gebhart/patrepeval huggingface dataset:
Endoprotease PACE4 is Ca2+-dependent and temperature-sensitive and can partly rescue the phenotype of a furin-deficient cell strain (1999)

PACE4 is a member of the eukaryotic subtilisin-like endoprotease family. The expression of human PACE4 in RPE.40 cells (furin-null mutants derived from Chinese hamster ovary K1 cells) resulted in the rescue of a number of wild-type characteristics, including sensitivity to Sindbis virus and the ability to process the low-density-lipoprotein receptor-related protein. Expression of PACE4 in these cells failed to restore wild-type sensitivity to Pseudomonas exotoxin A. Co-expression of human PACE4 in these cells with either a secreted form of the human insulin pro-receptor or the precursor form of von Willebrand factor resulted in both proproteins being processed; RPE.40 cells were unable to process either precursor protein in the absence of co-expressed PACE4. Northern analysis demonstrated that untransfected RPE.40 cells express mRNA species for four PACE4 isoforms, suggesting that any endogenous PACE4 proteins produced by these cells are either non-functional or sequestered in a compartment outside of the secretory pathway. In experiments in vitro, PACE4 processed diphtheria toxin and anthrax toxin protective antigen, but not Pseudomonas exotoxin A. The activity of PACE4 in vitro was Ca2+-dependent and, unlike furin, was sensitive to temperature changes between 22 and 37 °C. RPE.40 cells stably expressing human PACE4 secreted an endoprotease with the same Ca2+ dependence and temperature sensitivity as that observed in membrane fractions of these cells assayed in vitro. These results, in conjunction with other published work, demonstrate that PACE4 is an endoprotease with more stringent substrate specificity and more limited operating parameters than furin.
Effect of Luminance Noise on Contrast Thresholds (1964)

This paper deals with the effect on contrast thresholds of the fluctuations in the background luminance or “luminance noise.” Targets of several sizes are produced on a television screen, imbedded in fine-grain luminance noise of controllable magnitude. The results indicate that luminance fluctuations of small magnitude do not affect the threshold very much when the mean luminance of the screen is 0.01 and 0.1 ft-L, while they do change it appreciably at 1.0 ft-L. When luminance fluctuations are large, contrast thresholds at the above three luminance levels are nearly the same, indicating that the degree of luminance fluctuation governs the contrast threshold.The extent to which luminance noise increases the contrast threshold is used to estimate the internal noise of the vision channel and an attempt is made to compare this with the noise that might be expected on account of fluctuations in the number of quanta absorbed in the retina.
The Qin Synthesis of (+)-Gelsemine (2015)

(+)-Gelsemine 3 has no particular biological activity, but its intricate architecture continues to inspire the ingenuity of organic synthesis chemists. Yong Qin of Sichuan University devised (Angew. Chem. Int. Ed. 2012, 51, 4909) an enantiospecific synthesis of 3, a key step of which was the cyclization of 1 to 2. The starting material for the synthesis was the inexpensive diethyl tartrate 4, which was converted over six steps into the N-sulfonyl aziridine 5. The addition of 6 was highly regioselective, leading, after N-methylation, to the alkyne 7. After alcohol protection, the sulfonyl group was smoothly removed by sonication with Mg powder in methanol. Addition to acryonitrile then gave 8. Semihydrogenation of 8 set the stage for construction of the lactone 1. The anion of 1, generated by exposure to LDA, cyclized to 2 with significant diastereoselectivity. The lactone of 2 was selectively reduced with Dibal, to give an aldehyde that was protected as the acetal. The exposed primary alcohol was then oxidized to the aldehyde 9. Condensation of 9 with the enolate of 10 followed by dehydration delivered the alkene 11, with the stage set for a second intramolecular nitrile anion addition. In the event, the cyclization of 11 delivered 12, the wrong diastereomer. This was corrected by selenation and oxidation to give an alkene, which was hydrogenated to 13. Exposure to acid deprotected both the MOM group of 13 and the acetal, then promoted cyclization to 14. Reduction of the nitrile to the aldehyde followed by methylenation completed the synthesis of (+)-gelsemine 3. It should be noted that the hydrogenation to form 13 had to be carried out carefully to avoid premature removal of the N-methoxy group. That group was critical for the successful conversion of 13 to 14.
Validation of an Enzyme-Linked Immunosorbent Assay Screening Method and a Liquid Chromatography-Tandem Mass Spectrometry Confirmation Method for the Identification and Quantification of Ketamine and Norketamine in Urine Samples from Malaysia (2009)

An ELISA and a liquid chromatography-tandem mass spectrometry (LC-MS-MS) confirmation method were developed and validated for the identification and quantitation of ketamine and its major metabolite norketamine in urine samples. The Neogen ketamine microplate ELISA was optimized with respect to sample and enzyme conjugate volumes and the sample preincubation time before addition of the enzyme conjugate. The ELISA kit was validated to include an assessment of the dose-response curve, intra- and interday precision, limit of detection (LOD), and cross-reactivity. The sensitivity and specificity were calculated by comparison to the results from the validated LC-MS-MS confirmation method. An LC-MS-MS method was developed and validated with respect to LOD, lower limit of quantitation (LLOQ), linearity, recovery, intra- and interday precision, and matrix effects. The ELISA dose-response curve was a typical S-shaped binding curve, with a linear portion of the graph observed between 25 and 500 ng/mL for ketamine. The cross-reactivity of 200 ng/mL norketamine to ketamine was 2.1%, and no cross-reactivity was detected with 13 common drugs tested at 10,000 ng/mL. The ELISA LOD was calculated to be 5 ng/mL. Both intra- (n = 10) and interday (n = 50) precisions were below 5.0% at 25 ng/mL. The LOD for ketamine and norketamine was calculated statistically to be 0.6 ng/mL. The LLOQ values were also calculated statistically and were 1.9 ng/mL and 2.1 ng/mL for ketamine and norketamine, respectively. The test linearity was 0-1200 ng/mL with correlation coefficient (R(2)) > 0.99 for both analytes. Recoveries at 50, 500, and 1000 ng/mL range from 97.9% to 113.3%. Intra- (n = 5) and interday (n = 25) precisions between extracts for ketamine and norketamine were excellent (< 10%). Matrix effects analysis showed an average ion suppression of 5.7% for ketamine and an average ion enhancement of 13.0% for norketamine for urine samples collected from six individuals. A comparison of ELISA and LC-MS-MS results demonstrated a sensitivity, specificity, and efficiency of 100%. These results indicated that a cutoff value of 25 ng/mL ketamine in the ELISA screen is particularly suitable and reliable for urine testing in a forensic toxicology setting. Furthermore, both ketamine and norketamine were detected in all 34 urine samples collected from individuals socializing in pubs by the Royal Malaysian Police. Ketamine concentrations detected by LC-MS-MS ranged from 22 to 31,670 ng/mL, and norketamine concentrations ranged from 25 to 10,990 ng/mL. The concentrations of ketamine and norketamine detected in the samples are most ikely indicative of ketamine abuse.
High-Density Gamma Radiation Spectrometry Surveys of Contaminated Land (2011)

The design of gamma radiation surveys of contaminated land has always had to compromise between the density of sampling and the accuracy of measurement. Large-area contamination is readily detected by a variety of measurement techniques, while the detection of small areas or ‘particles’ requires a high density of measurement, generally one measurement per square metre. High Resolution Gamma-radiation Spectrometry (HRGS) can provide accurate qualitative (radionuclide identification) and quantitative (Bq.g−1 of the radionuclide for a stated scenario) assessment of the state of the land, but are not cost effective at high density. In contrast, simple walk-over or ‘scan’ surveys using standard Health Physics instruments can provide a high density of measurement, but cannot provide the qualitative and quantitative accuracy of HRGS. In 1996, Nuvia Limited adopted methods to address some of these issues, by allowing scan surveys to include a degree of qualitative analysis of the gamma radiation detected using Low Resolution Gamma-radiation Spectrometry systems with Sodium Iodide detectors, while maintaining a high density of measurement. While low-resolution systems (including medium-resolution Lanthanum Bromide) have become the de-facto standard for large area land surveys, the use of the technology has changed little. High density scan surveys can be conducted using, for example, simple gross-gamma techniques, doserate or region-of-interest logging. However, if spectra are required for qualitative purposes, they are normally collected at fixed locations and for inconveniently long counting periods. The ideal would be to collect spectra at every measurement location, preferably once per second, and then ‘aggregate’ the spectra using spatially-aware techniques. This would allow a scan survey to be performed rapidly, while losing no spectral information. It would thus be possible to analyse the data in a number of ways, for example, producing justifiable doserate measurements or using neural-network techniques to search the measurements for spectral anomalies. This paper describes the work done by Nuvia to develop a system to collect spectra efficiently and to make the spectra readily available for a number of analyses. The efficiency of spectrum acquisition and compression are discussed, along with methods of managing the potentially large volumes of data. The analysis of the data, using a customised Geographical Information System is described, including spatial aggregation of spectra and semi-automatic analysis of spectral structure for identifying common ‘background’ features. Examples of the use of these facilities in Nuvia’s ‘Groundhog’ site survey service are provided.
Instance Guided Proposal Network for Person Search (2020)

Person detection networks have been widely used in person search. These detectors discriminate persons from the background and generate proposals of all the persons from a gallery of scene images for each query. However, such a large number of proposals have a negative influence on the following identity matching process because many distractors are involved. In this paper, we propose a new detection network for person search, named Instance Guided Proposal Network (IGPN), which can learn the similarity between query persons and proposals. Thus, we can decrease proposals according to the similarity scores. To incorporate information of the query into the detection network, we introduce the Siamese region proposal network to Faster-RCNN and we propose improved cross-correlation layers to alleviate the imbalance of parameters distribution. Furthermore, we design a local relation block and a global relation branch to leverage the proposal-proposal relations and query-scene relations, respectively. Extensive experiments show that our method improves the person search performance through decreasing proposals and achieves competitive performance on two large person search benchmark datasets, CUHK-SYSU and PRW.
Macrophage-mediated fungistasis in vitro: requirements for intracellular and extracellular cytotoxicity. (1986)

Macrophage cytotoxicity for Cryptococcus neoformans was investigated by culturing mouse peritoneal macrophages with a thin-capsuled clone of cryptococcus under conditions permitting efficient phagocytosis. Yeast replication was quantitated by electronic particle counting after detergent lysis of macrophages, and viability was determined by quantitative plate counts. Under appropriate conditions, reproduction was completely inhibited; stasis began at 2 hr after addition of yeasts and lasted for 30 hr. During this time organisms in medium alone proliferated rapidly, doubling their number every 2.5 hr. After removal from macrophages, 60 to 100% of macrophage-inhibited cryptococci formed colonies, indicating that the cytotoxic effect was primarily fungistatic. When yeast cells were removed from macrophages, replication recommenced within 5 hr. Supernatant medium from fungistatic co-cultures was not inhibitory for fresh yeast cells. Conditions required for complete fungistasis were 1) peritoneal macrophages induced by peptone from BCG-infected mice, 2) endotoxin in nanogram per milliliter range added to serum-containing cell culture medium, 3) confluent macrophage monolayers, and 4) macrophage:cryptococci ratios of 20 to 100:1. Fungistasis occurred without phagocytosis but was more efficient when cryptococci were engulfed. For efficient fungistasis, macrophages must differentiate to and be maintained in the activated state. These results with yeast cells agree with the known requirements for macrophage effector function against neoplastic target cells.
150. The synthesis of thyroxine and related substances. Part IX. Analogues of thyroxine with modified side chains (1952)

R. C. Cookson and G. F. H. Green, J. Chem. Soc., 1952, 827 DOI: 10.1039/JR9520000827
X-linked thrombocytopenia (XLT) due to WAS mutations: clinical characteristics, long-term outcome, and treatment options (2010)

A large proportion of patients with mutations in the Wiskott-Aldrich syndrome (WAS) protein gene exhibit the milder phenotype termed X-linked thrombocytopenia (XLT). Whereas stem cell transplantation at an early age is the treatment of choice for patients with WAS, therapeutic options for patients with XLT are controversial. In a retrospective multicenter study we defined the clinical phenotype of XLT and determined the probability of severe disease-related complications in patients older than 2 years with documented WAS gene mutations and mild-to-moderate eczema or mild, infrequent infections. Enrolled were 173 patients (median age, 11.5 years) from 12 countries spanning 2830 patient-years. Serious bleeding episodes occurred in 13.9%, life-threatening infections in 6.9%, autoimmunity in 12.1%, and malignancy in 5.2% of patients. Overall and event-free survival probabilities were not significantly influenced by the type of mutation or intravenous immunoglobulin or antibiotic prophylaxis. Splenectomy resulted in increased risk of severe infections. This analysis of the clinical outcome and molecular basis of patients with XLT shows excellent long-term survival but also a high probability of severe disease-related complications. These observations will allow better decision making when considering treatment options for individual patients with XLT.
Capturing Brain Metrics of Neuropathic Pain Using Nuclear Magnetic Resonance (2013)

SUMMARY Neuropathic pain is typically caused by a lesion or dysfunction in the nervous system that results in both negative (i.e., reduced sensitivity) and positive symptoms (i.e., paraesthesia, spontaneous ongoing pain with shooting, electric shock-like sensations and abnormal responses to evoked pain). Intriguingly, chronic pain disorders manifest profound alterations in brain structure and function, and thus, modern nuclear magnetic resonance (NMR) techniques have allowed us to begin to dissect the complexities of how neuropathic pain affects the brain. NMR approaches can be used as an independent measure to improve our understanding of key changes in brain structure, function and chemistry in chronic neuropathic pain. Accordingly, NMR techniques provide neurobiological metrics that allow us to understand the neurobiological basis of chronic neuropathic pain. Additionally, although at an early stage, NMR methods can also be useful to define clinical metrics to predict chronification of neuropathic pain and responses to drugs. This article provides a review of NMR techniques and their capacity to study spontaneous pain and evoked pain, as well as structural, functional and neurochemical alterations that have repeatedly been associated with chronic neuropathic pain. Finally, the importance for quantifying disease state and treatment efficacy in neuropathic pain using NMR techniques is discussed.
Modélisation inverse du transport de pesticide en colonne de sol insaturé (2008)

communication orale invitée<br/>communication orale invitée
Great Ape Phenome Project? (1998)

We applaud the notion recently highlighted by Ann Gibbons (News Focus, 4 Sept., p. [1433][1]) about “Pushing a primate genome project.” There is much to be learned by comparing human genomic sequences with those of other primates, particularly those of our closest evolutionary cousins, the great apes. This information can also be obtained by noninvasive methods that would not harm these individuals. However, part of the value of the Human Genome Project lies in interpreting genomic data in the context of the large body of existing information about humans, ranging from the biochemistry of cells to the physiology of organ systems to the functional output of complex systems like the brain. In contrast, the corresponding information about the great apes is limited. We suggest that the funding of such a Great Ape Genome Project should be complemented by a “Great Ape Phenome Project,” which would support comparative studies of humans and apes at all levels, from expression patterns of messenger RNA, to biochemistry and cell biology, all the way to neural systems and cognitive functions. Not to do so would be like funding the Human Genome Project without supporting much of the rest of the National Institutes of Health. Indeed, with the exception of gross deletional or nonsense mutations, the significance of most genomic sequence differences found between humans and apes will not be obvious unless such a detailed comparative phenotypic database is also available. Notably, such a database could be obtained without undue harm to the primate subjects, with the use of ethical principles similar to those guiding human experimentation. Such a project would also heighten awareness of the urgent need to protect and conserve these endangered hominoids who are so closely related to us.

 [1]: /lookup/doi/10.1126/science.281.5382.1433
Inhibitory Mechanism of an Extract of Althaea officinalis L. on Endothelin-1-Induced Melanocyte Activation. (2002)

It is known that expression of endothelin-1 (ET-1) increases in the epidermis after UVB irradiation, and that this plays an important role during the induction of pigmentation both as a mitogen and as a melanogen for normal human melanocytes (NHMC). When ET-1 acts on NHMC via the endothelin B receptor (ET(B)R) on their cell surface, mobilization of intracellular calcium is induced, which is followed by activation of Raf-1 located upstream of mitogen activated protein kinase (MAPK). We have continued the search for new agent which inhibit this calcium mobilization and we have found that an extract of Althaea officinalis L. has such an action. In this study, we investigated the precise inhibitory mechanism of this botanical extract on the ET-1-induced activation of melanocytes. Treatment of NHMC with this extract abrogated the stimulatory effect of ET-1 on proliferation and also on activation of MAPK in the intracellular signal transduction pathway, but did not affect the binding of ET-1 to the ET(B)R or the production of Inositol 1,4,5-Trisphosphate (IP3). Further, when this extract was used to treat normal human keratinocytes (NHKC), secretion of ET-1 by those cells was reduced. Taken together, these findings indicate that an extract of A. officinalis inhibits both the secretion of ET-1 from NHKC and the action of ET-1 on NHMC mainly by suppressing the ET-1-induced calcium mobilization without the modification of IP3 production, which in turn suggests that this extract is a useful ingredient for a whitening agent.
<title>Calculation of uncertainty in laser-damage thresholds determined by use of the damage-frequency method</title> (1995)

The reported uncertainty is a key parameter in comparing laser damage test results for statistically significant differences. Yet, this important statistic is frequently determined in a nonrigorous manner. This paper presents a Monte Carlo based calculation of the expected distribution of results from a single laser damage threshold (LDT) measurement. The uncertainties in the measured damage frequency and test fluence are used to estimate the probability distributions used in the Monte Carlo model. The model is run many times and the resulting distribution is analzed to yield and estimate the uncertainty in the LDT measurement. It is demonstrated that the distribution of results is not symmetric thus invalidating the use of more conventional closed form formulations for threshold uncertainty.
Immunological detection of cytochrome P450 from insecticide resistant and susceptible house flies (Musca domestica) (1990)

An antiserum was raised in a rabbit against a cytochrome P450, termed P450lpr, purified from the pyrethroid resistant LPR strain of house fly. This polyclonal antiserum was specific for P450lpr as judged by both rocket immunoelectrophoresis and immunoblotting. The antiserum was used to detect immunoreactive cytochrome P450s in insecticide susceptible and resistant house flies. Single immunoreactive bands of a slightly variable position were obtained when crude microsomes from six insecticide resistant house fly strains (LPR, Dairy, Kashiwagura, 3rd-Y, EPR, ASPR) were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by immunoblotting, while immunoreactive bands were barely detectable in insecticide susceptible (aabys, S+) strains. The immunoreactive cytochrome P450s were isolated from each of eight house fly strains by high-performance liquid chromatography. The isolated immunoreactive cytochrome P450s from all strains were immunologically identical to P450lpr by fused rocket immunoelectrophoresis, and only those from the Kashiwagura and ASPR strains differed in chromatographic and/or electrophoretic properties from P450lpr. Amounts of immunoreactive P450 were determined in house fly microsomes. Immunoreactive P450 represented 68% (specific content: 0.48 nmol/mg protein) of the total (0.72 nmol/mg) cytochrome P450 in LPR microsomes and 6.6% (0.011 nmol/mg) of the total (0.15 nmol/mg) cytochrome P450 in S+. Thus, immunoreactive P450 was constituitively expressed at 44-fold higher levels in insecticide resistant LPR flies compared to the susceptible S+ strain.
Kinetic and Mechanistic Study of the Reduction of Chromium(VI) by Lactic Acid (2008)

The kinetics and mechanism of the reduction of chromium(VI) by lactic acid (Lac) in aqueous acidic medium was studied with spectrophotometry in a temperature range of 298.15 K~313.15 K. Under the conditions of the pseudo‐first order ([Lac] 0 ≫ [Cr(VI)] 0 ), the observed rate constant ( k obs ) increased with the increase in [Lac] and [H + ]. There is no salt effect. Based on the experimental results, a probable reaction mechanism of oxidation was proposed. The rate equation derived from the mechanism could explain all the experimental phenomena. Activation parameters along with rate constant of the rate‐determining step have been evaluated.