gebhart/patrepeval huggingface dataset:
High-Resolution Crystal Structures Reveal Plasticity in the Metal Binding Site of Apurinic/Apyrimidinic Endonuclease I (2014)

Apurinic/apyrimidinic endonuclease I (APE1) is an essential base excision repair enzyme that catalyzes a Mg²⁺-dependent reaction in which the phosphodiester backbone is cleaved 5' of an abasic site in duplex DNA. This reaction has been proposed to involve either one or two metal ions bound to the active site. In the present study, we report crystal structures of Mg²⁺, Mn²⁺, and apo-APE1 determined at 1.4, 2.2, and 1.65 Å, respectively, representing two of the highest resolution structures yet reported for APE1. In our structures, a single well-ordered Mn²⁺ ion was observed coordinated by D70 and E96; the Mg²⁺ site exhibited disorder modeled as two closely positioned sites coordinated by D70 and E96 or E96 alone. Direct metal binding analysis of wild-type, D70A, and E96A APE1, as assessed by differential scanning fluorimetry, indicated a role for D70 and E96 in binding of Mg²⁺ or Mn²⁺ to APE1. Consistent with the disorder exhibited by Mg²⁺ bound to the active site, two different conformations of E96 were observed coordinated to Mg²⁺. A third conformation for E96 in the apo structure is similar to that observed in the APE1-DNA-Mg²⁺ complex structure. Thus, binding of Mg²⁺ in three different positions within the active site of APE1 in these crystal structures corresponds directly with three different conformations of E96. Taken together, our results are consistent with the initial capture of metal by D70 and E96 and repositioning of Mg²⁺ facilitated by the structural plasticity of E96 in the active site.
Role of Cyclic AMP in Mediating the Effects of MSH, Norepinephrine, and Melatonin on Frog Skin Color (1969)

Evidence has previously been published indicating that melanocyte stimulating hormone (MSH) acts on the frog skin to increase intracellular concentrations of adenosine 3′,5′- monophosphate (cyclic AMP) and that this nucleotide in turn mediates the action of MSH in causing dispersion of melanin granules with consequent darkening of the frog skin. In the present study both norepinephrine and melatonin were found to inhibit the increase in cyclic AMP levels in response to MSH, and both agents prevented or reversed MSH-induced darkening of frog skin. Neither agent had any effect on frog skin darkening induced by exogenous cyclic AMP or on the in vitro enzymatic degradation of cyclic AMP. The inhibitory effects of norepinephrine on the actions of MSH were prevented by the α-adrenergic blocking agents dihydroergotamine and phentolamine, but these drugs were ineffective against melatonin. In contrast, the β-adrenergic agent isoproterenol had no significant inhibitory effect on MSH-induced cyclic AMP accumulation, and the marked inhibitory effect of norepinephrine could not be prevented by α-adrenergic blocking agents. It is concluded that norepinephrine and melatonin both inhibit the action of MSH by preventing the formation of cyclic AMP in response to this hormone. Since the inhibitory effect of norepinephrine can be prevented by α-adrenergic blocking agents while the effect of melatonin cannot, it is inferred that the action of norepinephrine is mediated by an α-adrenergic receptor while that of melatonin might be mediated by a different type of receptor. Both types of receptors, nevertheless, seem to be closely related to adenyl cyclase. These data lend support to the hypothesis that α-adrenergic responses in general might be mediated by decreases in intracellular concentrations of cyclic AMP. (Endocrinology85: 674, 1969)
Visual Analytics Presentation Tools Applied in HTML Documents (2008)

In this paper we present novel means to communicate and present gained knowledge using semi-guided interactive visualizations embedded in standard HTML documents. The goal of the work is to let the analyst (author) explore data and simultaneously save important discoveries and thus enable collaboration and sharing of gained insights over the Internet. The readers of the document will benefit from receiving an integrated and interactive document that can "coach" them in the understanding and testing of hypotheses leading to faster understanding and a higher confidence level in the presented visual information. The approach is based on the Visual Analytics (VA) toolkit (GAV), which also provides a mechanism that supports the storage of interactive events in an analytical reasoning process through "memorized interactive visualization views" or snapshots that can be saved at any time during an explorative data analysis process. In a typical scenario an application, comprised of GAV VA components, is embedded in the HTML document together with target data and the snapshots of discoveries. Any standard HTML event, such as the user clicking a textual link or an image can be used to instantiate a snapshot, creating a link between a descriptive text and an interactive visualization presentation. As the GAV application and corresponding data are integrated with the HTML code, residing on the client machine, hardware accelerated graphics can be used to provide interactive performance of demanding visualizations. We demonstrate the potential of the developed methods in the context of GeoAnalytics and molecular visualization scenarios.
A simple and sensitive color test for the detection of human chorionic gonadotropin. (1981)

A simple, rapid, sensitive, and reliable ELISA test for the detection of urinary human chorionic gonadotropin (hCG) has been developed using penicillinase (EC no. 3.5.2.6) as the label and a microtiter ELISA plate as a solid support for antibody. The results of the test is assessed visually for the dark blue that indicates the presence of hCG. A minimum of 500 mU of hCG/ml of urine can be detected easily and the test can be completed in 2 hours with good precision. Accurate negative results are obtained in urine samples of normally ovulatory women, postmenopausal women, and adult males, suggesting that the physiologic concentrations of luteinizing hormone do not influence the assay results. In samples referred for pregnancy detection 95.5% accurate results were obtained when compared with histopathologic and/or clinical findings. There were 2 false-negative results, and only in 4 of 132 subjects studied were false-positive results obtained. This test, if properly performed, should prove a valuable tool in the detection of hCG as early as 30 to 35 days from the last menstrual period.
Formation of covalent circles of lambda DNA by E. coli extracts. (1967)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Derivatization of unprotected polynucleotides (1983)

A simple and efficient method for attaching amines to the terminal 5'-phosphate of unprotected oligonucleotides or nucleic acids in aqueous solution is described. The method is applicable to low molecular-weight amines, polypeptides, or proteins. The terminal 5'-phosphate of an oligonucleotide or nucleic acid reacts with a water-soluble carbodiimide in imidazole buffer at pH 6 to give good yields of the 5'-phosphorimidazolide. Exposure of the phosphorimidazolide to amine-containing molecules in aqueous solution results in the production of a wide range of stable phosphoramidates in high yield. The exposure of polynucleotides to carbodiimide does not result in significant breakage of phosphodiester bonds or damage to nucleoside bases. The biological activity of a drug resistant plasmid is not affected. The direct condensation of polynucleotides with amines in 1-methylimidazole buffer is also possible. However, it is not a satisfactory preparative method if the ligand is sensitive to carbodiimide.
Control of elementary chemical reactions by femtosecond light pulses (2001)

Essentially new approaches are proposed for controlling the yield of products of a chemical reaction by femto-second laser pulses. The main attention is paid to the method based on the change in phase characteristics of femtosecond pulses. The quantum yield of the product NH(c1Π) upon multiphoton photodissociation of ammonium in gas is shown to increase by a factor of twelve with chirp variation from —1250 fs2 to 2000 fs2. It is demonstrated by the example of two-proton transfer in [2,2'-bipyridyl],3,3'-diol in solution that the approach based on the variation in phase characteristics of a pump femtosecond pulse can be also used for controlling reactions in solutions.
A New Method for Monitoring Deep Body Temperature from the Skin Surface (1973)

1. A new technique for monitoring the deep body temperature is described. The technique depends on creating a zone of zero heat-flow across the body shell; this brings the deep body temperature to the skin surface where it is measured with a simple electronic thermometer. 2. The new device gives a temperature closely comparable with other methods for measuring the deep body temperature in the resting subject, and is simple to use and socially acceptable.
DNAzyme-Mediated Silencing of Ornithine Decarboxylase (2005)

The value of reducing the activity of ornithine decarboxylase (ODC), a key enzyme in the biosynthesis of polyamines, is well-appreciated. Polyamines are necessary components for cell growth, and manipulation of polyamine homeostasis may be an effective strategy for the treatment of a number of disorders, including neoplastic diseases. An approach to develop an effective DNAzyme, using the 10-23 model, against ODC is described in these studies. DNAzymes able to cleave the target ODC RNA were identified in vitro and further characterized by the effect each had on ODC protein and activity levels using in vitro translated ODC RNA. ODC protein levels and activity correlated well with the RNA cleavage activity of the DNAzyme. One of the DNAzymes, DZ IV, which exhibited good activity, was optimized for use in cell culture studies. The DNAzyme hybridization arms were altered from equal length arms varying in length (8, 9, 10, or 11 nucleotides) or to unequal length arms (7/11 nucleotides), and kinetic analyses were performed to identify the most catalytically efficient configuration. DZ IV with equal arms nine nucleotides in length proved to be the most catalytically efficient. In HEK 293 cells, DZ IV was able to reduce the amount of translated ODC protein, resulting in approximately 80% reduction in ODC activity-a statistically significant enhancement over the apparent antisense effect of a catalytically inactive DNAzyme. These results indicate that this DNAzyme may be a useful tool to study the function of ODC and may have potential therapeutic uses.
The history of sweet taste: not exactly a piece of cake (2006)

Understanding the molecular bases of sweet taste is of crucial importance not only in biotechnology but also for its medical implications, since an increasing number of people is affected by food-related diseases like, diabetes, hyperlipemia, caries, that are more or less directly linked to the secondary effects of sugar intake. Despite the interest paid to the field, it is only through the recent identification and functional expression of the receptor for sweet taste that new perspectives have been opened, drastically changing our approach to the development of new sweeteners. We shall give an overview of the field starting from the early days up to discussing the newest developments. After a review of early models of the active site, the mechanisms of interaction of small and macromolecular sweet molecules will be examined in the light of accurate modeling of the sweet taste receptor. The analysis of the homology models of all possible dimers allowed by combinations of the human T1R2 and T1R3 sequences of the sweet receptor and the closed (A) and open (B) conformations of the mGluR1 glutamate receptor shows that only 'type B' sites, either T1R2(B) and T1R3(B), can host the majority of small molecular weight sweeteners. Simultaneous binding to the A and B sites is not possible with two large sweeteners but is possible with a small molecule in site A and a large one in site B. This observation accounted for the first time for the peculiar phenomenon of synergy between some sweeteners. In addition to these two sites, the models showed an external binding site that can host sweet proteins.
Biphasic Creep and Stress Relaxation of Articular Cartilage in Compression: Theory and Experiments (1980)

Articular cartilage is a biphasic material composed of a solid matrix phase (∼ 20 percent of the total tissue mass by weight) and an interstitial fluid phase (∼ 80 percent). The intrinsic mechanical properties of each phase as well as the mechanical interaction between these two phases afford the tissue its interesting rheological behavior. In this investigation, the solid matrix was assumed to be intrinsically incompressible, linearly elastic and nondissipative while the interstitial fluid was assumed to be intrinsically incompressible and nondissipative. Further, it was assumed that the only dissipation comes from the frictional drag of relative motion between the phases. However, more general constitutive equations, including a viscoelastic dissipation of the solid matrix as well as a viscous dissipation of interstitial fluid were also developed. A constant “average” permeability of the tissue was assumed, i.e., independent of deformation, and a solid content function Vs/Vf (the ratio of the volume of each of the phases) was assumed to vary with depth in accordance with the experimentally determined weight ratios. This linear, nonhomogeneous theory was applied to describe the experimentally obtained biphasic creep and biphasic stress relaxation data via a nonlinear regression technique. The determined intrinsic “aggregate” elastic modulus, from ten creep experiments, is 0.70 ± 0.09 MN/m2 and, from six stress relaxation experiments, is 0.76 ± 0.03 MN/m2. The “average” permeability of the tissue is (0.76 ± 0.42) × 10−14 m4 /N•s. We concluded that the large spread in the permeability coefficients is due to the assumption of a constant deformation independent permeability. We also concluded that 1) a nonlinearly permeable biphasic model, where the permeability function is given by an experimentally determined empirical law: k = A(p) exp [α(p)e], can be used to describe more accurately the rheological properties of articular cartilage, and 2) the frictional drag of relative motion is the most important factor governing the fluid/solid viscoelastic properties of the tissue in compression.
SDQR migrations in Caenorhabditis elegans are controlled by multiple guidance cues and changing responses to netrin UNC-6 (1999)

The netrin guidance cue, UNC-6, and the netrin receptors, UNC-5 and UNC-40, guide SDQR cell and axon migrations in C. elegans. In wild-type larvae, SDQR migrations are away from ventral UNC-6-expressing cells, suggesting that UNC-6 repels SDQR. In unc-6 null larvae, SDQR migrations are towards the ventral midline, indicating a response to other guidance cues that directs the migrations ventrally. Although ectopic UNC-6 expression dorsal to the SDQR cell body would be predicted to cause ventral SDQR migrations in unc-6 null larvae, in fact, more migrations are directed dorsally, suggesting that SDQR is not always repelled from the dorsal source of UNC-6. UNC-5 is required for dorsal SDQR migrations, but not for the ventral migrations in unc-6 null larvae. UNC-40 appears to moderate both the response to UNC-6 and to the other cues. Our results show that SDQR responds to multiple guidance cues and they suggest that, besides UNC-6, other factors influence whether an UNC-6 responsive cell migrates toward or away from an UNC-6 source in vivo. We propose that multiple signals elicited by the guidance cues are integrated and interpreted by SDQR and that the response to UNC-6 can change depending on the combination of cues encountered during migration. These responses determine the final dorsoventral position of the SDQR cell and axon.
Cross-language speech retrieval (1997)

article Free Access Share on Cross-language speech retrieval: establishing a baseline performance Authors: Páraic Sheridan Swiss Federal Institute of Technology (ETH), CH-8092 Zurich, Switzerland Swiss Federal Institute of Technology (ETH), CH-8092 Zurich, SwitzerlandView Profile , Martin Wechsler Swiss Federal Institute of Technology (ETH), CH-8092 Zurich, Switzerland Swiss Federal Institute of Technology (ETH), CH-8092 Zurich, SwitzerlandView Profile , Peter Schäuble Swiss Federal Institute of Technology (ETH), CH-8092 Zurich, Switzerland Swiss Federal Institute of Technology (ETH), CH-8092 Zurich, SwitzerlandView Profile Authors Info & Claims ACM SIGIR ForumVolume 31Issue SIDecember 1997 pp 99–108https://doi.org/10.1145/278459.258544Published:01 July 1997Publication History 21citation594DownloadsMetricsTotal Citations21Total Downloads594Last 12 Months22Last 6 weeks7 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my Alerts New Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Perioperative management of obstructive sleep apnea: Ready for prime time? (2009)

Obstructive sleep apnea (OSA) is associated with increased risks of cardiovascular disease and stroke and with elevated rates of postoperative complications (including cardiac ischemia and respiratory failure) in surgical patients. Additionally, the prevalence of OSA is higher in surgical patients than in the general population. Screening for OSA prior to surgery is recommended to identify patients at risk for postoperative complications. The presence of moderate or severe OSA calls for modified strategies of perioperative anesthesia, pain management, and postoperative monitoring to reduce the chance of OSA-associated complications.
Atomic-Level Characterization of the Structural Dynamics of Proteins (2010)

Molecular dynamics (MD) simulations are widely used to study protein motions at an atomic level of detail, but they have been limited to time scales shorter than those of many biologically critical conformational changes. We examined two fundamental processes in protein dynamics--protein folding and conformational change within the folded state--by means of extremely long all-atom MD simulations conducted on a special-purpose machine. Equilibrium simulations of a WW protein domain captured multiple folding and unfolding events that consistently follow a well-defined folding pathway; separate simulations of the protein's constituent substructures shed light on possible determinants of this pathway. A 1-millisecond simulation of the folded protein BPTI reveals a small number of structurally distinct conformational states whose reversible interconversion is slower than local relaxations within those states by a factor of more than 1000.
Centiles for adult head circumference. (1992)

Reference range for head circumference on the Tanner charts do not go beyond age 16. In this study the head circumference and heights of 354 adults in two British centres were measured. The centile charts constructed from these measurements show that adult head circumference is related to height. The mean head circumference of a male of average height is above the 97th centile for a 16 year old on the Tanner charts. The paediatric charts are therefore inappropriate for use in adult males.
A MEMS Reactor for Atomic-Scale Microscopy of Nanomaterials Under Industrially Relevant Conditions (2010)

We present a microelectromechanical systems (MEMS) nanoreactor that enables high-resolution transmission electron microscopy (TEM) (HRTEM) of nanostructured materials with atomic-scale resolution during exposure to reactive gases at 1 atm of pressure. This pressure exceeds that of existing HRTEM systems by a factor of 100, thereby entering a pressure range that is relevant to industrial purposes. The nanoreactor integrates a shallow flow channel (35 ¿m high) with a microheater and with an array of electron transparent windows of silicon nitride. The windows are only 10 nm thick but are mechanically robust. The heater has the geometry of a microhotplate and is made of Pt embedded in a silicon nitride membrane. To interface the nanoreactor, a dedicated TEM specimen holder has been developed. The performance is demonstrated by the <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">live</i> formation of Cu nanoparticles in a catalyst for the production of methanol. At 120 kPa and for temperatures of up to 500°C , the formation of these nanoparticles can be observed clearly and with an exceptionally low thermal drift. HRTEM images of the nanoparticles show atomic lattice fringes with spacings down to 0.18 nm.
Characterization of RNA in Saliva (2006)

Saliva harbors both full-length and partially degraded forms of mRNA. RNA enters the oral cavity from different sources, and association with macromolecules may protect salivary RNA from degradation.
Genome Engineering Reveals Large Dispensable Regions in Bacillus subtilis (2003)

Bacterial genomes contain 250 to 500 essential genes, as suggested by single gene disruptions and theoretical considerations. If this view is correct, the remaining nonessential genes of an organism, such as Bacillus subtilis, have been acquired during evolution in its perpetually changing ecological niches. Notably, approximately 47% of the approximately 4,100 genes of B. subtilis belong to paralogous gene families in which several members have overlapping functions. Thus, essential gene functions will outnumber essential genes. To answer the question to what extent the most recently acquired DNA contributes to the life of B. subtilis under standard laboratory growth conditions, we initiated a "reconstruction" of the B. subtilis genome by removing prophages and AT-rich islands. Stepwise deletion of two prophages (SPbeta, PBSX), three prophage-like regions, and the largest operon of B. subtilis (pks) resulted in a genome reduction of 7.7% and elimination of 332 genes. The resulting strain was phenotypically characterized by metabolic flux analysis, proteomics, and specific assays for protein secretion, competence development, sporulation, and cell motility. We show that genome engineering is a feasible strategy for functional analysis of large gene clusters, and that removal of dispensable genomic regions may pave the way toward an optimized Bacillus cell factory.
Experimental Colitis in Animal Models (1992)

Colitis may be induced in animals by oral administration of sulfated polysaccharides (carrageenan, amylopectin sulfate, dextran sulfate), chemical irritation by rectal instillation of diluted acetic acid, delayed hypersensitivity reaction after sensitization to DNCB or after one single administration of TNBS, and Arthus reaction induced by intravenous injection of immune complexes after chemical irritation of the colon, and by chemoattractant peptides such as FMLP. It appears that all models of colon inflammation in the rat, mouse, or rabbit produce increased amounts of eicosanoids similar to that found in human colitis. Thus, animal studies provide useful information on the origin, regulation, and function of inflammatory mediators. However, with the possible exception of the cotton-top tamarin, no animal model of induced or spontaneous inflammation of the colon is analogous to human ulcerative colitis in etiology, course of disease activity, or histology (114). The observation that two different immune-mediated models gave similar results suggests that the colitis is not a specific response to delayed-type hypersensitivity or immune-complex-mediated reactions but rather an unspecific, stereotype response (125). The original disturbance may not determine the nature of the lesions ultimately produced but may instead serve as an initiator of a final common immunologic pathway.