gebhart/patrepeval huggingface dataset:
The Nrf2–ARE Pathway (2008)

Transcriptional activation of protective genes is mediated by a cis-acting element called the antioxidant responsive element (ARE). The transcription factor Nrf2 (NF-E2-related factor 2) binds to the ARE. Activation of this pathway protects cells from oxidative stress-induced cell death. Increased oxidative stress is associated with neuronal cell death during the pathogenesis of multiple chronic neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. We hypothesize that Nrf2-ARE activation is a novel neuroprotective pathway that confers resistance to a variety of oxidative, stress-related, neurodegenerative insults. In recent studies, primary neuronal cultures treated with chemical activators of the Nrf2-ARE pathway displayed significantly greater resistance to oxidative stress-induced neurotoxicity. Similar cultures generated from ARE-hPAP reporter mice demonstrated selective activation of the Nrf2-ARE pathway in astrocytes, suggesting that Nrf2 activation in astrocytes somehow confers resistance to naive neurons. Further, in chemical models of neurodegeneration, Nrf2 knockout mice are significantly more sensitive to mitochondrial complex I and II inhibitors. Combining these observations with the results implying that the astrocyte is central to Nrf2-ARE-mediated neuroprotection, we transplanted Nrf2-overexpressing astrocytes into the mouse striatum prior to lesioning with malonate. This procedure led to dramatic protection against malonate-induced neurotoxicity. Translating this to other chemical and genetic models of neurodegeneration will be discussed.
Low Serum Levels of Dehydroepiandrosterone Sulfate Predict All-Cause and Cardiovascular Mortality in Elderly Swedish Men (2010)

Low serum levels of DHEA(-S) predict death from all causes, CVD, and ischemic heart disease in older men.
Successful Treatment of Melanoma Brain Metastases with Adoptive Cell Therapy (2010)

ACT with a nonmyeloablative preparative regimen using either TIL- or TCR gene-transduced cells and interleukin-2 can mediate complete and durable regression of melanoma brain metastases. This strategy can be used safely in selected patients with metastatic melanoma to the brain.
From HMM's to segment models: a unified view of stochastic modeling for speech recognition (1996)

Many alternative models have been proposed to address some of the shortcomings of the hidden Markov model (HMM), which is currently the most popular approach to speech recognition. In particular, a variety of models that could be broadly classified as segment models have been described for representing a variable-length sequence of observation vectors in speech recognition applications. Since there are many aspects in common between these approaches, including the general recognition and training problems, it is useful to consider them in a unified framework. The paper describes a general stochastic model that encompasses most of the models proposed in the literature, pointing out similarities of the models in terms of correlation and parameter tying assumptions, and drawing analogies between segment models and HMMs. In addition, we summarize experimental results assessing different modeling assumptions and point out remaining open questions.
Coupling of histone deacetylation to NAD breakdown by the yeast silencing protein Sir2: Evidence for acetyl transfer from substrate to an NAD breakdown product (2000)

The Saccharomyces cerevisiae silencing protein Sir2 is the founding member of a universally conserved family of proteins that have been shown to possess NAD-dependent histone deacetylation and ADP-ribosylation activities. Here we show that histone deacetylation by Sir2 is coupled to cleavage of the high-energy bond that links the ADP-ribose moiety of NAD to nicotinamide. Analysis of the NAD cleavage products revealed the presence of nicotinamide, ADP-ribose, and a third product that appeared to be related to ADP-ribose. With the use of label transfer experiments, we show that the acetyl group in the histone substrate is transferred to this NAD breakdown product during deacetylation, forming a product that we conclude to be O-acetyl-ADP-ribose. Detection of this species strongly argues for obligate coupling of histone deacetylation to NAD breakdown by Sir2. We propose reaction mechanisms that could account for this coupling via acetyl-ADP-ribose formation. The unprecedented coupling of amide bond cleavage to cleavage of a high-energy bond raises the possibility that NAD breakdown by Sir2 plays an important role in silencing that is independent of its requirement for deacetylation.
2X Super-Resolution Hardware Using Edge-Orientation-Based Linear Mapping for Real-Time 4K UHD 60 fps Video Applications (2018)

Based on our previous super-interpolation method, we propose a novel hardware-friendly super-resolution (SR) algorithm, called HSI method, and its dedicated hardware architecture for up-scaling full-high-definition (FHD) video streams to 4K ultra-high-definition (UHD) video streams in real-time. Our proposed HSI method involves training and up-scaling steps. In the training step, an edge-orientation-based clustering is applied for low-resolution (LR) training patches to obtain a training patch set for each class, and a linear mapping kernel is learned from LR to high-resolution (HR) based on the training patch set for each class. In the up-scaling step, each LR input patch is transformed to an HR patch by applying the linear mapping kernel for its class. We implemented the up-scaling step of our HSI method by a dedicated hardware (HW) with the pre-trained linear mapping kernels stored in a look-up table. Our HW implementation, called HSI HW, contains 159K gate counts and achieves about 880 Mpixels/s throughput by using the TSMC 0.13-um CMOS process, and thus performing the SR operation from FHD to 4K UHD in real-time. Compared with conventional SR methods, our HW implementation of HSI reconstructs HR images of higher peak signal to noise ratio values and better visual quality.
Hazelcast Jet: Low-latency Stream Processing at the 99.99th Percentile (2021)

Jet is an open-source, high-performance, distributed stream processor built at Hazelcast during the last five years. Jet was engineered with millisecond latency on the 99.99th percentile as its primary design goal. Originally Jet's purpose was to be an execution engine that performs complex business logic on top of streams generated by Hazelcast's In-memory Data Grid (IMDG): a set of high-performance, in-memory, partitioned and replicated data structures. With time, Jet evolved into a full-fledged, scale-out stream processor that can handle out-of-order streams and exactly-once processing guarantees. Jet's end-to-end latency lies in the order of milliseconds, and its throughput in the order of millions of events per CPU-core. This paper presents main design decisions we made in order to maximize the performance per CPU-core, alongside lessons learned, and an empirical performance evaluation.
Paired-End Mapping Reveals Extensive Structural Variation in the Human Genome (2007)

Structural variation of the genome involves kilobase- to megabase-sized deletions, duplications, insertions, inversions, and complex combinations of rearrangements. We introduce high-throughput and massive paired-end mapping (PEM), a large-scale genome-sequencing method to identify structural variants (SVs) approximately 3 kilobases (kb) or larger that combines the rescue and capture of paired ends of 3-kb fragments, massive 454 sequencing, and a computational approach to map DNA reads onto a reference genome. PEM was used to map SVs in an African and in a putatively European individual and identified shared and divergent SVs relative to the reference genome. Overall, we fine-mapped more than 1000 SVs and documented that the number of SVs among humans is much larger than initially hypothesized; many of the SVs potentially affect gene function. The breakpoint junction sequences of more than 200 SVs were determined with a novel pooling strategy and computational analysis. Our analysis provided insights into the mechanisms of SV formation in humans.
Creatine and Creatinine Metabolism (2000)

The goal of this review is to present a comprehensive survey of the many intriguing facets of creatine (Cr) and creatinine metabolism, encompassing the pathways and regulation of Cr biosynthesis and degradation, species and tissue distribution of the enzymes and metabolites involved, and of the inherent implications for physiology and human pathology. Very recently, a series of new discoveries have been made that are bound to have distinguished implications for bioenergetics, physiology, human pathology, and clinical diagnosis and that suggest that deregulation of the creatine kinase (CK) system is associated with a variety of diseases. Disturbances of the CK system have been observed in muscle, brain, cardiac, and renal diseases as well as in cancer. On the other hand, Cr and Cr analogs such as cyclocreatine were found to have antitumor, antiviral, and antidiabetic effects and to protect tissues from hypoxic, ischemic, neurodegenerative, or muscle damage. Oral Cr ingestion is used in sports as an ergogenic aid, and some data suggest that Cr and creatinine may be precursors of food mutagens and uremic toxins. These findings are discussed in depth, the interrelationships are outlined, and all is put into a broader context to provide a more detailed understanding of the biological functions of Cr and of the CK system.
Absence of evidence of infection with divergent primate T‐lymphotropic viruses in United States blood donors who have seroindeterminate HTLV test results (2000)

Although the epidemiologic data suggest the possibility of undiagnosed HTLV-I, HTLV-II, or a cross-reactive virus such as PTLV among older, black, and Hispanic blood donors, the PCR data do not support the presence of divergent PTLV infection among US blood donors with HTLV-I-indeterminate results.
Persistent and Stable Gene Expression by a Cytoplasmic RNA Replicon Based on a Noncytopathic Variant Sendai Virus (2007)

Persistent and stable expression of foreign genes has been achieved in mammalian cells by integrating the genes into the host chromosomes. However, this approach has several shortcomings in practical applications. For example, large scale production of protein pharmaceutics frequently requires laborious amplification of the inserted genes to optimize the gene expression. The random chromosomal insertion of exogenous DNA also results occasionally in malignant transformation of normal tissue cells, raising safety concerns in medical applications. Here we report a novel cytoplasmic RNA replicon capable of expressing installed genes stably without chromosome insertion. This system is based on the RNA genome of a noncytopathic variant Sendai virus strain, Cl.151. We found that this variant virus establishes stable symbiosis with host cells by escaping from retinoic acid-inducible gene I-interferon regulatory factor 3-mediated antiviral machinery. Using a cloned genome cDNA of Sendai virus Cl.151, we developed a recombinant RNA installed with exogenous marker genes that was maintained stably in the cytoplasm as a high copy replicon (about 4 x 10(4) copies/cell) without interfering with normal cellular function. Strong expression of the marker genes persisted for more than 6 months in various types of cultured cells and for at least two months in rat colonic mucosa without any apparent side effects. This stable RNA replicon is a potentially valuable genetic platform for various biological applications.
Region-Specific Developmental Specialization of GABA–Glycine Cosynapses in Laminas I–II of the Rat Spinal Dorsal Horn (2001)

The spinal dorsal horn is the first level of the CNS in which nociceptive input from sensory afferents is integrated and transmitted. Although inhibitory control in this region has a crucial impact on pain transmission, the respective contribution of GABA and glycine to this inhibition remains elusive. We have previously documented co-release of GABA and glycine at the same inhibitory synapse in spinal laminas I-II of adult rats [older than postnatal day 30 (P30)]. However, despite this co-release, individual miniature inhibitory postsynaptic currents (mIPSCs) were mediated by either glycine receptors (GlyR) or GABA(A) receptors (GABA(A)R), yet never by the two together. In contrast, recent studies of ventral horn immature inhibitory synapses (</=P21) reported individual mIPSCs that were mediated by both GABA(A)Rs and GlyRs. This raises the question of whether mixed mIPSCs are present in immature lamina I-II neurons yet are lost through a maturation-dependent synaptic specialization. To test this, we recorded mIPSCs using patch-clamp techniques in lamina I-II neurons in spinal slices taken at different stages of development. We found that, in neurons younger than P23, both GlyR-only and GABA(A)R-only mIPSCs could be recorded, in addition to mixed GABA(A)R-GlyR mIPSCs. With maturation however, both lamina I-II neurons gradually discontinued exhibiting mixed mIPSCs, although with differing patterns of specialization. Yet, at all developmental stages, benzodiazepine administration could unmask mixed mIPSCs. Together, these findings indicate that, although GABA and glycine are continually co-released throughout development, junctional codetection ceases by adulthood. This indicates an age-dependent postsynaptic tuning of inhibitory synapses that occurs in a region-specific manner.
New Compounds - N,N,N'N'-Tetraalkylhomopiperazinium Salts. (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNew Compounds - N,N,N'N'-Tetraalkylhomopiperazinium Salts.William Hart and Kenneth JonesCite this: J. Med. Chem. 1968, 11, 6, 1270–1271Publication Date (Print):November 1, 1968Publication History Published online20 September 2004Published inissue 1 November 1968https://pubs.acs.org/doi/10.1021/jm00312a617https://doi.org/10.1021/jm00312a617research-articleACS PublicationsRequest reuse permissionsArticle Views27Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
2-Substituted Piperazines as Constrained Amino Acids. Application to the Synthesis of Potent, Non Carboxylic Acid Inhibitors of Farnesyltransferase (1996)

ADVERTISEMENT RETURN TO ISSUELetterNEXT2-Substituted Piperazines as Constrained Amino Acids. Application to the Synthesis of Potent, Non Carboxylic Acid Inhibitors of FarnesyltransferaseTheresa M. Williams, Terrence M. Ciccarone, Suzanne C. MacTough, Rhonda L. Bock, Michael W. Conner, Joseph P. Davide, Kelly Hamilton, Kenneth S. Koblan, Nancy E. Kohl, Astrid M. Kral, Scott D. Mosser, Charles A. Omer, David L. Pompliano, Elaine Rands, Michael D. Schaber, Daksha Shah, Francine R. Wilson, Jackson B. Gibbs, Samuel L. Graham, George D. Hartman, Allen I. Oliff, and Robert L. SmithView Author Information Departments of Medicinal Chemistry, Cancer Research, and Safety Assessment, Merck Research Laboratories, West Point, Pennsylvania 19486, and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 Cite this: J. Med. Chem. 1996, 39, 7, 1345–1348Publication Date (Web):March 29, 1996Publication History Received2 November 1995Published online29 March 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/jm9508090https://doi.org/10.1021/jm9508090rapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views759Altmetric-Citations52LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Cells,Inhibition,Inhibitors,Monomers,Peptides and proteins Get e-Alerts
Chemical Transformations of Ibogaine (1966)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemical Transformations of IbogaineG. Büchi and R. E. ManningCite this: J. Am. Chem. Soc. 1966, 88, 11, 2532–2535Publication Date (Print):June 1, 1966Publication History Published online1 May 2002Published inissue 1 June 1966https://pubs.acs.org/doi/10.1021/ja00963a031https://doi.org/10.1021/ja00963a031research-articleACS PublicationsRequest reuse permissionsArticle Views597Altmetric-Citations34LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Highly Efficient Stress Transfer Techniques in Dual Stress Liner CMOS Integration (2007)

Double disposable sidewall spacers (DDSW) process and adhesion reinforcement technique (ART) are proposed, for the first time, demonstrating efficient stress-transfer from the dual stress liner (DSL) to the FET channel region. A thin L-shape sidewall formed by the DDSW process was designed to compensate decreased channel stress resulted from the aggressive pitch scaling. A +10% enhancement of channel conductance has been achieved for NTETs by the DDSW process compared with a conventional DSL one. For PFETs, achieved +23% I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">on</sub> enhancement by using the ART, was resulted from avoiding stress degradation in the DSL process and optimizing the DSL layout.
Adaptive binary coding for diversity communication systems (2002)

Coding and diversity are two powerful techniques to combat fading effects on communication channels. In this paper the available diversity channels are utilized by forward error correction coding in an adaptive fashion to improve the reliability of the system. Based on the quality of the diversity channels, the code rate over each channel is determined using discrete optimization of the overall error probability, subject to the constraint of fixed overall throughput rate. It is found that the proposed system provides noticeable gain over the classical diversity system when binary BCH codes with hard-decision decoding are used. Moreover, the proposed system offers flexibility in choosing the throughput of the system, which the diversity system lacks. The advantages of the proposed system are obtained at only slight increase in implementation complexity.
Inverse Agonistic Action of 3-Iodothyronamine at the Human Trace Amine-Associated Receptor 5 (2015)

Application of 3-iodothyronamine (3-T1AM) results in decreased body temperature and body weight in rodents. The trace amine-associated receptor (TAAR) 1, a family A G protein-coupled receptor, is a target of 3-T1AM. However, 3-T1AM effects still persist in mTaar1 knockout mice, which suggest so far unknown further receptor targets that are of physiological relevance. TAAR5 is a highly conserved TAAR subtype among mammals and we here tested TAAR5 as a potential 3-T1AM target. First, we investigated mouse Taar5 (mTaar5) expression in several brain regions of the mouse in comparison to mTaar1. Secondly, to unravel the full spectrum of signaling capacities, we examined the distinct Gs-, Gi/o-, G12/13-, Gq/11- and MAP kinase-mediated signaling pathways of mouse and human TAAR5 under ligand-independent conditions and after application of 3-T1AM. We found overlapping localization of mTaar1 and mTaar5 in the amygdala and ventromedial hypothalamus of the mouse brain. Second, the murine and human TAAR5 (hTAAR5) display significant basal activity in the Gq/11 pathway but show differences in the basal activity in Gs and MAP kinase signaling. In contrast to mTaar5, 3-T1AM application at hTAAR5 resulted in significant reduction in basal IP3 formation and MAP kinase signaling. In conclusion, our data suggest that the human TAAR5 is a target for 3-T1AM, exhibiting inhibitory effects on IP3 formation and MAP kinase signaling pathways, but does not mediate Gs signaling effects as observed for TAAR1. This study also indicates differences between TAAR5 orthologs with respect to their signaling profile. In consequence, 3-T1AM-mediated effects may differ between rodents and humans.
Aluminum nanowire polarizing grids: Fabrication and analysis (2006)

We have produced metal wire grids with 33nm periodicity, using a thin film of a self-assembling diblock copolymer as a template. These grids, supported on fused quartz wafers, function as transmission polarizers for visible and near-ultraviolet lights. Their polarization efficiency is measured to be near 50% in the visible. Quantitative comparison with a new theoretical analysis of such wire grids indicates that they should perform well into the far UV. This analysis also explains the reversal in polarization direction at shorter wavelengths which we observe in our specimens.