gebhart/patrepeval huggingface dataset:
Development of biomaterial scaffold for nerve tissue engineering: Biomaterial mediated neural regeneration (2009)

Neural tissue repair and regeneration strategies have received a great deal of attention because it directly affects the quality of the patient's life. There are many scientific challenges to regenerate nerve while using conventional autologous nerve grafts and from the newly developed therapeutic strategies for the reconstruction of damaged nerves. Recent advancements in nerve regeneration have involved the application of tissue engineering principles and this has evolved a new perspective to neural therapy. The success of neural tissue engineering is mainly based on the regulation of cell behavior and tissue progression through the development of a synthetic scaffold that is analogous to the natural extracellular matrix and can support three-dimensional cell cultures. As the natural extracellular matrix provides an ideal environment for topographical, electrical and chemical cues to the adhesion and proliferation of neural cells, there exists a need to develop a synthetic scaffold that would be biocompatible, immunologically inert, conducting, biodegradable, and infection-resistant biomaterial to support neurite outgrowth. This review outlines the rationale for effective neural tissue engineering through the use of suitable biomaterials and scaffolding techniques for fabrication of a construct that would allow the neurons to adhere, proliferate and eventually form nerves.
Label‐retaining, quiescent globose basal cells are found in the olfactory epithelium (2013)

The vertebrate olfactory epithelium (OE) is known for its ability to renew itself throughout life as well as to reconstitute after injury. Although this remarkable capacity demonstrates the persistence of stem cells and multipotent progenitor cells, their nature in the OE remains undefined and controversial, as both horizontal basal cells (HBCs) and globose basal cells (GBCs) have features in common with each other and with stem cells in other tissues. Here, we investigate whether some among the population of GBCs satisfy a key feature of stem cells, i.e., mitotic quiescence with retention of thymidine analogue label and activation by injury. Accordingly, we demonstrate that some GBCs express p27(Kip1) , a member of the Kip/Cip family of cyclin-dependent kinase inhibitors. In addition, some GBCs retain bromodeoxyuridine or ethynyldeoxyuridine for an extended period when the pulse is administered in neonates followed by a 1-month chase. Their identity as GBCs was confirmed by electron microscopy. All spared GBCs express Ki-67 in the methyl bromide (MeBr)-lesioned OE initially after lesion, indicating that the label-retaining (LR) GBCs are activated in response to injury. LR-GBCs reappear during the acute recovery period following MeBr exposure, as demonstrated with 2- or 4-week chase periods after labeling. Taken together, our data demonstrate the existence of LR-GBCs that are seemingly activated in response to epithelial injury and then re-established after the initial phase of recovery is completed. In this regard, some among the GBCs satisfy a common criterion for functioning like stem cells.
Near-Infrared Spectrophotometry (1968)

Abstract Near-infrared spectroscopy is usually considered to cover that part of the electromagnetic spectrum which falls between 0.71μ. and approximately 3 p. From the theoretical viewpoint, one might place the upper wavelength limit near 2.51μ. and define near-infrared spectroscopy as the study of low-energy electronic transitions and overtones and combinations of hydrogenic (C-H, N-H, 0-H, etc.) stretching and bending vibrations. This definition is favored by the fact that several commercial near-infrared instruments have an upper wavelength limit of about 2.65μ. Some instruments cover wavelengths up to 3.6μ) however, and the definition of near-infrared spectroscopy is sometimes broadened to include the study of fundamental hydrogenic stretching vibrations.
The runaway brain (1994)

Does Darwinian theory really explain Mozart and Michelangelo? Biologists would have us believe that the processes of random mutation, natural selection, and survival of the fittest are enough to explain the whole process of evolution. Primitive man is said to have evolved in the Rift Valley in Africa somewhere between 1 1/2 and 3 1/2 million years ago. Evolutionary pressures would presumably have focused on survival from predators, success in food gathering and breeding, and adaptation to climatic changes. It is difficult to believe that the genes that contribute to artistic creativity and mathematical innovation have any practical value to a hunter-gatherer. Does primitive man …
Antigenic and Genetic Characterization of the Haemagglutinins of Recent Cocirculating Strains of Influenza B Virus (1992)

The antigenic and genetic characteristics of the haemagglutinins of influenza type B viruses isolated since 1988 during periods of both widespread activity (1990/1991) and sporadic activity (1989/1990) were examined using microneutralization tests and direct RNA sequencing. During 1989/1990, influenza B viruses representative of two distinct lineages antigenically and genetically related to either B/Victoria/2/87 or B/Yamagata/16/88 were isolated, and a minor drift variant of B/Yamagata/16/88, B/Hong Kong/22/89, was identified. In 1990/1991, B/Hong Kong/22/89- or B/Yamagata/16/88-like viruses accounted for the majority of the influenza virus isolates in most countries. Sequence analysis of the HA1 domains of representative viruses confirmed the continued existence of two main lineages among recent strains of influenza B virus and identified unique amino acid changes that could account for the altered antigenic reactivity of some variants. Sequence analysis of the HA2 domains of some of the recent influenza B viruses allowed for a comparison of the evolutionary rates and patterns between the HA1 and HA2 domains.
Strand displacement amplification: a versatile tool for molecular diagnostics (2004)

Strand displacement amplification is an isothermal process that permits 10(10)-fold amplification of a DNA target sequence in as little as 15 min. In the form of the BD ProbeTec ET System, strand displacement amplification was the first nucleic acid amplification technology to be coupled with real-time homogeneous fluorescence-based detection for routine application in the clinical laboratory. The isothermal nature of the reaction process offers distinct advantages with regard to the cost and simplicity of instrumentation, while a universal detection format permits the use of the same fluorescent detector probes across multiple analytes. This has important potential in the field of genetic analysis, in which disease predisposition and therapeutic efficacy are frequently determined by multiple nucleic acid markers.
The Plymouth Brethren in Illawarra (A missed Centenary (1996)

The Victorian Church, "They began first as a little extreme evangelical group
Quantifying E. coli Proteome and Transcriptome with Single-Molecule Sensitivity in Single Cells (2010)

Protein and messenger RNA (mRNA) copy numbers vary from cell to cell in isogenic bacterial populations. However, these molecules often exist in low copy numbers and are difficult to detect in single cells. We carried out quantitative system-wide analyses of protein and mRNA expression in individual cells with single-molecule sensitivity using a newly constructed yellow fluorescent protein fusion library for Escherichia coli. We found that almost all protein number distributions can be described by the gamma distribution with two fitting parameters which, at low expression levels, have clear physical interpretations as the transcription rate and protein burst size. At high expression levels, the distributions are dominated by extrinsic noise. We found that a single cell's protein and mRNA copy numbers for any given gene are uncorrelated.
Mutational spectrum of phenylalanine hydroxylase deficiency in Sicily: implications for diagnosis of hyperphenyl-alaninemia in Southern Europe (1993)

Hyperphenylalaninemia due to a deficiency of hepatic phenylalanine hydroxylase (PAH) is the most common inborn error of amino acid metabolism. Clinically, the disorder is highly heterogeneous, spanning from nonphenylketonuria hyperphenylalaninemia to classical phenylketonuria. Only little is known about the molecular defects underlying hyperphenylalaninemia in Southern Europe. In this study, we conducted a systematic analysis of 53 patients from the Sicilian population. Each patient included in the study had persistently elevated blood levels of phenylalanine and met the differential criteria for PAH deficiency. Genomic DNA was analysed by scanning all PAH-coding exons for mutations by PCR in combination with denaturing gradient gel electrophoresis (DGGE). 52 patients were completely genotyped. A spectrum of 40 different mutations was established including 17 novel PAH mutations. Our results explain the clinical heterogeneity of hyperphenylalaninemia in Southern Europe, and form the basis for the establishment of phenotype-genotype correlations in Sicily and surrounding countries.
New insights regarding the potential of the pronucleotide approach in antiviral chemotherapy. (1996)

The rationale for a pronucleotide approach based on the use of phosphotriesters which incorporate enzyme-mediated bio-labile protection is discussed in detail. Among the studied bio-labile phosphate protecting groups, the S-acyl-2-thioethyl (SATE) groups appeared the most promising as exemplified in cell culture systems in the case of the pronucleotides of 3'-azido-3'-deoxythymidine, 2',3'-didehydro-3'-deoxythymidine, 2',3'-dideoxyadenosine and acyclovir In vivo implementations of such bis(SATE) pronucleotides have been planned for future animal studies.
Restoration of TEA-Induced Calcium Responses in Fibroblasts from Alzheimer's Disease Patients by a PKC Activator (1998)

Several alterations in fibroblasts of Alzheimer's disease (AD) patients have been described, including alterations in calcium regulation, protein kinase C (PKC), and potassium (K+) channels. Studies have also found reduced levels of the alpha isoform of PKC in brains and fibroblasts of AD patients. Since PKC is known to regulate ion channels, we studied K+ channel activity in fibroblasts from AD patients in the presence of (2S, 5S)-8-(1-decynyl)benzolactam (BL), a novel activator of PKC with improved selectivity for the alpha, beta, and gamma isoforms. We present evidence for restoration of normal K+ channel function, as measured by TEA-induced [Ca2+]i elevations, due to activation of PKC by BL. Representative patch-clamp data further substantiate the effect of BL on restoration of 113pS K+ channel activity. Immunoblotting analyses using an alpha-isozyme-specific PKC antibody confirm that BL-treated fibroblasts of AD patients show increased PKC activation. The present study suggests that PKC activator-based restoration of K+ channels may offer another approach to the investigation of AD pathophysiology, which in turn could lead to the development of a useful model for AD therapeutics.
Generation of ultrashort electrical pulses through screening by virtual populations in biased quantum wells (1987)

We consider theoretically a semiconductor quantum well subject to an electrostatic field normal to the layer and a strong monochromatic laser field in the transparency region below the absorption edge. We show that ultrashort optical pulses generate ultrashort voltage pulses because the virtual electron-hole population induced by the laser field partially screens the applied static field. We predict that voltages &gt;1 V could be generated in micron-thick multiple quantum well structures by use of low-power short-pulse lasers.
Facilitatory coupling between a glutamate metabotropic receptor and dihydropyridine-sensitive calcium channels in cultured cerebellar granule cells (1995)

The effect of metabotropic glutamate receptor activation on Ca dihydropyridine (DHP)-sensitive channels recorded in the presence of 1 microM Bay K 8644 was examined on cultured cerebellar granule cells using the patch-clamp technique in the cell-attached configuration. Bath-applied agonist (trans-ACPD, 1S,3R-, and 1R,3S-ACPD isomers, and glutamate or quisqualate in the presence of CPP and CNQX) evoked an increase in Ca channel activity with a variable latency of 8.9 +/- 8.6 sec in 40% of the recorded cells. Neither L-CCG1, L-AP3, L-AP4, nor AMPA or NMDA activated Ca channels. Two dihydropyridine-sensitive channels present in this cell type were activated by trans-ACPD: the classical 24 pS L-type channel and a smaller-conductance 7 pS channel. The effect was shown to be mediated by neither intracellular Ca2+ nor a pertussis toxin (PTX)-sensitive G protein. Interestingly treatment with BAPTA-AM increased the number of responding patches and the activity was more sustained throughout the drug application. After overnight PTX treatment, activation of the Ca channels persisted even after washout of the agonist. These results indicate that mGluR1/mGluR5 probably mediate the facilitation of dihydropyridine-sensitive Ca channels.
Differential Effects of Food on the Bioavailability of Controlled-Release Oxycodone Tablets and Immediate-Release Oxycodone Solution (1996)

The effects of a high-fat meal on the bioavailability of oxycodone hydrochloride, administered as a recently developed 40 mg controlled-release (CR) tablet or a 20 mg immediate-release (IR) solution, were evaluated in a randomized crossover study in 22 normal male and female subjects. Serial blood samples were collected for 36 h after dosing and analyzed for oxycodone by a validated method using gas chromatography/mass spectrometry. There was no significant food effect with CR oxycodone as judged by 90% confidence interval (CI) analysis of AUC0−∞and Cmax values under fed and fasted conditions. For the IR solution, both oxycodone bioavailability and peak plasma oxycodone concentration were significantly altered by consumption of the high-fat meal, with the mean value for AUC0−∞ increasing to 120% (CI=109– 132%) and the mean value for Cmax decreasing to 82% (CI=47–91%) of values observed in the fasted condition. Adverse events reported for both formulations were mostly mild to moderate in severity and typical of those observed with opioids.
Expression of the normal H-ras1 gene can suppress the transformed and tumorigenic phenotypes induced by mutant ras genes. (1991)

The transformed phenotype of rat 208F cells transfected with the T24 H-ras1 oncogene is suppressed by simultaneous or subsequent transfection with the normal H-ras1 gene. The suppressed cells express both the normal and mutant forms of ras p21 but the normal form predominates. Rare transformed cells obtained after simultaneous transfection express mainly the T24 p21. Some suppressed cells induce tumours in nude mice after a long lag period and these tumour cell lines have much reduced expression of normal p21. The normal H-ras1 gene also suppresses the transformed phenotype induced by mutant N-ras, albeit less effectively. The tumorigenicity of the EJ bladder carcinoma cell line, which contains only the T24 mutant allele of H-ras1, is also suppressed following transfection with the normal H-ras1 gene. The results suggest that transforming alleles of ras genes do not behave in a fully dominant manner and that expression of the normal allele at elevated levels can lead to suppression of the transformed and tumorigenic phenotypes.
Neurological aspects of biopterin metabolism. (1986)

Plasma total biopterin concentration was measured by bioassay in 59 infants with hyperphenylalaninaemia and in 50 children with developmental regression and or movement disorder with normal plasma phenylalanine concentrations. In infants with raised phenylalanine concentrations plasma biopterin concentrations were significantly raised in proportion to the phenylalanine values. Five patients had plasma biopterin concentrations at the extremes of the range, and of these two had defective biopterin metabolism. One with low plasma biopterin concentration apparently had a partial defect of biopterin synthesis but died before investigations were complete. One with high plasma biopterin concentration, even when phenylalanine concentrations had fallen to the normal range, had dihydropteridine reductase deficiency. In this patient concentrations of homovanillic acid and 5-hydroxyindolacetic acid in the cerebrospinal fluid (CSF) were severely reduced. In children without hyperphenylalaninaemia plasma biopterin concentrations were normal. Twenty two patients were subjected to lumbar puncture, of whom six with developmental regression without movement disorder had normal CSF biopterin concentrations, and 11 with movement disorder other than torsion dystonia had significantly lower CSF biopterin concentrations. Five patients with torsion dystonia had normal biopterin concentrations.
Differentiation of Human Embryonal Carcinomas In vitro and In vivo Reveals Expression Profiles Relevant to Normal Development (2005)

Embryonal carcinoma is a histologic subgroup of testicular germ cell tumors (TGCTs), and its cells may follow differentiation lineages in a manner similar to early embryogenesis. To acquire new knowledge about the transcriptional programs operating in this tumor development model, we used 22k oligo DNA microarrays to analyze normal and neoplastic tissue samples from human testis. Additionally, retinoic acid-induced in vitro differentiation was studied in relevant cell lines. We identified genes characterizing each of the known histologic subtypes, adding up to a total set of 687 differentially expressed genes. Among these, there was a significant overrepresentation of gene categories, such as genomic imprinting and gene transcripts associated to embryonic stem cells. Selection for genes highly expressed in the undifferentiated embryonal carcinomas resulted in the identification of 58 genes, including pluripotency markers, such as the homeobox genes NANOG and POU5F1 (OCT3/4), as well as GAL, DPPA4, and NALP7. Interestingly, abundant expression of several of the pluripotency genes was also detected in precursor lesions and seminomas. By use of tissue microarrays containing 510 clinical testicular samples, GAL and POU5F1 were up-regulated in TGCT also at the protein level and hence validated as diagnostic markers for undifferentiated tumor cells. The present study shows the unique gene expression profiles of each histologic subtype of TGCT from which we have identified deregulated components in selected processes operating in normal development, such as WNT signaling and DNA methylation.
All-trans retinoic acid for the treatment of newly diagnosed acute promyelocytic leukemia. Japan Adult Leukemia Study Group [see comments] (1995)

We conducted a multicenter trial of treatment with all-trans retinoic acid (ATRA) for newly diagnosed acute promyelocytic leukemia (APL) in the AML-92 study and compared it with our previous study with standard intensive chemotherapy, the AML-89 study, in the view of complete remission (CR) rate, incidence of early death, and event-free survival (EFS). Patients were scheduled to receive oral ATRA 45 mg/m2 daily until CR. If patients had leukocyte counts above 3 x 10(9)/L at the start of therapy, they received daunorubicine (DNR) 40 mg/m2 for 3 days and behenoyl cytosine arabinoside (BHAC) 200 mg/m2 for 5 days in addition to ATRA. During the ATRA therapy, if patients showed myeloblast plus promyelocyte counts higher than 1 x 10(9)/L in the peripheral blood, they received additional DNR and BHAC in the same schedule, as well. A total of 110 patients were entered into the study. Median age was 43 years (range, 16 to 74). Twenty-eight (26%) of 109 patients (one died before the start of therapy) received ATRA alone. Ninety-seven patients (89%) achieved CR; 48 of 49 (98%) aged less than 40 years, 44 of 52 (84%) aged between 40 and 69, and 5 of 8 (63%) aged above 70 achieved CR, respectively; 25 of 28 (89%) with ATRA alone, 46 of 51 (90%) with ATRA plus initial chemotherapy and 26 of 30 (87%) with ATRA plus later chemotherapy attained CR, respectively. Nine (8%) patients died within 28 days after the start of therapy. In contrast, 44 of 62 patients (71%) attained CR, and 13 (21%) died within 28 days in the AML-89 study with the combination of DNR, BHAC, 6-mercaptopurine and prednisolone. Seven developed retinoic acid syndrome and one died of it in the present study. Other toxicities associated with this drug included cheilitis, desquamation, muscle pain, and hypertriglyceridemia. Predicted 23 months EFS for all ATRA-treated patients and disease-free survival (DFS) in the CR cases were 75% and 81%, respectively, in a median follow-up period of 21 months. Compared to the AML-89 study, there was a highly significant difference in remission rate (P = .004), EFS (P = .0007), and also early mortality rate (P = .02). Present results demonstrated that ATRA with or without chemotherapy gives a statistical improvement in CR rate and early mortality rate, as well as superior survival in newly diagnosed APL.
Clinical trials in mild cognitive impairment: lessons for the future (2005)

Mild cognitive impairment (MCI) is an operational definition for a cognitive decline in individuals with a greater risk of developing dementia. The amnestic subtype of MCI is of particular interest because these individuals most likely progress to Alzheimer's disease (AD). Currently hypothesised therapeutic approaches in MCI are mainly based on AD treatment strategies. Long term secondary prevention randomised clinical trials have been completed in amnestic MCI populations, encompassing agents with various mechanisms of action: acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine), antioxidants (vitamin E), anti-inflammatories (rofecoxib), and nootropics (piracetam). The design of clinical trials in MCI is influenced by study objectives and definition of primary end points: time to clinical diagnosis of dementia, and AD in particular, or symptom progression. As none of the drugs previously shown to have clinical efficacy in AD trials or benefit in everyday practice have met the primary objectives of the respective trials, design of future clinical trials in MCI should be further developed particularly as regards the selection of more homogeneous samples at entry, optimal treatment duration, and multidimensional and reliable outcomes.
Analogs of the ATP-Sensitive Potassium (KATP) Channel Opener Cromakalim with in Vivo Ocular Hypotensive Activity (2016)

ATP-sensitive potassium (KATP) channel openers have emerged as potential therapeutics for the treatment of glaucoma, lowering intraocular pressure (IOP) in animal models and cultured human anterior segments. We have prepared water-soluble phosphate and dipeptide derivatives of the KATP channel opener cromakalim and evaluated their IOP lowering capabilities in vivo. In general, the phosphate derivatives proved to be more chemically robust and efficacious at lowering IOP with once daily dosing in a normotensive mouse model. Two of these phosphate derivatives were further evaluated in a normotensive rabbit model, with a significant difference in activity observed. No toxic effects on cell structure or alterations in morphology of the aqueous humor outflow pathway were observed after treatment with the most efficacious compound, (3S,4R)-2, suggesting that it is a strong candidate for development as an ocular hypotensive agent.