gebhart/patrepeval huggingface dataset:
The MIQE Guidelines: Minimum Information for Publication of Quantitative Real-Time PCR Experiments (2009)

Following these guidelines will encourage better experimental practice, allowing more reliable and unequivocal interpretation of qPCR results.
FraC nanopores with adjustable diameter identify the mass of opposite-charge peptides with 44 dalton resolution (2019)

A high throughput single-molecule method for identifying peptides and sequencing proteins based on nanopores could reduce costs and increase speeds of sequencing, allow the fabrication of portable home-diagnostic devices, and permit the characterization of low abundance proteins and heterogeneity in post-translational modifications. Here we engineer the size of Fragaceatoxin C (FraC) biological nanopore to allow the analysis of a wide range of peptide lengths. Ionic blockades through engineered nanopores distinguish a variety of peptides, including two peptides differing only by the substitution of alanine with glutamate. We also find that at pH 3.8 the depth of the peptide current blockades scales with the mass of the peptides irrespectively of the chemical composition of the analyte. Hence, this work shows that FraC nanopores allow direct readout of the mass of single peptide in solution, which is a crucial step towards the developing of a real-time and single-molecule protein sequencing device.
A New Synthesis of 5-Bromo-DL-tryptophan (1993)

Abstract A new synthesis of 5-bromotryptophan, a potential antisickling agent, from 5-bromo-3-methylindole is described.
Systems Properties of the Haemophilus influenzaeRd Metabolic Genotype (1999)

Haemophilus influenzae Rd was the first free-living organism for which the complete genomic sequence was established. The annotated sequence and known biochemical information was used to define the H. influenzae Rd metabolic genotype. This genotype contains 488 metabolic reactions operating on 343 metabolites. The stoichiometric matrix was used to determine the systems characteristics of the metabolic genotype and to assess the metabolic capabilities of H. influenzae. The need to balance cofactor and biosynthetic precursor production during growth on mixed substrates led to the definition of six different optimal metabolic phenotypes arising from the same metabolic genotype, each with different constraining features. The effects of variations in the metabolic genotype were also studied, and it was shown that the H. influenzae Rd metabolic genotype contains redundant functions under defined conditions. We thus show that the synthesis of in silico metabolic genotypes from annotated genome sequences is possible and that systems analysis methods are available that can be used to analyze and interpret phenotypic behavior of such genotypes.
Modulation of Phospholipase A2Activity by Aminoglycosides and Daptomycin:  A Fourier Transform Infrared Spectroscopic Study (1998)

The antibiotics known as aminoglycosides are commonly used to treat severe infections caused by Gram-negative bacteria. Unfortunately, they often lead to acute renal failure after their accumulation in the lysosomes of renal cells, where an inhibition of the phospholipid catabolism is observed. The lipopeptidic antibiotic daptomycin has been shown to reduce the nephrotoxicity of aminoglycosides, but the exact mechanism of this protection is still unknown. In the present study, Fourier transform infrared spectroscopy (FTIR) has been used to monitor the hydrolysis of phosphatidylcholine by phospholipase A2 (PLA2) from Naja mocambique mocambique venom in the presence of various aminoglycosides and/or daptomycin. Gentamicin and amikacin inhibited the reaction in its early stage. Kanamycin A, tobramycin, and especially kanamycin B enhanced the initial enzyme activity by reducing the lag time. After the initiation period, the reaction proceeded at a much slower rate in the presence of gentamicin. On the other hand, daptomycin led to dramatic alterations of the hydrolysis profile: the initial latency period was eliminated, and the maximal extent of hydrolysis was reduced. When both daptomycin and any of the aminoglycosides were present, the latency period also disappeared, and the phospholipase activity was higher than with the lipopeptide alone. The most drastic change occurred with gentamicin, which was the most inhibitory aminoglycoside when used alone but worked synergistically with daptomycin to yield the most dramatic activation of PLA2.
Immunoreactivity of Tissue Plasminogen Activator and of Its Inhibitor Complexes (1989)

An enzyme linked immunosorbent assay (ELISA) based on goat polyclonal antibodies against human tissue plasminogen activator (tPA) was evaluated. The relative immunoreactivity of tPA in free form and tPA in complex with inhibitors was estimated by ELISA and found to be 100, 74, 94, 92 and 81% for free tPA and tPA in complex with PAI-1, PAI-2, alpha 2-antiplasmin and C1-inhibitor, respectively. Addition of tPA to PAI-1 rich plasma resulted in rapid and total loss of tPA activity without detectable loss of ELISA response, indicating an immunoreactivity of tPA in tPA/PAI-1 complex of about 100%. Three different treatments of citrated plasma samples (acidification/reneutralization, addition of 5 mM EDTA or of 0.5 M lysine) prior to determination by ELISA all resulted in increased tPA levels. The fact that the increase was equally large in all three cases along with good analytical recovery of tPA added to plasma, supported the notion that all tPA antigen present in plasma samples is measured by the ELISA. Analysis by ELISA of fractions obtained by gel filtration of plasma from a patient undergoing tPA treatment identified tPA/inhibitor complexes and free tPA but no low molecular weight degradation products of tPA. Determinations of tPA antigen were made at seven French clinical laboratories on coded and randomized plasma samples with known tPA antigen content. For undiluted samples there was no significant difference between the tPA levels found and those known to be present. The between-assay coefficient of variation was 7 to 10%. In conclusion, the ELISA appeared suited for determination of total tPA antigen in human plasma samples.
Comprehensive analysis of transcriptional promoter structure and function in 1% of the human genome (2005)

Transcriptional promoters comprise one of many classes of eukaryotic transcriptional regulatory elements. Identification and characterization of these elements are vital to understanding the complex network of human gene regulation. Using full-length cDNA sequences to identify transcription start sites (TSS), we predicted more than 900 putative human transcriptional promoters in the ENCODE regions, representing a comprehensive sampling of promoters in 1% of the genome. We identified 387 fragments that function as promoters in at least one of 16 cell lines by measuring promoter activity in high-throughput transient transfection reporter assays. These positive functional results demonstrate widespread use of alternative promoters. We show a strong correlation between promoter activity and the corresponding endogenous RNA transcript levels, providing the first experimental quantitative estimate of promoter contribution to gene regulation. Finally, we identified functional regions within a randomly selected subset of 45 promoters using deletion analyses. These experiments showed that, on average, the sequence -300 to -50 bp of the TSS positively contributes to core promoter activity. Interestingly, putative negative elements were identified -1000 to -500 bp upstream of the TSS for 55% of genes tested. These data provide the largest and most comprehensive view of promoter function in the human genome.
The Interictal Behavior Syndrome of Temporal Lobe Epilepsy (1975)

A distinct syndrome of interictal behavior changes occurs in many patients with temporal lobe epilepsy. These changes include alterations in sexual behavior, religiosity, and a tendency toward extensive, and in some cases compulsive, writing and drawing. The concomitants of abnormal limbic acitivity therefore include behavior alterations as well as manifest seizures. The demonstration of interictal spike activity in temporal structures provides a pathophysiologic basis for this syndrome. The constellation of behavioral changes may be of great diagnostic value. In addition, it provides an example of a human behavioral syndrome assocaited with dysfunction at specific anatomic loci. The behavior syndrome of temporal lobe epilepsy may prove to be a useful model in studies on the neural substrates for behavior.
Chronic hepatic artery ligation does not prevent liver from differentiating portal vs. peripheral glucose delivery (2003)

Infusion of glucose into the hepatic artery blocks the stimulatory effect of the "portal signal" on net hepatic glucose uptake (NHGU) during portal glucose delivery. We hypothesized that hepatic artery ligation (HAL) would result in enhanced NHGU during peripheral glucose infusion because the arterial glucose concentration would be perceived as lower than that in the portal vein. Fourteen dogs underwent HAL approximately 16 days before study. Conscious 42-h-fasted dogs received somatostatin, intraportal insulin, and glucagon infusions at fourfold basal and at basal rates, respectively, and peripheral glucose infusion to create hyperglycemia. After 90 min (period 1), seven dogs (HALpo) received intraportal glucose (3.8 mg. kg-1. min-1) and seven (HALpe) continued to receive only peripheral glucose for 90 min (period 2). These two groups were compared with nine non-HAL control dogs (control) treated as were HALpe. During period 2, the arterial plasma insulin concentrations (24 +/- 3, 20 +/- 1, and 24 +/- 2 microU/ml) and hepatic glucose loads (39.1 +/- 2.5, 43.8 +/- 2.9, and 37.7 +/- 3.7 mg. kg-1. min-1) were not different in HALpe, HALpo, and control, respectively. HALpo exhibited greater (P < 0.05) NHGU than HALpe and control (3.1 +/- 0.3, 2.0 +/- 0.4, and 2.0 +/- 0.1 mg. kg-1. min-1, respectively). Net hepatic carbon retention was approximately twofold greater (P < 0.05) in HALpo than in HALpe and control. NHGU and net hepatic glycogen synthesis during peripheral glucose infusion were not enhanced by HAL. Even though there exists an intrahepatic arterial reference site for the portal vein glucose concentration, the failure of HAL to result in enhanced NHGU during peripheral glucose infusion suggests the existence of one or more comparison sites outside the liver.
Flagellar preparations from Pseudomonas aeruginosa: animal protection studies (1982)

Recent reports have suggested that motility is associated with virulence in Pseudomonas aeruginosa. We have confirmed this observation by showing that groups of mice immunized with P. aeruginosa flagellar-antigen preparations display enhanced survival when they are subsequently burned and challenged locally in the burned area with strains of P. aeruginosa. The protection appears to be due to the immobilization of the microorganisms in the burned skin tissue. Liver elongation factor 2 is also protected. The protection afforded by immunization with flagellar-antigen preparations is independent of the somatic antigenic type of the challenging strain but is flagellar-antigen specific. These data suggest that vaccination with flagellar-antigen preparations may provide a viable prophylactic or therapeutic alternative to antibiotic therapy for use in compromised patient population in which P. aeruginosa poses a serious infection threat.
Transferrin Synthesis Is Increased in Nephrotic Patients Insufficiently to Replace Urinary Losses (2001)

The urinary loss of transferrin is sufficient to reduce plasma transferrin concentrations in the nephrotic syndrome. Hypotransferrinemia may lead to iron loss and microcytic anemia. The mechanism responsible for the hypotransferrinemia in the nephrotic syndrome is, however, unknown. In the present study, synthesis rate of transferrin was measured in vivo in nephrotic patients (n = 7) compared with control subjects (n = 6) using L-[1-(13)C]-valine. Plasma transferrin and iron concentration in the patients were significantly lower than in control subjects (transferrin, 1.39 +/- 0.08 versus 2.57 +/- 0.11 g/L, P < 0.0001; iron, 10.2 +/- 0.8 versus 21.1 +/- 4.5 micromol/L, P = 0.02). Furthermore, albuminuria correlated with transferrinuria (r(2) = 0.901, P = 0.001). The absolute synthesis rate of transferrin was increased in the patients (10.0 +/- 1.1 versus 7.4 +/- 0.7 mg/kg per d, P = 0.07), although this value failed to achieve significance. C-reactive protein, plasma iron, and proteinuria did not correlate with transferrin synthesis. In contrast, transferrin synthesis correlated with albumin synthesis (r(2) = 0.648, P = 0.03; n = 7). The present study indicates that increased transferrin synthesis occurs in nephrotic patients but is insufficient to compensate for urinary losses. Because, overall, no significant relationship was found between transferrin synthesis and either C-reactive protein or iron, it is unlikely that inflammation suppresses or that iron deficiency stimulates increased transferrin synthesis in these patients. The correlation between transferrin synthesis and albumin synthesis suggests that transferrin synthesis is a component of a general response in hepatic protein synthesis in the nephrotic syndrome. This suggests that a therapeutic approach to maximize plasma transferrin concentrations in nephrotic patients should be aimed primarily at reducing urinary protein excretion.
Histone deacetylase inhibition-mediated neuronal differentiation of multipotent adult neural progenitor cells (2004)

It has become apparent that chromatin modification plays a critical role in the regulation of cell-type-specific gene expression. Here, we show that an inhibitor of histone deacetylase, valproic acid (VPA), induced neuronal differentiation of adult hippocampal neural progenitors. In addition, VPA inhibited astrocyte and oligodendrocyte differentiation, even in conditions that favored lineage-specific differentiation. Among the VPA-up-regulated, neuron-specific genes, a neurogenic basic helix-loop-helix transcription factor, NeuroD, was identified. Overexpression of NeuroD resulted in the induction and suppression of neuronal and glial differentiation, respectively. These results suggest that VPA promotes neuronal fate and inhibits glial fate simultaneously through the induction of neurogenic transcription factors including NeuroD.
PEG-3, a nontransforming cancer progression gene, is a positive regulator of cancer aggressiveness and angiogenesis (1999)

Cancer is a progressive disease culminating in acquisition of metastatic potential by a subset of evolving tumor cells. Generation of an adequate blood supply in tumors by production of new blood vessels, angiogenesis, is a defining element in this process. Although extensively investigated, the precise molecular events underlying tumor development, cancer progression, and angiogenesis remain unclear. Subtraction hybridization identified a genetic element, progression elevated gene-3 (PEG-3), whose expression directly correlates with cancer progression and acquisition of oncogenic potential by transformed rodent cells. We presently demonstrate that forced expression of PEG-3 in tumorigenic rodent cells, and in human cancer cells, increases their oncogenic potential in nude mice as reflected by a shorter tumor latency time and the production of larger tumors with increased vascularization. Moreover, inhibiting endogenous PEG-3 expression in progressed rodent cancer cells by stable expression of an antisense expression vector extinguishes the progressed cancer phenotype. Cancer aggressiveness of PEG-3 expressing rodent cells correlates directly with increased RNA transcription, elevated mRNA levels, and augmented secretion of vascular endothelial growth factor (VEGF). Furthermore, transient ectopic expression of PEG-3 transcriptionally activates VEGF in transformed rodent and human cancer cells. Taken together these data demonstrate that PEG-3 is a positive regulator of cancer aggressiveness, a process regulated by augmented VEGF production. These studies also support an association between expression of a single nontransforming cancer progression-inducing gene, PEG-3, and the processes of cancer aggressiveness and angiogenesis. In these contexts, PEG-3 may represent an important target molecule for developing cancer therapeutics and inhibitors of angiogenesis.
Transferability of thermostabilizing mutations between β-adrenergic receptors (2009)

In previous work we described six point mutations that thermostabilised the turkey beta(1)-adrenergic receptor (tbeta(1)AR). The thermostable mutant, tbeta(1)AR-m23, had an apparent T(m) 21 degrees C higher than the native protein when solubilized in dodecylmaltoside (DDM) and, in addition, was significantly more stable in short chain detergents, which allowed its crystallization and structure determination. Identification of thermostabilizing mutations in tbeta(1)AR was performed by systematic mutagenesis followed by expressing and assaying each of the 318 mutants for their thermostability. This is time-consuming, so to facilitate studies on related receptors, we have studied the transferability of these mutations to the human adrenergic receptors, hbeta(1)AR and hbeta(2)AR, which have, respectively, 76% and 59% sequence identity to tbeta(2)AR, excluding the N- and C-termini. Thermostability assays revealed that hbeta(1)AR was much more unstable than tbeta(2)AR, whereas hbeta(2)AR was more stable than tbeta(1)AR. Addition of the 6 thermostabilizing mutations in tbeta(2)AR-m23 into both hbeta(2)AR and hbeta(2)AR increased their apparent T(m)s by 17 degrees C and 11 degrees C, respectively. In addition, the mutations affected the global conformation of the human receptors so that they were predominantly in the antagonist bound form, as was originally observed for tbeta(2)AR-m23. Thus, once thermostabilizing mutations have been identified in one G protein-coupled receptor, stabilization of close members within the subfamily is rapidly obtainable.
Inhibition of the Spontaneous Rate of Contraction of Neonatal Cardiac Myocytes by Protein Kinase C Isozymes (1995)

Protein kinase C (PKC) enzymes regulate numerous cardiac functions. In the present study, we determined the effects of the PKC-activating drug 4-beta phorbol 12-myristate 13-acetate (4-beta PMA) on the rate of contraction and correlated these changes with the distribution and levels of alpha-, beta-, delta-, epsilon-, and zeta-PKC isozymes by using neonatal rat cardiac myocytes in culture. Treatment with 0.3 to 100 nmol/L 4-beta PMA caused negative chronotropic effects on contraction. This effect was maximal at a concentration of 3 nmol/L 4-beta PMA and correlated with redistribution of the alpha- and epsilon-PKC isozymes from the cytosolic to the particulate cell fraction. After a 1-hour treatment with 100 nmol/L PMA, the alpha- and beta-PKC isozymes and an 80-kD zeta-like PKC isozyme were greatly diminished (downregulated), yet the negative chronotropic effect was sustained. Therefore, our results are most consistent with a role for the epsilon-PKC isozyme in suppressing the contraction rate of neonatal rat cardiac myocytes. Understanding the role(s) of individual PKC isozymes in the modulation of cardiac functions may ultimately yield more selective targets for therapies of cardiac disorders.
Greedy function approximation: A gradient boosting machine. (2001)

Function estimation/approximation is viewed from the perspective of numerical optimization in function space, rather than parameter space. A connection is made between stagewise additive expansions and steepest-descent minimization. A general gradient descent “boosting” paradigm is developed for additive expansions based on any fitting criterion.Specific algorithms are presented for least-squares, least absolute deviation, and Huber-M loss functions for regression, and multiclass logistic likelihood for classification. Special enhancements are derived for the particular case where the individual additive components are regression trees, and tools for interpreting such “TreeBoost” models are presented. Gradient boosting of regression trees produces competitive, highly robust, interpretable procedures for both regression and classification, especially appropriate for mining less than clean data. Connections between this approach and the boosting methods of Freund and Shapire and Friedman, Hastie and Tibshirani are discussed.
Contributions to Multilingual Low-Footprint TTS System for Hand-Held Devices (2007)

Speech technology in the form of automatic speech recognition (ASR) and speech synthesis (text-to-speech or TTS) has become common in everyday use. Applications such as in-car navigation, hands-free control of devices, aids for visually impaired people, telephone-based schedule and reservation services, military applications and even some dictation applications can be found on the market today. The advancement of technology has made it possible to provide voice-based applications also on smaller, hand-held devices.This thesis focuses on describing the challenges and solutions in optimizing a multilingual text-to-speech (TTS) system for hand-held devices. The challenges in development are introduced by the mismatch between the application requirements and available resources. The requirements include application features, speech quality, language support and portability. The main resources are memory size, performance, development time and cost. The trade-off between requirements and resources are especially challenging in cost-optimized embedded devices targeted for consumer market.In this thesis, a multilingual TTS framework is designed and optimized to meet the application requirements according to the availability of various resources. The TTS system uses a Klatt88 formant synthesizer or unit selection synthesis depending on the configuration. Novel approaches and improvements are applied to text normalization, text-to-phoneme conversion, control of synthesis parameters, system framework, and development tools.It is shown that commercially viable multilingual TTS-based applications can be created by the following four main methods. First, the limitations of the TTS technology can be hidden or alleviated by limiting the scope of the application. Second, optimization in memory consumption and performance makes the TTS technology more attractive for hand-held devices. Third, multilingualism and rapid development of new synthesis languages are enabled through system design and proper development methods and tools. Finally, the separated TTS engine software and language dependent data make it possible to hide the software engineering details by providing language developers an interface with a higher level of abstractness.
The Psychological Meaning of Words: LIWC and Computerized Text Analysis Methods (2009)

We are in the midst of a technological revolution whereby, for the first time, researchers can link daily word use to a broad array of real-world behaviors. This article reviews several computerized text analysis methods and describes how Linguistic Inquiry and Word Count (LIWC) was created and validated. LIWC is a transparent text analysis program that counts words in psychologically meaningful categories. Empirical results using LIWC demonstrate its ability to detect meaning in a wide variety of experimental settings, including to show attentional focus, emotionality, social relationships, thinking styles, and individual differences.