gebhart/patrepeval huggingface dataset:
Protein/Amphipathic Polyamine Complexes Enable Highly Efficient Transfection with Minimal Toxicity (1997)

Ternary complexes of plasmid DNA, histone H1 protein and amphipathic polyamines (PAPA) were able to mediate the efficient transfection of 3T3. HeLa and COS cells in culture. Using both the beta-galactosidase and luciferase reporter gene systems, the transfection efficiency of PAPA complexes was comparable to that of DOSPA/PE cationic liposomes, considered to be a highly-efficient transfection reagent. Using three different assays of cellular toxicity (propidium iodide, BCECF-AM and Trypan Blue), the PAPA complexes caused minimal cellular toxicity. These results indicate that PAPA complexes are useful transfection reagents for the study of gene expression and function in cultured cells.
Carrier-induced epitopic suppression, a major issue for future synthetic vaccines. (1985)

Synthetic antigens have been shown, in experimental models, to induce protective immunity against a variety of pathogens. These studies have demonstrated that, due to their low immunogenicity, these synthetic antigens required conjugation to carrier molecules. Therefore, the choice of appropriate carriers for human immunization by future synthetic vaccines is a major issue. Tetanus toxoid is generally considered to be an effective potential carrier devoid of side-effects. However, the present study performed in mice with two synthetic vaccine models demonstrates that the immune response against the synthetic epitopes conjugated to tetanus toxoid can be suppressed by pre-existing immunity against this same carrier. Because most humans have been exposed to this antigen, this effect may have important implications for the development of synthetic vaccines.
Analysis of angular and radial distributions of gamma's energy deposition in scintillation optical fiber based on GEANT3 system (2000)

This article gives the method and result of measuring angular and radialdistributions of gamma's energy deposition in scintillation optical fiber by numericsimulation of GEANT3 system.
The Arg7Lys Mutant of Heat-Labile Enterotoxin Exhibits Great Flexibility of Active Site Loop 47-56 of the A Subunit (1995)

The heat-labile enterotoxin from Escherichia coli (LT) is a member of the cholera toxin family. These and other members of the larger class of AB5 bacterial toxins act through catalyzing the ADP-ribosylation of various intracellular targets including Gs alpha. The A subunit is responsible for this covalent modification, while the B pentamer is involved in receptor recognition. We report here the crystal structure of an inactive single-site mutant of LT in which arginine 7 of the A subunit has been replaced by a lysine residue. The final model contains 103 residues for each of the five B subunits, 175 residues for the A1 subunit, and 41 residues for the A2 subunit. In this Arg7Lys structure the active site cleft within the A subunit is wider by approximately 1 A than is seen in the wild-type LT. Furthermore, a loop near the active site consisting of residues 47-56 is disordered in the Arg7Lys structure, even though the new lysine residue at position 7 assumes a position which virtually coincides with that of Arg7 in the wild-type structure. The displacement of residues 47-56 as seen in the mutant structure is proposed to be necessary for allowing NAD access to the active site of the wild-type LT. On the basis of the differences observed between the wild-type and Arg7Lys structures, we propose a model for a coordinated sequence of conformational changes required for full activation of LT upon reduction of disulfide bridge 187-199 and cleavage of the peptide loop between the two cysteines in the A subunit.(ABSTRACT TRUNCATED AT 250 WORDS)
Tactile imaging: a method for documenting breast masses (2003)

We present a new method of imaging soft tissues that promises to improve the documentation of the size of breast masses. This system makes a series of distributed pressure measurements and averages them into a composite tactile map of the palpable structure. We estimated mass size from tactile maps made in a limited clinical trial. The system proved to be nearly three times as accurate as ultrasound and manual estimates of mass size.
Lipid peroxidation and alteration of membrane lipids in isolated hepatocytes exposed to carbon tetrachloride. (1976)

Lipid peroxidation, determined by malondialdehyde formation, occurs at a low, but detectable, rate in parenchymal cells isolated from livers of fasted rats. Pretreatment of rats with phenobarbital increased malondialdehyde formation about 2-fold, probably because of the increased amount of endoplasmic reticulum. Lipid peroxidation was increased in the cells by the addition of either NADPH or CCl4, and the effect of the two agents together was more than additive. Phenobarbital pretreatment increased peroxidation due to exposure of the cells to CCl4 but not that associated with NADPH addition. The amount of CCl4 producing a 50% increase in malondialdehyde formation was about 3-fold less for cells from phenobarbital-treated rats than for those from control rats. Decreased cytochrome P450 levels in isolated hepatocytes produced by prior treatment of rats with allylisopropylacetamide enhanced lipid peroxidation from endogenous substrates but did not affect lipid peroxidation caused by the addition of NADPH. Allylisopropylacetamide markedly lowered lipid peroxidation caused by CCl4 in proportion to the loss of cytochrome P450. Malondialdehyde production associated with metabolism of endogenous substrates in the cells, or resulting from incubation of the cells with NADPH was not accompanied by changes in the fatty acid or protein content of three membranous fractions (microsomal mitochondrial, and cell debris) isolated from homogenates of these cells. Exposure of liver cells to CCl4, however, caused major losses in all fatty acids and of protein from the microsomal fraction, but only polyunsaturated fatty acids were decreased in the cellular debris fraction. Incubation with NADPH and CCl4 together enhanced malondialdehyde formation, but caused no further decrease in fatty acid content in these two fractions. Mitochondrial fatty acids were not decreased by any treatments described.
Multiscale MAP filtering of SAR images (2001)

Synthetic aperture radar (SAR) images are disturbed by a multiplicative noise depending on the signal (the ground reflectivity) due to the radar wave coherence. Images have a strong variability from one pixel to another reducing essentially the efficiency of the algorithms of detection and classification. We propose to filter this noise with a multiresolution analysis of the image. The wavelet coefficient of the reflectivity is estimated with a Bayesian model, maximizing the a posteriori probability density function. The different probability density function are modeled with the Pearson system of distributions. The resulting filter combines the classical adaptive approach with wavelet decomposition where the local variance of high-frequency images is used in order to segment and filter wavelet coefficients.
Involvement of STAT3 in the Granulocyte Colony-stimulating Factor-induced Differentiation of Myeloid Cells (1997)

Granulocyte colony-stimulating factor (G-CSF) stimulates proliferation and differentiation of the progenitor cells of neutrophilic granulocytes. The binding of G-CSF to its receptor specifically activates JAK1 and JAK2 kinases, as well as STAT3, a signal transducer and activator of transcription (STAT). To examine the role of STAT3 in G-CSF receptor-mediated signal transduction, two different forms of the dominant negative STAT3 were introduced into a mouse myeloid cell line that exogenously expresses the mouse G-CSF receptor. In response to G-CSF, the parental myeloid cells grew for about 4 days, and then they stopped dividing and differentiated into cells with lobulated nuclei. During this period, the expression of the myeloperoxidase (MPO) gene was induced, while c-myc gene expression was down-regulated. In contrast, in the cells expressing the dominant negative STAT3, G-CSF could induce neither growth arrest nor morphological change. However, the induction of the MPO gene by G-CSF was not affected by the dominant negative STAT3. These results indicate that STAT3 activation is responsible for part of the G-CSF-induced differentiation of neutrophils but that another pathway, involving the expression of the MPO gene, that does not utilize the activated STAT3, is also required to fully differentiate the cells.
Regulatory Lymphocytes and Intestinal Inflammation (2009)

The immune system is pivotal in mediating the interactions between host and microbiota that shape the intestinal environment. Intestinal homeostasis arises from a highly dynamic balance between host protective immunity and regulatory mechanisms. This regulation is achieved by a number of cell populations acting through a set of shared regulatory pathways. In this review, we summarize the main lymphocyte subsets controlling immune responsiveness in the gut and their mechanisms of control, which involve maintenance of intestinal barrier function and suppression of chronic inflammation. CD4(+)Foxp3(+) T cells play a nonredundant role in the maintenance of intestinal homeostasis through IL-10- and TGF-beta-dependent mechanisms. Their activity is complemented by other T and B lymphocytes. Because breakdown in immune regulatory networks in the intestine leads to chronic inflammatory diseases of the gut, such as inflammatory bowel disease and celiac disease, regulatory lymphocytes are an attractive target for therapies of intestinal inflammation.
Retinal transplants can drive a pupillary reflex in host rat brains. (1987)

Retinae taken from embryonic rats were transplanted over the midbrain of neonatal rats, from whom one eye had been removed. After 5 months, the optic nerve of the remaining eye was cut, and the transplant was exposed. Illumination of the transplant caused pupilloconstriction of the host eye, a response abolished by damaging the transplant. Thus neural transplants are capable of driving specific reflexes in response to natural stimuli.
Differences in brain gene expression between sleep and waking as revealed by mRNA differential display and cDNA microarray technology (1999)

The consequences of sleep and sleep deprivation at the molecular level are largely unexplored. Knowledge of such molecular events is essential to understand the restorative processes occurring during sleep as well as the cellular mechanisms of sleep regulation. Here we review the available data about changes in neural gene expression across different behavioural states using candidate gene approaches such as in situ hybridization and immunocytochemistry. We then describe new techniques for systematic screening of gene expression in the brain, such as subtractive hybridization, mRNA differential display, and cDNA microarray technology, outlining advantages and disadvantages of these methods. Finally, we summarize our initial results of a systematic screening of gene expression in the rat brain across behavioural states using mRNA differential display and cDNA microarray technology. The expression pattern of approximately 7000 genes was analysed in the cerebral cortex of rats after 3 h of spontaneous sleep, 3 h of spontaneous waking, or 3 h of sleep deprivation. While the majority of transcripts were expressed at the same level among these three conditions, 14 mRNAs were modulated by sleep and waking. Six transcripts, four more expressed in waking and two more expressed in sleep, corresponded to novel genes. The eight known transcripts were all expressed at higher levels in waking than in sleep and included transcription factors and mitochondrial genes. A possible role for these known transcripts in mediating neural plasticity during waking is discussed.
Effects of α-Phenyl-N-tert-butyl Nitrone (PBN) on Compression Injury of Rat Spinal Cord (1997)

alpha-Phenyl-N-tert-butyl Nitrone (PBN) is a free radical scavenger which recently has proved to be neuroprotective in experimental studies on focal cerebral ischemia and infarction. We therefore studied the effect of this drug in a model of moderate compression injury to rat spinal cord at the midthoracic level. The compound was given intraperitoneally 0.5 h before (100 mg/kg b.w) and at 1.5 h (50 mg/kg b.w) and 3.5 h (50 mg/kg b.w) after compression. Treated animals and controls (vehicle alone) were allowed to survive for 1 or 9 days following trauma. The functional outcome was tested by the inclined plane method and the motor performance score. By using MAP2 immunostaining the number of nerve cell bodies in the ventral horn and the ratio of MAP2 immunostained area to area of whole section of the cord were assessed to detect loss of neurons and loss of dendrites in the compressed segment. beta APP and PGP9.5 immunostaining was used to demonstrate axonal lesions. Treated and control rats showed at day 1 when tested with the inclined plane method a marked reduction of the capacity angle. This abnormality recovered gradually over the following days and was normalized at day 9. The motor performance score showed a marked reduction at day 1 which almost normalized at day 9. There was no difference regarding the functional outcome between rats given PBN and controls in none one of these functional tests. The spinal cord of normal rats presented immunoreactivity to MAP2 in nerve cell bodies and dendrites but not in axons and other structures. Following compression there was at day 1 and 9 a marked loss of MAP2 immunoreactivity in dendrites and nerve cell bodies. We could not detect any difference between the PBN and the control rats regarding the degree of cell loss or degree of reduction of dendrite staining. No difference between the two groups was seen with the axonal immunostainings (beta APP and PGP9.5). In conclusion, our study did not reveal any neuroprotective effect of PBN on the functional outcome and morphology (immunostaining to MAP2, beta APP and PGP9.5) in this model of moderate compression trauma to rat spinal cord.
Combinatorial Screenings in Patients (2004)

Direct screening of combinatorial peptide libraries in patients may allow the identification of ligands that target biochemical differences in the endothelium of blood vessels. In a screening performed in a patient, we selected and isolated a mimic motif of interleukin 11 (IL-11) from prostate biopsies after an i.v. administration of a phage display peptide library. We also demonstrated that the IL-11 phage mimic (displaying the cyclic nonapeptide CGRRAGGSC) bound specifically to a corresponding IL-11 receptor (IL-11Ralpha). Here we show that IL-11Ralpha is a potential target for intervention in human prostate cancer through morphological and functional analyses. First, a comprehensive serial immunohistochemical analysis of primary and metastatic prostate cancer samples showed increased stage-specific expression of IL-11Ralpha during disease progression. Second, a proapoptotic peptide was specifically targeted and internalized through this functional IL-11Ralpha-based ligand-receptor pair: treatment of prostate cancer cells in vitro with a proapoptotic peptide guided by the CGRRAGGSC peptide to the IL-11Ralpha resulted in dose-dependent apoptosis. Together, these data indicate that the IL-11Ralpha is a candidate target for translational clinical trials against advanced and metastatic prostate cancer. Moreover, our results illustrate the ability of direct combinatorial screening systems in cancer patients for identification of relevant targets in the context of human disease.
Involvement of the multilineage CD38 molecule in a unique pathway of cell activation and proliferation. (1990)

We report clear evidence that the interaction of the CD38 molecule with the specific mAb A10 on normal human cells and lines modulates the expression of surface activation markers relevant to T, NK, and plasma cell biology and functions. Moreover A10 mAb binding is followed by proliferation effects on all the target cells analyzed, and the phenomenon is accessory cell and IL-2 dependent. The effects of A10 mAb synergizing both CD2 and CD3 activation pathways indicate that CD38 signal transduction mechanism(s) are apparently different from the aforementioned. Nevertheless the decreased A10-driven proliferation after CD3-Ti modulation suggests a possible functional interdependence between these activation pathways. Taken together, the results indicate that the CD38 molecule might play a physiologic role in T, NK, and plasma cell regulation.
Proliferation, morphology, and protein expression by osteoblasts cultured on poly(anhydride-co-imides) (1999)

In vitro cell biocompatibility models are crucial in the study of any newly synthesized material. Our focus has been on the development of a new class of biocompatible, degradable, high-strength polymeric materials, the poly(anhydride-co-imides), for use in bone regeneration. This study examined osteoblast cell adherence, proliferation, viability, and phenotypic preservation on the surface of the poly(anhydride-co-imide) poly[pyromellitylimidoalanine (PMA-ala):1,6-bis(carboxyphenoxy) hexane (CPH)] over a period of time. Cell proliferation on PMA-ala:CPH degradable matrices over 21 days was examined. Throughout the 21-day period of study, osteoblast proliferation was similar on PMA-ala:CPH and on tissue culture polystyrene controls. Osteoblasts maintained their characteristic morphology as demonstrated by both scanning electron microscopy and immunofluorescence studies. Alkaline phosphatase activity for cells grown on PMA-ala:CPH was confirmed. Retention of the osteoblastic phenotype was demonstrated using immunofluorescence techniques and staining with antibodies against osteocalcin (an extracellular matrix protein of bone) and osteopontin (a marker of cell adhesion). Radioimmunoassay results provided evidence that levels of osteocalcin production by osteoblasts were similar when cells were cultured on PMA-ala:CPH and on tissue culture polystyrene controls. The present study provided evidence of normal osteoblast function on PMA-ala:CPH surfaces. PMA-ala:CPH may therefore be useful as a synthetic material for orthopedic applications.
Suicide gene therapy of chemically induced mammary tumor in rat: efficacy and distant bystander effect. (1998)

We examined the efficacy of suicide gene therapy for nitrosomethylurea-induced mammary tumors in rats. Individual tumors were directly injected with a retrovirus-producing cell line that releases retroviral vectors that transduce the herpes simplex virus type 1 thymidine kinase (HSV1-TK) gene. HSV1-TK specifically converts the nucleoside analogue ganciclovir (GCV) into a toxic metabolite. Compared to control rats receiving saline, we observed a significant tumor regression of the injected tumors following GCV administration, accompanied by a stromal inflammation and an extensive lymphocyte infiltration invading the tumor epithelium. It is noteworthy that the neighboring uninjected tumors also regressed, demonstrating the occurrence of a distant bystander effect. This is the first demonstration that HSV1-TK/GCV can efficiently treat multiple solid tumors directly generated from an epithelial tissue.
Complete Genome Structure of the Nitrogen-fixing Symbiotic Bacterium Mesorhizobium loti (2000)

The complete nucleotide sequence of the genome of a symbiotic bacterium Mesorhizobium loti strain MAFF303099 was determined. The genome of M. loti consisted of a single chromosome (7,036,071 bp) and two plasmids, designated as pMLa (351,911 bp) and pMLb (208, 315 bp). The chromosome comprises 6752 potential protein-coding genes, two sets of rRNA genes and 50 tRNA genes representing 47 tRNA species. Fifty-four percent of the potential protein genes showed sequence similarity to genes of known function, 21% to hypothetical genes, and the remaining 25% had no apparent similarity to reported genes. A 611-kb DNA segment, a highly probable candidate of a symbiotic island, was identified, and 30 genes for nitrogen fixation and 24 genes for nodulation were assigned in this region. Codon usage analysis suggested that the symbiotic island as well as the plasmids originated and were transmitted from other genetic systems. The genomes of two plasmids, pMLa and pMLb, contained 320 and 209 potential protein-coding genes, respectively, for a variety of biological functions. These include genes for the ABC-transporter system, phosphate assimilation, two-component system, DNA replication and conjugation, but only one gene for nodulation was identified.
A Phase 2 Cancer Chemoprevention Biomarker Trial of Isoflavone G-2535 (Genistein) in Presurgical Bladder Cancer Patients (2012)

The soy compound genistein has been observed preclinically to inhibit bladder cancer growth with one potential mechanism being the inhibition of epidermal growth factor receptor phosphorylation (p-EGFR). A phase 2 randomized, placebo-controlled trial investigated whether daily, oral genistein (300 or 600 mg/d as the purified soy extract G-2535) for 14 to 21 days before surgery alters molecular pathways in bladder epithelial tissue in 59 subjects diagnosed with urothelial bladder cancer (median age, 71 years). G-2535 treatment was well tolerated; observed toxicities were primarily mild to moderate gastrointestinal or metabolic and usually not attributed to study drug. Genistein was detected in plasma and urine of subjects receiving G-2535 at concentrations greater than placebo subjects' but were not dose-dependent. Reduction in bladder cancer tissue p-EGFR staining between the placebo arm and the combined genistein arms was significant at the protocol-specified significance level of 0.10 (P = 0.07). This difference was most prominent when comparing the 300-mg group with placebo (P = 0.015), but there was no significant reduction in p-EGFR staining between the 600-mg group and placebo. No difference in normal bladder epithelium p-EGFR staining was observed between treatment groups. No significant differences in tumor tissue staining between treatment groups were observed for COX-2, Ki-67, activated caspase-3, Akt, p-Akt, mitogen-activated protein kinase (MAPK), or p-MAPK. No significant differences in urinary survivin or BLCA-4 levels between treatment groups were observed. Genistein displayed a possible bimodal effect (more effective at the lower dose) on bladder cancer tissue EGFR phosphorylation that should be evaluated further, possibly in combination with other agents.
Neural Machine Translation of Rare Words with Subword Units (2016)

Neural machine translation (NMT) models typically operate with a fixed vocabulary, but translation is an open-vocabulary problem. Previous work addresses the translation of out-of-vocabulary words by backing off to a dictionary. In this paper, we introduce a simpler and more effective approach, making the NMT model capable of open-vocabulary translation by encoding rare and unknown words as sequences of subword units. This is based on the intuition that various word classes are translatable via smaller units than words, for instance names (via character copying or transliteration), compounds (via compositional translation), and cognates and loanwords (via phonological and morphological transformations). We discuss the suitability of different word segmentation techniques, including simple character ngram models and a segmentation based on the byte pair encoding compression algorithm, and empirically show that subword models improve over a back-off dictionary baseline for the WMT 15 translation tasks EnglishGerman and EnglishRussian by up to 1.1 and 1.3 BLEU, respectively.