gebhart/patrepeval huggingface dataset:
RelE toxins from Bacteria and Archaea cleave mRNAs on translating ribosomes, which are rescued by tmRNA (2003)

RelE of Escherichia coli is a global inhibitor of translation that is activated by nutritional stress. Activation of RelE depends on Lon-mediated degradation of RelB, the antagonist that neutralizes RelE. In vitro, RelE cleaves synthetic mRNAs positioned at the ribosomal A-site. We show here that in vivo overexpression of RelE confers cleavage of mRNA and tmRNA in their coding regions. RelE-mediated cleavage depended on translation of the RNAs and occurred at both sense and stop codons. RelE cleavage of mRNA and tmRNA was also induced by amino acid starvation. An ssrA deletion strain was hypersensitive to RelE, whereas overproduction of tmRNA counteracted RelE toxicity. After neutralization of RelE by RelB, rapid recovery of translation required tmRNA, indicating that tmRNA alleviated RelE toxicity by rescuing ribosomes stalled on damaged mRNAs. RelE proteins from Gram-positive Bacteria and Archaea cleaved tmRNA with a pattern similar to that of E. coli RelE, suggesting that the function and target of RelE may be conserved across the prokaryotic domains.
ISSLS Prize Winner: A Study of Diffusion in Human Lumbar Discs: A Serial Magnetic Resonance Imaging Study Documenting the Influence of the Endplate on Diffusion in Normal and Degenerate Discs (2004)

Serial postcontrast magnetic resonance imaging studies offer a reliable method of assessing the diffusion of the discs and the functional status of the endplate cartilage. Endplate cartilage damage increases with age and produces considerable changes in diffusion. The present study has described reliable signs by which these damages can be identified in vivo. Aging and degeneration have been shown to be two separate processes by documenting clear-cut differences in diffusion. The present data encourage use of diffusion studies as a noninvasive method to assess the physiologic status of the disc and endplate and to study the effect of drugs, smoking, mechanical loading, exercises, etc. on the physiology of the disc.
Higher expression of human kallikrein 10 in breast cancer tissue predicts tamoxifen resistance (2002)

The human tissue kallikreins are secreted serine proteases, encoded by a group of homologous genes clustered in tandem on chromosome 19q13.3-4. Human kallikrein 6 and human kallikrein 10 are two new members of this family. Recently, we developed highly sensitive and specific immunofluorometric assays for human kallikrein 6 and human kallikrein 10, which allow for their quantification in tissue extracts and biological fluids. Both human kallikrein 6 and human kallikrein 10 are found to be down-regulated in breast cancer cell lines, suggesting that they may be involved in breast cancer pathogenesis and progression. In this study, we investigated the potential value of human kallikrein 6 and human kallikrein 10 as prognostic and predictive factors in breast cancer. We quantified human kallikrein 6 and human kallikrein 10 protein levels in 749 breast tumour cytosolic extracts and correlated this data with various clinicopathological variables and patient outcomes. Human kallikrein 6 and human kallikrein 10 are positively correlated with each other. Higher human kallikrein 6 and human kallikrein 10 protein levels are associated with younger age, pre-menopausal, status and tumours which are negative for oestrogen and progesterone receptors. No correlation was found between human kallikrein 6 and human kallikrein 10 levels and tumour size, grade, and nodal status. Survival analysis showed that neither human kallikrein 6 nor human kallikrein 10 are related to the rate of relapse-free and overall survival. In the analysis with respect to response to tamoxifen therapy, although human kallikrein 6 levels were not associated with tamoxifen responsiveness, higher levels of human kallikrein 10 were significantly associated with a poor response rate. This association remained significant in the multivariate analysis. Furthermore, higher human kallikrein 10 levels were significantly related with a short progression-free and post-relapse overall survival after start of tamoxifen treatment for advanced disease. Taken together, our results suggest that although human kallikrein 6 and human kallikrein 10 are not prognostic markers for breast cancer, human kallikrein 10 is an independent predictive marker for response of tamoxifen therapy.
Allergen- and bacterial antigen-specific T-cell clones established from atopic donors show a different profile of cytokine production. (1991)

We have established a large panel of T-cell clones (TCCs) specific for Dermatophagoides pteronyssinus and Lolium perenne group I grass pollen allergens (total, 61) and for tetanus toxoid and protein purified derivative bacterial antigens (total, 38) from the peripheral blood of two atopic individuals and then analyzed their ability to produce interleukin 4 (IL-4), IL-5, and interferon gamma (IFN-gamma). Upon stimulation with phorbol 12-myristate 13-acetate plus anti-CD3 antibody, the great majority of TCCs specific for bacterial components was able to produce both IL-4 and IFN-gamma, whereas most D. pteronyssinus- and L. perenne group I-specific TCCs produced IL-4, but no, or limited, IFN-gamma. Moreover, the mean amounts of IL-4 and IFN-gamma released by allergen-specific TCCs were significantly higher and lower, respectively, than the mean amounts produced by TCCs specific for bacterial components. Under the same experimental conditions, virtually all allergen-specific TCCs, but only one-third of tested TCCs specific for bacterial components, expressed IL-5 RNA and secreted IL-5 in their supernatants. Eighteen TCCs (nine specific for allergens and nine specific for bacterial components) were also assessed for their ability to induce IgE synthesis by autologous B cells in response to stimulation with the specific antigen. Under these experimental conditions, all allergen-specific TCCs, but only one-third of TCCs specific for bacterial components that produced IL-4 but no, or little, IFN-gamma induced the synthesis of detectable amounts of IgE. The demonstration that most allergen-specific helper T cells in atopic individuals are able to produce high amounts of IL-4 (and IL-5), but no IFN-gamma, may explain why allergens induce production of IgE antibodies and increase eosinophils.
Molecular targets for autoimmune and genetic disorders of neuromuscular transmission (2000)

The neuromuscular junction is the target of a variety of autoimmune, neurotoxic and genetic disorders, most of which result in muscle weakness. Most of the diseases, and many neurotoxins, target the ion channels that are essential for neuromuscular transmission. Myasthenia gravis is an acquired autoimmune disease caused in the majority of patients by antibodies to the acetylcholine receptor, a ligand-gated ion channel. The antibodies lead to loss of acetylcholine receptor, reduced efficiency of neuromuscular transmission and muscle weakness and fatigue. Placental transfer of these antibodies in women with myasthenia can cause fetal or neonatal weakness and occasionally severe deformities. Lambert Eaton myasthenic syndrome and acquired neuromyotonia are caused by antibodies to voltage-gated calcium or potassium channels, respectively. In the rare acquired neuromyotonia, reduced repolarization of the nerve terminal leads to spontaneous and repetitive muscle activity. In each of these disorders, the antibodies are detected by immunoprecipitation of the relevant ion channel labelled with radioactive neurotoxins. Genetic disorders of neuromuscular transmission are due mainly to mutations in the genes for the acetylcholine receptor. These conditions show recessive or dominant inheritance and result in either loss of receptors or altered kinetics of acetylcholine receptor channel properties. Study of these conditions has greatly increased our understanding of synaptic function and of disease aetiology.
Material-related fundamentals of cutting techniques for GaAs wafer manufacturing (2005)

Abstract Driven by the requirement of high cutting efficiency and improvement of wafer flatness, wire sawing of GaAs single crystals under brittle material removal conditions has been studied. Crack nucleation and crack propagation were investigated by indentation and scratching tests on polished {100}-oriented semi-insulating GaAs wafers. Based on these results a concept has been developed that allows to control the force balance in the cutting slits so that the deflection of the wires perpendicular to the cutting planes is minimal resulting in cuts of high flatness. The concept has been successfully introduced in mass production of GaAs wafers.
Discriminative models for spoken language understanding (2006)

This paper studies several discriminative models for spoken language understanding (SLU). While all of them fall into the conditional model framework, different optimization criteria lead to conditional random fields, perceptron, minimum classification error and large margin models. The paper discusses the relationship amongst these models and compares them in terms of accuracy, training speed and robustness.
A convenient approach to synthesizing peptide C‐terminal N‐alkyl amides (2011)

Peptide C-terminal N-alkyl amides have gained more attention over the past decade due to their biological properties, including improved pharmacokinetic and pharmacodynamic profiles. However, the synthesis of this type of peptide on solid phase by current available methods can be challenging. Here we report a convenient method to synthesize peptide C-terminal N-alkyl amides using the well-known Fukuyama N-alkylation reaction on a standard resin commonly used for the synthesis of peptide C-terminal primary amides, the peptide amide linker-polyethylene glycol-polystyrene (PAL-PEG-PS) resin. The alkylation and oNBS deprotection were conducted under basic conditions and were therefore compatible with this acid labile resin. The alkylation reaction was very efficient on this resin with a number of different alkyl iodides or bromides, and the synthesis of model enkephalin N-alkyl amide analogs using this method gave consistently high yields and purities, demonstrating the applicability of this methodology. The synthesis of N-alkyl amides was more difficult on a Rink amide resin, especially the coupling of the first amino acid to the N-alkyl amine, resulting in lower yields for loading the first amino acid onto the resin. This method can be widely applied in the synthesis of peptide N-alkyl amides.
Human gliomas and epileptic foci express high levels of a mRNA related to rat testicular sulfated glycoprotein 2, a purported marker of cell death. (1991)

Clone pTB16 has been isolated by differential screening of a human glioma cDNA library. Northern blot analysis has shown that pTB16 expression is several times (greater than 11-fold) higher in gliomas than in a primitive neuroectodermal tumor. This observation was supported by in situ hybridization and extended to nine other gliomas. Expression was virtually absent in adenocarcinoma cells metastasized to brain. Malignant gliomas showed stronger hybridization than benign gliomas, while blood capillaries did not show hybridization. pTB16 mRNA was also shown to be expressed in established glioma cell lines and at high levels in epileptic foci, indicating that expression of the gene may be limited to certain cell types and that its upregulation is not merely a consequence of cellular proliferation. Nucleotide sequence analysis identified pTB16 as the human counterpart for rat testicular sulfated glycoprotein 2 (SGP-2), whose function in the reproductive system remains unknown. Although SGP-2 transcripts, and hence pTB16, were recently shown to be increased in neurodegenerative diseases such as scrapie in hamsters and Alzheimer disease in humans, our observations with brain tumors and epilepsy are suggestive of a role for pTB16 in neuropathologies in general and support the hypothesis of its involvement in tissue remodeling and cell death.
Data structures : from arrays to priority queues (1985)

Part I: Mainstream algorithms and timing analysis. The array structure. List processing. Stacks. Queues. General lists: multiple access paths to data. Recursion. Binary trees. Graph algorithms. Part II: Expansions and applications. References. Index.
Temporal dynamics of PARK2/parkin and OPTN/optineurin recruitment during the mitophagy of damaged mitochondria (2015)

Damaged mitochondria are selectively degraded via autophagy in a regulated pathway known as mitophagy. Parkinson disease-linked proteins PINK1 (PTEN induced putative kinase 1) and PARK2 (parkin RBR E3 ubiquitin protein ligase) are recruited to the outer mitochondrial membrane upon mitochondrial damage, leading to the PARK2-mediated ubiquitination of mitochondrial proteins. Here, we discuss our recent work demonstrating that OPTN (optineurin) is recruited to damaged mitochondria, serving as an autophagy receptor for autophagosome formation around mitochondria. Using high-resolution live-cell imaging, we find that OPTN is recruited to ubiquitinated mitochondria downstream of PARK2, and induces autophagosome assembly around mitochondria via its LC3-interacting region. Mutations in OPTN are linked to both glaucoma and ALS (amyotrophic lateral sclerosis), and an ALS-associated E478G mutation in OPTN's ubiquitin binding domain leads to defective mitophagy and accumulation of damaged mitochondria. Importantly, our results highlight a role for mitophagy defects in ALS pathogenesis, and demonstrate that defects in the same pathway for mitochondrial homeostasis are causal for both familial Parkinson disease and ALS.
Perturbation study via rotational-resolved spectrum in the triplet band d(3)Delta-a(3)II (2,1) of CO (2005)

The triplet band d(3)Delta - a(3)Pi (2, 1) of the CO molecule in the near infrared region of 12350-12850cm(-1) has been observed and analysed by taking into account the perturbation interaction between the d(3)Delta(v= 2) and a(3)Pi (v= 9) states. The most perturbed lines and most precise perturbation parameters, alpha(2) and beta(2), and electronic perturbation constants, xi(e) and eta(e), for the d(3)Delta (v= 2) and a(3)Pi (v= 9) states have been obtained.
Zinc Content and Function in Human Fibroblast Collagenase (1995)

The zinc contents of samples of human fibroblast collagenase (HFC) purified by different procedures and of samples purified by the same procedure but prepared for analysis by different dialysis protocols have been determined by atomic absorption spectroscopy. Both the purification method and dialysis conditions affect the zinc stoichiometry. Samples purified with and without the use of a zinc-chelate chromatography step and prepared by dialysis against 1 mM CaCl2 had zinc to enzyme ratios of 1.46 and 1.22, respectively. When the first sample was prepared by dialysis against 0 and 10 mM CaCl2, the values changed to 0.15 and 1.94, respectively. Thus, the zinc content of HFC is critically dependent upon the dialysis conditions used to free the enzyme from adventitious metals. This could account for the disparate reports in the literature that give zinc stoichiometries for members of the matrix metalloproteinase (MMP) family of between 1 and 2. The mechanism of inhibition of the one zinc form of HFC by 1,10-phenanthroline (OP) and 4-(2-pyridylazo)resorcinol has been studied in detail. Inhibition by both chelating agents is time dependent and biphasic. There is an initial, instantaneous inhibition characterized by the involvement of a single inhibitor molecule that corresponds to the formation of a ternary complex between the zinc atom, enzyme, and chelator. This is followed by a second, slower phase involving removal of the zinc atom from the enzyme and its chelation by two molecules of inhibitor. Inhibition of four other human MMPs by OP shows similar characteristics and is thought to occur by the same mechanism.
Monitoring disease activity in multiple sclerosis using serum neurofilament light protein (2017)

Serum and CSF NFL levels were highly correlated, indicating that blood sampling can replace CSF taps for this particular marker. Disease activity and DMT had similar effects on serum and CSF NFL concentrations. Repeated NFL determinations in peripheral blood for detecting axonal damage may represent new possibilities in MS monitoring.
The deuterium isotope effect for the α-hydroxylation of tamoxifen by rat liver microsomes accounts for the reduced genotoxicity of [D5-ethyl]tamoxifen (1995)

This study describes the application of on line HPLC-electrospray ionization MS in the structural determination of the metabolites formed following incubation with rat liver microsomes of an equimolar mixture of the anticancer drug tamoxifen and its [D5-ethyl]-analogue. The ratio of ca 3:1 between unlabelled and D4-labelled alpha-hydroxytamoxifen, indicating a large isotope effect for this metabolic process, accounted for the previously observed lower yield of DNA adducts formed in the livers of rats treated with D5-tamoxifen compared with unlabelled drug. The loss of one deuterium atom on metabolism discriminated hydroxyethylated metabolites from others and enabled two further such metabolites to be detected, namely alpha-hydroxytamoxifen N-oxide and alpha-hydroxy-N-desmethyltamoxifen of which the latter is novel. Furthermore, the use of [alpha-D2-ethyl]- and [beta-D3-ethyl] tamoxifens discriminated alpha- from beta-hydroxylated metabolites and proved that the metabolites described here were alpha-hydroxylated. In contrast to the alpha-hydroxylated metabolites, the other metabolites identified, namely tamoxifen N-oxide, N-desmethyltamoxifen, 4-hydroxytamoxifen and their deuterated counterparts were not depleted in the deuterated components. The use of on line HPLC-electrospray ionization MS combined with isotopic labelling is a powerful technique for probing the structures of metabolites, and, applied to tamoxifen, has provided further evidence that alpha-hydroxylation is an important pathway for the conversion of the drug into a DNA-reactive metabolite.
High-performance capillary electrophoresis of meat, dairy, and cereal proteins (2001)

Food proteins play important roles in food functionality, nutrition, and human health. For these reasons, new analytical methods are continually being developed to separate and characterize these important proteins. High-performance capillary electrophoresis (HPCE) is one of the latest analytical methods to be applied to the separation of food proteins. This review covers methods and applications for the separation of three major groups of food proteins, meat, dairy, and cereal proteins.
Evolution of the Friedreich’s ataxia trinucleotide repeat expansion: Founder effect and premutations (1997)

Friedreich's ataxia, the most frequent inherited ataxia, is caused, in the vast majority of cases, by large GAA repeat expansions in the first intron of the frataxin gene. The normal sequence corresponds to a moderately polymorphic trinucleotide repeat with bimodal size distribution. Small normal alleles have approximately eight to nine repeats whereas a more heterogeneous mode of large normal alleles ranges from 16 to 34 GAA. The latter class accounts for approximately 17% of normal alleles. To identify the origin of the expansion mutation, we analyzed linkage disequilibrium between expansion mutations or normal alleles and a haplotype of five polymorphic markers within or close to the frataxin gene; 51% of the expansions were associated with a single haplotype, and the other expansions were associated with haplotypes that could be related to the major one by mutation at a polymorphic marker or by ancient recombination. Of interest, the major haplotype associated with expansion is also the major haplotype associated with the larger alleles in the normal size range and was almost never found associated with the smaller normal alleles. The results indicate that most if not all large normal alleles derive from a single founder chromosome and that they represent a reservoir for larger expansion events, possibly through "premutation" intermediates. Indeed, we found two such alleles (42 and 60 GAA) that underwent cataclysmic expansion to pathological range in a single generation. This stepwise evolution to large trinucleotide expansions already was suggested for myotonic dystrophy and fragile X syndrome and may relate to a common mutational mechanism, despite sequence motif differences.
In Vitro Fertilization (2007)

A 37-year-old woman who has never been pregnant and her 40-year-old husband have been attempting to conceive a child for the past 3 years. An infertility evaluation has shown no cause for the difficulty. She is ovulating regularly, and a hysterosalpingogram shows that her reproductive tract is anatomically normal. He has a normal sperm count; he has not fathered any children. They are frustrated and want to proceed with in vitro fertilization. What should you advise?
End-to-End Answer Chunk Extraction and Ranking for Reading Comprehension (2016)

This paper proposes dynamic chunk reader (DCR), an end-to-end neural reading comprehension (RC) model that is able to extract and rank a set of answer candidates from a given document to answer questions. DCR is able to predict answers of variable lengths, whereas previous neural RC models primarily focused on predicting single tokens or entities. DCR encodes a document and an input question with recurrent neural networks, and then applies a word-by-word attention mechanism to acquire question-aware representations for the document, followed by the generation of chunk representations and a ranking module to propose the top-ranked chunk as the answer. Experimental results show that DCR achieves state-of-the-art exact match and F1 scores on the SQuAD dataset.
Bone Marrow Stromal Damage after Chemo/Radiotherapy: Occurrence, Consequences and Possibilities of Treatment (2001)

High dose chemotherapy (CT) followed by bone marrow transplant (BMT) is increasingly used for the treatment of both hematological and solid neoplasms, but an understanding of its late consequences on the marrow microenvironment is still only at its beginning. It is in fact known that marrow stroma is damaged by high-dose cytotoxic therapy and by radiation exposure. However little is known on the extent of this damage and on the self-repair ability of the stroma. The damage of the stromal microenvironment affects the long-term stem cell engraftment and the maintenance of hemopoietic functions. Furthermore, marrow stroma also represents a progenitor compartment for endosteal osteoblasts, and therefore its damage implies alterations of bone metabolism. Indeed, osteoporosis has recently been recognized as a consequence, of BMT, but only a few studies have been performed to establish the functional status of the stromal compartment after treatment with cytotoxic drugs with or without total body irradiation (TBI) and its role in post-BMT sequelae.
Enabling workflow in UPNP networks (2005)

UPnP networks can be enriched by integrating workflow management systems with UPnP capabilities. Thus, interactions between UPnP devices become manageable and UPnP networks can be used for entire technical or business processes. On the other hand the integration of UPnP capability opens new perspectives for workflow management systems (e.g. controlling devices). This paper describes how to enable workflow management systems in UPnP networks. We identified two levels of integration: workflow management systems that control UPnP networks and workflow management systems that act as an UPnP device at the same time. In the latter case we propose two UPnP services: WorkflowControl service offering actions for creating process instances, actions for controlling and for observing them and ProcessDefinition service allowing installing/uninstalling process definitions. This approach was successfully implemented and tested within an UPnP audio video network. We are not aware of any other approach integrating workflow services into UPnP enabled embedded systems.