gebhart/patrepeval huggingface dataset:
O(n)-depth circuit algorithm for modular exponentiation (2002)

An O(n)-depth polynomial-size combinational circuit algorithm is proposed for n-bit modular exponentiation, i.e., for the computation of "x/sup y/ mod m" for arbitrary integers x, y and m. Represented as n-bit binary integers, within bounds 2/sup n-1//spl les/m<2/sup n/ and 0/spl les/x,y<m. The algorithm is a generalization of the square-and-multiply method. An obvious implementation of the square-and-multiply method yields a circuit of depth O(nlogn) and size O(n/sup 3/). In the proposed algorithm, the terms x/sup 2/ mod m's for all i's /spl epsiv.<<ETX>>
The use of spirocyclic scaffolds in drug discovery (2014)

Owing to their inherent three-dimensionality and structural novelty, spiro scaffolds have been increasingly utilized in drug discovery. In this brief review, we highlight selected examples from the primary medicinal chemistry literature during the last three years to demonstrate the versatility of spiro scaffolds. With recent progress in synthetic methods providing access to spiro building blocks, spiro scaffolds are likely to be used more frequently in drug discovery.
Transforming growth factor (TGF)beta, fibroblast growth factor (FGF) and retinoid signalling pathways promote pancreatic exocrine gene expression in mouse embryonic stem cells (2004)

Extracellular signalling cues play a major role in the activation of differentiation programmes. Mouse embryonic stem (ES) cells are pluripotent and can differentiate into a wide variety of specialized cells. Recently, protocols designed to induce endocrine pancreatic differentiation in vitro have been designed but little information is currently available concerning the potential of ES cells to differentiate into acinar pancreatic cells. By using conditioned media of cultured foetal pancreatic rudiments, we demonstrate that ES cells can respond in vitro to signalling pathways involved in exocrine development and differentiation. In particular, modulation of the hedgehog, transforming growth factor beta, retinoid, and fibroblast growth factor pathways in ES cell-derived embryoid bodies (EB) resulted in increased levels of transcripts encoding pancreatic transcription factors and cytodifferentiation markers, as demonstrated by RT-PCR. In EB undergoing spontaneous differentiation, expression of the majority of the acinar genes (i.e. amylase, carboxypeptidase A and elastase) was induced after the expression of endocrine genes, as occurs in vivo during development. These data indicate that ES cells can undergo exocrine pancreatic differentiation with a kinetic pattern of expression reminiscent of pancreas development in vivo and that ES cells can be coaxed to express an acinar phenotype by activation of signalling pathways known to play a role in pancreatic development and differentiation.
Senile Dementia of Alzheimer Type: Early Diagnosis, Neuropathology and Animal Models (1985)

Early Diagnosis of Senile Dementia of the Alzheimer Type.- I. Behavioral and Clinical Aspects.- Cognitive Function in Normal Aging and Early Dementia.- Senile Dementia of the Alzheimer Type: Diagnostic and Differential Diagnostic Features with Special Reference to Functional Assessment Staging.- Assessment of Cognition and Affective Symptoms in Dementia.- The AGP System: Assessment of Symptoms in Psychogeriatric Patients.- Cognitive Deficits in Parkinson's Disease.- Differential Diagnosis: Depression Versus Dementia.- Early Diagnosis of Dementia: Possible Contributions of Neuropsychology.- II. Brain Tissue Parameters.- EEG and Evoked Potentials in the Diagnosis of Dementias.- Nuclear Magnetic Resonance and Early Diagnosis of Brain Pathology.- Positron Tomography and the Differential Diagnosis and Pathophysiology of Alzheimer's Disease.- Investigation of Regional Cerebral Blood Flow and Metabolism in Dementia.- Novel Developments in the Neuropathology of Senile Dementia of the Alzheimer Type.- Are Neurons of the Human Cerebral Cortex Really Lost During Aging? A Morphometric Examination.- Senile Dementia of the Alzheimer Type: Morphological and Immunocytochemical Studies.- Neurotransmitter Receptor Alterations in Alzheimer's Disease.- Co-Localization of Aluminium and Silicon in Senile Plaques: Implications for the Neurochemical Pathology of Alzheimer's Disease.- Biochemical Changes in Alzheimer's Disease: A Comment.- The Nature of Neurofibrillary Tangles.- Brain Plasticity and Trophic Factors.- Trophic Factors in Brain Aging and Disease.- Melanocortin Peptides and Neural Plasticity.- Brain Plasticity and Aging.- Animal Models.- Parallels and Contrasts Between Scrapie and Dementia of the Alzheimer Type and Ageing: Strategies and Problems for Experiments Involving Life Span Studies.- Animal Models of Geriatric Cognitive Dysfunction: Evidence for an Important Cholinergie Involvement.- Animal Models of Jacksonian Dissolution of Memory in the Aged.- Mechanisms Underlying Pharmacologic Modifications of the Hippocampal Lesion Syndrome.- Lesions of the Nucleus Basalis in the Rat: Functional Changes.- AF64A Cholinotoxicity: Functional Aspects.- Novel Approaches in the Study of Brain Acetylcholine Function: Neuropharmacology, Neuroanatomy, and Behavior.- Immunologic Factors Related to Cognitive/Behavioral Dysfunctions in Aging.- Morphological Studies on Brain Structures of the NZB Mouse: An Animal Model for the Aging Human Brain?.
Adenovirus core protein V is delivered by the invading virus to the nucleus of the infected cell and later in infection is associated with nucleoli. (1998)

A 'west-Western' blotting procedure indicates that adenovirus core protein V is linked to the capsid via protein VI. Double-labelling techniques employing confocal microscopy and immunofluorescence suggest that this linkage is disrupted following infection and penetration of the host cell. Protein V enters the nucleus presumably still in association with the other core proteins attached to the virus genome. Later in infection protein V rapidly accumulates in the nucleus in close association with nucleoli.
Purification and characterization of heparin lyases from Flavobacterium heparinum. (1992)

Heparin lyase I has been purified from Flavobacterium heparinum and has been partially characterized (Yang, V. C., Linhardt, R. J., Berstein, H., Cooney, C. L., and Langer, R. (1985) J. Biol. Chem. 260, 1849-1857). There has been no report of the purification of the other polysaccharide lyases from this organism. Although all three of these heparin/heparan sulfate lyases are widely used, with the exception of heparin lyase I, there is no information on their purity or their physical and kinetic characteristics. The absence of pure heparin lyases and a lack of understanding of the optimal catalytic conditions and substrate specificity has stood in the way of the use of these enzymes as reagents for the specific depolymerization of heparin and heparan sulfate into oligosaccharides for structure and activity studies. This paper describes a single, reproducible scheme to simultaneously purify all three of the heparin lyases from F. heparinum to apparent homogeneity. Heparin lyase I (heparinase, EC 4.2.2.7), heparin lyase II (no EC number), and heparin lyase III (heparitinase, EC 4.2.2.8) have molecular weights (by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) and isoelectric points (by isoelectric focusing) of M(r) 42,800, pI 9.1-9.2, M(r) 84,100, pI 8.9-9.1, M(r) 70,800, pI 9.9-10.1, respectively. Their amino acid analyses and peptide maps demonstrate that while these proteins are different gene products they are closely related. The kinetic properties of the heparin lyases have been determined as well as the conditions to optimize their activity and stability. These data should improve the application of these important enzymes in the study of heparin and heparan sulfate.
Rearrangement of 4-oxothiochroman-1-io(bismethoxycarbonyl)methanides to tetrahydro-1-benzothiepin-5-ones (1981)

Heating thiochroman-4-ones with dimethyl diazomalonate without solvent or in refluxing toluene in the presence of copper(II) sulphate gave the corresponding bismethoxycarbonylmethanides (4) and dimethyl 5-oxo-2,3,4,5-tetrahydro-1-benzothiepin-2,2-dicarboxylates (5). Treatment of the sulphonium methanides (4) with triethylamine afforded (5).
Targeting Mitochondrial Dysfunction: Role for PINK1 and Parkin in Mitochondrial Quality Control (2011)

Mitochondria, which convert energy for the cell, accumulate damage with age, and the resulting mitochondrial dysfunction has been linked to the development of degenerative diseases and aging. To curb the accumulation of damaged mitochondria, the cell has elaborated a number of mitochondrial quality control processes. We describe recent work suggesting that Parkin and PTEN-induced putative kinase 1 (PINK1), two gene products linked to familial forms of parkinsonism, may constitute one of the cell's mitochondrial quality control pathways-identifying impaired mitochondria and selectively trimming them from the mitochondrial network by mitophagy. In particular, we discuss the regulation of PINK1 protein expression and Parkin localization by the bioenergetic status of individual mitochondria; the mechanism by which PINK1 recruits Parkin to the outer mitochondrial membrane; and Parkin's promotion of mitophagy through its ubiquitination of outer mitochondrial membrane proteins. This recent work suggests that Parkin and PINK1 may be among the first mammalian proteins identified with a direct role in regulating mitophagy, and implicate a failure of mitophagy in the pathogenesis of Parkinson's disease.
Evaluation of Real-Time PCR for Detection of and Discrimination between Bordetella pertussis , Bordetella parapertussis , and Bordetella holmesii for Clinical Diagnosis (2003)

PCR is increasingly being used as a diagnostic test for the detection of Bordetella pertussis and Bordetella parapertussis DNA, as it has improved sensitivity and specificity in comparison to conventional techniques. The assay described here uses the two insertion sequences IS481 and IS1001 for B. pertussis and B. parapertussis, respectively, with detection by molecular beacons. The real-time PCR for IS481 detects both B. pertussis and Bordetella holmesii, and the real-time PCR for IS1001 detects both B. parapertussis and B. holmesii. By performing both assays discrimination between B. pertussis and B. parapertussis can be obtained. The sensitivity was 1 to 10 CFU/ml for B. pertussis, 10 CFU/ml for B. parapertussis, and 10 CFU/ml for B. holmesii in both assays. The clinical sensitivity of the B. pertussis assay was not affected by duplexing with an internal control PCR. Real-time PCR, conventional PCR, and culture were performed on 57 clinical samples. Eight of the 57 (14%) were found positive by culture, 19 of 57 (33%) were found positive by conventional PCR, and 22 of 57 (39%) were found positive by real-time PCR. One sample was inhibitory. When the B. pertussis assay was compared with a clinical standard for B. pertussis infection, sensitivity was 38, 83, and 100% and specificity was 100, 97, and 97% for culture, conventional PCR, and real-time PCR, respectively. The real-time PCR designed for B. pertussis and B. parapertussis provides sensitive and specific diagnosis of B. pertussis and B. parapertussis infections and is therefore suitable for implementation in the diagnostic laboratory.
E1A RNA transcripts amplify adenovirus-mediated tumor reduction. (1996)

Previous work by this group has established that E1-defective, recombinant adenoviruses can be replication-enabled by the codelivery of a plasmid encoding the deleted E1 functions, a strategy now designated conditional replication-enablement system for adenovirus (CRESA). In the studies reported here, the original replication-enabling plasmid was replaced by two separate plasmids that encoded the necessary E1A and E1B functions, respectively. An RNA transcript encoding the requisite E1A functions was shown to substitute functionally for the E1A plasmid without significant loss of new adenovirus production in in vitro experiments. No replication competent adenovirus was detectable in the cells treated with the plasmids, or the RNA and plasmid combinations. Subcutaneous human tumor nodules containing a fraction of cells cotransduced with the replication-enabling RNA + DNA and an adenovirus containing a herpes simplex virus thymidine kinase (HSVtk) expression cassette were reduced to a greater extent than control nodules containing the same fraction of cells cotransduced with the virus and an irrelevant plasmid. These experiments show that an E1-defective adenovirus can be conditionally replication-enabled by an RNA transcript encoding the required E1 functions, and that the replication-enablement is sufficient to produce an augmentation of an adenovirus-mediated therapeutic effect in vivo.
Online Multi-Target Tracking Using Recurrent Neural Networks (2017)

We present a novel approach to online multi-target tracking based on recurrent neural networks (RNNs). Tracking multiple objects in real-world scenes involves many challenges, including a) an a-priori unknown and time-varying number of targets, b) a continuous state estimation of all present targets, and c) a discrete combinatorial problem of data association. Most previous methods involve complex models that require tedious tuning of parameters. Here, we propose for the first time, an end-to-end learning approach for online multi-target tracking. Existing deep learning methods are not designed for the above challenges and cannot be trivially applied to the task. Our solution addresses all of the above points in a principled way. Experiments on both synthetic and real data show promising results obtained at ~300 Hz on a standard CPU, and pave the way towards future research in this direction.
Isolation and nucleotide sequence of the gene encoding human rhodopsin. (1984)

We have isolated and completely sequenced the gene encoding human rhodopsin. The coding region of the human rhodopsin gene is interrupted by four introns, which are located at positions analogous to those found in the previously characterized bovine rhodopsin gene. The amino acid sequence of human rhodopsin, deduced from the nucleotide sequence of its gene, is 348 residues long and is 93.4% homologous to that of bovine rhodopsin. Interestingly, those portions of the polypeptide chain predicted to form loops on the cytoplasmic face of rhodopsin are perfectly conserved between the human and bovine proteins.
ESLpred: SVM-based method for subcellular localization of eukaryotic proteins using dipeptide composition and PSI-BLAST (2004)

Automated prediction of subcellular localization of proteins is an important step in the functional annotation of genomes. The existing subcellular localization prediction methods are based on either amino acid composition or N-terminal characteristics of the proteins. In this paper, support vector machine (SVM) has been used to predict the subcellular location of eukaryotic proteins from their different features such as amino acid composition, dipeptide composition and physico-chemical properties. The SVM module based on dipeptide composition performed better than the SVM modules based on amino acid composition or physico-chemical properties. In addition, PSI-BLAST was also used to search the query sequence against the dataset of proteins (experimentally annotated proteins) to predict its subcellular location. In order to improve the prediction accuracy, we developed a hybrid module using all features of a protein, which consisted of an input vector of 458 dimensions (400 dipeptide compositions, 33 properties, 20 amino acid compositions of the protein and 5 from PSI-BLAST output). Using this hybrid approach, the prediction accuracies of nuclear, cytoplasmic, mitochondrial and extracellular proteins reached 95.3, 85.2, 68.2 and 88.9%, respectively. The overall prediction accuracy of SVM modules based on amino acid composition, physico-chemical properties, dipeptide composition and the hybrid approach was 78.1, 77.8, 82.9 and 88.0%, respectively. The accuracy of all the modules was evaluated using a 5-fold cross-validation technique. Assigning a reliability index (reliability index > or =3), 73.5% of prediction can be made with an accuracy of 96.4%. Based on the above approach, an online web server ESLpred was developed, which is available at http://www.imtech.res.in/raghava/eslpred/.
Molecular pathways in cancer-related inflammation (2011)

Accumulating evidence shows that chronic inflammation is associated to increased risk of cancer. An inflammatory component is present also in the microenvironment of tumours epidemiologically unrelated to inflammation. Extensive investigations over the past decade have uncovered many of the important mechanistic pathways underlying cancer-related inflammation. Pathways linking inflammation and cancer have been identified: an intrinsic one (driven by genetic events that cause neoplasia) and an extrinsic one (driven by inflammatory conditions which predispose to cancer). Smouldering inflammation is a component of the tumour microenvironment and is a recognized hallmark of cancer. Key orchestrators at the intersection of the intrinsic and extrinsic pathways include transcription factors (e.g. Nuclear Factor kappa-B, NFKB) that modulate the inflammatory response through soluble mediators (cytokines, chemokines) and cellular components (e.g. tumor-associated macrophages), promoting tumorigenesis. NFKB aids in the proliferation and survival of malignant cells, promotes angiogenesis and metastasis, subverts adaptive immunity, and alters responses to hormones and chemotherapeutic agents. Emerging evidence also suggests that persistent inflammation promotes genetic instability. Thus, cancer-related inflammation represents a target for innovative diagnostic and therapeutic strategies.
Induction of Human Immunodeficiency Virus (HIV)-Specific CD8 T-Cell Responses byListeria monocytogenesand a HyperattenuatedListeriaStrain Engineered To Express HIV Antigens (2000)

Induction of cell-mediated immunity may be essential for an effective AIDS vaccine. Listeria monocytogenes is an attractive bacterial vector to elicit T-cell immunity to human immunodeficiency virus (HIV) because it specifically infects monocytes, key antigen-presenting cells, and because natural infection originates at the mucosa. Immunization with recombinant L. monocytogenes has been shown to protect mice from lymphocytic choriomeningitis virus, influenza virus, and tumor inoculation. L. monocytogenes expressing HIV gag elicits sustained high levels of Gag-specific cytotoxic T lymphocytes (CTLs) in mice. We have examined the ability of Listeria to infect human monocytes and present HIV antigens to CD8 T lymphocytes of HIV-infected donors to induce a secondary T-cell immune response. Using this in vitro vaccination protocol, we show that L. monocytogenes expressing the HIV-1 gag gene efficiently provides a strong stimulus for Gag-specific CTLs in HIV-infected donor peripheral blood mononuclear cells. Listeria expressing Nef also elicits a secondary in vitro anti-Nef CTL response. Since L. monocytogenes is a pathogen, before it can be seriously considered as a human vaccine vector, safety concerns must be addressed. We therefore have produced a highly attenuated strain of L. monocytogenes that requires D-alanine for viability. The recombinant bacteria are attenuated at least 10(5)-fold. We show that when these hyperattenuated bacteria are engineered to express HIV-1 Gag, they are at least as efficient at stimulating Gag-specific human CTLs in vitro as wild-type recombinants. These results suggest that attenuated Listeria is an attractive candidate vaccine vector to induce T-cell immunity to HIV in humans.
ChemOS: Orchestrating autonomous experimentation (2018)

ChemOS aims to catalyze the expansion of autonomous laboratories and to disrupt the conventional approach to experimentation.
A biocompatible inverse electron demand Diels–Alder reaction of aldehyde and tetrazine promoted by proline (2016)

A biocompatible inverse electron demand Diels–Alder reaction of aldehyde and tetrazine mediated by <sc>l</sc>-proline is disclosed, with apparent <italic>k</italic><sub>2</sub> up to 13.8 M<sup>−1</sup> s<sup>−1</sup>.
Interception of the radicals produced in electrophilic fluorination with radical traps (Tempo, Dmpo) studied by electrospray ionization mass spectrometry (2006)

The interaction of the nitroxide radical traps (Tempo and Dmpo) and radicals produced in the electrophilic fluorination of olefins (styrene and alpha-methylstyrene) and Selectfluor (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octanebis(tetrafluoroborate) (F-TEDA-BF(4)) (1)) was investigated by electrospray ionization mass spectrometry (ESI-MS). Tempo succeeded in intercepting the radical cationic intermediates and the radical adduct ions were detected at m/z 260 (for styrene) and m/z 274 (for alpha-methylstyrene). Dmpo could also intercept the fluorine radical and radical adduct ions were detected at m/z 131, 132 and 152. The interception of the radical cationic intermediates and fluorine radical is good evidence for the presence of a single-electron transfer mechanism in the electrophilic fluorination.
Revised mechanism of complement lectin-pathway activation revealing the role of serine protease MASP-1 as the exclusive activator of MASP-2 (2012)

The lectin pathway of complement activation is an important component of the innate immune defense. The initiation complexes of the lectin pathway consist of a recognition molecule and associated serine proteases. Until now the autoactivating mannose-binding lectin-associated serine protease (MASP)-2 has been considered the autonomous initiator of the proteolytic cascade. The role of the much more abundant MASP-1 protease was controversial. Using unique, monospecific inhibitors against MASP-1 and MASP-2, we corrected the mechanism of lectin-pathway activation. In normal human serum, MASP-2 activation strictly depends on MASP-1. MASP-1 activates MASP-2 and, moreover, inhibition of MASP-1 prevents autoactivation of MASP-2. Furthermore we demonstrated that MASP-1 produces 60% of C2a responsible for C3 convertase formation.
USGS Optimistic on World Oil Prospects (2000)

According to the latest estimates by the U.S. Geological Survey, the world has 20% more oil awaiting discovery in yet-to-be-found fields than the USGS estimated 6 years ago. And a newly analyzed category--oil lurking in and around known fields--offers almost as much additional oil as in those undiscovered reservoirs. But even if the additional oil is really there, pessimists argue that it pushes back the global production peak--and the end of the era of cheap oil--by years, not decades.