gebhart/patrepeval huggingface dataset:
Importance of disulfide bridges in the structure and activity of Escherichia coli enterotoxin ST1b. (1987)

A 13-amino acid sequence of the Escherichia coli heat-stable enterotoxin ST1b encodes its receptor-binding and diarrheal functions. This sequence includes six cysteines involved in three intramolecular disulfide bridges. To determine the importance of disulfide bridges to the biological activity of ST1b, we synthesized 15 analogues of the tridecapeptide representing all possible replacements of two of the six cysteines by alanines. Only 2 analogues--namely, A6,11ST1b-(6-18) and A10,18ST1b(6-18)--could inhibit the binding of a radiolabeled analogue of ST1b to rat intestinal cells. The purified peptides were, respectively, 4200 and 130 times less effective as inhibitors than ST1b(6-18), the sequence that includes all six cysteines. In addition, both peptides produce diarrhea when given orally to suckling mice. These analogues share in common only two cysteines (Cys-7 and Cys-15), suggesting that four cysteines, two of which are Cys-7 and Cys-15, are necessary for activity. A pattern of disulfide linkages is proposed where Cys-7 is paired to Cys-15, Cys-6 to Cys-11, and Cys-10 to Cys-18, the preceding disulfide bridges being ranked in descending order of importance in terms of their respective contribution to the activity of the enterotoxin. Using this disulfide bridge arrangement and constraints derived from NMR spectroscopy, we propose a folding pattern for the toxic domain of ST1b.
Ex Vivo and In Vitro Effect of Human Immunodeficiency Virus Protease Inhibitors on Neutrophil Apoptosis (2000)

Polymorphonuclear leukocytes (PMNL) from human immunodeficiency virus (HIV)-infected patients exhibit accelerated apoptosis and impaired functional activity. HIV protease inhibitor-based therapy produces improvements in both acquired and innate immune responses. Ex vivo and in vitro effects of HIV protease inhibitors on apoptosis and chemotaxis of PMNL were evaluated. After therapy, there was a rapid and significant decrease of PMNL apoptosis, which correlated with increased chemotactic function. These findings were found both in patients with immunological and virological response and in control subjects who showed an increase in CD4(+) T cell counts but no concomitant decline in HIV load. After in vitro treatment with ritonavir or indinavir, apoptosis of both HIV-infected and -uninfected PMNL markedly decreased and correlated with significant enhancement of chemotaxis. These results suggest that HIV protease inhibitors may improve the PMNL function by reducing the apoptosis rate and that this effect may, at least in part, be independent of their antiviral activity.
Automatic Extraction of the Face Identity-Subspace (1999)

Abstract Facial variation divides into a number of functional subspaces, and variation unique to the ensemble. An improved method of measuring these is presented, within the space defined by an appearance model. Initial estimates of the subspaces (lighting, pose, identity and expression) are obtained by principal components analysis on appropriate groups of faces. A recoding algorithm is applied to image codings to maximise the probability of coding across these non-orthogonal subspaces. Ensemble-specific variation is then removed by measuring the spatial predictability of the eigenvectors excluding those, which are less predictable than the ensemble. These procedures significantly enhance identity recognition for a disjoint test set.
Protective Efficacy and Immunogenicity of a Combinatory DNA Vaccine against Influenza A Virus and the Respiratory Syncytial Virus (2013)

The Respiratory Syncytial Virus (RSV) and Influenza A Virus (IAV) are both two major causative agents of severe respiratory tract infections in humans leading to hospitalization and thousands of deaths each year. In this study, we evaluated the immunogenicity and efficacy of a combinatory DNA vaccine in comparison to the single component vaccines against both diseases in a mouse model. Intramuscular electroporation with plasmids expressing the hemagglutinin (HA) of IAV and the F protein of RSV induced strong humoral immune responses regardless if they were delivered in combination or alone. In consequence, high neutralizing antibody titers were detected, which conferred protection against a lethal challenge with IAV. Furthermore, the viral load in the lungs after a RSV infection could be dramatically reduced in vaccinated mice. Concurrently, substantial amounts of antigen-specific, polyfunctional CD8⁺ T-cells were measured after vaccination. Interestingly, the cellular response to the hemagglutinin was significantly reduced in the presence of the RSV-F encoding plasmid, but not vice versa. Although these results indicate a suppressive effect of the RSV-F protein, the protective efficacy of the combinatory vaccine was comparable to the efficacy of both single-component vaccines. In conclusion, the novel combinatory vaccine against RSV and IAV may have great potential to reduce the rate of severe respiratory tract infections in humans without increasing the number of necessary vaccinations.
Age at First Viral Infection Determines the Pattern of T Cell–mediated Disease during Reinfection in Adulthood (2002)

Infants experiencing severe respiratory syncytial virus (RSV) bronchiolitis have an increased frequency of wheeze and asthma in later childhood. Since most severe RSV infections occur between the 8th and 24th postnatal week, we examined whether age at first infection determines the balance of cytokine production and lung pathology during subsequent rechallenge. Primary RSV infection in newborn mice followed the same viral kinetics as in adults but was associated with reduced and delayed IFN-gamma responses. To study rechallenge, mice were infected at 1 day or 1, 4, or 8 weeks of age and reinfected at 12 weeks. Neonatal priming produced more severe weight loss and increased inflammatory cell recruitment (including T helper 2 cells and eosinophils) during reinfection, whereas delayed priming led to enhanced interferon gamma production and less severe disease during reinfection. These results show the crucial importance of age at first infection in determining the outcome of reinfection and suggest that the environment of the neonatal lung is a major determinant of cytokine production and disease patterns in later life. Thus, simply delaying RSV infection beyond infancy might reduce subsequent respiratory morbidity in later childhood.
Pigeon ovalbumin glycans labeled with digoxin can be used for identification of uropathogenic E. coli. 8th Annual Meeting of The Society of Glycobiology, San Diego, December 3-6, 2003. (2003)

E. coli is by far the most common cause of urinary tract infections. Standard methods for identification of uropathogenic E. coli (UPEC) in urine are semi-quantitative and usually take 2-3 days, so development of a more rapid, molecular approach to detect UPEC may lead to earlier diagnosis and improve management of urinary tract infections. Attachment of UPEC to host cell receptors is mediated by interaction of the bacterial lectin (adhesin) localized at the top of fimbriae and specific carbohydrate moiety of the host membrane glycoconjugates. The most common type of UPEC causing pyelonephritis expresses type P adhesin (UPEC-P) that specifically recognizes P1 antigen (Gal alpha(1-4)Gal moiety - galabiose). Pigeon glycoproteins are rich in galabiose sequences at the terminal positions of N-glycans that makes them potent inhibitors of UPEC-P adhesion. Oligosaccharides were purified from pigeon ovalbumin, reductively aminated with hydrazine and labelled with digoxin that was previously activated with CNBr. Microtitar plates were coated with purified pigeon ovalbumin and incubated with solution containing bacteria or a model lectin. Pigeon ovalbumin glycans conjugated with digoxin were added and detected with antibodies against digoxigenin (that also recognize digoxin) conjugated with alkaline phosphatase Linear response was observed in a wide range of concentrations, indicating that this model might be useful for quantifying bacteria. As far as we know this is the first case of labelling glycans with digoxin as well as their application. Our preliminary study indicates that specific glycoproteins and glycans labeled with digoxin can be used for development of a rapid, species-specific molecular tool for detection of uropathogenic E. coli. Similar approach may be further utilized for detection of other bacterial species, measurement of bacterial virulence and sensitivity of antibiotic.
Enhancement of protein secretion in Pichia pastoris by overexpression of protein disulfide isomerase (2005)

A potential vaccine candidate, Necator americanus secretory protein (Na-ASP1), against hookworm infections, has been expressed in Pichia pastoris. Na-ASP1, a 45 kDa protein containing 20 cysteines, was directed outside the cell by fusing the protein to the preprosequence of the alpha-mating factor of Saccharomyces cerevisiae. Most of the protein produced by single copy clones was secreted outside the cell. However, increasing gene copy number of Na-ASP1 protein in P. pastoris saturated secretory capacity and therefore, decreased the amount of secreted protein in clones harboring multiple copies of Na-ASP1 gene. Overexpression of the endoplasmic reticulum (ER) resident, homologous chaperone protein, protein disulfide isomerase (PDI) was able to increase the secretion of (Na-ASP1) protein in high copy clones. The effect of PDI levels on secretion of Na-ASP1 protein was examined in clones with varying copy number of PDI gene. Increase in secreted Na-ASP1 secretion is correlated well with the PDI copy number. Increasing levels of PDI also increased overall Na-ASP1 protein production in all the clones. Nevertheless, there was still accumulation of intracellular Na-ASP1 protein in P. pastoris clones over-expressing Na-ASP1 and PDI proteins.
Mdm-2 phosphorylation by DNA-dependent protein kinase prevents interaction with p53. (1997)

In response to genotoxic stress, the p53 tumor suppressor protein exerts a G1 cell cycle arrest that is dependent on its ability to transactivate downstream target genes. This p53-dependent G1 block is reversed by the binding of Mdm-2 to p53, preventing further transactivation. Interestingly, following DNA damage, the mdm-2 gene is also transcriptionally activated by p53, and therefore, the question of how p53 can continue to transactivate genes in the presence of its own negative regulator has remained unanswered. Here, we provide evidence that phosphorylation of Mdm-2 protein by DNA-dependent protein kinase (DNA-PK) blocks its ability to associate with p53 and regulate p53 transactivation. The data support a model by which DNA-PK activation by DNA damage and phosphorylation of Mdm-2 renders the Mdm-2 protein unable to inhibit p53 transactivation, resulting in cell cycle arrest. Following DNA repair, the loss of DNA-PK activity results in newly synthesized Mdm-2 protein that is unphosphorylated and, therefore, capable of binding to p53, allowing cell cycle progression.
FDA Evaluations Using In Vitro Metabolism to Predict and Interpret In Vivo Metabolic Drug‐Drug Interactions: Impact on Labeling (1999)

Recent advances in in vitro metabolism methods have led to an improved ability to predict clinically relevant metabolic drug-drug interactions. To address the relationships of in vitro metabolism data and in vivo metabolism outcomes, the Office of Clinical Pharmacology and Biopharmaceutics in the Center for Drug Evaluation and Research, Food and Drug Administration, evaluated a number of recently approved new drug applications. The goal of these evaluations was to determine the contribution of in vitro metabolism data in (1) predicting in vivo drug-drug interactions, (2) determining the need to conduct an in vivo drug-drug interaction study, and (3) incorporating findings into drug product labeling. Ten cases are presented in this article. They fall into two major groups: (1) in vitro data were predictive of in vivo results, and (2) in vitro data were not predictive of in vivo results. Discussion of these cases highlights factors limiting predictability of in vivo metabolic interactions from in vitro metabolism data. The integration of these findings into drug product labeling is also discussed.
Robust vision-based object tracking (1998)

A vision-based object tracking system takes live image sequences as input and determines the evolving geometric or physical properties (position, orientation, velocity, etc.) of a target object. Ideally, an object tracking system returns complete and accurate information about its target object, but ideal conditions rarely hold in the real world. For example, objects are difficult to track when moving too rapidly or when occluded by other objects. This dissertation presents work that makes vision-based object tracking robust to such circumstances.
The primary contribution of this dissertation is Incremental Focus of Attention (IFA), an architecture for performing robust vision-based object tracking. IFA systems combine several visual search and visual tracking algorithms into a layered hierarchy. The architecture controls the transitions between layers and executes algorithms appropriate to the visual environment at hand: When conditions are good, tracking is accurate and precise; as conditions deteriorate, less accurate, yet more robust, algorithms take over; when tracking is lost altogether, layers cooperate to perform a rapid search for the target in order to recover tracking.
Implemented IFA systems are extremely robust to most common types of temporary visual disturbances. They recover quickly after full occlusions, illumination changes, major distractions, and target disappearances. In particular, recovery times after lost tracking will be shown to depend primarily on the number of objects that are visually similar to the target in the field of view.
Finally, IFA systems will be compared favorably to other methods of robust visual tracking: basic window-based tracking, tracking with adaptive subsampling, tracker fusion, and two-layer attention-based tracking. Each of these methods will be described in some detail prior to the presentation of IFA.
Phoneshell (1993)

This paper describes Phoneshell, a telephone based application providing remote voice access to personal desktop databases such as voice mail, email, calendar, and rolodex. Several forms of information can also be faxed on demand. Phoneshell offers its users numerous opportunities to record voice entries into its underlying databases; this new utility for stored voice as a data type, necessitates multimedia support for the traditional graphical user interfaces to these same databases. The experiences of a small Phoneshell user community are discussed, with emphasis on key features which are most important to its success. The underlying software architecture used by Phoneshell includes a toolkit for building interactive telephone-based services.
Evidence for a functional role of the cholecystokinin-B/gastrin receptor in the human fetal and adult pancreas. (1999)

Gastrin (G) and cholecystokinin (CCK) are gastrointestinal neuropeptides that are released into circulation during a meal. G is also transiently expressed during embryogenic and early ontogenic development of the pancreas and is believed to act on islet-cell development. Both peptides act on pancreatic endocrine function; however, the effects are dependent on the species and on cellular and molecular underlying mechanisms that remain poorly characterized. Since CCK-B/G subtype receptor is predominant over the CCK-A subtype in the human pancreas, we hypothesized that it could be expressed by islet cells. Here we present reverse transcription-polymerase chain reaction and immunohistochemistry data demonstrating that the CCK-B/G receptor is expressed in islet cells and that islet glucagon-producing cells are the major site of CCK-B/G receptor expression in adult and fetal pancreas. Moreover, G immunoreactivity was detected in the fetal human pancreas at embryogenic week 22. G- and CCK-stimulated glucagon are released from purified human islets. Concentration of CCK and G eliciting a half-maximal level of glucagon secretion were 13 +/- 6 and 8 +/- 5 pmol/l, respectively. Maximal glucagon secretion was achieved in the presence of 30 pmol/l peptides and was similar to that obtained in the presence of 10 mmol/l L-arginine (1.6 pmol x ml(-1) x 90 min(-1)). The nonpeptide antagonist of the CCK-B/G receptor, RPR-101048, fully inhibited CCK- and G-stimulated glucagon secretion at 100 nmol/l concentration. These data are consistent with the view that the CCK-B/G receptor is involved in glucose homeostasis in adult humans and mediates the autocrine effects of G on islet differentiation and growth in the fetal pancreas.
Photocontrol of Tyrosine Phosphorylation in Mammalian Cells via Genetic Encoding of Photocaged Tyrosine (2012)

We report the first site-specific genetic encoding of photocaged tyrosine into proteins in mammalian cells. By photocaging Tyr701 of STAT1 we demonstrate that it is possible to photocontrol tyrosine phosphorylation and signal transduction in mammalian cells.
A Finding of Highly Selective Synthetic Inhibitor of Plasma Kallikrein; Its Action to Bradykinin Generation, Intrinsic Coagulation and Experimental DIC (1992)

We found a novel and highly selective synthetic inhibitor of plasma kallikrein (PK), called PKSI-527; the Ki value was 0.81 microM. PKSI-527 inhibited the bradykinin (BK) generation induced by kaolin and prolonged partial thromboplastin time (PTT). PKSI-527 prevented the decrease of fibrinogen (Fg) levels due to i.v. injection of ellagic acid in mice and ameliorated the endotoxin (ET)-induced DIC in rats.
Uncomplicated Baseline Fetal Tachycardia or Bradycardia in Postterm Pregnancies and Perinatal Outcome (1998)

Uncomplicated baseline fetal tachycardia or bradycardia in postterm patients are not associated with an increase in the incidence of adverse perinatal outcome.
Synthesis of Nearly Uniform Single-Walled Carbon Nanotubes Using Identical Metal-Containing Molecular Nanoclusters as Catalysts (2002)

Uniform and small-diameter single-walled carbon nanotubes (SWNTs) have been produced using identical molecular nanoclusters containing Fe and Mo atoms with a defined molecular formula and a specific structure as catalysts in a chemical vapor deposition method. The average diameter of the SWNTs produced in these experiments is 1.0 nm with a standard deviation for the diameter distribution of 17%. The diameters of SWNTs were obtained by atomic force microscopy and Raman spectroscopy.
Sleep-Dependent θ Oscillations in the Human Hippocampus and Neocortex (2003)

Hippocampal theta waves recorded during rapid eye movement (REM) sleep are thought to play a critical role in memory consolidation in lower mammals, but previous attempts to detect similar theta oscillations in the human hippocampus have been unsuccessful. Using subdural and depth recordings from epileptic patients, we now report the first evidence of state-dependent hippocampal theta waves (4-7 Hz) in humans. Unlike the continuous theta in rodents, however, these oscillations were consistently observed during REM sleep in short (approximately 1 sec) bursts and during transitions to wake in longer epochs. Theta waves were also observed in the basal temporal lobe and frontal cortex during transitions from sleep to wake and in quiet wakefulness but not in REM, and they were not coherent with hippocampal theta oscillations. The absence of functional coupling between neocortex and hippocampus during theta periods indicates that multiple theta generators exist in the human brain, and that they are dynamically regulated by brain state. Gamma oscillations were also present during REM theta bursts, but the fluctuations in gamma power were not associated with theta phase, pointing out another significant difference between rodent and human theta properties. Together, these findings suggest that the generation mechanisms of theta oscillations in humans might have evolved from tonic to phasic in hippocampus during REM sleep and extended from hippocampus to cortex, where they appear in certain wakefulness-related states.
PCR amplification of mRNA directly from a crude cell lysate prepared by thermophilic protease digestion (1991)

Journal Article PCR amplification of mRNA directly from a crude cell lysate prepared by thermophilic protease digestion Get access Ming-Chiu Fung, Ming-Chiu Fung Division of Biochemistry and Molecular Biology, The John Curtin School of Medical Research, The Australian National UniversityCanberra, ACT 2601, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar Katherine Yin-Mei Fung Katherine Yin-Mei Fung Division of Biochemistry and Molecular Biology, The John Curtin School of Medical Research, The Australian National UniversityCanberra, ACT 2601, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 19, Issue 15, 11 August 1991, Page 4300, https://doi.org/10.1093/nar/19.15.4300 Published: 11 August 1991 Article history Accepted: 01 May 1991 Published: 11 August 1991
Synthesis and coronary vasodilating activity of 2-substituted adenosines. (1975)

A large scale preparation of 2-haloadenosines (1) was attained by acetylation of 2-haloinosines (3), followed by chlorination and amination. 2-Alkoxyadenosines (5) were prepared in fairly good yields by protection of both 2'- and 3'-hydroxyl groups of 2-chloroadenosine (1a) or 2-chloroinosine (3a), followed by substitution of the chlorine atom with alkoxy group. In the reaction of 1a with sodium alkoxide, there were obtained some oligomers of 5, of which the structures were elucidated. The reaction of 5-amino-4-cyano-1-β-D-ribofuranosylimidazole with carbon disulfide afforded 2, 6-di-mercapto-9-β-D-ribofuranosylpurine (15), which was converted to 2-mercaptoadenosine (14e) and its S-substituted derivatives. 2-Phenylaminoadenosine (29e) was prepared with comparative ease via 2-phenylamino-2', 3', 5'-tri-O-acetylinosine (32), the synthesis of which was effected by acetylation of 2-phenylaminoinosine (30) with acetylchloride in acetic acid. Many 2-substituted adenosines including O-substituted 2-hydroxyadenosines, S-substituted 2-mercaptoadenosines, N2-substituted 2-aminoadenosines, 2-alkyl- and -aryl-adenosines were prepared, among which several compounds were found to have a remarkable coronary vasodilating potency. Compound (29e) showed not only a strong potency, but also a longer duration of the effect than that of 1a. The structure-coronary vasodilating activity relationship was also discussed.
Food Balance Estimation by Using Personal Dietary Tendencies in a Multimedia Food Log (2013)

We have investigated the “FoodLog” multimedia food-recording tool, whereby users upload photographs of their meals and a food diary is constructed using image-processing functions such as food-image detection and food-balance estimation. In this paper, following a brief introduction to FoodLog, we propose a Bayesian framework that makes use of personal dietary tendencies to improve both food-image detection and food-balance estimation. The Bayesian framework facilitates incremental learning. It incorporates three personal dietary tendencies that influence food analysis: likelihood, prior distribution, and mealtime category. In the evaluation of the proposed method using images uploaded to FoodLog, both food-image detection and food-balance estimation are improved. In particular, in the food-balance estimation, the mean absolute error is significantly reduced from 0.69 servings to 0.28 servings on average for two persons using more than 200 personal images, and 0.59 servings to 0.48 servings on average for four persons using 100 personal images. Among the works analyzing food images, this is the first to make use of statistical personal bias to improve the performance of the analysis.