and a native data set was collected to 2.7 A. The results of a self-rotation function analysis revealed threefold symmetry, suggesting three molecules of Hsc20 in the asymmetric unit and, hence, 12 molecules in the unit cell; this corresponds to a V,, value of 2.6 A3/Da and a solvent content of -53% in the crystals. Structure determination by isomorphous replacement is in progress.
TNF α induces sustained signaling and a prolonged and unremitting inflammatory response in synovial fibroblasts

, Abstract Objective— The non resolving character of synovial inflammation in rheumatoid arthritis (RA) is a conundrum. To identify the contribution of fibroblast-like synoviocytes (FLS) to the perpetuation of synovitis, we investigated the molecular mechanisms that govern the TNF α -driven inflammatory program in human FLS. Methods— FLS obtained from synovial tissues of patients with RA or osteoarthritis were stimulated with TNF α and assayed for gene expression and cytokine production by qPCR and ELISA. NF- κ B signaling was evaluated using Western blotting. Histone acetylation, chromatin accessibility, and NF- κ B p65 and RNA polymerase II (Pol II) occupancy at the IL6 promoter were measured by chromatin immunoprecipitation and restriction enzyme accessibility assays. Results— In FLS, TNF α induced prolonged transcription of IL6 and progressive accumulation of IL-6 protein over four days. Similarly, induction of CXCL8/IL-8, CCL5/RANTES, MMP1 and MMP3 mRNA after TNF α stimulation was sustained for several days. This contrasted with the macrophage response to TNF α , which characteristically involved a transient increase in the expression of pro-inflammatory genes. In FLS, TNF α induced prolonged activation of NF- κ B signaling and sustained transcriptional activity indicated by increased histone acetylation, chromatin accessibility, and p65 and Pol II occupancy at the IL6 promoter. Furthermore, FLS expressed low levels of the feedback inhibitors ABIN3, IRAK-M, SOCS3 and ATF3 that terminate inflammatory responses in macrophages. Conclusions— TNF α signaling is not effectively terminated in FLS, leading to an uncontrolled inflammatory response. The results suggest that prolonged and sustained inflammatory responses by FLS, in response to synovial TNF α , contribute to the persistence of synovial inflammation in RA.
P22 Arc repressor: Enhanced expression mutants by addition of polar C-terminal of unstable sequences

Many mutant variants of the P22 Arc repressor are subject to intracellular proteolysis in Escherichia coli, which precludes their expression at levels sufficient for purification and subsequent biochemical characterization. Here we examine the effects of several different C-terminal extension sequences on the expression and activity of a set of Arc mutants. We show that two tail sequences, KNQHE (st5) and H,KNQHE (st1 I), increase the expression levels of most mutants from 10- to 20-fold and, in some cases, result in restoration of biological activity in the cell. A third tail sequence, HHHHHH (st@, was not as effective in increasing mutant expression levels. All three tail sequences are functionally and structurally silent, as judged by their lack of effects on the DNA binding activity and stability of otherwise wild-type Arc. The properties of the st1 1 tail sequence make it an efficient system for the expression and purification of mutant Arc proteins, both because mutant expression levels are increased and because the proteins can be rapidly purified using nickel-chelate affinity chromatography. Arc mutants containing the EA28, RL31, and SA32 mutations were purified in the st1 1 background. The thermodynamic stability of the EA28 mutant (AAG, = -0.4 kcal/mol) is reduced modestly compared to the st1 1 parent, whereas the RL31 mutant (AAG, = -3.0 kcal/mol) and SA32 mutant (AAG, = -3.3 kcal/mol) are substantially less stable.
Comparison of autoantibody specificities between traditional and bead-based assays in a large, diverse collection of SLE patients and family members

Objective— The replacement of standard immunofluorescence anti-nuclear antibody (ANA) methods with bead-based assays is a new clinical option. A large, multi-racial cohort of SLE patients, blood relatives and unaffected control individuals was evaluated for familial aggregation and subset clustering of autoantibodies by high-throughput serum screening technology and traditional methods. Methods— Serum samples (1,540 SLE patients, 1,127 unaffected relatives, and 906 healthy, population-based controls) were analyzed for SLE autoantibodies using a bead-based assay, immunofluorescence, and immunodiffusion. Autoantibody prevalence, disease sensitivity, clustering, and association with standard immunodiffusion results were evaluated. Results— ANA frequency in SLE patient sera were 89%, 73%, and 67% by BioPlex 2200 and 94%, 84%, and 86% by immunofluorescence in African-American, Hispanic, and European-American patients respectively. 60kD values across racial groups, provide useful information for clinical care, and provide unique insights to familial aggregation and autoantibody clustering.
The 3His Triad in Dke1: Comparisons to the Classical Facial Triad

The oxygen activating mononuclear non-heme ferrous enzymes catalyze a diverse range of chemistry yet typically maintain a common structural motif: two histidines and a carboxylate coordinating the iron center in a facial triad. A new Fe II coordinating triad has been observed in two enzymes, diketone cleaving dioxygenase, Dke1, and cysteine dioxygenase (CDO) and is composed of three histidine residues. The effect of this 3 His motif in Dke1 on the geometric and electronic structure of the Fe II center is explored via a combination of absorption, CD, MCD and VTVH MCD spectroscopies and DFT calculations. This geometric and electronic structure of the 3 His triad is compared to that of the classical (2-His-1-carboxylate) facial triad in the α ketoglutarate ( α KG) dependent dioxygenases clavaminate synthase 2 (CS2) and hydroxyphenylpyruvate dioxygenase (HPPD). Comparison of the ligand fields at the Fe II shows little difference between the 3 His and 2-His-1-carboxylate facial triad sites. Acac, the substrate for Dke1, will also bind to HPPD and is determined to be a strong donor, similar to α KG. The major difference between the 3 His and 2-His-1-carboxylate facial triad sites is in MLCT transitions observed for both types of triads and reflects their difference in charge. These studies provide insight into the effects of perturbation of the facial triad ligation of the non-heme ferrous enzymes on their geometric and electronic structure