gebhart/patrepeval huggingface dataset:
Temperature‐regulated expression of invasion genes in Shigella flexneri is controlled through the transcriptional activation of the virB gene on the large plasmid (1991)

The invasion phenotype of shigellae is subject to thermoregulation that is known to be expressed through activation of some invasion (inv) genes such as ipaB, ipaC, and ipaD encoded by the large virulence plasmid of Shigella flexneri. The expression of ipa genes is regulated positively by virF through the activation of virB on the plasmid. To identify the mediator for the thermoregulation of the large plasmid, we have studied the effect of temperature on the transcription of virF and virB genes and ipa and the other two inv operons. The results showed that transcription of virB was affected by temperature more strictly than that of virF. Analysis of the mRNA level of virB at different levels of virF transcription indicated that virB transcription depended upon both temperature and virF. On the other hand, transcriptions of ipa and the other two inv operons depended on the activation of virB transcription but not on temperature. By inducing virB transcription from a tac promoter fused with the virB region, invasion ability was restored to a virF-deletion mutant at 30 degrees C as well as at 37 degrees C. By using conditions in which the temperature-dependent expression of the invasion phenotype was circumvented by the induction of virB transcription, intercellular spreading ability in a virF+, virB::Tn5 strain was shown to be expressed even at 30 degrees C. These results suggest that the virB transcription stage is the main target for the thermoregulation.
Regression of tumors in mice vaccinated with professional antigen-presenting cells pulsed with tumor extracts (1997)

Vaccination with tumor extracts circumvents the need to identify specific tumor rejection antigens and extends the use of active immunotherapy to the vast majority of cancers, in which specific tumor antigens have not yet been identified. In this study we examined the efficacy of tumor vaccines comprised of unfractionated tumor material presented by professional antigen-presenting cells (APC): dendritic cells (DC) or macrophages (M phi). To enhance the relevance of these studies for human patients we used 2 poorly immunogenic murine tumor models and evaluated the effectiveness of the vaccination protocols in tumor-bearing animals. APC (in particular DC) pulsed with unfractionated extracts from these "poorly immunogenic" tumors were highly effective in eliciting tumor-specific cytotoxic T lymphocytes. A measurable CTL response could be detected after even a single immunization with tumor extract-pulsed DC. DC or M phi pulsed with tumor extract were also effective vaccines in tumor-bearing animals. In the murine bladder tumor (MBT-2) model a modest extension of survival and 40% cure rate was seen in the animal groups immunized with DC or M phi pulsed with MBT-2 tumor extract. DC or M phi pulsed with B16/F10.9 tumor extract were also remarkably effective in the B16 melanoma lung metastasis model, as shown by the observation that treatment with APC caused a significant reduction in lung metastases. Cumulatively, the CTL and immunotherapy data from the two murine tumor systems suggest that APC (in particular DC) pulsed with unfractionated cell extracts as a source of tumor antigen may be equally or more effective than genetically modified tumor vaccines.
Adoptive cell transfer as personalized immunotherapy for human cancer (2015)

Adoptive cell therapy (ACT) is a highly personalized cancer therapy that involves administration to the cancer-bearing host of immune cells with direct anticancer activity. ACT using naturally occurring tumor-reactive lymphocytes has mediated durable, complete regressions in patients with melanoma, probably by targeting somatic mutations exclusive to each cancer. These results have expanded the reach of ACT to the treatment of common epithelial cancers. In addition, the ability to genetically engineer lymphocytes to express conventional T cell receptors or chimeric antigen receptors has further extended the successful application of ACT for cancer treatment.
Influence of Power Changes in Single Cut Rigid Contact Lenses on Tear Pump Efficiency (1992)

Differences between corneal oxygen uptake rates measured after 5 min of static (without blinking) and 5 min of dynamic (with blinking once every 5 s) non-gas permeable (polymethyl methacrylate) contact lens wear, referenced to the oxygen uptake rates of the normal open eye, were used as indications of tear pump efficiencies associated with each of seven contact lens back vertex powers (-9.00 to +9.00 D, in 3.00 D steps). Measurements were made in vivo on six human corneas showing with-the-rule (0.25 to 0.87 D) toricity. Lens overall diameter was 8.8 mm, optic zone diameter was 7.4 mm, and base curve radius was fitted "on K." Lens center thickness was 0.14 mm for all minus-powered lenses, and 0.19, 0.26, 0.34, and 0.41 mm for the plano, +3.00, +6.00, and +9.00 D lenses, respectively, maintaining an edge thickness of 0.11 mm. Under both static and dynamic wearing conditions, no significant differences were found among the corneal oxygen uptake rates associated with the various contact lens back vertex powers; however, the difference between the static and dynamic condition data, an indication of tear pump efficiency, was greatest for the -3.00 D lens. The difference values associated with the +9.00 and +6.00 D lenses were significantly lower than those associated with the minus power lenses.
Consumption of dietary caffeine and coffee in physically active populations: physiological interactions (2008)

Caffeine is a proven ergogenic aid, increasing athletic performance, endurance, and mental chronometry at doses as low as 1-3 mg.kg-1. As coffee is a readily available and commonly ingested form of caffeine, the two are often equated. However, coffee also contains hundreds of other biologically active compounds, many of which are metabolically distinct from caffeine. The purpose of this review was to examine the prevalence of coffee and (or) caffeine consumption among elite Canadian athletes, and to delineate the effects of coffee and caffeine on physical activity, weight maintenance, performance, and metabolism. A total of 270 self-reported 3-day food records were examined for caffeine intake from athletes registered with Canadian Sport Centres in 2005 and 2006. Athletes ranged in age from 16-45 years, and competed in 38 different sports. Results showed that 30% of athletes ingested >1 mg.kg-1.day-1 from a variety of sources. Average daily intake was 0.85 +/- 13 mg.kg-1. Caffeine intake was not correlated with any 1 sport; the 10 highest caffeine users were athletes from 9 different sports, including skill, endurance, and power sports. No differences were noted for average caffeine ingestion between summer and winter sports. High caffeine intakes corresponded to coffee ingestion, with the 25 highest individual intakes (193-895 mg.day-1) from coffee drinkers. In summary, it can be concluded that the majority of high-level Canadian athletes consume dietary caffeine primarily in the form of coffee. However, levels consumed are insufficient to elicit performance enhancement. Potential detrimental effects of caffeine consumption on exercise performance include gastric upset, withdrawal, sleep disturbance, and interactions with other dietary supplements.
Optimization of Unnatural Base Pair Packing for Polymerase Recognition (2006)

As part of an effort to expand the genetic alphabet, we have been examining the ability of predominately hydrophobic nucleobase analogues to pair in duplex DNA and during polymerase-mediated replication. We previously reported the synthesis and thermal stability of unnatural base pairs formed between nucleotides bearing simple methyl-substituted phenyl ring nucleobase analogues. Several of these pairs are virtually as stable and selective as natural base pairs in the same sequence context. Here, we report the characterization of polymerase-mediated replication of the same unnatural base pairs. We find that every facet of replication, including correct and incorrect base pair synthesis, as well as continued primer extension beyond the unnatural base pair, is sensitive to the specific methyl substitution pattern of the nucleobase analogue. The results demonstrate that neither hydrogen bonding nor large aromatic surface area is required for polymerase recognition, and that interstrand interactions between small aromatic rings may be optimized for replication. Combined with our previous results, these studies suggest that appropriately derivatized phenyl nucleobase analogues represent a promising approach toward developing a third base pair and expanding the genetic alphabet.
Synthetic studies of the thieno[3,2-d]pyrimidine C-nucleoside isostere of inosine (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthetic studies of the thieno[3,2-d]pyrimidine C-nucleoside isostere of inosineWu Yun Ren, Mu Ill Lim, Brian A. Otter, and Robert S. KleinCite this: J. Org. Chem. 1982, 47, 24, 4633–4637Publication Date (Print):November 1, 1982Publication History Published online1 May 2002Published inissue 1 November 1982https://doi.org/10.1021/jo00145a005Request reuse permissionsArticle Views194Altmetric-Citations31LEARN 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 InReddit PDF (683 KB) Get e-Alertsclose Get e-Alerts
Designing Two-In-One Antibodies (2009)

Evaluation of: Bostrom J, Shang-Fan Y, Kan D et al.: Variants of the antibody Herceptin that interact with HER2 and VEGF at the antigen binding site. Science 323, 1610-1614 (2009). The longstanding held notion that one antibody equals one antigen and, hence, one function has been challenged in recent years. Improved technology in antibody production, especially the accumulation of sequence data of immunoglobulin genes and the advent of PCR have made it possible to clone antibody gene repertoires. The current paper provides further challenge to the notion of one antibody = one antigen by developing 'two-in-one' antibodies with an antigen-binding site that binds two distinct proteins with high affinity. A therapeutic variant antibody of Herceptin (Genentech, CA, USA) was isolated that binds the human EGF receptor (HER)2 and also to VEGF. This development may represent a breakthrough discovery and may have significant implications in the therapy of malignant, infectious, allergic and autoimmune disorders.
Crystal engineering of the composition of pharmaceutical phases (2002)

The carboxylic acid-pyridine supramolecular heterosynthon can be exploited to predictably generate binary crystalline phases involving rac-ibuprofen, rac-flurbiprofen or aspirin.
Mixotrophy: a widespread and important ecological strategy for planktonic and sea-ice nanoflagellates in the Ross Sea, Antarctica (2009)

Mixotrophic nanoflagellates (MNF) were quantified in plankton and sea ice of the Ross Sea, Antarctica, during austral spring. Tracer experiments using fluorescently labeled bacteria (FLB) were conducted to enumerate MNF and determine their contribution to total chloroplastidic and total bacterivorous nanoflagellates. Absolute abundances of MNF were typically < 200 ml -1 in plankton assemblages south of the Polar Front, but they comprised 8 to 42% and 3 to 25% of bacterivorous nanoflagellates in the water column and ice cores, respectively. Moreover, they represented up to 10% of all chloroplastidic nanoflagellates in the water column when the prymnesiophyte Phaeocystis antarctica was blooming (up to 23% if P. antarctica, which did not ingest FLB, was excluded from calculations). In ice cores, MNF comprised 5 to 10% of chloroplastidic nanoflagellates. The highest proportions of MNF were found in some surface water samples and in plankton assemblages beneath ice, suggesting a potentially large effect as bacterial grazers in those locations. This study is the first to report abundances and distributions of mixotrophic flagellates in the Southern Ocean. The presence of MNF in every ice and water sample examined suggests that mixotrophy is an important alternative dietary strategy in this region.
Mechanics of the Mammalian Cochlea (2001)

In mammals, environmental sounds stimulate the auditory receptor, the cochlea, via vibrations of the stapes, the innermost of the middle ear ossicles. These vibrations produce displacement waves that travel on the elongated and spirally wound basilar membrane (BM). As they travel, waves grow in amplitude, reaching a maximum and then dying out. The location of maximum BM motion is a function of stimulus frequency, with high-frequency waves being localized to the "base" of the cochlea (near the stapes) and low-frequency waves approaching the "apex" of the cochlea. Thus each cochlear site has a characteristic frequency (CF), to which it responds maximally. BM vibrations produce motion of hair cell stereocilia, which gates stereociliar transduction channels leading to the generation of hair cell receptor potentials and the excitation of afferent auditory nerve fibers. At the base of the cochlea, BM motion exhibits a CF-specific and level-dependent compressive nonlinearity such that responses to low-level, near-CF stimuli are sensitive and sharply frequency-tuned and responses to intense stimuli are insensitive and poorly tuned. The high sensitivity and sharp-frequency tuning, as well as compression and other nonlinearities (two-tone suppression and intermodulation distortion), are highly labile, indicating the presence in normal cochleae of a positive feedback from the organ of Corti, the "cochlear amplifier." This mechanism involves forces generated by the outer hair cells and controlled, directly or indirectly, by their transduction currents. At the apex of the cochlea, nonlinearities appear to be less prominent than at the base, perhaps implying that the cochlear amplifier plays a lesser role in determining apical mechanical responses to sound. Whether at the base or the apex, the properties of BM vibration adequately account for most frequency-specific properties of the responses to sound of auditory nerve fibers.
Monte Carlo modelling of an extended DXA technique (1998)

The precision achieved in measuring bone mineral density (BMD) by commercial dual-energy x-ray absorptiometry (DXA) machines is typically better than 1%, but accuracy is considerably worse. Errors, due to inhomogeneous distributions of fat, of up to 10% have been reported. These errors arise because the DXA technique assumes a two-component model for the human body, i.e. bone mineral and soft tissue. This paper describes an extended DXA technique that uses a three-component model of human tissue and significantly reduces errors due to inhomogeneous fat distribution. In addition to two x-ray transmission measurements, a measurement of the path length of the x-ray beam within the patient is required. This provides a third equation, i.e. T = ts + tb + tf where T, ts, tb and tf are the total, lean soft tissue, bone mineral and fatty tissue thicknesses respectively. Monte Carlo modelling was undertaken to make a comparison of the standard and extended DXA techniques in the presence of inhomogeneous fat distribution. Two geometries of varying complexity were simulated. In each case the extended DXA technique produced BMD measurements that were independent of soft tissue composition whereas the standard technique produced BMD measurements that were strongly dependent on soft tissue composition. For example, in one case, the gradients of the plots of BMD versus fractional fat content were for standard DXA (-0.183+/-0.037) g cm(-2) and for extended DXA (0.027+/-0.044) g cm(-2). In all cases the extended DXA method produced more accurate but less precise results than the standard DXA technique.
Controlled fabrication of single-walled carbon nanotube electrodes by electron-beam-induced oxidation (2011)

The fabrication of metallic single-walled carbon nanotube electrodes separated by gaps of typically 20 nm width by electron-beam-induced oxidation is studied within an active device configuration. The tube conductance is measured continuously during the process. The experiment provides a statistical evaluation of gap sizes as well as the electron dose needed for gap formation. Also, the ability to precisely cut many carbon nanotubes in parallel is demonstrated. To show the practicality of the approach, devices of different scales were fabricated using sorted carbon nanotubes and dielectrophoretic deposition.
Coronaviruses in bats from Mexico (2013)

Bats are reservoirs for a wide range of human pathogens including Nipah, Hendra, rabies, Ebola, Marburg and severe acute respiratory syndrome coronavirus (CoV). The recent implication of a novel beta (β)-CoV as the cause of fatal respiratory disease in the Middle East emphasizes the importance of surveillance for CoVs that have potential to move from bats into the human population. In a screen of 606 bats from 42 different species in Campeche, Chiapas and Mexico City we identified 13 distinct CoVs. Nine were alpha (α)-CoVs; four were β-CoVs. Twelve were novel. Analyses of these viruses in the context of their hosts and ecological habitat indicated that host species is a strong selective driver in CoV evolution, even in allopatric populations separated by significant geographical distance; and that a single species/genus of bat can contain multiple CoVs. A β-CoV with 96.5 % amino acid identity to the β-CoV associated with human disease in the Middle East was found in a Nyctinomops laticaudatus bat, suggesting that efforts to identify the viral reservoir should include surveillance of the bat families Molossidae/Vespertilionidae, or the closely related Nycteridae/Emballonuridae. While it is important to investigate unknown viral diversity in bats, it is also important to remember that the majority of viruses they carry will not pose any clinical risk, and bats should not be stigmatized ubiquitously as significant threats to public health.
Staphylococcus aureus alpha-toxin. Production of functionally intact, site-specifically modifiable protein by introduction of cysteine at positions 69, 130, and 186 (1993)

Staphylococcal alpha-toxin, the prototype of an oligomerizing, pore-forming cytotoxin, is sensitive to biochemical modifications and cannot be labeled with biotin or fluorescein under preservation of its biological activity. In this study, we have used site-directed mutagenesis to introduce cysteine residues at positions 69, 130, and 186. Each mutant was fully and rapidly reactive with several sulfhydryl-specific reagents, indicating superficial location. Coupling of SH-groups with fluorescein-maleimide or biotin-maleimide was tolerated without loss of hemolytic activity at position 130, and the formed hexamers were visible on target cells by fluorescence microscopy and could be detected on electroblots by reaction with streptavidin-peroxidase. At the two other positions, modification caused significant loss of activity. However, the labeled proteins still bound to red cells, as shown by fluorescence microscopy and electroblotting. Intrinsically labeled alpha-toxin represents a novel tool to study the interaction of this pore-former with target membranes.
Improvement of K-means clustering algorithm with better initial centroids based on weighted average (2012)

Clustering is the process of grouping similar data into a set of clusters. Cluster analysis is one of the major data analysis techniques and k-means one of the most popular partitioning clustering algorithm that is widely used. But the original k-means algorithm is computationally expensive and the resulting set of clusters strongly depends on the selection of initial centroids. Several methods have been proposed to improve the performance of k-means clustering algorithm. In this paper we propose a heuristic method to find better initial centroids as well as more accurate clusters with less computational time. Experimental results show that the proposed algorithm generates clusters with better accuracy thus improve the performance of k-means clustering algorithm.
Parallel Array and Mixture-Based Synthetic Combinatorial Chemistry: Tools for the Next Millennium (2000)

Technological advances continue to be a central driving force in the acceleration of the drug discovery process. Combinatorial chemistry methods, developed over the past 15 years, represent a paradigm shift in drug discovery. Initially viewed as a curiosity by the pharmaceutical industry, combinatorial chemistry is now recognized as an essential tool that decreases the time of discovery and increases the throughput of chemical screening by as much as 1000-fold. The use of parallel array synthesis approaches and mixture-based combinatorial libraries for drug discovery is reviewed.
Specific and stable labeling of antibodies with technetium-99m with a diamide dithiolate chelating agent. (1988)

Technetium-99m labeling of antibodies has been suboptimal because of low affinity adventitious binding, nonspecific labeling, and loss of immunoreactivity. The diamide dithiolate ligand system (N2S2) forms highly stable, well-defined tetradentate complexes with Tc(V). Antibodies and their fragments have been labeled by conjugation of preformed 99mTc-4,5-bis(thioacetamido)pentanoate active ester to protein amine groups to give a chemically known 99mTc-N2S2 complex covalently linked to antibody. Evaluations of the 99mTc-N2S2-bound antibodies and their fragments have shown high stability and retained immunoreactivity.
Phase III Randomized Multicenter Study of a Humanized Anti-CD33 Monoclonal Antibody, Lintuzumab, in Combination With Chemotherapy, Versus Chemotherapy Alone in Patients With Refractory or First-Relapsed Acute Myeloid Leukemia (2005)

The addition of lintuzumab to salvage induction chemotherapy was safe, but did not result in a statistically significant improvement in response rate or survival in patients with refractory/relapsed AML.
Zika Virus in the Americas — Yet Another Arbovirus Threat (2016)

The explosive pandemic of Zika virus infection in South and Central America is the most recent of four unexpected arrivals of important arthropod-borne viral diseases in the Western Hemisphere over the past 20 years. Is this an important new disease-emergence pattern?