gebhart/patrepeval huggingface dataset:
1,2-Diarylpyrroles as Potent and Selective Inhibitors of Cyclooxygenase-2 (1997)

Series of 1,2-diarylpyrroles has been synthesized and found to contain very potent and selective inhibitors of the human cyclooxygenase-2 (COX-2) enzyme. The paper describes short and practical syntheses of the target molecules utilizing the Paal-Knorr reaction. Electrophilic substitution on 1 proceeds in a regioselective fashion, and the method was used to generate a number of tetrasubstituted pyrroles. Detailed SAR on the series has been studied by modifications of the aryl rings and the substituents in the pyrrole ring. Diarylpyrrole 1 is a very potent (COX-2, IC50 = 60 nm) and selective (COX-1/COX-2 = > 1700) inhibitor whereas the isomeric 2 is completely inactive against COX-2. Modifications of the substituents on the fluorophenyl ring in 1 yields very potent inhibitors of COX-2 (IC50 = 40-80 nm) with excellent selectivity (1200 to > 2500) vs COX-1. Analog 20 containing a sulfonamide group is an excellent inhibitor of COX-2 with an IC50 of 14 nm. Tetrasubstituted pyrroles containing groups such as COCF3, SO2CF3, or CH2OAr at position 3 in the pyrrole ring give excellent inhibitors (COX-2, IC50 = 30-120 nm). In vivo testing in the carrageenan-induced paw edema model in the rat establishes that the 1,2-diarylpyrroles are orally active antiinflammatory agents. Compound 3 is the most potent inhibitor of edema with an ED50 of 4.7 mpk.
Biochemical and mutagenic analysis of the melanoma tumor suppressor gene product/p16. (1995)

P16 was originally discovered by its ability to interact with CDK4 and to specifically inhibit the catalytic activity of the CDK4/D1 kinase. Increased attention has focused on the p16 gene because of its location on chromosome 9p21, a region involved in chromosomal rearrangements in a large number of tumor types. The p16 gene is also mutated in a large number of tumor cell lines and primary tumor cells. Furthermore, linkage analysis studies suggest that the p16 gene is involved in familial melanoma susceptibility. Due to the oncogenic potential of mutations in this tumor suppressor, it is important to identify and characterize those mutations which alter p16 activity. We have performed a systematic analysis of melanoma associated p16 mutants and of mutants generated in charge to Ala mutagenesis. Using microtiter plate assays to measure both p16-cdk4 binding and cdk4/D1 kinase activity, we show here that the melanoma associated mutants are defective, as are some of the Ala mutants. These results support the idea that p16 mutation, via its deregulation of the cdk4/D1 pathway, is of biological significance in the development of melanoma. Furthermore, we have defined a region within the p16 molecule in which changes are likely to result in a defective protein.
Fastpass (2014)

An ideal datacenter network should provide several properties, including low median and tail latency, high utilization (throughput), fair allocation of network resources between users or applications, deadline-aware scheduling, and congestion (loss) avoidance. Current datacenter networks inherit the principles that went into the design of the Internet, where packet transmission and path selection decisions are distributed among the endpoints and routers. Instead, we propose that each sender should delegate control---to a centralized arbiter---of when each packet should be transmitted and what path it should follow. This paper describes Fastpass, a datacenter network architecture built using this principle. Fastpass incorporates two fast algorithms: the first determines the time at which each packet should be transmitted, while the second determines the path to use for that packet. In addition, Fastpass uses an efficient protocol between the endpoints and the arbiter and an arbiter replication strategy for fault-tolerant failover. We deployed and evaluated Fastpass in a portion of Facebook's datacenter network. Our results show that Fastpass achieves high throughput comparable to current networks at a 240x reduction is queue lengths (4.35 Mbytes reducing to 18 Kbytes), achieves much fairer and consistent flow throughputs than the baseline TCP (5200x reduction in the standard deviation of per-flow throughput with five concurrent connections), scalability from 1 to 8 cores in the arbiter implementation with the ability to schedule 2.21 Terabits/s of traffic in software on eight cores, and a 2.5x reduction in the number of TCP retransmissions in a latency-sensitive service at Facebook.
Internally quenched fluorescent peptide substrates disclose the subsite preferences of human caspases 1, 3, 6, 7 and 8 (2000)

Subsite interactions are considered to define the stringent specificity of proteases for their natural substrates. To probe this issue in the proteolytic pathways leading to apoptosis we have examined the P(4), P(1) and P(1)' subsite preferences of human caspases 1, 3, 6, 7 and 8, using internally quenched fluorescent peptide substrates containing o-aminobenzoyl (also known as anthranilic acid) and 3-nitro-tyrosine. Previous work has demonstrated the importance of the S(4) subsite in directing specificity within the caspase family. Here we demonstrate the influence of the S(1) and S(1)' subsites that flank the scissile peptide bond. The S(1) subsite, the major specificity-determining site of the caspases, demonstrates tremendous selectivity, with a 20000-fold preference for cleaving substrates containing aspartic acid over glutamic acid at this position. Thus caspases are among the most selective of known endopeptidases. We find that the caspases show an unexpected degree of discrimination in the P(1)' position, with a general preference for small amino acid residues such as alanine, glycine and serine, with glycine being the preferred substituent. Large aromatic residues are also surprisingly well-tolerated, but charged residues are prohibited. While this describes the general order of P(1)' subsite preferences within the caspase family, there are some differences in individual profiles, with caspase-3 being particularly promiscuous. Overall, the subsite preferences can be used to predict natural substrates, but in certain cases the cleavage site within a presumed natural substrate cannot be predicted by looking for the preferred peptide cleavage sites. In the latter case we conclude that second-site interactions may overcome otherwise sub-optimal cleavage sequences.
Oncolytic Herpes Simplex Virus 1 Encoding 15-Prostaglandin Dehydrogenase Mitigates Immune Suppression and Reduces Ectopic Primary and Metastatic Breast Cancer in Mice (2011)

Oncolytic herpes simplex virus 1 (HSV-1) viruses armed with immunomodulatory transgenes have shown potential for enhanced antitumor therapy by overcoming tumor-based immune suppression and promoting antitumor effector cell development. Previously, we reported that the new oncolytic HSV-1 virus, OncSyn (OS), engineered to fuse tumor cells, prevented tumor growth and metastasis to distal organs in the 4T1/BALB/c immunocompetent breast cancer mouse model, suggesting the elicitation of antitumor immune responses (Israyelyan et al., Hum. Gen. Ther. 18:5, 2007, and Israyelyan et al., Virol. J. 5:68, 2008). The OSV virus was constructed by deleting the OS viral host shutoff gene (vhs; UL41) to further attenuate the virus and permit dendritic cell activation and antigen presentation. Subsequently, the OSVP virus was constructed by inserting into the OSV viral genome a murine 15-prostaglandin dehydrogenase (15-PGDH) expression cassette, designed to constitutively express 15-PGDH upon infection. 15-PGDH is a tumor suppressor protein and the primary enzyme responsible for the degradation of prostaglandin E2 (PGE2), which is known to promote tumor development. OSVP, OSV, and OS treatment of 4T1 tumors in BALB/c mice effectively reduced primary tumor growth and inhibited metastatic development of secondary tumors. OSVP was able to significantly inhibit the development and accumulation of 4T1 metastatic tumor cells in the lungs of treated mice. Ex vivo analysis of immune cells following treatment showed increased inflammatory cytokine production and the presence of mature dendritic cells for the OSVP, OSV, and OS viruses. A statistically significant decrease in splenic myeloid-derived suppressor cells (MDSC) was observed only for OSVP-treated mice. These results show that intratumoral oncolytic herpes is highly immunogenic and suggest that 15-PGDH expression by OSVP enhanced the antitumor immune response initiated by viral infection of primary tumor cells, leading to reduced development of pulmonary metastases. The availability of the OSVP genome as a bacterial artificial chromosome allows for the rapid insertion of additional immunomodulatory genes that could further assist in the induction of potent antitumor immune responses against primary and metastatic tumors.
Über carbocyclische Reduktone. Dihydropyrogallol und Dihydrogallussäure (1955)

Abstract Gallussäure ergibt bei der katalytischen Hydrierung in alkalischem Medium Cyclohexen‐(4)‐diol‐(4.5)‐on‐(3)‐carbonsäure‐(1). Diese Dihydrogallussäure erweist sich wie das Dihydropyrogallol als ein typisches Reduktion. Von beiden Verbindungen werden Anilin‐, Phenylhydrazin‐ und Methylderivate beschrieben. Die Weiterhydrierung der Dihydrogallussäure führt zur Cyclohexan‐triol‐(3.4.5)‐carbonsäure‐(1). Bei der Dehydrierung mit Luftsauerstoff liefern beide Reduktone kristallisierte Dihydrate der entsprechenden Triketone, die als Triketo‐Isomere des Pyrogallols bzw. der Gallussäure aufzufassen sind. Diese Triketone isomerisieren sich sehr leicht zu Pyrogallol bzw. zu Gallussäure; mit verd. Alkali erleiden sie Aufspaltung zur α‐Oxyadipinsäure bzw. zur α‐Oxy‐γM‐carboxy‐adipinsäure, mit Natriumperjodat zu den entsprechenden α‐Ketocarbonsäuren. Der Mechanismus der katalytischen Hydrierung von Pyrogallol und Gallussäure wird erörtert.
The Role of Dipeptidyl Peptidase IV in Lung Metastasis of Breast Cancer Cells (1999)

Our studies focused on (1) cloning and sequencing of wild-type endothelial DPP IV (wtDPP IV) and preparation of truncated DPP IV (tDPP IV); (2) identification of surface-associated fibronectin polymers (polyFN) as DPP IV ligand; (3) use of DPP IV Fischer 344/CRJ rats as protein-knock-outs in metastasis; and (4) identification of the DPP IV/FN binding domains. A lull-length clone of endothelial wtDPP IV was isolated from a rat lung cDNA library that was identical to hepatic DPP IV. Acid extraction of rat lung yielded a tDPP IV, which was an effective inhibitor of breast cancer cell adhesion to wtDPP IV and lung metastasis. The DPP IV ligand, polyFN, provides multiple binding sites for DPP IV, thereby allowing lung vascular arrest of cancer cells under hemodynamic conditions. Fischer 344/CRJ rats are unsuitable as DPP IV protein knock-out model, because lung endothelia leak expression of DPP IV and are able to support breast cancer cell arrest. The DPP IV binding domains of FN was localized to an N- terminal 30-kDa region and FN type III repeats 13 to 14. Three approximately equal size fragments of the extracellular domain of DPP IV were expressed as GST fusion proteins and are currently studied for FN binding.
Microsoft Research IME Corpus (2005)

This document describes the Microsoft Research IME (MSR-IME) Cor- pus, a test corpus for language modeling research based on the task of Japanese character conversion for text input. The aim of the corpus is to facilitate research in language modeling by providing a data set on a realistic, non-trivial task that is yet easy to use. The corpus consists of 6,000 sentences, and includes the gold-standard output of conversion, the corresponding input phonetic stream in kana, and the 100- best list of conversion candidates, specifically prepared for the re-ranking formula- tion of the task. This report includes the description of the task of Japanese character conversion for text input, the details of the corpus as well as the guidelines used to assign the readings to the reference file.
Stenosis of the Lumbar Spinal Canal (1971)

Neurosurgery: January 1971 - Volume 18 - Issue - p 86-105 doi: 10.1093/neurosurgery/18.CN_suppl_1.86
The NMDA Receptor as a Therapeutic Target in Major Depressive Disorder (2007)

Ample evidence indicates that glutamate homeostasis and neurotransmission are disrupted in major depressive disorder; but the nature of this disruption and the mechanisms by which it contributes to the syndrome are unclear. Likewise, the effect of existing antidepressants on glutamate is unclear, as is the potential of drugs directly targeting glutamatergic neurotransmission to act as novel antidepressant medications. These are areas of active research. Here we review current knowledge of the contribution of the NMDA receptor, one of the several types of glutamate receptor, to depression and its treatment. Several lines of evidence, in humans and in animal models, support the contention that neurotransmission via the NMDA receptor is dysregulated in depression. Drugs that target the NMDA receptor have shown antidepressant properties in both clinical and preclinical studies. Nevertheless, other effects of such medications, including both cognitive side effects and their psychotomimetic properties, complicate such an application and represent a challenge to the development of clinically useful agents.
Optical directional coupler using tapered sections in multimode fibers (1976)

An optical directional coupler with high efficiency has been fabricated using tapered sections in multimode fibers. In the biconical taper sections of the coupler, some of the higher-order modes are converted into radiation modes launched into a clear adhesive and subsequently reconverted into guided modes of two arms of the coupler. The insertion loss, power coupling, and directivity were measured to be 1.0, 10.2, and 20 dB, respectively.
A monoclonal antibody exhibiting reactivity with both X‐hapten‐ and lactose‐bearing glycolipids (1991)

The tissue reactivity of a monoclonal antibody raised against human granulocytes, FMC 34, was shown to overlap with antibodies including FMC 10, which is directed against the X-hapten, and with T5A7, which is directed against lactose-bearing antigens. Reactivity of FMC 34 on sections of human cornea was more widespread than that of either FMC 10 or T5A7. High sensitivity fluorescence testing revealed that both FMC 34 and T5A7 reacted weakly with the T-lymphocyte cell line JM, unlike the CD15 antibody FMC 10. Competitive binding experiments showed that binding of FMC 34 to granulocytes was inhibited by preincubation with T5A7, while FMC 34 itself was able to inhibit the binding of both FMC 10 and T5A7. The binding of FMC 10 was not inhibited by preincubation of cells with T5A7. Saturation-binding analyses revealed that each human granulocyte could bind 17.5 x 10(5) molecyles of FMC 34, which was more than three times the number of molecules of FMC 10 which could be bound to each cell. The additional reactivity of FMC 34 appears to be due to its capacity to bind fucosylated and non-fucosylated lactose-bearing structures.
Iatrogenic Botulism Due to Therapeutic Botulinum Toxin A Injection in a Pediatric Patient (2007)

Botulinum toxin A is commonly used to reduce spasticity and dystonia in children with cerebral palsy. We report a pediatric patient who developed systemic botulism as a result of a severe overdose of the injected toxin (40 U/kg). This case highlights the importance of physicians having adequate knowledge of primate and human literature on the lethal dose, 50% of botulinum toxin A before injecting children.
Advanced Surfactant-Modified Wet Anisotropic Etching (2012)

In the area of Micro Electro Mechanical Systems (MEMS), bulk micromachining and surface micromachining are two main technologies. Bulk micromachining defines structures by selectively etching inside a substrate while surface micromachining uses a succession of thin film deposition and selective etching on top of a substrate. The two technologies are quite different, resulting in different dimensions and different mechanical properties. Although bulk micromachining is usually considered to be the older technology, the two developments run parallel. This is due to the fact that the two different approaches have trade-offs. Taking an example of MEMS capacitance accelerometers, surface micromachined structures use smaller chip area, thus leaving more space for the electronics. On the other hand, in bulk micromachining the larger mass gives greater sensitivity for accelerometers and the larger area leads to larger capacitances for easy read out, which are extremely useful in the inertial device fabrication.
Inferences on the Genome Structure of Progenitor Maize Through Comparative Analysis of Rice, Maize and the Domesticated Panicoids (1999)

Corn and rice genetic linkage map alignments were extended and refined by the addition of 262 new, reciprocally mapped maize cDNA loci. Twenty chromosomal rearrangements were identified in maize relative to rice and these included telomeric fusions between rice linkage groups, nested insertion of rice linkage groups, intrachromosomal inversions, and a nonreciprocal translocation. Maize genome evolution was inferred relative to other species within the Panicoideae and a progenitor maize genome with eight linkage groups was proposed. Conservation of composite linkage groups indicates that the tetrasomic state arose during maize evolution either from duplication of one progenitor corn genome (autoploidy) or from a cross between species that shared the composite linkages observed in modern maize (alloploidy). New evidence of a quadruplicated homeologous segment on maize chromosomes 2 and 10, and 3 and 4, corresponded to the internally duplicated region on rice chromosomes 11 and 12 and suggested that this duplication in the rice genome predated the divergence of the Panicoideae and Oryzoideae subfamilies. Charting of the macroevolutionary steps leading to the modern maize genome clarifies the interpretation of intercladal comparative maps and facilitates alignments and genomic cross-referencing of genes and phenotypes among grass family members.
Near-Infrared Surface Plasmon Resonance Measurements of Ultrathin Films. 1. Angle Shift and SPR Imaging Experiments (1999)

The application of surface plasmon resonance (SPR) measurements to the study of ultrathin organic and inorganic films adsorbed onto gold surfaces utilizing near-infrared (NIR) excitation from 800 to 1152 nm is described. SPR scanning angle measurements of film thickness are demonstrated at 814 and 1152 nm using low-power diode and HeNe laser sources, respectively. Several advantages of SPR in the NIR are noted. The in situ reflectivity versus angle of incidence curves sharpen greatly (as compared to 632.8 nm) at longer wavelengths so that there is no loss in sensitivity in the measurement of film thickness despite a doubling of the excitation wavelength. The sharper resonance and longer wavelengths also allow for the measurement of thicker films. Examples of SPR thickness measurements for self-assembled alkanethiol monolayers and composite biopolymer/SiO2 nanoparticle electrostatic multilayer films are given. SPR imaging experiments are also performed at various NIR wavelengths using an incoherent white light source and narrow band-pass filters. The incoherent white light source eliminates laser fringes that have been observed in previous SPR imaging experiments, and the use of narrow band-pass filters allows for the easy selection and variation of excitation wavelength. The narrowness of the reflectivity versus angle curves leads to greater contrast in NIR SPR images compared to the same features examined with excitation from visible light. The combination of these changes results in nearly 1 order of magnitude enhancement in the SPR differential reflectivity image, indicating that SPR imaging is best conducted with incoherent NIR excitation. One disadvantage of using NIR wavelengths for SPR imaging is that the surface plasmon propagation length increases in the NIR so that the lateral image resolution is reduced; however, image features larger than 50 μm can easily be resolved. A NIR SPR image of a DNA array onto which single-stranded DNA binding protein has bound is shown as an example of how NIR SPR imaging experiments have sufficient sensitivity to monitor DNA−protein interactions.
Synthetic amorphous calcium phosphate and its relation to bone mineral structure (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthetic amorphous calcium phosphate and its relation to bone mineral structureAaron S. Posner and Foster BettsCite this: Acc. Chem. Res. 1975, 8, 8, 273–281Publication Date (Print):August 1, 1975Publication History Published online1 May 2002Published inissue 1 August 1975https://pubs.acs.org/doi/10.1021/ar50092a003https://doi.org/10.1021/ar50092a003research-articleACS PublicationsRequest reuse permissionsArticle Views2707Altmetric-Citations489LEARN 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
Creating and Using a Database with Perl (1997)

There are a variety of different database formats in a UNIX environment available to the Perl programmer
Multiple sclerosis presented as clinically isolated syndrome: the need for early diagnosis and treatment (2008)

In light of new treatments available, MRIs at 3 month intervals are helpful to obtain the definite diagnosis of MS as early as possible.
Comparative Studies of the Antioxidant Effects of Cis- and Trans- Resveratrol (2005)

Resveratrol (3,4,5-trihydroxystilbene, RESV) is a natural phenolic compound that exists as cis and trans isomers [c-RESV or (Z)-RESV and t-RESV or (E)-RESV, respectively]. t-RESV is a natural component of Vitis vinifera L. (Vitaceae), abundant in the skin of grapes (but not in the flesh) and in the leaf epidermis, and present in wines, especially red wines. In in vitro, ex vivo and in vivo experiments t-RESV exhibits a number of biological activities, including anti-inflammatory and anticarcinogenic properties. RESV also exists in wines as a cis isomer, which (unlike t-RESV) is not currently available commercially; as a result, little is known about this isomers pharmacological activity. In this review, I will focus on the few comparative studies of the antioxidant effects of the two RESV isomers in different experimental models. Keywords: Resveratrol isomers, NAD(P)H oxidase, xanthine oxidase, inducible nitric oxide synthase, murine macrophages, antioxidant activity, free radicals, wine
Animal productivity and animal welfare. (2002)

Dear Sir,

I agree with Dr. Rollin's statements regarding animal productivity and animal welfare (Can Vet J 2002;43:83), but I would like to take it a step further.

The reason that intensive farming practices have become common is because of the rapid increase in the global human population. The old style of agriculture can no longer produce enough food to feed all the hungry people in the world. Overpopulation also affects the environment, adequate health care, and the availability of jobs.

It is time that we recognized that more is not better when it comes to human population.