gebhart/patrepeval huggingface dataset:
Path delay fault simulation of sequential circuits (2000)

A differential algorithm for concurrent simulation of path delay faults in sequential circuits is presented. The simulator analyzes all three conditions, namely, initialization, signal transition propagation through the path, and fault effect observation at a primary output for vector pairs and considers the hazard states occurring between vectors. The main contribution is in methods of propagating signals between time frames. An optimistic method assumes that all nondestination flip-flops are not affected by delays. The pessimistic method converts all nondestination flip-flops with nonsteady values to the unknown state before these values are propagated beyond the time frame in which a path is activated. A 13-valued algebra is shown to improve the efficiency of fault simulation.
Microwave interrogation of dielectric targets. Part II: By microwave time delay spectroscopy (1978)

A method is described which overcomes the problems of multipath propagation and range ambiguity that is suffered by the single-frequency continuous-wave microwave-imaging system described in part I. This technique is essentially a variation of chrip radar techniques, which have been adapted to time delay and attenuation measurements through a target. The feasibility of discriminating between paths whose differential time delay is on the order of 100 ps is demonstrated. Further, the need for small physical aperture in the transmitting and receiving antennas is demonstrated.
Combination of light sources and light distribution using manifold optics (2006)

Light from several LEDs or other light sources may be combined using light guides shaped as manifolds. These manifolds are composed of smaller elements such as CPCs, angle transformers, angle rotators, light shifters, light guides or others. Although some components, such as CPCs or angle transformers, have all-optical surfaces, other devices may be designed with non-optical surfaces. These may be used to place the injection gate in the case of injection-molded optics, to attach handles or holders and other non-optical components to the manifold without affecting the optical performance. Also, in some of these devices, the geometry can be changed by simple changes in the position of the curves that compose the optic profile. These optics may be applied in efficiently combining light from several LEDs into one single large source, changing the aspect ratio of a light source or in distributing light from one (or more) sources onto several targets.
Electron Decelerator for Improved CCD Performance In Intermediate Voltage Electron Microscopy (2000)

Abstract There are many advantages of IVEMs over more conventional microscopes, all of which make it possible to obtain more accurate data at higher resolution. One significant drawback of higher accelerating voltages is degraded performance of the electron detector, a problem that is particularly serious with CCD cameras. At any voltage, one faces a tradeoff with the CCD performance between sensitivity and resolution. Electron scattering within the scintillator and its support broaden the point spread function, while the decreased scattering cross section at higher voltages decreases the light output from the scintillator. At voltages much above 100 kV these effects have been found to seriously limit CCD performance. With the trend towards electronic data collection and microscope automation, it is essential that a high performance detector be developed for the IVEM. One approach to optimizing the performance tradeoff employs lens coupling to improve resolution, at the expense of sensitivity.
A three-stage enhanced reactive power and voltage optimization method for high penetration of solar (2017)

This paper presents a three-stage enhanced volt/var optimization method to stabilize voltage fluctuations in transmission networks by optimizing the usage of reactive power control devices. In contrast with existing volt/var optimization algorithms, the proposed method optimizes the voltage profiles of the system, while keeping the voltage and real power output of the generators as close to the original scheduling values as possible. This allows the method to accommodate realistic power system operation and market scenarios, in which the original generation dispatch schedule will not be affected. The proposed method was tested and validated on a modified IEEE 118-bus system with photovoltaic data.
Tissue-Engineered Tendon for Enthesis Regeneration in a Rat Rotator Cuff Model (2017)

Healing of rotator cuff (RC) injuries with current suture or augmented scaffold techniques fails to regenerate the enthesis and instead forms a weaker fibrovascular scar that is prone to subsequent failure. Regeneration of the enthesis is the key to improving clinical outcomes for RC injuries. We hypothesized that the utilization of our tissue-engineered tendon to repair either an acute or a chronic full-thickness supraspinatus tear would regenerate a functional enthesis and return the biomechanics of the tendon back to that found in native tissue. Engineered tendons were fabricated from bone marrow-derived mesenchymal stem cells utilizing our well-described fabrication technology. Forty-three rats underwent unilateral detachment of the supraspinatus tendon followed by acute (immediate) or chronic (4 weeks retracted) repair by using either our engineered tendon or a trans-osseous suture technique. Animals were sacrificed at 8 weeks. Biomechanical and histological analyses of the regenerated enthesis and tendon were performed. Statistical analysis was performed by using a one-way analysis of variance with significance set at <i>p</i> < 0.05. Acute repairs using engineered tendon had improved enthesis structure and lower biomechanical failures compared with suture repairs. Chronic repairs with engineered tendon had a more native-like enthesis with increased fibrocartilage formation, reduced scar formation, and lower biomechanical failure compared with suture repair. Thus, the utilization of our tissue-engineered tendon showed improve enthesis regeneration and improved function in chronic RC repairs compared with suture repair. <i>Clinical Significance:</i> Our engineered tendon construct shows promise as a clinically relevant method for repair of RC injuries.
Discovery and Application of Doubly Quaternized Cinchona‐Alkaloid‐Based Phase‐Transfer Catalysts (2014)

Abstract We report the discovery of novel N , N ′‐disubstituted cinchona alkaloids as efficient phase‐transfer catalysts for the assembly of stereogenic quaternary centers. In comparison to traditional cinchona‐alkaloid‐based phase‐transfer catalysts, these new catalysts afford substantial improvements in enantioselectivity and reaction rate for intramolecular spirocyclization reactions with catalyst loadings as low as 0.3 mol % under mild conditions.
A WT1 protein‐derived, naturally processed 16‐mer peptide, WT1<sub>332</sub>, is a promiscuous helper peptide for induction of WT1‐specific Th1‐type CD4<sup>+</sup> T cells (2008)

The Wilms' tumor gene WT1 is overexpressed in various tumors, and the WT1 protein has been demonstrated to be an attractive target antigen for cancer immunotherapy. A WT1 protein-derived 16-mer peptide, WT1(332) (KRYFKLSHLQMHSRKH), which was naturally generated through processing in cells and could elicit Th1-type CD4(+) helper T cell responses with an HLA-DRB1*0405-restriction has previously been identified by us. In the present study, it has been demonstrated that WT1(332) can induce WT1(332)-specific CD4(+) T cell responses with the restriction of not only HLA-DRB1*0405 but also HLA-DRB1*1501, -DRB1*1502, or -DPB1*0901. These HLA class II-restricted WT1(332)-specific CD4(+) T cell lines produced IFN-gamma but neither IL-4 nor IL-10 with WT1(332) stimulation, thus showing a Th1-type cytokine profile. Furthermore, HLA-DRB1*1501 or -DRB1*1502-restricted WT1(332)-specific CD4(+) T cell lines responded to WT1-expressing transformed cells in an HLA-DRB1-restricted manner, which is consistent with our previous finding that WT1(332) is a naturally processed peptide. These results indicate that the natural peptide, WT1(332), is a promiscuous WT1-specific helper epitope. WT1(332) is expected to apply to cancer patients with various types of HLA class II as a WT1-specific helper peptide in combination with HLA class I-restricted WT1 peptides.
Measurement of particle-size distribution and volume fraction in concentrated suspensions with photon migration techniques (1997)

The determination of the particle size distribution and the volume fraction in concentrated suspensions from the multiwavelength measurement of isotropic-scattering coefficients by use of frequency-domain photon migration techniques is demonstrated for three different polydisperse polystyrene suspensions. When a Newton-type inverse algorithm is used, the successful recovery of the particle size distribution, in the form of a Weibull function, and the volume fraction of polystyrene suspensions is achieved. Our results are in excellent agreement with dynamic light-scattering size distribution measurements. On consideration of the particle mass conservation as an additional constraint penalty term in the inverse algorithm, it is shown that the quality of the particle size distribution reconstruction can be improved. Because no calibration is needed, photon migration techniques are especially suited for on-line measurement of the particle size distribution and the volume fraction in the chemical- and the pharmaceutical-based industries.
An anti-EGFR × cotinine bispecific antibody complexed with cotinine-conjugated duocarmycin inhibits growth of EGFR-positive cancer cells with KRAS mutations (2018)

Antibody-drug conjugates (ADCs) can selectively deliver cytotoxic agents to tumor cells and are frequently more potent than naked antibodies. However, optimization of the conjugation process between antibodies and cytotoxic agents and characterization of ADCs are laborious and time-consuming processes. Here, we describe a novel ADC platform using a tetravalent bispecific antibody that simultaneously binds to the tumor-associated antigen and a hapten conjugated to a cytotoxic agent. We selected cotinine as the hapten because it is not present in biological systems and is inert and nontoxic. We prepared an anti-epidermal growth factor receptor (EGFR) × cotinine bispecific antibody and mixed it with an equimolar amount of cotinine-conjugated duocarmycin to form the ADC. This ADC showed significant in vitro and in vivo antitumor activity against EGFR-positive, cetuximab-refractory lung adenocarcinoma cells with KRAS mutations.
Noncalcemic Actions of Vitamin D Receptor Ligands (2005)

1alpha,25-Dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], the active metabolite of vitamin D(3), is known for the maintenance of mineral homeostasis and normal skeletal architecture. However, apart from these traditional calcium-related actions, 1,25-(OH)(2)D(3) and its synthetic analogs are being increasingly recognized for their potent antiproliferative, prodifferentiative, and immunomodulatory activities. These actions of 1,25-(OH)(2)D(3) are mediated through vitamin D receptor (VDR), which belongs to the superfamily of steroid/thyroid hormone nuclear receptors. Physiological and pharmacological actions of 1,25-(OH)(2)D(3) in various systems, along with the detection of VDR in target cells, have indicated potential therapeutic applications of VDR ligands in inflammation (rheumatoid arthritis, psoriatic arthritis), dermatological indications (psoriasis, actinic keratosis, seborrheic dermatitis, photoaging), osteoporosis (postmenopausal and steroid-induced osteoporosis), cancers (prostate, colon, breast, myelodysplasia, leukemia, head and neck squamous cell carcinoma, and basal cell carcinoma), secondary hyperparathyroidism, and autoimmune diseases (systemic lupus erythematosus, type I diabetes, multiple sclerosis, and organ transplantation). As a result, VDR ligands have been developed for the treatment of psoriasis, osteoporosis, and secondary hyperparathyroidism. Furthermore, encouraging results have been obtained with VDR ligands in clinical trials of prostate cancer and hepatocellular carcinoma. This review deals with the molecular aspects of noncalcemic actions of vitamin D analogs that account for the efficacy of VDR ligands in the above-mentioned indications.
Modeling and design of a tunable refractive lens based on liquid crystals (2011)

We show the modeling, design and fabrication for a tunable refractive lens based on liquid crystals. The lens has about 80 rings of transparent ITO conductor with an inter-ring resistor network. The width of each electrode is calculated to have maximum phase step within each electrode region about 1/8 λ. The gap between any 2 adjacent electrodes is 3 μm. The active diameter is about 4.7 mm, and our lens has a substrate gap of 10 μm, filled with a LC material of a large birefringence of Δn = 0.27. Through a via in a SiO<sub>2</sub> layer deposited on the ITO pattern, we run metal lines to every 10<sup>th</sup> ring electrode for establishing the voltage profile, which is calculated by our simulation, taking into account the details of the electrode structure, the properties of the LC material used, and the desired focal length. To characterize the optical performance: we use a Mach-Zehnder interferometer to obtain the actual phase profile across the lens aperture, which fits the calculation very well in parabolic shape. An eye chart image through the lens is also taken, which shows very good resolution and contrast.
Cyclic Sulfones as Novel P3-Caps for Hepatitis C Virus NS3/4A (HCV NS3/4A) Protease Inhibitors: Synthesis and Evaluation of Inhibitors with Improved Potency and Pharmacokinetic Profiles (2010)

HCV infection affects more than 170 million people worldwide and many of those patients will reach the end stage complications of the disease which include hepatocarcinoma and liver failure. The success rate for treatment of patients infected with genotype-1 is about 40%. Therefore, novel treatments are needed to combat the infection. The HCV NS3 protease inhibitor Boceprevir (1) was reported by our research group and efforts continue for the discovery of more potent compounds with improved pharmacokinetic profiles. A new series of HCV NS3 protease inhibitors having a cyclic sulfone P3-cap have been discovered. Compounds 43 and 44 showed K(i)* values in the single-digit nM range and their cellular potency was improved by 10-fold compared to 1. The pharmacokinetic profiles of 43 and 44 in rats and monkeys were also improved to achieve higher plasma levels after oral administration.
Renally Clearable PSMA Inhibitors Conjugated Ultrasmall Silica Nanoparticles Enhance the Specific Detection of Prostate Cancer In Vivo (2018)

467 Objectives: To investigate in vivo pharmacokinetics and prostate cancer active targeting capability of novel renally-clearable zirconium-89 (89Zr, t1/2=78.4 h)-labeled, PSMA inhibitor (PSMAi)-conjugated, ultrasmall fluorescent silica nanoparticles. Methods: Sub-10-nm diameter, DFO-, PSMAi-, PEG- and Cy5-functionalized C’ dots (i.e., DFO-PSMAi-PEG-Cy5-C’ dots) were synthesized in water-based environments. High resolution chromatographic techniques, including size exclusion/gel permeation chromatography, high-performance liquid chromatography, and fluorescence correlation spectroscopy were used to initially purify and characterize synthesized DFO-PSMAi-PEG-Cy5-C’ dots. Optimized nano-conjugates were additionally assessed in terms of their radio-stability, pharmacokinetic/clearance profiles, radiation dosimetry, PSMA- targeting and tumor-to-background ratios using serial positron emission tomography (PET) imaging. Results: DFO-PSMAi-PEG-Cy5-C’ dots were surface-functionalized with 3-4 DFO chelators and ~10 PSMA inhibitors for 89Zr radiolabeling and active prostate cancer targeting, respectively. Fluorescence-activated cell sorting showed significantly enhanced uptake of DFO-PSMAi-PEG-Cy5-C’ dots in LNCaP (PSMA positive) cells when compared with PC-3 (PSMA negative) cells. Radiolabeled C’ dots (89Zr-DFO-PSMAi-PEG-Cy5-C’ dots) demonstrated high in vivo radiostability, indicated by low bone and joint uptake in healthy nude mice. The biodistribution study confirmed dominant renal clearance within the first 24 hours. Unlike other PSMA-targeting molecular probes, which exhibit high uptake and retention in the kidneys and salivary glands, radiolabeled particles demonstrate only minimal accumulation in the liver, spleen, kidney and salivary glands, yielding favorable dosimetry. PET scans revealed marked radioactivity in the heart and bladder at 2 h post-injection, suggesting dominant blood pool activity and renal clearance in murine models. Significantly enhanced prostate tumor uptake (9.0 %ID/g vs 3.5 %ID/g) and tumor-to-muscle ratios (>13 vs
Hepatitis Delta Virus Detected in Salivary Glands of Sjögren’s Syndrome Patients and Recapitulates a Sjögren’s Syndrome-Like Phenotype in Vivo (2016)

Identification of HDV in pSS patients and induction of a complete pSS-like phenotype <i>in vivo</i> provides further support of a viral-mediated etiopathology in the development of pSS.
Novel isoprenylated proteins identified by an expression library screen. (1994)

Isoprenylated proteins are involved in eukaryotic cell growth and signal transduction. The protein determinant for prenylation is a short carboxyl-terminal motif containing a cysteine, to which the isoprenoid is covalently attached via thioether linkage. To date, isoprenylated proteins have almost all been identified by demonstrating the attachment of an isoprenoid to previously known proteins. Thus, many isoprenylated proteins probably remain undiscovered. To identify novel isoprenylated proteins for subsequent biochemical study, colony blots of a Glycine max cDNA expression library were [3H]farnesyl-labeled in vitro. Proteins identified by this screen contained several different carboxyl termini that conform to consensus farnesylation motifs. These proteins included known farnesylated proteins (DnaJ homologs) and several novel proteins, two of which contained six or more tandem repeats of a hexapeptide having the consensus sequence (E/G)(G/P)EK(P/K)K. Thus, plants contain a diverse array of genes encoding farnesylated proteins, and our results indicate that fundamental differences in the identities of farnesylated proteins may exist between plants and other eukaryotes. Expression library screening by direct labeling can be adapted to identify isoprenylated proteins from other organisms, as well as proteins with other post-translational modifications.
P‐83: A New Reflective Twisted Nematic Liquid Crystal Display Mode with Large Cell Gap for Direct View Applications (2001)

Abstract We propose a new reflective twisted nematic display mode, which is called the second minimum RTN mode. This mode has a larger dΔn value compared with the first minimum RTN mode which we proposed previously. A cell gap of 7 μm or larger can be used for this mode which makes the fabrication processing of this kind of reflective LCDs easier and more compatible with that of TN LCDs. The color dispersion in both bright and dark states of this display mode is small, and the response is reasonably fast considering the 7 μm cell gap. This display mode can be used in conjunction with TFT active matrix for high quality reflective displays for PDAs, and cell phones. It is also suitable for passive low cost applications such as watches and games.
Clubfoot Kickbar: Development of an Improved Brace for Use Following Correction of Clubfoot (2020)

Abstract The critical final phase of treatment for congenital talipes equinovarus, commonly referred to as clubfoot, using the Ponseti Method requires parents to use a brace in order to maintain the correct foot posture for 12–14 hours each night until four years of age. Parents have been vocal about a desire to allow their children some mobility while maintaining correct alignment for the treatment of this deformity. To that end, the University of Iowa’s medical device prototyping facility Protostudios utilizes 3D CAD design, rapid prototyping principles and state of the art 3D printers to quickly iterate upon the concept of a reciprocating brace that allows for the prescribed posture of abduction and dorsiflexion in a corrected clubfoot while allowing more mobility and higher degrees of comfort for the child. Each iteration of the design was tested for fitment with the commercially available shoe and platform system developed for the Ponseti Method of Clubfoot correction. Special attention was paid to the attachment and removal process of the brace to ensure that parents of children with the deformity would have no problem employing the brace for the prescribed frequency and duration while preventing the children from removing or destroying the brace or being pinched by its reciprocating action.
Repairing folding-defective α-sarcoglycan mutants by CFTR correctors, a potential therapy for limb-girdle muscular dystrophy 2D (2018)

Limb-girdle muscular dystrophy type 2D (LGMD2D) is a rare autosomal-recessive disease, affecting striated muscle, due to mutation of SGCA, the gene coding for α-sarcoglycan. Nowadays, more than 50 different SGCA missense mutations have been reported. They are supposed to impact folding and trafficking of α-sarcoglycan because the defective polypeptide, although potentially functional, is recognized and disposed of by the quality control of the cell. The secondary reduction of α-sarcoglycan partners, β-, γ- and δ-sarcoglycan, disrupts a key membrane complex that, associated to dystrophin, contributes to assure sarcolemma stability during muscle contraction. The complex deficiency is responsible for muscle wasting and the development of a severe form of dystrophy. Here, we show that the application of small molecules developed to rescue ΔF508-CFTR trafficking, and known as CFTR correctors, also improved the maturation of several α-sarcoglycan mutants that were consequently rescued at the plasma membrane. Remarkably, in myotubes from a patient with LGMD2D, treatment with CFTR correctors induced the proper re-localization of the whole sarcoglycan complex, with a consequent reduction of sarcolemma fragility. Although the mechanism of action of CFTR correctors on defective α-sarcoglycan needs further investigation, this is the first report showing a quantitative and functional recovery of the sarcoglycan-complex in human pathologic samples, upon small molecule treatment. It represents the proof of principle of a pharmacological strategy that acts on the sarcoglycan maturation process and we believe it has a great potential to develop as a cure for most of the patients with LGMD2D.
Development of low-cost plastic microfluidic sensors toward rapid and point-of-use detection of arsenic in drinking water for global health (2013)

The difficulty of detecting small quantities of arsenic in water currently threatens the health of millions of people worldwide, as long-term exposure to arsenic has been associated with both cancerous and noncancerous health risks. Existing technologies make it possible to very accurately quantify arsenic levels in water; however the expense, extensive training, and off-site analysis required by these methods impede wide scale-use. Electrochemical detection in a microfluidic platform offers many advantages, such as portability, minimal use of instrumentation, and ready integration with electronics. Toward a solution to water quality interventions, we have demonstrated an affordable and point-of-use microfluidic platform capable of detecting trace amounts of arsenic in groundwater samples. Our electrochemical sensor utilizes a three-electrode system with carbon, silver, and silver/silver chloride ink electrodes printed onto a disposable plastic substrate. A small water sample is applied to the electrodes and the current response is quickly captured, returning quantitative information to the user, which alleviates the lag times and imprecise colorimetric assays that encumber current arsenic detection systems.