gebhart/patrepeval huggingface dataset:
In Vitro Activities of New Antimicrobials against Nocardia brasiliensis (2004)

The in vitro sensitivities of 30 strains of Nocardia brasiliensis to DA-7867, gatifloxacin, moxifloxacin, and BMS-284756 (garenoxacin) were determined using the broth microdilution method. All N. brasiliensis strains were sensitive to these antimicrobials. The most active drug in vitro was DA-7867, with a MIC at which 90% of the isolates tested were inhibited of 0.03 micro g/ml and a MIC at which 50% of the isolates tested were inhibited of 0.06 micro g/ml.
Low-Cost Printing of Poly(dimethylsiloxane) Barriers To Define Microchannels in Paper (2008)

This paper describes the use of a modified x,y-plotter to generate hydrophilic channels by printing a solution of hydrophobic polymer (pol(dimethylsiloxane; PDMS) dissolved in hexanes onto filter paper. The PDMS penetrates the depth of the paper and forms a hydrophobic wall that aqueous solutions cannot cross. The minimum size of printed features is approximately 1 mm; this resolution is adequate for the rapid prototyping of hand-held, visually read, diagnostic assays (and other microfluidic systems) based on paper. After curing the printed PDMS, the paper-based devices can be bent or folded to generate three-dimensional systems of channels. Capillary action pulls aqueous samples into the paper channels. Colorimetric assays for the presence of glucose and protein are demonstrated in the printed devices; spots of Bromothymol Blue distinguished samples with slightly basic pH (8.0) from samples with slightly acidic pH (6.5). The work also describes using printed devices that can be loaded using multipipets and printed flexible, foldable channels in paper over areas larger than 100 cm2.
Surrogate Antibodies That Specifically Bind and Neutralize CCL17 But Not CCL22 (2013)

The chemokines CCL17 (TARC) and CCL22 (MDC) function through the same receptor, CCR4, but have been proposed to differentially affect the immune response. To better understand the role of the individual ligands, a panel of rat anti-mouse CCL17 surrogate antibodies was generated that can be used to differentiate CCL17 and CCL22 function in vitro and in vivo. We have successfully identified a panel of neutralizing antibodies by screening hybridomas for the ability to inhibit CCL17-mediated calcium mobilization. Chemotaxis in response to CCL17 is also inhibited, providing further evidence that the antibodies in this panel are antagonistic. Using a recombinant cell line expressing human CCR4, we show that the antibodies block β-arrestin recruitment as evidence that the antibodies are specifically blocking CCL17 signaling through CCR4. The antibodies within this panel inhibit calcium mobilization with varying potency in the calcium flux assay, having apparent IC50 ranging from approximately 1 to >400 ng/mL. Although both CCL17 and CCL22 function through CCR4, only a single antibody was identified as having detectable binding to CCL22. This panel of CCL17-specific antibodies provides tools that can be used to differentiate CCL17 and CCL22 function through CCR4 interaction in vitro and in vivo.
Improved iodine radiolabels for monoclonal antibody therapy. (2003)

A major disadvantage of (131)iodine (I)-labeled monoclonal antibodies (MAbs) for radioimmunotherapy has been the rapid diffusion of iodotyrosine from target cells after internalization and catabolism of the radioiodinated MAbs. We recently reported that a radioiodinated, diethylenetriaminepentaacetic acid-appended peptide, designated immunomedics' residualizing peptide 1 (IMP-R1), was a residualizing iodine label that overcame many of the limitations that had impeded the development of residualizing iodine for clinical use. To determine the factors governing the therapeutic index of the labeled MAb, as well as the factors required for production of radioiodinated MAb in high yield and with high specific activity, variations in the peptide structure of IMP-R1 were evaluated. A series of radioiodinated, diethylenetriaminepentaacetic acid-appended peptide moieties (IMP-R1 through IMP-R8) that differed in overall hydrophilicity and charge were compared. Radioiodinations of the peptides followed by conjugations to disulfide-reduced RS7 (an anti-epithelial glycoprotein-1 MAb) furnished radioimmunoconjugates in good overall incorporations, with immunoreactivities comparable to that of directly radioiodinated RS7. Specific activities of up to 8 mCi/mg and yields > 80% have been achieved. In vitro processing experiments showed marked increases in radioiodine retention with all of the adducts; radioiodine retention at 45 h was up to 86% greater in cells than with directly iodinated RS7. Each of the (125)I-peptide-RS7 conjugates was compared with (131)I-RS7 (labeled by the chloramine-T method) in paired-label biodistribution studies in nude mice bearing human lung tumor xenografts. All of the residualizing substrates exhibited significantly enhanced retention in tumor in comparison to directly radioiodinated RS7, but the nontarget uptakes differed significantly among the residualizing labels. The best labels were IMP-R4 and IMP-R8, showing superior tumor-to-non-tumor ratios by virtue of high tumor uptake and retention and low normal organ uptake, as well as superior radiochemical properties. The therapeutic efficacy of (131)I-IMP-R4-RS7 was compared with that of conventionally (131)I-labeled RS7 and (90)yttrium-RS7 in the nude mice lung cancer model. The therapeutic efficacy of (131)I-IMP-R4-RS7 and (90)yttrium-RS7 were equivalent, and both agents yielded significantly improved control of tumor growth compared with conventional (131)I-labeled RS7.
The third spectrum of copper (cu III) (1975)

An analysis of Cu iii based on observations from 500 to 6900 Å is presented. The low structures 3<i>d</i> <sup>9</sup> and 3<i>d</i> <sup>8</sup>4<i>s</i> are complete, including the rarely, if ever before, found 3<i>d</i> <sup>8</sup>(<sup>1</sup>S)4<i>s</i> <sup>2</sup>S. The 3<i>d</i> <sup>7</sup>4<i>s</i> <sup>2</sup> includes <sup>4</sup>F, <sup>2</sup>F, <sup>2</sup>G, and <sup>2</sup>H but the <sup>4</sup>P, <sup>2</sup>P, <i>a</i> <sup>2</sup>D, <i>b</i> <sup>2</sup>D have eluded all attempts to find them. The ionization potential calculated from 4<i>s</i>, 5<i>s</i>, 6<i>s</i> <sup>4</sup> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow><mml:msup><mml:mrow></mml:mrow> <mml:mn>4</mml:mn></mml:msup> <mml:msub><mml:mtext>F</mml:mtext> <mml:mrow><mml:msup><mml:mn>4</mml:mn> <mml:mrow><mml:mn>1</mml:mn> <mml:mo>/</mml:mo> <mml:mn>2</mml:mn></mml:mrow> </mml:msup> </mml:mrow> </mml:msub> </mml:mrow> </mml:math> is 296 980 cm<sub>-1</sub> but by a comparison with Ni II which has a longer series an approximate value of 297 140 can be estimated. The 3<i>d</i> <sup>8</sup>4<i>d</i> group is complete, except for one level, as is 5<i>d</i>based on <sup>3</sup>F and <sup>1</sup>G, the other 5<i>d</i> groups being incomplete. 3<i>d</i> <sup>8</sup>(<sup>3</sup>F)4<i>f</i> is complete and 26 levels based on <sup>1</sup>D, <sup>3</sup>P, <sup>1</sup>G are known. 3<i>d</i> <sup>8</sup>(<sup>3</sup>F)5<i>g</i> is incomplete and a few levels based on <sup>1</sup>D and <sup>1</sup>G have been found. A discussion of the validity of the analysis of Cu iv by J. F. Schröder and Th. A. M. Van Kleef is given.
Identification of (R)-N-((4-Methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide (CPI-1205), a Potent and Selective Inhibitor of Histone Methyltransferase EZH2, Suitable for Phase I Clinical Trials for B-Cell Lymphomas (2016)

Polycomb repressive complex 2 (PRC2) has been shown to play a major role in transcriptional silencing in part by installing methylation marks on lysine 27 of histone 3. Dysregulation of PRC2 function correlates with certain malignancies and poor prognosis. EZH2 is the catalytic engine of the PRC2 complex and thus represents a key candidate oncology target for pharmacological intervention. Here we report the optimization of our indole-based EZH2 inhibitor series that led to the identification of CPI-1205, a highly potent (biochemical IC<sub>50</sub> = 0.002 μM, cellular EC<sub>50</sub> = 0.032 μM) and selective inhibitor of EZH2. This compound demonstrates robust antitumor effects in a Karpas-422 xenograft model when dosed at 160 mg/kg BID and is currently in Phase I clinical trials. Additionally, we disclose the co-crystal structure of our inhibitor series bound to the human PRC2 complex.
Domain Adaptation of Rule-Based Annotators for Named-Entity Recognition Tasks (2010)

Named-entity recognition (NER) is an important task required in a wide variety of applications. While rule-based systems are appealing due to their well-known “explainability,” most, if not all, state-of-the-art results for NER tasks are based on machine learning techniques. Motivated by these results, we explore the following natural question in this paper: Are rule-based systems still a viable approach to named-entity recognition? Specifically, we have designed and implemented a high-level language NERL on top of SystemT, a general-purpose algebraic information extraction system. NERL is tuned to the needs of NER tasks and simplifies the process of building, understanding, and customizing complex rule-based named-entity annotators. We show that these customized annotators match or outperform the best published results achieved with machine learning techniques. These results confirm that we can reap the benefits of rule-based extractors ’ explainability without sacrificing accuracy. We conclude by discussing lessons learned while building and customizing complex rule-based annotators and outlining several research directions towards facilitating rule development. 1
13C-Pattern of Natural Glycerol:  Origin and Practical Importance (1997)

The average δ13C-value of glycerol from plant origin is 4−5‰ more negative than that of carbohydrates from the same source. This depletion is exclusively dealing with position C-1 of the molecule. This is also observed for glycerol from other natural sources, although to a smaller extent, while synthetic glycerol shows a statistical 13C-pattern. On the basis of these data an illegal addition of glycerol to wine should be detectable. In fermentations of glucose with yeast the extent of the depletion in position C-1 of glycerol proved to be reciprocal to its yield. Furthermore a total carbon and isotope balance showed that the depletion of glycerol is a compensation for small 13C-enrichments in the corresponding positions of main products. An isotope effect on the aldolase reaction and a noncomplete equilibration of the triose phosphates are discussed as main reasons for these findings. Keywords: Authenticity proof; carbon-13; glycerol; isotopic pattern; stable isotopes; wine
Molecular replacement withMOLREP (2009)

MOLREP is an automated program for molecular replacement that utilizes a number of original approaches to rotational and translational search and data preparation. Since the first publication describing the program, MOLREP has acquired a variety of features that include weighting of the X-ray data and search models, multi-copy search, fitting the model into electron density, structural superposition of two models and rigid-body refinement. The program can run in a fully automatic mode using optimized parameters calculated from the input data.
Phosphorus pentoxide in organic synthesis. XX. Synthesis of N‐aryl‐7H‐pyrrolo[2,3‐d]pyrimidin‐4‐amines (1985)

Abstract N ‐Aryl‐7 H ‐pyrrolo[2,3‐ d ]pyrimidine‐4‐amines 7 were prepared in 30‐67% yields by treating N7‐(1‐phenyl‐ethyl)pyrrolo[2,3‐ d ]pyrimidin‐4(3 H )‐ones 2 with a mixture of phosphorus pentoxide, triethylamine hydrochloride, and an appropriate arylamine hydrochloride at 240° for 3‐7 hours.
Synthesis and ECL performance of highly efficient bimetallic ruthenium tris-bipyridyl complexes (2012)

In order to find the ideal carbon chain linkage number n for achieving the highest ECL in bimetallic ruthenium tris-bipyridyl complexes, a series of novel complexes [(bpy)(2)Ru(bpy')(CH(2))(n)(bpy')Ru(bpy)(2)](4+) (, where bpy is 2,2'-bipyridyl, n = 10, 12, 14) for a coreactant electrochemiluminescence (ECL) system have been synthesized. Their ECL properties at a Au electrode have been studied in 0.1 M phosphate buffer by using tripropylamine (TPrA), 2-(dibutylamino)ethanol (DBAE) and melamine as the coreactant, to compare with that of the previously reported bimetallic ruthenium analogous complex [(bpy)(2)Ru(bpy')(CH(2))(8)(bpy')Ru(bpy)(2)](4+). The results demonstrate that the ECL intensity depends largely on the length of the saturated carbon chain linkage number n. The highest ECL is reached when n = 10, suggesting that a synergistic effect on ECL enhancement co-exists between the two intramolecular linked ruthenium activating centers. Density functional theory (DFT) calculation demonstrated that the optimized bond distances between Ru and N(bpy') are the longest both in the ground and the excited triplet states in the case of n = 10, while those for Ru and N(bpy) are the shortest in the excited triplet states. All these factors may be responsible for the above mentioned results. This study provided a methodology to further improve and tune ECL efficiency by using bimetallic ruthenium complexes linked by a flexible saturated carbon chain.
Hierarchical recognition of articulated objects from single perspective views (2002)

This paper presents an approach to the recognition of articulated 3D objects in monocular video images. A hierarchical object representation models objects as a composition of rigid components which are explicitly connected by specific kinematic constraints, e.g., rotational and/or translational joints. The recognition task follows this tree-like structure by first estimating the 3D pose of the static component (root) and afterwards determining the relative 3D pose of the remaining components recursively. This method limits the search space for the actual correspondences between image and model features and copes with the problem of self-occlusion. Experiments in the context of autonomous, mobile robots show the practicability of this approach.
Serum procalcitonin levels in bacterial and abacterial meningitis (2000)

Our results indicate that PCT is a useful additional variable for distinguishing bacterial from abacterial meningitis. In patients with abacterial meningitis, PCT levels do not increase even in cases of viral sepsis. Elevated PCT levels indicate a bacterial origin with high specificity, but false-negative results can occur.
Current and emerging therapies for the treatment of age-related macular degeneration (2008)

Age-related macular degeneration (AMD) is the leading cause of vision loss in the industrialized world. In the last few decades, the mainstay of treatment for choroidal neovascularization (CNV) due to AMD has been thermal laser photocoagulation. In the last decade, photodynamic therapy with verteporfin extended treatment for more patients. While both of these treatments have prevented further vision loss in a subset of patients, improvement in visual acuity is rare. Anti-vascular endothelial growth factor A (VEGF) therapy has revolutionized the treatment of AMD-related CNV. Pegaptanib, an anti-VEGF aptamer prevents vision loss in CNV, although the performance is similar to that of photodynamic therapy. Ranibizumab, an antibody fragment and bevacizumab, a full-length humanized monoclonal antibody against VEGF have both shown promising results with improvements in visual acuity with either agent. VEGF trap, a modified soluble VEGF receptor analogue, binds VEGF more tightly than all other anti-VEGF agents and has also shown promising results in early trials. Other treatment strategies to decrease the effect of VEGF have used small interfering ribonucleic acid (RNA) to inhibit VEGF production and VEGF receptor production. Steroids, including anecortave acetate in the treatment and prevention of CNV, have shown promise in controlled trials. Receptor tyrosine kinase inhibitors, such as vatalanib, inhibit downstream effects of VEGF, and have been effective in the treatment of CNV in early studies. Squalamine lactate inhibits plasma membrane ion channels with downstream effects on VEGF, and has shown promising results with systemic administration. Other growth factors, including pigment epithelium-derived growth factor that has been administered via an adenoviral vector has shown promising initial results. In some patients ciliary neurotrophic factor is currently being studied for the inhibition of progression of geographic atrophy. Combination therapy has been investigated, and may prove to be more effective in the management of AMD-associated CNV. Ongoing and future studies will be crucial for optimizing the treatment of patients with AMD.
Low-Overhead Spatial and Temporal Data Locality Analysis (2003)

Performance is getting increasingly sensitive to cache behavior because of the growing gap between processor cycle time and memory latency. To improve performance, applications need to be optimized for data locality. Run-time analysis of spatial and temporal data locality can be used to facilitate this and should help both manual tuning and feedback-based compiler optimizations. Identifying cache behavior of individual data structures further enhances the optimization process. Current methods to perform such analysis include simulation combined with set sampling or time sampling, and hardware monitoring. Sampling often suffers from either poor accuracy or large run-time overhead, while hardware measurements have limited flexibility. We present DLTune, a prototype tool that performs spatial and temporal data-locality analysis in run time. It measures both spatial and temporal locality for the entire application and individual data structures in a single run, and effectively exposes poor data locality based on miss ratio estimates of fully-associative caches. The tool is based on an elaborate and novel sampling technique that allows all information to be collected in a single run with an overall sampling rate as low as one memory reference in ten million and an average slowdown below five on large workloads. 2 1 Introduction The use of caches and advanced memory hierarchies in modern computers assumes locality of data to perform well. Poor data locality causes the processor to stall frequently because many data accesses miss in the cache. Analysis of data locality helps in designing efficient software, both when used in a compiler framework to guide optimization decisions, and as a programming aid in the form of profiling tools. It is essential that such a tool is fast enough to allow for real-sized data sets and provides short turn-around times.
Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation (1996)

The hippocampus is one of the few areas of the rodent brain that continues to produce neurons postnatally. Neurogenesis reportedly persists in rats up to 11 months of age. Using bromodeoxyuridine (BrdU) labeling, the present study confirms that in the adult rat brain, neuronal progenitor cells divide at the border between the hilus and the granule cell layer (GCL). In adult rats, the progeny of these cells migrate into the GCL and express the neuronal markers NeuN and calbindin-D28k. However, neurogenesis was drastically reduced in aged rats. Six-to 27-month-old Fischer rats were injected intraperitoneally with BrdU to detect newborn cells in vivo and to follow their fate in the dentate gyrus. When killed 4-6 weeks after BrdU labeling, 12- to 27-month-old rats exhibited a significant decline in the density of BrdU-positive cells in the granule cell layer compared with 6-month-old controls. Decreased neurogenesis in aging rats was accompanied by reduced immunoreactivity for poly-sialylated neural cell adhesion molecule, a molecule that is involved in migration and process elongation of developing neurons. When animals were killed immediately (12 hr) after BrdU injection, significantly fewer labeled cells were observed in the GCL and adjacent subgranular zone of aged rats, indicative of a decrease in mitotic activity of neuronal precursor cells. The reduced proliferation was not attributable to a general aged-related metabolic impairment, because the density of BrdU-positive cells was not altered in other brain regions with known mitotic activity (e.g., hilus and lateral ventricle wall). The decline in neurogenesis that occurs throughout the lifespan of an animal can thus be related to a decreasing proliferation of granule cell precursors.
HIV-1 nef suppression by virally encoded microRNA (2004)

Abstract Background MicroRNAs (miRNAs) are 21~25-nucleotides (nt) long and interact with mRNAs to trigger either translational repression or RNA cleavage through RNA interference (RNAi), depending on the degree of complementarity with the target mRNAs. Our recent study has shown that HIV-1 nef dsRNA from AIDS patients who are long-term non-progressors (LTNPs) inhibited the transcription of HIV-1. Results Here, we show the possibility that nef -derived miRNAs are produced in HIV-1 persistently infected cells. Furthermore, nef short hairpin RNA (shRNA) that corresponded to a predicted nef miRNA (~25 nt, miR-N367) can block HIV-1 Nef expression in vitro and the suppression by shRNA/miR-N367 would be related with low viremia in an LTNP (15-2-2). In the 15-2-2 model mice, the weight loss, which may be rendered by nef was also inhibited by shRNA/miR-N367 corresponding to suppression of nef expression in vivo . Conclusions These data suggest that nef /U3 miRNAs produced in HIV-1-infected cells may suppress both Nef function and HIV-1 virulence through the RNAi pathway.
Antibiotics in periodontal therapy: advantages and disadvantages* (1990)

Antibiotic treatment of periodontitis aims at eradicating or controlling specific pathogens. Prime candidates for antibiotic therapy are patients with recently diagnosed active periodontitis or a history of recurrent disease who fail to stabilize following mechanical/surgical therapy. Since a variety of microbes with differing antimicrobial susceptibility profiles may cause periodontitis, selection of antimicrobial agents should be based on proper microbial diagnosis and sensitivity testing, as well as consideration of the patient's medical status. The risk of treating chemotherapeutically solely on the basis of clinical features, radiographic findings or a limited microbiological analysis, is failure to control the pathogens or overgrowth of new pathogens. A review of published papers reveals that appropriate systemic antibiotic therapy may enhance healing in patients with recent or high risk of periodontal breakdown. Systemic antibiotic therapy seems more predictable than topical administration in eradicating periodontal pathogens from deep periodontal pockets. Several promising antimicrobial agents for periodontitis treatment need testing in placebo-controlled, double-blind, randomized clinical trials.
Gout and hyperuricemia (2002)

Gout continues to be a health problem around the world despite the availability of effective therapies. Although the prevalence is influenced by genetic factors, the associations of alcohol consumption, obesity, and hypertension appear to be partially responsible for the increased prevalence of gout and hyperuricemia in African and Oriental countries. The association between hyperuricemia and cardiovascular disease seems linked to insulin resistance. This relation, in part, explains the common coexistence of hyperlipidemia and glucose intolerance in patients with gout. Accordingly, it is recommended that one pay more attention to dietary manipulation in patients with gout in addition to managing hypertension, obesity, and other medical problems. Although acute gout attacks can be treated, eliminating gout requires effective removal of urate from the body. Allopurinol remains a dominant urate-lowering agent, however its use may be limited by allergic reactions. Uricosuric agents are also effective urate-lowering agents and provide an alternative to allopurinol. Strategies to treat patients who are sensitive to allopurinol continue to evolve.