gebhart/patrepeval huggingface dataset:
Chemical Similarity Searching (1998)

This paper reviews the use of similarity searching in chemical databases. It begins by introducing the concept of similarity searching, differentiating it from the more common substructure searching, and then discusses the current generation of fragment-based measures that are used for searching chemical structure databases. The next sections focus upon two of the principal characteristics of a similarity measure: the coefficient that is used to quantify the degree of structural resemblance between pairs of molecules and the structural representations that are used to characterize molecules that are being compared in a similarity calculation. New types of similarity measure are then compared with current approaches, and examples are given of several applications that are related to similarity searching.
Computer-controlled, adaptive beam steering, implemented in a FLC-SLM free-space optical switch (2000)

We have used a dynamic diffractive spatial light modulator for adaptive beam steering. With adaptive beam steering it is possible to substantially reduce the alignment accuracy needed for the assembly of a free-space optical switch and to make it adaptive to changes in the environment during operation.
Identification of ras Oncogene Mutations in the Stool of Patients with Curable Colorectal Tumors (1992)

Colorectal (CR) tumors are usually curable if detected before metastasis. Because genetic alterations are associated with the development of these tumors, mutant genes may be found in the stool of individuals with CR neoplasms. The stools of nine patients whose tumors contained mutations of K-ras were analyzed. In eight of the nine cases, the ras mutations were detectable in DNA purified from the stool. These patients included those with benign and malignant neoplasms from proximal and distal colonic epithelium. Thus, colorectal tumors can be detected by a noninvasive method based on the molecular pathogenesis of the disease.
Effects of spray-dried animal plasma and immunoglobulins on performance of early weaned pigs1,2 (2005)

Five experiments were conducted to evaluate the effects of dietary spray-dried porcine plasma (SDPP) and spray-dried bovine plasma (SDBP) and their various molecular weight fractions on performance of pigs weaned at approximately 14 or 21 d of age. In addition, the efficacy of various levels of the immunoglobulin G (IgG)-rich fraction of SDPP and SDBP were evaluated. Experiment 1 evaluated the dietary addition of SDPP and three of its fractions (IgG-rich, albumin-rich, and low molecular weight fractions). Pigs fed SDPP grew faster and consumed more feed than the controls during the first week (P < 0.05). The IgG-rich fraction resulted in improvements in ADG and ADFI that were similar to those of pigs fed SDPP. The albumin-rich fraction had no effect on growth rate, but the low molecular weight fraction decreased feed intake as well as growth rate. Experiments 2 and 3 evaluated SDPP and graded levels of its IgG-rich fraction in pigs weaned at 21 or 14 d, respectively. In Exp. 2, pigs fed SDPP grew faster and consumed more feed than the controls during the first week (P < 0.05). Pig performance was enhanced with the addition of the IgG-rich fraction that provided 80% of the amount of IgG in the SDPP diet. In Exp. 3, there was no response to SDPP during the first week, but a positive growth response to SDPP (P < 0.01) occurred by the end of wk 2 (0 to 14 d). Feeding the IgG-rich fraction increased growth rate compared with controls (P < 0.05). Over the entire experiment, the greatest ADG occurred with the IgG-rich fraction that provided 128% of the amount of IgG provided by SDPP (quadratic; P < 0.05). Two additional experiments assessed feeding SDBP and bovine IgG-rich fractions to early weaned pigs. In Exp. 4, SDPP was superior to SDBP in stimulating growth and feed intake, but this difference did not occur in Exp. 5. In both experiments, the IgG fraction of bovine plasma seemed to be as effective at improving growth as SDPP and more effective than SDBP. The results indicate that both porcine and bovine plasma are beneficial to young pig performance during the first week after weaning and that the IgG fraction of plasma is the component that is responsible for the enhancement in growth rate and feed intake.
Characterization of long-term cultures of hepatitis C virus (1996)

The human T- and B-cell lines HPBMa10-2 and Daudi produced infectious hepatitis C virus (HCV) for more than 1 year after infection. The infectivity titer of the cell culture-grown HCV and its genome titer were comparable. The virion density in sucrose was around 1.12 g/ml. Among the 13 variants detected in the inoculum, 7 were adsorbed by the cells and one particular HCV sequence which was present in minor quantities in the inoculum persisted.
Neue Synthesen von Pyrazolo[1,5‐a]‐s‐triazinen (1975)

Abstract Two new syntheses of pyrazolo[1,5‐ a ]‐ s ‐triazines are reported: (a) Addition of acetyl isocyanate to 5‐amino‐3‐methyl‐pyrazole followed by hydrolysis yields N‐(3‐methyl‐5‐pyrazolyl)‐urea ( 15 ), which on cyclisation with triethyl orthoacetate gives 2‐hydroxy‐4,7‐dimethylpyrazolo[1, 5‐ a ]‐ s ‐triazine ( 16 ). (b) Condensation of aminoguanidine with β‐oxo‐nitriles affords 1‐amidino‐5‐aminopyrazoles 18 . These are cyclised to pyrazolo[1,5‐ a ]‐ s ‐triazines 19‐‐21 by reaction with orthoesters, acetic‐formic anhydride, phenylisocyanide dichloride, dimethyl oxalate, N, N′‐carbonyldiimidazole, and N, N′‐thiocarbonyldiimidazole. The 4‐amino group in 19 is converted by standard procedures to OH, SH, SCH 3 , Cl and NRR′. Reaction of pyrazolo[1,5‐ a ]‐ s ‐triazines 30 with electrophiles leads to compounds substituted at position 8, e.g. 32a‐‐e .
Therapeutic antibody production technologies: molecules, applications, expression and purification. (2001)

Antibody-based therapeutics are currently being tested in an increasingly diverse range of therapeutic modalities. Many different engineered formats for the antibody molecule and multiple methods for raising and tailoring binding specificities are currently available. Comparison of the relative function and efficacy of these molecules and the many competing methods for their production is crucial for making an informed selection of a new therapeutic entity. In addition, these choices may be influenced by the attached intellectual property burden.
Velocity recovery cycles of C fibres innervating human skin (2003)

Velocity changes following single and double conditioning impulses were studied by microneurography in single human C fibres to provide information about axonal membrane properties. C units were identified as mechano‐responsive ( n = 19 ) or mechano‐insensitive (12) nociceptors, cold‐sensitive (8) or sympathetic fibres (9), and excited by single, double and triple electrical stimuli to the skin at mean rates of 0.25–2 Hz. The interval between single or paired (20 ms apart) conditioning stimuli and test stimulus was then varied between 500 and 2 ms, and recovery curves of velocity change against inter‐spike interval constructed, allowing for changes in these variables with distance. All fibres exhibited an initial (4–24 ms) relative refractory phase, and a long‐lasting (&gt;500 ms) ‘H2’ phase of reduced velocity, attributed to activation of Na + /K + ‐ATPase. Mechano‐responsive nociceptors exhibited an intermediate phase of either supernormality or subnormality, depending on stimulation rate. Mechano‐insensitive nociceptors behaved similarly, but all were supernormal at 1 Hz. Sympathetic units exhibited only a long‐lasting supernormality, while cold fibres exhibited a briefer supernormal and a late subnormal phase (H1), similar to A fibres. A pre‐conditioning impulse doubled H2 and increased H1, but did not augment supernormality or the subnormality of similar time course. Like A fibre supernormality, these phenomena were explained by a passive cable model, so that they provide an estimate of membrane time constant. Nociceptor membrane time constants (median 110 ms, n = 17 ) were rather insensitive to membrane potential, indicating few active voltage‐dependent potassium channels, whereas sympathetic time constants were longer and reduced by activity‐dependent hyperpolarisation.
News (2002)

Caring for an elderly, frail or disabled person has effects on physical and psychological health as well as financial and social consequences. There are 6 million informal carers in the UK and the primary care team together with other community services is expected to provide the support they need. However, most primary care team members feel ill equipped to do so and there is very little evidence about which interventions are effective. This article reviews the reasons for this problem and suggests a strategy primary care team members could adopt until new evidence about effective strategies is available.
Phagocytosis, killing, lymphocyte-mediated antibacterial activity, serum autoantibodies, and plasma endotoxins in inflammatory bowel disease (2000)

Our data demonstrate an impairment of natural immunity exerted by peripheral blood phagocytes and lymphocytes in patients with UC and CD. ANCA and anti-LF antibodies were present mainly in UC patients but their presence did not affect PMN-mediated phagocytosis and killing. Finally, plasma endotoxins may contribute to the chronic inflammatory status, likely by inducing release of proinflammatory mediators.
Tumor necrosis factor-alpha decreases neutrophil chemotaxis to N-formyl-1-methionyl-1-leucyl-1-phenylalanine: analysis of single cell movement (1992)

Tumor necrosis factor-alpha (TNF-alpha), a cytokine produced by mononuclear cells in response to endotoxin, inhibits neutrophil chemotaxis. We analyzed the effects of TNF-alpha on the orientation and movement of individual neutrophils in a chemoattractant gradient. Neutrophils, treated or untreated with TNF-alpha, were observed migrating in a gradient of the chemotactic peptide N-formyl-1-methionyl-1-leucyl-1-phenylalanine (fMLP) on a specially constructed chamber (Zigmond bridge). The movement of these cells was videotaped, digitized, and then tracked using a newly designed computer algorithm. The data obtained from this algorithm were then utilized to calculate distance traveled, speed and ability to polarize and migrate in a directed manner for each individual cell. TNF-alpha-treated cells behaved like cells not exposed to fMLP in that they failed to orient in a chemotactic gradient and moved in a manner similar to randomly migrating cells. This study provides unique observations of the effect of TNF-alpha on multiple parameters of PMN migration.
Selection and Characterization of Her2 Binding-designed Ankyrin Repeat Proteins (2006)

Designed ankyrin repeat proteins (DARPins) are a novel class of binding proteins that bind their target protein with high affinity and specificity and have very favorable expression and stability properties. We describe here the in vitro selection of DARPins against human epidermal growth factor receptor 2 (Her2), an important target for cancer therapy and diagnosis. Several DARPins bind to the same epitope as trastuzumab (Herceptin), but none were selected that bind to the epitope of pertuzumab (Omnitarg). Some of the selected DARPins bind with low nanomolar affinity (Kd=7.3 nm) to the target. Further analysis revealed that all DARPins are highly specific and do not cross-react with epidermal growth factor receptor I (EGFR1) or any other investigated protein. The selected DARPins specifically bind to strongly Her2-overexpressing cell lines such as SKBR-3 but also recognize small amounts of Her2 on weakly expressing cell lines such as MCF-7. Furthermore, the DARPins also lead to a highly specific and strong staining of plasma membranes of paraffinated sections of human mamma-carcinoma tissue. Thus, the selected DARPins might be used for the development of diagnostic tests for the status of Her2 overexpression in different adenocarcinomas, and they may be further evaluated for their potential in targeted therapy since their favorable expression properties make the construction of fusion proteins very convenient.
An open-label, multi centre, phase II, non-comparative trial of ZD1839 monotherapy in chemotherapy-naive patients with stage IV or stage III non-operable non-small cell lung cancer (NSCLC) (2005)

7098 Background: Second- or third-line gefitinib (IRESSA) monotherapy is active and well tolerated in patients with advanced non-small-cell lung cancer (NSCLC). The aim of this study was to determine the efficacy and safety of gefitinib as monotherapy in chemotherapy-naïve patients with good performance status (PS). Methods: Chemotherapy-naïve patients who had PS 0–2 with histologically confirmed, non-operable, stage III/IV NSCLC were enrolled. Patients received gefitinib 250 mg/day until disease progression. To ensure that the best available treatment was not withheld for an undue length of time, tumors were assessed by X-ray at weeks 3 and 9, and by computed tomography every 6 weeks following start of treatment. Results: 58 out of 59 patients were evaluable: Histology: Adeno carcinoma (CA) (32); bronchioalveolar CA (10); squamous cell CA (8); large cell CA (4); other (4). Median age: 67 years (range 41–84). Smoking history: current 33%, former 48%, never 19%. PS 0/1/2: 10%;66%,24%. Response: complete response (CR; n=1; 2%), partial response (PR; n=2; 3%), stable disease (SD; n=23; 40%); progressive disease (PD; n=28; 48%). Median progression free survival to date: 52 days. 14 patients are still undergoing treatment. There were no therapy-related serious adverse events. Grade 3 toxicities were rash 1,7%, nausea 1,7%, fatigue 6,9%, cough 3,4%, pain 1,7%. Conclusions: Gefitinib as first-line monotherapy has activity in patients with advanced NSCLC, with clinical benefit (CR+PR+SD) observed in 45% (26/58) of patients. Due to the favorable tolerability profile, gefitinib should be investigated further in controlled, randomized studies in those patients who are unable to tolerate, or who refuse, chemotherapy. IRESSA is a trademark of the AstraZeneca group of companies Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca
Phage HK022-based integrative vectors for the insertion of genes in the chromosome of multiply marked Escherichia coli strains (2002)

We constructed a series of plasmids that allow the insertion of cloned DNA in the Escherichia coli chromosome by site-specific integration into the bacteriophage HK022 bacterial attachment site. These plasmids make use of a ColE1 origin of replication, the phage HK022 attachment site att P, antibiotic resistance genes for selection and unique restriction sites. Circularisation of non-replicative fragments containing the HK022 attachment site att P is performed in vitro and site-specific integration of att P containing molecules is ensured by transfer into cells transiently expressing the HK022 integrase gene carried by a thermosensitive replicon. Insertion is very efficient and the inserted fragments are stably maintained without selection pressure. Since integrative fragments carry rarely used antibiotic markers conferring resistance to antibiotics hygromycin or apramycin, they can be used in most E. coli strains in conjunction with many replicative or integrative vectors.
Speech recognition technology in the ubiquitous/wearable computing environment (2002)

Due principally to the technology of making computers smaller, more powerful and cheaper, the ubiquitous and wearable computing era is expected to come into being in the beginning of 21st century. In such an environment, speech recognition will be widely used as one of the principal methods of human-computer interaction, and in most of cases it will be performed using a microphone and a networked computer worn and tailored to each person. Accordingly, speech recognition systems will comprise very different structures than do present systems. Promptly retrieving environmental information, such as noise, which is regularly monitored by computers, and task-dependent information transmitted according to each application to the personalized recognizers will significantly improve system adaptability to the new tasks and robustness. Nonetheless, a number of salient issues remain to be resolved to generate the ubiquitous/wearable computing environment.
Pancreatic Lipase Structure−Function Relationships by Domain Exchange (1997)

We designed chimeric mutants by exchanging the lid domains of the classical human pancreatic lipase (HPL) and the guinea pig pancreatic lipase related protein 2 (GPLRP2). This latter enzyme possesses naturally a large deletion within the lid domain and is not activated by lipid/water interfaces. Furthermore, GPLRP2 exhibits phospholipase A1 and lipase activities in the same order of magnitude, whereas HPL has no significant phospholipase activity and displays a clear interfacial activation. An HPL mutant [HPL(−lid)] with GPLRP2 mini-lid domain does not display interfacial activation. Its specific activity toward triglycerides is, however, dramatically reduced. A GPLRP2 mutant [GPLRP2(+lid)] with HPL full-length lid domain is not interfacially activated, and its lid domain probably exists under a permanent open conformation. Therefore, the phenomenon of interfacial activation in HPL is not only due to the presence of a full-length lid domain but also to other structural elements which probably allow the existence of stabilized closed and open conformations of the lid. GPLRP2(+lid) phospholipase activity is significantly reduced as compared to GPLRP2, whereas its lipase activity remains at the same level. Therefore, the lid domain plays a major role in substrate selectivity and can be considered as part of the active site. However, the presence of a full-length lid domain is not sufficient to explain the absence of phospholipase activity in HPL since HPL(−lid) does not display any phospholipase activity. We also produced a chimeric GPLRP2 mutant in which the C-terminal domain was substituted by the HPL C-terminal domain. The colipase effects, i.e., anchoring and stabilization of the lipase at the interface, are clearly observed with the chimera, whereas GPLRP2 is insensitive to colipase. The kinetic characterization of this chimera reveals for the first time that the interfacial stability of pancreatic lipases depends on the structure of the C-terminal domain.
Interactions between the cytochrome P450 system and the second-generation antipsychotics (2003)

Awareness of the metabolism of second-generation antipsychotics by the cytochrome P450 (CYP) system can inform the clinician about how to avoid and manage drug-drug interactions involving these enzymes. Clozapine is metabolized primarily by CYP1A2, with additional contributions by CYP2C19, CYP2D6 and CYP3A4. Risperidone is metabolized primarily by CYP2D6 and to a lesser extent by CYP3A4. Olanzapine is metabolized primarily by CYP1A2 and to a lesser extent by CYP2D6. Quetiapine and ziprasidone are metabolized by CYP3A4. At the usual clinical doses, these drugs appear not to significantly affect the metabolism of other medications. There is, however, a lack of in vivo metabolic data, especially for the 3 newest second-generation antipsychotics: olanzapine, quetiapine and ziprasidone.
The floating web (1998)

For centuries now, textiles and the skills required in their creationspinning, weaving, embroidery, sewing, quilting-have been considered to be women's work, occupying them indoors while men engaged in more serious activities like warfare. In Homer's Iliad, Andromache, wife to the Trojan prince, Hector, begs him not to risk his life in battle, leaving her widowed and his son an orphan, only to have him send her home:
Template synthesis of organic microtubules (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTemplate synthesis of organic microtubulesCharles R. Martin, Leon S. Van Dyke, Zhihua Cai, and Wenbin LiangCite this: J. Am. Chem. Soc. 1990, 112, 24, 8976–8977Publication Date (Print):November 1, 1990Publication History Published online1 May 2002Published inissue 1 November 1990https://pubs.acs.org/doi/10.1021/ja00180a050https://doi.org/10.1021/ja00180a050research-articleACS PublicationsRequest reuse permissionsArticle Views1236Altmetric-Citations196LEARN 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
Homogeneous antibody-based proximity extension assays provide sensitive and specific detection of low-abundant proteins in human blood (2011)

Convenient and well-performing protein detection methods for a wide range of targets are in great demand for biomedical research and future diagnostics. Assays without the need for washing steps while still unaffected when analyzing complex biological samples are difficult to develop. Herein, we report a well-characterized nucleic acid proximity-based assay using antibodies, called Proximity Extension Assay (PEA), showing good performance in plasma samples. Target-specific antibody pairs are linked to DNA strands that upon simultaneous binding to the target analyte create a real-time PCR amplicon in a proximity-dependent manner enabled by the action of a DNA polymerase. 3'Exonuclease-capable polymerases were found to be clearly superior in sensitivity over non-3'exonuclease ones. A PEA was set up for IL-8 and GDNF in a user-friendly, homogenous assay displaying femtomolar detection sensitivity, good recovery in human plasma, high specificity and up to 5-log dynamic range in 1 μL samples. Furthermore, we have illustrated the use of a macro-molecular crowding matrix in combination with this homogeneous assay to drive target binding for low-affinity antibodies, thereby improving the sensitivity and increasing affinity reagent availability by lowering assay development dependency on high-affinity antibodies. Assay performance was also confirmed for a multiplex version of PEA.