gebhart/patrepeval huggingface dataset:
Flexible Sequence Similarity Searching with the FASTA3 Program Package (2003)

The FASTA3 and FASTA2 packages provide a flexible set of sequence-comparison programs that are particularly valuable because of their accurate statistical estimates and high-quality alignments. Traditionally, sequence similarity searches have sought to ask one question: "Is my query sequence homologous to anything in the database?" Both FASTA and BLAST can provide reliable answers to this question with their statistical estimates; if the expectation value E is < 0.001-0.01 and you are not doing hundreds of searches a day, the answer is probably yes. In general, the most effective search strategies follow these rules: 1. Whenever possible, compare at the amino acid level, rather than the nucleotide level. Search first with protein sequences (blastp, fasta3, and ssearch3), then with translated DNA sequences (fastx, blastx), and only at the DNA level as a last resort (Table 5). 2. Search the smallest database that is likely to contain the sequence of interest (but it must contain many unrelated sequences for accurate statistical estimates). 3. Use sequence statistics, rather than percent identity or percent similarity, as your primary criterion for sequence homology. 4. Check that the statistics are likely to be accurate by looking for the highest-scoring unrelated sequence, using prss3 to confirm the expectation, and searching with shuffled copies of the query sequence [randseq, searches with shuffled sequences should have E approx 1.0]. 5. Consider searches with different gap penalties and other scoring matrices. Searches with long query sequences against full-length sequence libraries will not change dramatically when BLOSUM62 is used instead of BLOSUM50 (20), or a gap penalty of -14/-2 is used in place of -12/-2. However, shallower or more stringent scoring matrices are more effective at uncovering relationships in partial sequences (3,18), and they can be used to sharpen dramatically the scope of the similarity search. However, as illustrated in the last section, the E value is only the first step in characterizing a sequence relationship. Once one has confidence that the sequences are homologous, one should look at the sequence alignments and percent identities, particularly when searching with lower quality sequences. When sequence alignments are very short, the alignment should become more significant when a shallower scoring matrix is used, e.g., BLOSUM62 rather than BLOSUM50 (remember to change the gap penalties). Homology can be reliably inferred from statistically significant similarity. Whereas homology implies common three-dimensional structure, homology need not imply common function. Orthologous sequences usually have similar functions, but paralogous sequences often acquire very different functional roles. Motif databases, such as PROSITE (21), can provide evidence for the conservation of critical functional residues. However, motif identity in the absence of overall sequence similarity is not a reliable indicator of homology.
The Quantum Theory of Optical Coherence (1963)

The concept of coherence which has conventionally been used in optics is found to be inadequate to the needs of recently opened areas of experiment. To provide a fuller discussion of coherence, a succession of correlation functions for the complex field strengths is defined. The $n\mathrm{th}$ order function expresses the correlation of values of the fields at $2n$ different points of space and time. Certain values of these functions are measurable by means of $n$-fold delayed coincidence detection of photons. A fully coherent field is defined as one whose correlation functions satisfy an infinite succession of stated conditions. Various orders of incomplete coherence are distinguished, according to the number of coherence conditions actually satisfied. It is noted that the fields historically described as coherent in optics have only first-order coherence. On the other hand, the existence, in principle, of fields coherent to all orders is shown both in quantum theory and classical theory. The methods used in these discussions apply to fields of arbitrary time dependence. It is shown, as a result, that coherence does not require monochromaticity. Coherent fields can be generated with arbitrary spectra.
Purifications and Properties of Orotidine-phosphorolyzing Enzyme and Purine Nucleoside Phosphorylase from Erwinia carotovora AJ 2992. (1991)

An orotidine-phosphorolyzing enzyme and a purine nucleoside phosphorylase (PNPase) of Erwinia carotovora AJ 2992, which is a potent producer of ribavirin (1-β-D-ribofuranosyl-1, 2, 4-triazole-3-carboxamide), an antiviral agent, from orotidine and 1, 2, 4-triazole-3-carboxamide (TCA), were purified 23-fold and 103-fold, respectively. At each purification step, the orotidine-phosphorolyzing enzyme was always co-purified with an uridine phosphorylase (UPase) and its activity could not be separated from that of the UPase after it showed as a single band on SDS-polyacrylamide gel electrophoresis. These results suggest that this enzyme may be identical with UPase. The purified enzyme had a molecular weight of 68, 000 ± 2, 000, and seemed to be a dimer. The optimal temperatures and pH values were 60°C and 6.0 for orotidine phosphorolysis, and 70°C and 7.0 for uridine phosphorolysis. The Michaelis constants for uridine and orotidine were 0.75 mM and 10.87 mM, respectively, at 40°C. The PNPase of E. carotovora AJ 2992 had a molecular weight of 58, 000 ± 2, 000 and seemed to be a dimer. The Michaelis constants for inosine and guanosine were 1.92 mM and 1.85 mM, respectively, at 40°C. The PNPase was completely inactivated by p-chloromercuribenzoate.
Identification and Structural Elucidation of Lectin-Binding Oligosaccharides by Bioaffinity Matrix-Assisted Laser Desorption/Ionization Fourier Transform Mass Spectrometry (2001)

Cortical granule lectin (CGL) is released by the egg of the South African toad Xenopus laevis upon fertilization. The lectin binds to oligosaccharides in the extracellular matrix of the egg to form a physical block to prevent additional sperm penetration or polyspermy. To identify the oligosaccharides that bind to CGL, the lectin was immobilized on the surface of a matrix-assisted laser desorption/ionization probe. This bioaffinity probe was used to determine oligosaccharides that bind preferentially to CGL. Structural analyses based on collision-induced dissociation was used to determine that oligosaccharides with the sulfate esters at the nonreducing ends preferentially bind to the lectin.
Autophagy in Macrophages: Impacting Inflammation and Bacterial Infection (2014)

Macrophages are on the front line of host defense. They possess an array of germline-encoded pattern recognition receptors/sensors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) and which activate downstream effectors/pathways to help mediate innate immune responses and host defense. Innate immune responses include the rapid induction of transcriptional networks that trigger the production of cytokines, chemokines, and cytotoxic molecules; the mobilization of cells including neutrophils and other leukocytes; the engulfment of pathogens by phagocytosis and their delivery to lysosome for degradation; and the induction of autophagy. Autophagy is a catabolic process that normally maintains cellular homeostasis in a lysosome-dependent manner, but it also functions as a cytoprotective response that intersects with a variety of general stress-response pathways. This review focuses on the intimately linked molecular mechanisms that help govern the autophagic pathway and macrophage innate immune responses.
Oxidative Stress and Gene Transcription in Asthma and Chronic Obstructive Pulmonary Disease: Antioxidant Therapeutic Targets (2002)

Inflammatory lung diseases such as asthma and Chronic Obstructive Pulmonary Disease (COPD) are characterised by systemic and local chronic inflammation and oxidative stress. The sources of the increased oxidative stress in patients with asthma and COPD derive from the increased burden of inhaled oxidants, and from the increased amounts of reactive oxygen species (ROS) generated by several inflammatory, immune and structural cells of the airways. Increased levels of ROS produced in the airways are reflected by increased markers of oxidative stress in the airspaces, sputum, breath, lungs and blood in patients with asthma and COPD. ROS, either directly or via the formation of lipid peroxidation products such as acrolein, 4-hydroxy-2-nonenal and F(2)-isoprostanes, may play a role in enhancing the inflammation through the activation of stress kinases (JNK, MAPK, p38, phosphoinositide 3 (PI-3)-kinase/PI-3K-activated serine-threonine kinase Akt) and redox sensitive transcription factors such as NF-kappaB and AP-1. Recent data have also indicated that oxidative stress and pro-inflammatory mediators can alter nuclear histone acetylation/deacetylation allowing access for transcription factor DNA binding leading to enhanced pro-inflammatory gene expression in various lung cells. Furthermore, oxidative stress may alter the balance between gene expression of pro-inflammatory mediators and antioxidant enzymes in favor of inflammatory mediators in the lung. Thus, the presence of oxidative stress may have important consequences for the pathogenesis of asthma and COPD. Identification of genes that predispose to the development of asthma and COPD may identify novel therapeutic targets. Future work is directed to understand the molecular mechanisms of antioxidants on ROS-mediated cell signaling pathways and inhibition of inflammatory response that would provide information for the development of novel antioxidant therapeutic targets in asthma and COPD. Effective wide spectrum antioxidant therapy that has good bioavailability and potency is urgently needed to control the localised oxidative and inflammatory processes that occur in the pathogenesis of asthma and COPD. In addition, development of such novel antioxidant compounds would be therapeutically useful in monitoring the oxidative and inflammatory biomarkers in the progression/severity of asthma and COPD.
Gateways to clinical trials (2009)

(-)-Gossypol; Abacavir sulfate/lamivudine, ACAM-1000, ACE-011, Agomelatine, AGS-004, Alemtuzumab, Alvocidib hydrochloride, AMG-317, Amlodipine, Aripiprazole, Atazanavir sulfate, Azacitidine; Becatecarin, Belinostat, Bevacizumab, BMS-387032, BMS-690514, Bortezomib; Casopitant mesylate, Cetuximab, Choline fenofibrate, CK-1827452, Clofarabine, Conivaptan hydrochloride; Dabigatran etexilate, DADMe-Immucillin-H, Darbepoetin alfa, Darunavir, Dasatinib, DC-WT1, Decitabine, Deferasirox, Degarelix acetate, Denenicokin, Denosumab, Dienogest, Duloxetine hydrochloride; Ecogramostim, Eculizumab, Edoxaban tosilate, Elacytarabine, Elesclomol, Eltrombopag olamine, Enfuvirtide, Enzastaurin hydrochloride, Eribulin mesilate, Erlotinib hydrochloride, Escitalopram oxalate, Eszopiclone, Etravirine; Flibanserin, Fludarabine, Fondaparinux sodium, Fosamprenavir calcium; Gefitinib, Genistein; I-131-L19-SIP, Idrabiotaparinux sodium, Imatinib mesylate, IMGN-901, Ipilimumab; Laromustine, Lenalidomide, Liposomal cisplatin, Liraglutide, Lisdexamfetamine mesilate, Lopinavir, Lopinavir/ritonavir; Maraviroc, MDV-3100, Mecasermin rinfabate, MP-470, Mycophenolic acid sodium salt; Naproxcinod, NB-002, Nesiritide, Nilotinib hydrochloride monohydrate, NK-012; Palonosetron hydrochloride, Panobinostat, Pegfilgrastim, Peginterferon alfa-2a, Pitavastatin calcium, PL-3994, Plerixafor hydrochloride, Plitidepsin, PM-10450; Raltegravir potassium, Recombinant human soluble thrombomodulin, ReoT3D, RHAMM R3 peptide, Rivaroxaban, Romiplostim, Rosuvastatin calcium, Rozrolimupab; Sabarubicin hydrochloride, Salinosporamide A, Sirolimus-eluting stent, Smallpox (Vaccinia) Vaccine, Live, Sorafenib; Tenofovir disoproxil fumarate, Tenofovir disoproxil fumarate/emtricitabine, Teriparatide, Tipifarnib, Tipranavir, Trabectedin, Trifluridine/TPI; Vardenafil hydrochloride hydrate, Vinflunine, Volociximab, Vorinostat; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan; Ziprasidone hydrochloride, Zoledronic acid monohydrate.
DESATURATION AND RELATED MODIFICATIONS OF FATTY ACIDS (1998)

Desaturation of a fatty acid first involves the enzymatic removal of a hydrogen from a methylene group in an acyl chain, a highly energy-demanding step that requires an activated oxygen intermediate. Two types of desaturases have been identified, one soluble and the other membrane-bound, that have different consensus motifs. Database searching for these motifs reveals that these enzymes belong to two distinct multifunctional classes, each of which includes desaturases, hydroxylases, and epoxidases that act on fatty acids or other substrates. The soluble class has a consensus motif consisting of carboxylates and histidines that coordinate an active site diiron cluster. The integral membrane class contains a different consensus motif composed of histidines. Biochemical and structural similarities between the integral membrane enzymes suggest that this class also uses a diiron cluster for catalysis. Soluble and membrane enzymes have been successfully re-engineered for substrate specificity and reaction outcome. It is anticipated that rational design of these enzymes will result in new and desired activities that may form the basis for improved oil crops.
Neuropathological Classification of Huntingtonʼs Disease (1985)

In postmortem brain specimens from 163 clinically diagnosed cases of Huntington's disease (HD) the striatum exhibited marked variation in the severity of neuropathological involvement. A system for grading this severity was established by macroscopic and microscopic criteria, resulting in five grades (0-4) designated in ascending order of severity. The grade correlates closely with the extent of clinical disability as assessed by a rating scale. In five cases of clinically diagnosed HD there were no discernible neuropathological abnormalities (grade 0), suggesting that the anatomical changes lag behind the development of clinical abnormalities. In eight cases, neuropathological changes could only be recognized microscopically (grade 1). The earliest changes were seen in the medial paraventricular portions of the caudate nucleus (CN), in the tail of the CN, and in the dorsal part of the putamen. Counts of neurons in the CN reveal that 50% are lost in grade 1 and that 95% are lost in grade 4; astrocytes are greatly increased in grades 2-4. These studies indicate that analyses of the CN in grade 4 would reflect mainly its astrocytic composition with a component of remote neurons projecting to the striatum. Because of the relative preservation of the lateral half of the head of the CN in grades 1-2, these regions would reflect early cellular and biochemical changes in HD.
Diagnosis and treatment of uncomplicated acute bacterial rhinosinusitis: Summary of the Agency for Health Care Policy and Research evidence‐based report (2000)

The current literature shows that treatment of uncomplicated ABR with amoxicillin or folate inhibitors and based on clinical criteria is the most cost-effective strategy.
Increased Expression of Death Receptors 4 and 5 Synergizes the Apoptosis Response to Combined Treatment with Etoposide and TRAIL (2000)

Chemotherapeutic genotoxins induce apoptosis in epithelial-cell-derived cancer cells. The death receptor ligand TRAIL also induces apoptosis in epithelial-cell-derived cancer cells but generally fails to induce apoptosis in nontransformed cells. We show here that the treatment of four different epithelial cell lines with the topoisomerase II inhibitor etoposide in combination with TRAIL (tumor necrosis factor [TNF]-related apoptosis-inducing ligand) induces a synergistic apoptotic response. The mechanism of the synergistic effect results from the etoposide-mediated increase in the expression of the death receptors 4 (DR4) and 5 (DR5). Inhibition of NF-kappaB activation by expression of kinase-inactive MEK kinase 1(MEKK1) or dominant-negative IkappaB (DeltaIkappaB) blocked the increase in DR4 and DR5 expression following etoposide treatment. Addition of a soluble decoy DR4 fusion protein (DR4:Fc) to cell cultures reduced the amount of etoposide-induced apoptosis in a dose-dependent manner. The addition of a soluble TNF decoy receptor (TNFR:Fc) was without effect, demonstrating the specificity of DR4 binding ligands in the etoposide-induced apoptosis response. Thus, genotoxin treatment in combination with TRAIL is an effective inducer of epithelial-cell-derived tumor cell apoptosis relative to either treatment alone.
The C fibre reflex of the cat urinary bladder (1998)

1. Reflexes evoked in bladder parasympathetic neurones by electrical stimulation of bladder C afferent fibres were studied in cats anaesthetized with alpha-chloralose. The responses were compared with the ordinary micturition reflex evoked by low-threshold Adelta afferents from bladder mechanoreceptors and mediated by a spino-ponto-spinal reflex pathway. 2. The bladder was catheterized for fluid instillations and pressure recordings. Efferent reflex discharges were recorded from the cut central end of a small distal bladder branch of the pelvic nerve. The remaining bladder pelvic nerve branches were stimulated electrically close to the bladder. 3. Stimulation at C afferent intensity evoked a late reflex discharge in bladder pelvic efferents in all animals. The response was centrally mediated, had a latency of 150-250 ms, and was much weaker after stimulation on the contralateral nerve. 4. The bladder C fibre reflex differed in several functional aspects from the ordinary Adelta micturition reflex. It could be evoked at a low rate of stimulation, with an empty bladder and no background activity from bladder mechanoreceptors. In this situation, the normal Adelta micturition reflex is not elicited. The C fibre reflex also survived an acute spinalization at a low thoracic level. 5. The C fibre reflex was strongly inhibited by dorsal clitoris or dorsal penis nerve stimulation, an effect that was maintained after spinalization. It was facilitated by bladder or urethra exposure to cold and menthol, stimuli that activate specific cold-sensitive receptors associated with unmyelinated C afferents. 6. It is concluded that the central pathway of the C fibre reflex is spinal and partly separate from that of the ordinary micturition reflex. These observations are in keeping with the clinical finding that a bladder cooling reflex can be elicited in patients with disturbed descending control of the bladder.
Using Paxos to Build a Scalable, Consistent, and Highly Available Datastore (2011)

Spinnaker is an experimental datastore that is designed to run on a large cluster of commodity servers in a single datacenter. It features key-based range partitioning, 3-way replication, and a transactional get-put API with the option to choose either strong or timeline consistency on reads. This paper describes Spinnaker's Paxos-based replication protocol. The use of Paxos ensures that a data partition in Spinnaker will be available for reads and writes as long a majority of its replicas are alive. Unlike traditional master-slave replication, this is true regardless of the failure sequence that occurs. We show that Paxos replication can be competitive with alternatives that provide weaker consistency guarantees. Compared to an eventually consistent datastore, we show that Spinnaker can be as fast or even faster on reads and only 5% to 10% slower on writes.
Continuous location and direction estimation with multiple sensors using particle filtering (2006)

In this paper we discuss the use of particle filtering to estimate the values of several state variables describing a user's context. Since particle filtering algorithms are computationally efficient realizations of Bayesian filters they perform exceptionally well to optimally combine the a priori knowledge stemming from behavioral models, such as movement models, and the noisy measurements from sensors. The estimate at each time step is obtained in the form of a probability density function that represents the entire information and quantifies the inherent uncertainty about the context. The concept has been realized in simulations and experiments. In this paper, the applied movement model is presented with simulated measurements from GPS and compass sensors to illustrate the concept
Dynamic changes in gene expression during human early embryo development: from fundamental aspects to clinical applications (2010)

Omics analysis provides tools for understanding the molecular mechanisms and signaling pathways controlling early embryonic development. Furthermore, we discuss the clinical relevance of using a non-invasive molecular approach to embryo selection for the single-embryo transfer program.
Recombinant Escherichia coli engineered for production of L-lactic acid from hexose and pentose sugars (2001)

Recombinant Escherichia coli have been constructed for the conversion of glucose as well as pentose sugars into L-lactic acid. The strains carry the lactate dehydrogenase gene from Streptococcus bovis on a low copy number plasmid for production of L-lactate. Three E. coli strains were transformed with the plasmid for producing L-lactic acid. Strains FBR9 and FBR11 were serially transferred 10 times in anaerobic cultures in sugar-limited medium containing glucose or xylose without selective antibiotic. An average of 96% of both FBR9 and FBR11 cells maintained pVALDH1 in anaerobic cultures. The fermentation performances of FBR9, FBR10, and FBR11 were compared in pH-controlled batch fermentations with medium containing 10% w/v glucose. Fermentation results were superior for FBR11, an E. coli B strain, compared to those observed for FBR9 or FBR10. FBR11 exhausted the glucose within 30 h, and the maximum lactic acid concentration (7.32% w/v) was 93% of the theoretical maximum. The other side-products detected were cell mass and succinic acid (0.5 g/l).
Infrared sensor arrays with 3-12 mu m cutoff wavelengths in heteroepitaxial narrow-gap semiconductors on silicon substrates (1991)

The authors describe heteroepitaxy of IV-VI lead chalcogenide narrow-gap semiconductor (NGS) as well as II-VI materials (CdTe) on Si substrates. Epitaxy is achieved by using stacked intermediate CaF/sub 2/-BaF/sub 2/ bilayers to overcome the large lattice and thermal expansion mismatch. The authors use lead chalcogenides (PbS, PbTe, Pb/sub 1-x/Eu/sub x/Se, and Pb/sub 1-x/Sn/sub x/Se) rather than Hg/sub 1-x/Cd/sub x/Te (MCT) as IR-sensitive NGS material because growth and fabrication techniques are much easier and compositional homogeneity much less critical with lead salts, while maximum sensitivities are comparable to those of MCT. The high permittivity of lead salts yields much more fault-tolerant devices due to the effective shielding of charges resulting from defects. The authors have fabricated linear sensor arrays on Si substrates with cutoff wavelengths ranging from 3 to above 12 mu m. The sensitivities of the best PbTe on Si sensors (cutoff 5.5 mu m) are already comparable to those of MCT with the same cutoff wavelengths, while those of the first Pb/sub 1-x/Sn/sub x/Se devices are a factor of 2-5 below. Although many fabrication steps are rather crude and far from being optimized, this considerable improvement is easily possible.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A Study of Cryptosporidium parvum Genotypes and Population Structure (1998)

Genetic evidence for the occurrence of two Cryptosporidium parvum subgroups is presented. This evidence is based on restriction fragment length polymorphism analysis of several independent loci. Sequence analysis of the beta-tubulin intron revealed additional polymorphism. The stability of the genetic profiles following passage of C. parvum isolates between different hosts was investigated.