gebhart/patrepeval huggingface dataset:
Simulation and generation of IDDQ tests for bridging faults in combinational circuits (1996)

In the absence of information about the layout, test generation and fault simulation systems must target all bridging faults. A novel algorithm, that is both time and space efficient, for simulating I/sub DDQ/ tests for all two-line bridging faults in combinational circuits is presented. Simulation results using randomly generated test sets point to the computational feasibility of targeting all two-line bridging faults. On a more theoretical note, we show that the problem of computing I/sub DDQ/ tests for all two-line bridging faults, even in some restricted classes of circuits, is intractable, and, even under some pessimistic assumptions, a complete I/sub DDQ/ test set for all two-line bridging faults also covers all multiple line, single cluster bridging faults.
Empirically Based Guidelines for Selecting Vagus Nerve Stimulation Parameters in Epilepsy and Heart Failure (2018)

Vagus nerve stimulation (VNS) is a promising therapy to treat patients with epilepsy and heart failure. Outcomes of preclinical studies and clinical trials indicate that the selection of stimulation parameters has a direct impact on therapeutic efficacy and patient tolerability, suggesting that both the efficacy and tolerability of VNS could potentially be improved with a change in stimulation parameters. In this review, the success of translating stimulation parameters for epilepsy and heart failure from preclinical studies in animal models to human use in the clinic is evaluated on the basis of patient outcomes and stimulation-induced side effects. Data suggest that patients receiving VNS for epilepsy may experience improved seizure reduction by increasing the frequency and/or duty cycle of stimulation as well as incorporating closed-loop systems to deliver stimulation closer to seizure onset. Further, data suggest that VNS for heart failure is limited by the inability to activate the nerve fibers mediating therapeutic benefit without co-activation of side effect-inducing fibers. This may explain why pivotal trials of VNS for heart failure failed to meet primary efficacy outcomes despite promising preclinical outcomes in animal models. Improved characterization of the relationship between the stimulation parameter space and recruitment of the underlying fiber populations will likely expand the use of VNS to treat a variety of diseases and also improve upon current understanding of the mechanisms of action underlying VNS.
Parkinson disease age of onset GWAS: defining heritability, genetic loci and a-synuclein mechanisms (2018)

Abstract Increasing evidence supports an extensive and complex genetic contribution to Parkinson’s disease (PD). Previous genome-wide association studies (GWAS) have shed light on the genetic basis of risk for this disease. However, the genetic determinants of PD age of onset are largely unknown. Here we performed an age of onset GWAS based on 28,568 PD cases. We estimated that the heritability of PD age of onset due to common genetic variation was ~0.11, lower than the overall heritability of risk for PD (~0.27) likely in part because of the subjective nature of this measure. We found two genome-wide significant association signals, one at SNCA and the other a protein-coding variant in TMEM175 , both of which are known PD risk loci and a Bonferroni corrected significant effect at other known PD risk loci, INPP5F/BAG3 , FAM47E/SCARB2 , and MCCC1. In addition, we identified that GBA coding variant carriers had an earlier age of onset compared to non-carriers. Notably, SNCA , TMEM175 , SCARB2 , BAG3 and GBA have all been shown to either directly influence alpha-synuclein aggregation or are implicated in alpha-synuclein aggregation pathways. Remarkably, other well-established PD risk loci such as GCH1, MAPT and RAB7L1 /NUCKS1 (PARK16) did not show a significant effect on age of onset of PD. While for some loci, this may be a measure of power, this is clearly not the case for the MAPT locus; thus genetic variability at this locus influences whether but not when an individual develops disease. We believe this is an important mechanistic and therapeutic distinction. Furthermore, these data support a model in which alpha-synuclein and lysosomal mechanisms impact not only PD risk but also age of disease onset and highlights that therapies that target alpha-synuclein aggregation are more likely to be disease-modifying than therapies targeting other pathways.
Word-based confidence measures as a guide for stack search in speech recognition (2002)

The maximum a posteriori hypothesis is treated as the decoded truth in speech recognition. However, since the word recognition accuracy is not 100%, it is desirable to have an independent confidence measure on how good the maximum a posteriori hypothesis is relative to the spoken truth for some applications. Efforts are in progress to develop such confidence measures with the intent of applying them to the assessment of the confidence of whole utterances, rescoring of N-best lists, etc. In this paper, we explore the use of word-based confidence measures to adaptively modify the hypothesis score during searches in continuous speech recognition: specifically, based on the confidence of the current sequence of hypothesized words during the search, the weight of its prediction is changed as a function of the confidence. Experimental results are described for ATIS and SwitchBoard tasks. About 8% relative reduction in word error is obtained for ATIS.
Individualized Molecular Analyses Guide Efforts (IMAGE): A Prospective Study of Molecular Profiling of Tissue and Blood in Metastatic Triple-Negative Breast Cancer (2016)

This study demonstrates challenges of performing NGS on prospective tissue biopsies in patients with metastatic TNBC within 28 days, while also highlighting the potential use of blood as a more time-efficient and less invasive method of mutational assessment. Clin Cancer Res; 23(2); 379-86. ©2016 AACR.
An investigation into the composition of the unsaturated hydrocarbons present in coal-gas (1920)

F. S. Sinnatt and L. Slater, Analyst, 1920, 45, 85 DOI: 10.1039/AN9204500085
[Value of the study of circulating adrenergic receptors in the diagnosis and surveillance after surgery of pheochromocytoma]. (1988)

The purpose of the study was to investigate leukocyte beta adrenoceptors and platelet alpha 2 adrenoceptors in pheochromocytoma. The study concerned nine hypertensive patients, five men and four women (aged 42 +/- 8 years) with a pheochromocytoma demonstrated by high levels of urinary catecholamines and radiological data. Catecholamine plasma levels, assayed by HPLC were wide-ranging: 10.7 to 172.8 nM for noradrenaline and 0.7 to 3.9 nM for adrenaline. In each case the number of leukocyte beta adrenoceptors sites (measured with 125 I-cyanopindolol) significantly decreased: Bmax was 20.6 +/- 2.8 versus 48.5 +/- 1.5 fmol/mg protein in controls (p less than 0.05). In contrast, the number of platelet alpha 2 adrenoceptors sites (measured with 3H-yohimbine) was not modified: 206 +/- 22.6 versus 186.0 +/- 12.1 fmole/mg protein in controls. There was no change in affinity constant (Kd), neither for beta nor alpha2 adrenoceptors. After tumor removal, there was a significant increase in beta adrenoceptor number. We conclude that down regulation occurs in vivo for beta adrenoceptors but not for alpha2 adrenoceptors and that the decrease in leukocyte beta adrenoceptor number is an interesting and suitable index in the management of pheochromocytoma.
Conserved molecular portraits of bovine and human blastocysts as a consequence of the transition from maternal to embryonic control of gene expression (2007)

The present study investigated mRNA expression profiles of bovine oocytes and blastocysts by using a cross-species hybridization approach employing an array consisting of 15,529 human cDNAs as probe, thus enabling the identification of conserved genes during human and bovine preimplantation development. Our analysis revealed 419 genes that were expressed in both oocytes and blastocysts. The expression of 1,324 genes was detected exclusively in the blastocyst, in contrast to 164 in the oocyte including a significant number of novel genes. Genes indicative for transcriptional and translational control (ELAVL4, TACC3) were overexpressed in the oocyte, whereas cellular trafficking (SLC2A14, SLC1A3), proteasome (PSMA1, PSMB3), cell cycle (BUB3, CCNE1, GSPT1), and protein modification and turnover (TNK1, UBE3A) genes were found to be overexpressed in blastocysts. Transcripts implicated in chromatin remodeling were found in both oocytes (NASP, SMARCA2) and blastocysts (H2AFY, HDAC7A). The trophectodermal markers PSG2 and KRT18 were enriched 5- and 50-fold in the blastocyst. Pathway analysis revealed differential expression of genes involved in 107 distinct signaling and metabolic pathways. For example, phosphatidylinositol signaling and gluconeogenesis were prominent pathways identified in the blastocyst. Expression patterns in bovine and human blastocysts were to a large extent identical. This analysis compared the transcriptomes of bovine oocytes and blastocysts and provides a solid foundation for future studies on the first major differentiation events in blastocysts and identification of a set of markers indicative for regular mammalian development.
Data from The PSMA-targeting Half-life Extended BiTE Therapy AMG 160 has Potent Antitumor Activity in Preclinical Models of Metastatic Castration-resistant Prostate Cancer (2023)

&lt;div&gt;AbstractPurpose:&lt;p&gt;Metastatic castration-resistant prostate cancer (mCRPC) remains a disease with high unmet medical need, as most patients do not achieve durable response with available treatments. Prostate-specific membrane antigen (PSMA) is a compelling target for mCRPC. It is highly expressed by primary and metastatic prostate cancer cells, with increased expression after progression on androgen deprivation therapy.&lt;/p&gt;Experimental Design:&lt;p&gt;We developed AMG 160, a half-life extended, bispecific T-cell engager immuno-oncology therapy that binds PSMA on prostate cancer cells and cluster of differentiation 3 on T cells for treatment of mCRPC. AMG 160 was evaluated &lt;i&gt;in vitro&lt;/i&gt; and in mCRPC xenograft models. AMG 160 tolerability was assessed in nonhuman primates (NHP). AMG 160 activity as monotherapy and in combination with a PSMA-imaging agent, novel hormonal therapy, and immune checkpoint blockade was evaluated.&lt;/p&gt;Results:&lt;p&gt;AMG 160 induces potent, specific killing of PSMA-expressing prostate cancer cell lines &lt;i&gt;in vitro&lt;/i&gt;, with half-maximal lysis of 6–42 pmol/L. &lt;i&gt;In vivo&lt;/i&gt;, AMG 160 administered weekly at 0.2 mg/kg engages T cells administered systemically and promotes regression of established 22Rv-1 mCRPC xenograft tumors. AMG 160 is compatible with the imaging agent gallium 68–labeled PSMA-11, and shows enhanced cytotoxic activity when combined with enzalutamide or an anti-programmed death-1 antibody. AMG 160 exhibits an extended half-life and has an acceptable safety profile in NHPs.&lt;/p&gt;Conclusions:&lt;p&gt;The preclinical characterization of AMG 160 highlights its potent antitumor activity &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt;, and its potential for use with known diagnostic or therapeutic agents in mCRPC. These data support the ongoing clinical evaluation of AMG 160 in patients with mCRPC.&lt;/p&gt;&lt;p&gt;&lt;i&gt;See related commentary by Kamat et al., p. 2675&lt;/i&gt;&lt;/p&gt;&lt;/div&gt;
Total Synthesis of Botcinolides and Botcinins; Determination of the Structure of Natural Products Isolated from Botrytis cinerea (2009)

The first asymmetric total syntheses of botcinins A-F, homobotcinin E, botcinic acid, botcinic acid methyl ester, botcineric acid, and 3-O-acetylbotcinic acid methyl ester were achieved. The structures of these compounds have been unequivocally determined through their total syntheses and those of botcinin A, botcinin B, botcinin E, homobotcinin E, botcinic acid, botcinic acid methyl ester, botcineric acid, and 3-O-acetylbotcinic acid methyl ester are identified with the revised forms of the natural products formerly assumed to be 3-O-acetyl-2-epibotcinolide, 3-O-acetyl-2-epihomobotcinolide, 2-epibotcinolide, 2-epihomobotcinolide, botcinolide, 4-O-methylbotcinolide, homobotcinolide, and 3-O-acetyl-5-O-methylbotcinolide, respectively. It was further proved that the proposed nine-membered ring structure of 2-epibotcinolide is very unstable and the ineluctable translactonization easily occurred to form the corresponding γ-lactone.
Submicron Mask Repair Using Focused Ion Beam Technology (1986)

The establishment of the submicron device era brings out the problem of repairing advanced VLSI photomasks or reticles. Through recent advances in submicron focused ion beam (FIB) technology, a new method has been developed for repair of these photomasks. Using our specially designed FIB system, &quot;opaque&quot; repairs are performed by ion sputter etching. Repairing &quot;clear&quot; defects is carried out using the FIB to selectively deposit thin films using the &quot;Ion Beam Induced Chemical Effect&quot;. Using these techniques, both &quot;opaque&quot; and &quot;clear&quot; repairs are carried out without damage to the glass substrate. &quot;Clear&quot; defects are repaired using carbon film deposition. The thickness of the film need only by about 200nm to have an optical density of 3 and resistance to scratch and cleaning damage equivalent to Cr. The carbon film is formed when gas molecules are continuously jetted onto the mask surface as the FIB repeat scans the defect area. Repairs to X-ray mask are carried out in the same way, using special gases containing a heavy metal. &quot;Opaque&quot; defects are removed by direct scanning of the FIB over the defect area. The sputter etching is automatically stopped, after the repairs are finished, by the etching monitor. Secondary ion emission is stimulated by the scanning FIB. These secondary ions are detected by a built-in mass spectrometer. The signal from the mass spectrometer can be used to image the sample surface and defect position on the CRT. This system is designed for high reliability and ease of use. Because of advanced design features, this system will smooth the transition between &quot;micron&quot; and &quot;sub-micron&quot; geometry design.
ChemInform Abstract: Selective Protection and Relative Importance of the Carboxylic Acid Groups of Zargozic Acid A for Squalene Synthase Inhibition. (1994)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Learning to Write Stylized Chinese Characters by Reading a Handful of Examples (2018)

Automatically writing stylized characters is an attractive yet challenging task, especially for Chinese characters with complex shapes and structures. Most current methods are restricted to generate stylized characters already present in the training set, but required to retrain the model when generating characters of new styles. In this paper, we develop a novel framework of Style-Aware Variational Auto-Encoder (SA-VAE), which disentangles the content-relevant and style-relevant components of a Chinese character feature with a novel intercross pair-wise optimization method. In this case, our method can generate Chinese characters flexibly by reading a few examples. Experiments demonstrate that our method has a powerful one-shot/few-shot generalization ability by inferring the style representation, which is the first attempt to learn to write new-style Chinese characters by observing only one or a few examples.
Focused shock drilling exploratory research program: Final report (1988)

The program to investigate the feasibility of the focused shock spark drilling technique was formally initiated in February 1985 and the work was completed in April 1988. In its initial phase, the program was set to accomplish five objectives. These were: to develop a basic understanding of the physics of spark drilling; to determine rock fracture characteristics at energy levels ranging from 2 to 25 kilojoules (kJ); to demonstrate the feasibility of focusing and steering the high energy shock waves in water; to develop electrode and insulator material designs for an erodable drill face; and to develop a conceptual design for a fieldable spark drill bit. The results of the three-year investigation are reported in this document. The background and rationale are first given. Then a discussion on the following is given: the two pulsed power facilities built for the project; the phenomenology responsible for fracturing and breaking rock through the electrohydraulic effect; development of a conceptual design for a downhole spark drill; and finally, a number of near-term applications are identified for the electrohydraulic effect.
Suppression of endothelial miR-22 mediates non-small cell lung cancer cell-induced angiogenesis (2021)

MicroRNAs (miRNAs) expressed in endothelial cells (ECs) are powerful regulators of angiogenesis, which is essential for tumor growth and metastasis. Here, we demonstrated that miR-22 is preferentially and highly expressed in ECs, while its endothelial level is significantly downregulated in human non-small cell lung cancer (NSCLC) tissues when compared to matched nontumor lung tissues. This reduction of endothelial miR-22 is possibly induced by NSCLC cell-secreted interleukin-1β and subsequently activated transcription factor nuclear factor-κB. Endothelial miR-22 functions as a potent angiogenesis inhibitor that inhibits all of the key angiogenic activities of ECs and consequently NSCLC growth through directly targeting sirtuin 1 and fibroblast growth factor receptor 1 in ECs, leading to inactivation of AKT/mammalian target of rapamycin signaling. These findings provide insight into the molecular mechanisms of NSCLC angiogenesis and indicate that endothelial miR-22 represents a potential target for the future antiangiogenic treatment of NSCLC.
Abstract 1872: Generation of bispecific and trispecific T cell engagers (TCEs) and NK cell engagers (NKE)s without prior IgG reengineering (2021)

Abstract T cell and NK cell-redirecting antibodies are emerging as promising modalities in targeted immunotherapy. New technologies are overcoming the limitations of 1st generation immune cell-redirecting bispecifics, especially extending half-life, reducing immunogenicity and improving safety. For example, in the field of T cell engagers (TCEs), a plethora of molecular architectures has entered the clinic, the vast majority generated by genetic engineering of an IgG to bind both a tumor-associated antigen (TAA) and CD3 or 4-1BB. Similarly, recombinant DNA technology enables the C-terminal fusion of a cytokine (e.g. IL-2 or IL-15) to an IgG to obtain NK cell engagers (NKEs). We have shown earlier that the native glycan of a monoclonal antibody provides a privileged site for attachment of cytotoxic payloads,1 providing antibody-drug conjugates (ADCs) with significantly enhanced therapeutic index. This technology, known as GlycoConnect™, has been adapted by various drug developers (e.g. ADC Therapeutics, Mersana Therapeutics and others) and is now applied in two (2) clinical programs as well as multiple late-stage preclinical programs. Here we demonstrate how GlycoConnect™ technology can be applied to generate TCEs or NKEs by selective attachment of scFv (anti-CD3, anti-CD28) or cytokines (IL-15), with concomitant Fc-silencing. Moreover, an existing bispecific TCE (TAA/CD3) can be further boosted by attachment of anti-CD28 scFv for further T cell activation. Molecular architectures can be readily tailored to 2:2 or 2:1 ratio (TAA:scFv or cytokine) to mitigate adverse events like cytokine release syndrome, and even 2:1:1 formats. Structural and functional studies will be presented to corroborate the architecture and biological activity of these GlycoConnect™ bispecifics and trispecifics, in terms of binding, immune cell engagement and cell-killing potential. 1van Geel et al. Chemoenzymatic Conjugation of Toxic Payloads to the Globally Conserved N-Glycan of Native mAbs Provides Homogeneous and Highly Efficacious Antibody−Drug Conjugates. Bioconj. Chem. 2015, 26, 2233-2242. Citation Format: Remon van Geel, Floris van Delft. Generation of bispecific and trispecific T cell engagers (TCEs) and NK cell engagers (NKE)s without prior IgG reengineering [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1872.
High-Z metal-based underlayer to improve EUV stochastics (Conference Presentation) (2019)

Extending extreme ultraviolet (EUV) single exposure patterning to its limits is dependent on eliminating its stochastic defectivity. Along with developments in photoresist platforms, the patterning film stack also needs to be considered. The material immediately underneath the photoresist is expected to have significant impact on both lithographic and pattern transfer performance. By designing the resist substrate interface with high EUV absorbance, there is potential to increase the EUV quantum yield of the exposure process. This paper will demonstrate the patterning of a chemically amplified resist on a high-Z metal-based hardmask. The potential for dose reduction, higher etch selectivity, and defectivity improvement from a high-Z hardmask will be discussed. Deposition-trim etch techniques will be used for decreasing the transfer of stochastic defects to the underlying substrate. Sub-32nm pitch trench patterning, defectivity, and electrical yield for this patterning stack will be highlighted.
Epitaxial lift-off processed GaAs thin-film solar cells integrated with low-cost plastic mini-compound parabolic concentrators (2014)

We demonstrate the integration of GaAs thin-film solar cells with low-cost plastic mini-compound parabolic concentrators (CPC) by combing a non-destructive epitaxial lift-off (ND-ELO) technique and a vacuum-assisted thermoforming process. To simplify the thin film III-V active layer transfer and to eliminate the use of adhesives of the epi to the secondary plastic substrate, we employ cold-weld bonding. The integration of thin film GaAs photovoltaic cells with a low-cost plastic mini CPC that can track solar radiation increases energy harvesting by a factor of 2. The Combination of cost effective concentrators with previously demonstrated non-destructive wafer recycling utilizing epitaxial protection layers provides the potential for a dramatic cost reduction in the production of III-V semiconductor photovoltaic cells.