gebhart/patrepeval huggingface dataset:
Formal modeling and reasoning for reliability analysis (2010)

Transient faults in logic circuits are an important reliability concern for future technology nodes. In order to guide the design process and the choice of circuit optimization techniques, it is important to accurately and efficiently model transient faults and their propagation through logic circuits, while evaluating the error rates resulting from transient faults. To this end, we give an overview of the existing formal methods for modeling and reasoning about transient faults. We describe the main aspects of transient fault propagation and the advantages and drawbacks of different approaches to modeling them.
Analysis of Efficacy by Multifocal Visual Evoked Potentials in Subjects Treated with the Anti-LINGO-1 Monoclonal Antibody BIIB033 in Acute Optic Neuritis: the RENEW Trial (P7.208) (2015)

OBJECTIVE: To explore the use of multifocal visual evoked potentials (mfVEP) to measure treatment efficacy with the anti-LINGO-1 antibody BIIB033 in subjects with acute optic neuritis (AON). BACKGROUND: Increased latency of cortical responses to monocular stimulation, indicative of demyelinating events in the optic nerve, is a hallmark of AON and has been demonstrated using full-field VEP and mfVEP. In mfVEP, visual stimuli are provided sequentially to distinct regions of the visual field to provide a wider and more precise analysis. BIIB033 is a human monoclonal antibody that is being investigated as a potential treatment for CNS demyelinating disorders such as AON. BIIB033 antagonizes the function of LINGO-1 and has been shown to be safe and well-tolerated in Phase 1 studies. DESIGN/METHODS: RENEW (NCT01721161) is an ongoing, randomized, double-blind, placebo-controlled study in subjects with unilateral AON. Subjects were randomized 1:1 to receive 100 mg/kg BIIB033 IV or placebo once every 4 weeks (6 doses total). In a substudy, mfVEP was included as an exploratory endpoint in selected study sites. At 4-weekly intervals from randomization through week 24 (primary efficacy analysis) and week 32 (end-of-study follow-up), the treatment difference in the latency of mfVEP for the affected eye will be compared with that of the unaffected fellow eye. All readings will be analyzed by a central facility. RESULTS: 48[percnt] (N=39/82) of subjects in RENEW were enrolled in the mfVEP substudy. Detailed descriptions of the efficacy analyses of this novel mfVEP substudy will be presented. CONCLUSIONS: This is the first ever use of mfVEP in the context of a randomized clinical trial. Results from this substudy may help to provide evidence of potential BIIB033 efficacy when given after AON onset on neuroaxonal protection and remyelination and provide further evidence of the feasibility and reliability of this technique. Study Supported by: Biogen Idec
Globally Distributed Drug Discovery of New Antibiotics: Design and Combinatorial Synthesis of Amino Acid Derivatives in the Organic Chemistry Laboratory (2019)

An experiment for the synthesis of N-acyl derivatives of natural amino acids has been developed as part of the Distributed Drug Discovery (D3) program. Students use solid-phase synthesis techniques to complete a three-step, combinatorial synthesis of six products, which are analyzed using LC–MS and NMR spectroscopy. This protocol is suitable for introductory organic laboratory students and has been successfully implemented at multiple academic sites internationally. Accompanying prelab activities introduce students to SciFinder and to medicinal chemistry design principles. Pairing of these activities with the laboratory work provides students an authentic and cohesive research project experience.
Fabrication of polymer integrated optical microring resonator with photobleaching method (2007)

An optical-quality polymer film based on the AJL8/APC material is used for the fabrication of a single-mode microring resonator with photobleaching method. The measured transmission responses of the microring resonator present a high Q-factor of device.
Clinical development of an antisense therapy for the treatment of transthyretin-associated polyneuropathy (2012)

Transthyretin (TTR)-associated amyloidosis is a late-onset autosomal-dominant genetic disease. Over 100 amyloidogenic mutations have been identified in TTR which destabilize the TTR tetramer thereby inducing the formation of amyloid fibrils in tissues such as the heart and peripheral nerves. This disease mainly affects peripheral nerves, causing familial amyloid polyneuropathy (FAP) or heart, causing familial amyloid cardiomyopathy (FAC). Circulating TTR is predominantly produced by liver, and the only widely available clinical treatment for FAP is orthotopic liver transplantation (OLT), whereas no treatment currently exists for FAC. Using second-generation antisense technology, we identified an antisense oligonucleotide (ASO) targeting TTR, ISIS-TTR(Rx), for the treatment of TTR-associated amyloidosis. When tested in a human TTR transgenic mouse model (hTTR Ile84Ser), ISIS-TTR(Rx) showed a dose-dependent reduction of human TTR (up to >80%) at both the mRNA and protein levels. In cynomolgus monkeys, ISIS-TTR(Rx) treatment produced a time-dependent reduction in plasma TTR levels. After 12 weeks of treatment in monkey, liver TTR mRNA and plasma TTR protein levels were reduced by ~80%. As expected, treatment with ISIS-TTR(Rx) also produced a significant decrease in plasma RBP4 levels that correlated with reductions in TTR levels. ISIS-TTR(Rx) treatment was well tolerated in both rodents and monkeys and produced a PK/PD profile consistent with prior experiences using this chemistry platform. ISIS-TTR(Rx) is currently under evaluation in a Phase 1 clinical trial in normal healthy volunteers, and interim results of this trial will be presented.
Instantaneous frequency and its application to strain extraction in moire interferometry (2003)

Moire interferometry is an effective experimental technique for measurement of in-plane deformation. However, it is information on the derivatives of the deformation, i.e., strains, that is usually desired in experimental mechanics. It is shown that the desired strains are the instantaneous frequencies of the fringe pattern and that either an energy operator or wavelet ridges can be used to extract the instantaneous frequencies from a single fringe pattern. The energy operator is a pixelwise processor; thus the strain extraction can be done on the fly, but it is sensitive to noise. The wavelet ridges extract the local features in the fringe pattern. The strain extraction is thus insensitive to noise, and good results are obtainable at the cost of longer computation time. The two methods can thus be chosen for different needs in strain analysis. The properties of the two methods as well as their applications to a real fringe pattern are given. The effectiveness of the proposed methods is illustrated by their comparison with traditional methods.
Feasibility and safety of a novel 3D-printed biodegradable biliary stent in an in vivo porcine model: a preliminary study (2022)

To assess the feasibility and safety of a novel 3D-printed biodegradable biliary stent using polycaprolactone (PCL) in an in vivo porcine model. In this animal study using domestic pigs, biodegradable radiopaque biliary stents made of polycaprolactone (PCL) and barium sulfate were produced using 3D printing and surgically inserted into the common bile duct (CBD) of pigs (stent group, n = 12). Another five pigs were allocated to the control group that only underwent resection and anastomosis of the CBD without stent insertion. To check the position and status of the stents and stent-related complications, follow-up computed tomography (CT) was performed every month. The pigs were sacrificed 1 or 3 months after surgery, and their excised CBD specimens were examined at both the macroscopic and microscopic levels. Three pigs (one in the stent group and two in the control group) died within one day after surgery and were excluded from further analysis; the remaining 11 in the stent group and 3 in the control group survived the scheduled follow-up period (1 month, 5 and 1; and 3 months, 6 and 2 in stent and control groups, respectively). In all pigs, no clinical symptoms or radiologic evidence of biliary complications was observed. In the stent group (n = 11), stent migration (n = 1 at 3 months; n = 2 at 1 month) and stent fracture (n = 3 at 2 months) were detected on CT scans. Macroscopic evaluation of the stent indicated no significant change at 1 month (n = 3) or fragmentation with discoloration at 3 months (n = 5). On microscopic examination of CBD specimens, the tissue inflammation score was significantly higher in the stent group than in the control group (mean ± standard deviation (SD), 5.63 ± 2.07 vs. 2.00 ± 1.73; P = 0.039) and thickness of fibrosis of the CBD wall was significantly higher than that of the control group (0.46 ± 0.12 mm vs. 0.21 ± 0.05 mm; P = 0.012). Despite mild bile duct inflammation and fibrosis, 3D-printed biodegradable biliary stents showed good feasibility and safety in porcine bile ducts, suggesting their potential for use in the prevention of postoperative biliary strictures.
Mechanistic Insight into Enantioselective Palladium‐Catalyzed Oxidative Carbocyclization–Borylation of Enallenes (2017)

The asymmetric palladium-catalyzed oxidative carbocyclization-borylation of enallenes, employing a chiral phosphoric acid as co-catalyst, constitutes an efficient and convenient entry into functionalized building blocks with cyclopentene scaffolds in high enantiopurity. Up till now there has been a lack of knowledge concerning the origin of enantioselectivity of this reaction as well as the absolute configuration of the product. Herein, we report the crystal structure of one of the compounds generated via this carbocyclization, providing the link between the configuration of the products and the configuration of the chiral phosphoric acid used in the reaction. Furthermore, the origin of the enantioselectivity is thoroughly investigated with density functional theory (DFT) calculations. By careful examination of different possible coordination modes, it is shown that the chiral phosphoric acid and the corresponding phosphate anion serve as ligands for palladium during the key stereoselectivity-determining cyclization step. In addition, we examine reactions wherein an extra chiral reagent, a p-benzoquinone containing a chiral sulfoxide, is used. The combined experimental and theoretical studies provide insight into the details of complexation of palladium with various species present in the reaction mixture, furnishing a general understanding of the factors governing the stereoselectivity of this and related catalytic reactions.
Enhanced dipicolinic acid production during the stationary phase in <i>Bacillus subtilis</i> by blocking acetoin synthesis (2015)

Bacterial bio-production during the stationary phase is expected to lead to a high target yield because the cells do not consume the substrate for growth. Bacillus subtilis is widely used for bio-production, but little is known about the metabolism during the stationary phase. In this study, we focused on the dipicolinic acid (DPA) production by B. subtilis and investigated the metabolism. We found that DPA production competes with acetoin synthesis and that acetoin synthesis genes (alsSD) deletion increases DPA productivity by 1.4-fold. The mutant showed interesting features where the glucose uptake was inhibited, whereas the cell density increased by approximately 50%, resulting in similar volumetric glucose consumption to that of the parental strain. The metabolic profiles revealed accumulation of pyruvate, acetyl-CoA, and the TCA cycle intermediates in the alsSD mutant. Our results indicate that alsSD-deleted B. subtilis has potential as an effective host for stationary-phase production of compounds synthesized from these intermediates.
Bunch compression for the TLC (TeV Linear Collider) (1989)

The length of the bunch for the TeV Linear Collider (TLC) must be decreased, while simultaneously preserving its small transverse emittance. To achieve a short bunch length (/approximately/ 70 /mu/m) needed for the TLC, it is necessary to use two-step compression of a 5 mm bunch which is extracted from the damping ring. The corresponding increase of momentum spread requires that chromatic aberrations of the transport line must be corrected at least up to second order. This goal is achieved by building the compressor out of second-order achromats, which also eliminates geometric aberrations. The utilization of flat beams restricts the design to an uncoupled, mid-plane symmetric transport line. The first compression is performed by a conventional compressor. For the second, it is possible to use a 180/degree/ bend. The emittance growth due to the synchrotron radiation is kept to several percent. 10 refs., 3 tabs.
Reversible and Tunable Second‐Order Nonlinear Optical Susceptibility in PZT Thin Films for Integrated Optics (2021)

Abstract Second‐order nonlinear optical processes enable a wide range of applications used in research and industry. The majority of available second‐order nonlinear devices however relies on bulk nonlinear crystals with low second‐order nonlinearity. By exploiting the advancements made in integrated optics, materials with large second‐order nonlinearity can enable efficient and small‐sized on‐chip nonlinear devices at low cost. Unfortunately, silicon and silicon nitride, mostly used for photonics integrated circuits exhibit negligible second‐order nonlinearity (χ (2) ) and alternate materials have to be investigated. Lead zirconate titanate (PZT) thin films with high second‐order nonlinearity stand as a good candidate for on‐chip nonlinearity. An electric‐field induced tuning of χ (2) is demonstrated here in PZT thin films grown on glass substrates with a tuning efficiency of 3.35 pm V −2 . Strong second‐harmonic generation is recorded and a very high dominant tensor component of 128 pm V −1 is reported. The χ (2) of the PZT thin films can be reversed by poling with a DC electric field at room temperature. This opens avenues for highly efficient and tunable on‐chip nonlinear devices.
Achievable Information Rates and Coding for MIMO Systems Over ISI Channels and Frequency-Selective Fading Channels (2004)

We propose a simulation-based method to compute the achievable information rates for general multiple-input multiple-output (MIMO) intersymbol interference (ISI) channels with inputs chosen from a finite alphabet. This method is applicable to both deterministic and stochastic channels. As an example of the stochastic MIMO ISI channels, we consider the multiantenna systems over frequency-selective fading channels, and quantify the improvement in the achievable information rates provided by the additional frequency diversity (for both ergodic and nonergodic cases). In addition, we consider the multiaccess multiantenna system and present some results on the achievable information-rate region. As for the deterministic MIMO ISI channels, we use the binary-input multitrack magnetic recording system as an example, which employs multiple write and read heads for data storage. Our results show that the multitrack recording channels have significant advantages over the single-track channels, in terms of the achievable information rates when the intertrack interference is considered. We further consider practical coding schemes over both stochastic and deterministic MIMO ISI channels, and compare their performance with the information-theoretical limits. Specifically, we demonstrate that the performance of the turbo coding/decoding scheme is only about 1.0 dB away from the information-theoretical limits at a bit-error rate of 10/sup -5/ for large interleaver lengths.
Classification of Annotated Pulmonary Nodules with Pathologically Confirmed Malignant, Benign and Metastasis Cases (2014)

This paper presents a novel framework for combining well known shape, texture, size and resolution informatics descriptor of solitary pulmonary nodules (SPNs) detected by computed tomography (CT). The proposed methodology evaluates the performance of classifiers in differentiating benign, malignant as well as metastasis SPNs with 246 Chest CT scan of patients. 489 unique nodules were extracted from these CT scans. Using available 80 pathologically confirmed cases, 211 nodules were labeled as malignant (M), benign (B) and metastasis (MT). Performance evaluation was carried out using 83 extracted features of the nodules. A reduced set using principal component analysis (PCA) resulting 12 features was also considered. Support vector machine (SVM), decision tree and naive Bayes classifiers were evaluated for two classes (M and B) as well as for three classes (M, B and MT). The evaluation results indicate that most of the selected features have important contribution in differentiating SPNs. The Receiver –Operator- Characteristic curve (ROC) is plotted for two classes as well as for three class classification to strike a balance between sensitivity and specificity. Higher value of specificity obtained indicates the potential of the methodology to avoid unnecessary biopsies. These results can be used to build a highly efficient feature index of a content-based medical image retrieval system with pulmonary nodules system for CT.
Easy access to modified cyclodextrins by mechanosynthesis with supramolecular approach (2015)

International audience
Atomically precise digital e-beam lithography (2020)

Hydrogen Depassivation Lithography (HDL) is a version of electron beam lithography that uses scanning tunneling microscope (STM) instrumentation to expose a self–developing resist that is a monolayer of H chemisorbed to a Si (100) 2x1 H-passivated surface. Developed in the 1990s it has been largely a laboratory tool used in research for nanofabrication. The technique is capable of atomic resolution, the ability to remove single H atoms from the Si surface and has much higher precision than the best conventional e-beam lithography can possibly achieve exposing polymeric resists. However, its most promising attribute is that it can be used as a digital fabrication tool and is the first of a class of nanofabrication techniques that can be considered digital atomic scale fabrication technologies. Digital Atomic Scale Fabrication can be shown to have similar advantages over analog fabrication techniques that digital information technology has over analog information technology.
In Vitro Simulated Neuronal Environmental Conditions Qualify Umbilical Cord Derived Highly Potent Stem Cells for Neuronal Differentiation (2023)

The healing of neuronal injuries is still an unachieved goal. Medicine-based therapies can only extend the survival of patients, but not finally lead to a healing process. Currently, a variety of stem cell-based tissue engineering developments are the subject of many research projects to bridge this gap. As yet, neuronal differentiation of induced pluripotent stem cells (iPS), embryonic cell lines, or neuronal stem cells could be accomplished and produce functional neuronally differentiated cells. However, clinical application of cells from these sources is hampered by ethical considerations. To overcome these hurdles numerous studies investigated the potential of adult mesenchymal stem cells (MSCs) as a potential stem cell source. Adult MSCs have been approved as cellular therapeutical products due to their regenerative potential and immunomodulatory properties. Only a few of these studies could demonstrate the capacity to differentiate MSCs into active firing neuron like cells. With this study we investigated the potential of Wharton's Jelly (WJ) derived stem cells and focused on the intrinsic pluripotent stem cell pool and their potential to differentiate into active neurons. With a comprehensive neuronal differentiation protocol comprised of mechanical and biochemical inductive cues, we investigated the capacity of spontaneously forming stem cell spheroids (SCS) from cultured WJ stromal cells in regard to their neuronal differentiation potential and compared them to undifferentiated spheroids or adherent MSCs. Spontaneously formed SCSs show pluripotent and neuroectodermal lineage markers, meeting the pre-condition for neuronal differentiation and contain a higher amount of cells which can be differentiated into cells whose functional phenotypes in calcium and voltage responsive electrical activity are similar to neurons. In conclusion we show that up-concentration of stem cells from WJ with pluripotent characteristics is a tool to generate neuronal cell replacement.
Isolation of LMX1a Ventral Midbrain Progenitors Improves the Safety and Predictability of Human Pluripotent Stem Cell-Derived Neural Transplants in Parkinsonian Disease (2019)

Human pluripotent stem cells (hPSCs) are a promising resource for the replacement of degenerated ventral midbrain dopaminergic (vmDA) neurons in Parkinson's disease. Despite recent advances in protocols for the <i>in vitro</i> generation of vmDA neurons, the asynchronous and heterogeneous nature of the differentiations results in transplants of surprisingly low vmDA neuron purity. As the field advances toward the clinic, it will be optimal, if not essential, to remove poorly specified and potentially proliferative cells from donor preparations to ensure safety and predictable efficacy. Here, we use two novel hPSC knock-in reporter lines expressing GFP under the LMX1A and PITX3 promoters, to selectively isolate vm progenitors and DA precursors, respectively. For each cell line, unsorted, GFP<sup>+</sup>, and GFP<sup>-</sup> cells were transplanted into male or female Parkinsonian rodents. Only rats receiving unsorted cells, LMX1A-eGFP<sup>+</sup>, or PITX3-eGFP<sup>-</sup> cell grafts showed improved motor function over 6 months. Postmortem analysis revealed small grafts from PITX3-eGFP<sup>+</sup> cells, suggesting that these DA precursors were not compatible with cell survival and integration. In contrast, LMX1A-eGFP<sup>+</sup> grafts were highly enriched for vmDA neurons, and importantly excluded expansive proliferative populations and serotonergic neurons. These LMX1A-eGFP<sup>+</sup> progenitor grafts accelerated behavioral recovery and innervated developmentally appropriate forebrain targets, whereas LMX1A-eGFP<sup>-</sup> cell grafts failed to restore motor deficits, supported by increased fiber growth into nondopaminergic target nuclei. This is the first study to use an hPSC-derived reporter line to purify vm progenitors, resulting in improved safety, predictability of the graft composition, and enhanced motor function.<b>SIGNIFICANCE STATEMENT</b> Clinical trials have shown functional integration of transplanted fetal-derived dopamine progenitors in Parkinson's disease. Human pluripotent stem cell (hPSC)-derived midbrain progenitors are now being tested as an alternative cell source; however, despite current differentiation protocols generating >80% correctly specified cells for implantation, resultant grafts contain a small fraction of dopamine neurons. Cell-sorting approaches, to select for correctly patterned cells before implantation, are being explored yet have been suboptimal to date. This study provides the first evidence of using 2 hPSC reporter lines (LMX1A-GFP and PITX3-GFP) to isolate correctly specified cells for transplantation. We show LMX1A-GFP<sup>+</sup>, but not PITX3-GFP<sup>+</sup>, cell grafts are more predictable, with smaller grafts, enriched in dopamine neurons, showing appropriate integration and accelerated functional recovery in Parkinsonian rats.