gebhart/patrepeval huggingface dataset:
A Tale of Three Cell Types: Alkaloid Biosynthesis Is Localized to Sieve Elements in Opium Poppy (2003)

Opium poppy produces a diverse array of pharmaceutical alkaloids, including the narcotic analgesics morphine and codeine. The benzylisoquinoline alkaloids of opium poppy accumulate in the cytoplasm, or latex, of specialized laticifers that accompany vascular tissues throughout the plant. However, immunofluorescence labeling using affinity-purified antibodies showed that three key enzymes, (S)-N-methylcoclaurine 3'-hydroxylase (CYP80B1), berberine bridge enzyme (BBE), and codeinone reductase (COR), involved in the biosynthesis of morphine and the related antimicrobial alkaloid sanguinarine, are restricted to the parietal region of sieve elements adjacent or proximal to laticifers. The localization of laticifers was demonstrated using antibodies specific to the major latex protein (MLP), which is characteristic of the cell type. In situ hybridization showed that CYP80B1, BBE, and COR gene transcripts were found in the companion cell paired with each sieve element, whereas MLP transcripts were restricted to laticifers. The biosynthesis and accumulation of alkaloids in opium poppy involves cell types not implicated previously in plant secondary metabolism and dramatically extends the function of sieve elements beyond the transport of solutes and information macromolecules in plants.
Epithelial-to-Mesenchymal Transition in Early Transplant Tubulointerstitial Damage (2008)

It is unknown whether epithelial-to-mesenchymal transition (EMT) leads to tubulointerstitial fibrosis in renal transplants. In this study, interstitial fibrosis and markers of EMT were followed in protocol transplant biopsies in 24 patients. Tubulointerstitial damage (TID) increased from 34 to 54% between 1 and 3 mo after transplantation. Detection of EMT depended on the marker used; low levels of alpha-smooth muscle actin were found in 61% of biopsies, but the less specific marker S100 calcium binding protein-A4 (also known as Fsp1) suggested a higher incidence of EMT. The presence or development of TID did not correlate with EMT but instead significantly correlated with subclinical immune activity (P < 0.05). Among biopsies showing TID, microarray analysis revealed differential regulation of 127 genes at 1 mo and 67 genes at 3 mo compared with baseline; these genes were predominantly associated with fibrosis, tissue remodeling, and immune response. Of the 173 EMT-associated genes interrogated, however, only 8.1% showed an expression pattern consistent with EMT at 1 mo and 6.3% at 3 mo. The remainder were not differentially altered, or their changes in expression were opposite those expected to promote EMT. Quantitative reverse transcriptase-PCR revealed that the expression pattern of 12 EMT-associated genes was inconsistent over time, opposite that expected, or consistent with subclinical rejection or inflammation. In conclusion, EMT does not seem to play a significant role in the development of early allograft fibrosis.
Rapidly Acquired Resistance to EGFR Tyrosine Kinase Inhibitors in NSCLC Cell Lines through De-Repression of FGFR2 and FGFR3 Expression (2010)

Despite initial and sometimes dramatic responses of specific NSCLC tumors to EGFR TKIs, nearly all will develop resistance and relapse. Gene expression analysis of NSCLC cell lines treated with the EGFR TKI, gefitinib, revealed increased levels of FGFR2 and FGFR3 mRNA. Analysis of gefitinib action on a larger panel of NSCLC cell lines verified that FGFR2 and FGFR3 expression is increased at the mRNA and protein level in NSCLC cell lines in which the EGFR is dominant for growth signaling, but not in cell lines where EGFR signaling is absent. A luciferase reporter containing 2.5 kilobases of fgfr2 5' flanking sequence was activated after gefitinib treatment, indicating transcriptional regulation as a contributing mechanism controlling increased FGFR2 expression. Induction of FGFR2 and FGFR3 protein as well as fgfr2-luc activity was also observed with Erbitux, an EGFR-specific monoclonal antibody. Moreover, inhibitors of c-Src and MEK stimulated fgfr2-luc activity to a similar degree as gefitinib, suggesting that these pathways may mediate EGFR-dependent repression of FGFR2 and FGFR3. Importantly, our studies demonstrate that EGFR TKI-induced FGFR2 and FGFR3 are capable of mediating FGF2 and FGF7 stimulated ERK activation as well as FGF-stimulated transformed growth in the setting of EGFR TKIs. In conclusion, this study highlights EGFR TKI-induced FGFR2 and FGFR3 signaling as a novel and rapid mechanism of acquired resistance to EGFR TKIs and suggests that treatment of NSCLC patients with combinations of EGFR and FGFR specific TKIs may be a strategy to enhance efficacy of single EGFR inhibitors.
Transformation of rat hepatocytes by transfection with simian virus 40 DNA to yield proliferating differentiated cells. (1986)

Cultured hepatocytes from adult Fischer 344 rats were transformed by virion or cloned simian virus 40 (SV40) DNA using the calcium phosphate method. Transformation by SV40 occurred in either serum-supplemented medium or chemically defined medium (CDM). The frequency was greatest in serum-supplemented medium but transformants did not remain differentiated. In contrast, SV40 transformants developed less frequently in CDM, but retained differentiated functions. The frequency of transformation was enhanced by treatments that stimulated cell proliferation, in particular supplementing CDM with epidermal growth factor. Hepatocytes transformed in CDM were epithelial in morphology, secreted albumin, transferrin, hemopexin, and expressed the enzyme glucose-6-phosphatase, all characteristics of normal liver. Transformants did not produce detectable levels of alpha-fetoprotein, a marker of fetal or abnormal liver. We conclude that (a) hepatocytes can be transformed by transfection with SV40 DNA; (b) the frequency of transformation is enhanced by stimulating DNA synthesis; and (c) the transformed cells retain specific functions of normal hepatocytes in situ. Using this system it will be possible to study transformation of hepatocytes by viral and cellular oncogenes and to determine their effects on hepatocellular differentiation.
Patient-specific dosimetry in predicting renal toxicity with (90)Y-DOTATOC: relevance of kidney volume and dose rate in finding a dose-effect relationship. (2005)

Radiation nephrotoxicity after (90)Y-DOTATOC therapy is dose dependent. Individual renal volume, dose rate, and fractionation play important roles in an accurate dosimetry estimation that enables prediction of risk of renal function impairment.
Retro Diels−Alder Reactions of 5,6-Disubstituted-7-oxabicyclo[2.2.1]hept-2-enes:  Experimental and Density Functional Theory Studies (2000)

Several 5,6-disubstituted-7-oxabicyclo[2.2.1]hept-2-enes (1-4) were synthesized on > or = 0.1 mol scale. The heat-induced retro Diels-Alder (rDA) decomposition of these derivatives was studied by thermal analysis, and the kinetics of the rDA were measured for 4. First-order rate constants (k = 1.91-14.2 x 10(-5) s(-1)), measured at four temperatures between 124 and 150 degrees C, were used to calculate Arrhenius activation parameters Ea (34.5 +/- 0.5 kcal/mol) and ln A (1.77 +/- 0.03 x 10(4)). The observed activation energy was significantly larger (by 9.5 kcal/mol) than that previously measured for the maleic anhydride adduct 1, and this was attributed to the difference in LUMO energies for the two dienophiles. Modeling of the activation parameters found for 4 with density functional theory (DFT) calculations for similar compounds 5 and 6 gave close quantitative correlations for deltaH double dagger, deltaG double dagger, deltaS double dagger. The rDA reactions studied were found to be entropy-driven.
Inheritance of Enzyme Activity in the Mitochondrial Respiratory Chain of Mouse (1989)

マウスRR系統のミトコンドリアDNAの制限酵素切断型はC57 BL/6,BALB/cの型と異なってる.これら3近交系と,RRと他の2系統間で戻し交雑を10世代反復することによりミトコンドリアDNAを他の型と入れ替えた系統を用い,ミトコンドリア呼吸鎖酵素活性の遺伝様式を調べた.チトクロムc酸化酵素(複合体IV)の活性において,RRが他の系統より低く,その差の一部が母性遺伝をすることを新鮮,音波処理ミトコンドリア,亜ミトコンドリア粒子を用いた実験により確認した.NADH-フェリシアナイド還元酵素(複合体I)では,RRはC57 BL/6,BALB/cより高い活性を示したが,その系統差は母性遺伝しなかった.ロテノン感受性NADH-チトクロムc還元酵素(複合体I,III)とコハク酸-チトクロムc還元酵素(複合体II,III)に系統差は見られなかった.NADHからO2まで呼吸鎖酵素全体の活性を示すロテノン感受性NADH酸化酵素活性は,チトクロムc酸化酵素の活性と関連しており,RRが他の系統より低かった.RR, C57 BL/6とこれらの戻し交雑系を用いた実験では,この酵素活性の母性遺伝が観察されたが,RR, BALB/cとこれらの戻し交雑系を用いた実験では母性遺伝は明らかでなかった.
[Foundlings, population history, and information]. (1989)

The author critically examines research on abandoned children in Portugal during the eighteenth and nineteenth centuries. Sources of data and methods of analysis are described and evaluated, and the possibility of using automatic data processing in such investigations is considered.
Cellular dynamics associated with the genome-wide epigenetic reprogramming in migrating primordial germ cells in mice (2007)

We previously reported that primordial germ cells (PGCs) in mice erase genome-wide DNA methylation and histone H3 lysine9 dimethylation (H3K9me2), and instead acquire high levels of tri-methylation of H3K27 (H3K27me3) during their migration, a process that might be crucial for the re-establishment of potential totipotency in the germline. We here explored a cellular dynamics associated with this epigenetic reprogramming. We found that PGCs undergo erasure of H3K9me2 and upregulation of H3K27me3 in a progressive, cell-by-cell manner, presumably depending on their developmental maturation. Before or concomitant with the onset of H3K9 demethylation, PGCs entered the G2 arrest of the cell cycle, which apparently persisted until they acquired high H3K27me3 levels. Interestingly, PGCs exhibited repression of RNA polymerase II-dependent transcription, which began after the onset of H3K9me2 reduction in the G2 phase and tapered off after the acquisition of high-level H3K27me3. The epigenetic reprogramming and transcriptional quiescence were independent from the function of Nanos3. We found that before H3K9 demethylation, PGCs exclusively repress an essential histone methyltransferase, GLP, without specifically upregulating histone demethylases. We suggest the possibility that active repression of an essential enzyme and subsequent unique cellular dynamics ensures successful implementation of genome-wide epigenetic reprogramming in migrating PGCs.
Microalgae as bioreactors for bioplastic production (2011)

Our studies demonstrate the great potential of microalgae like the diatom P. tricornutum to serve as solar-powered expression factories and reveal great advantages compared to plant based production systems.
Distortion model for star tracker (2010)

In order to provide the beneficial expression of lens distortion for star trackers, the numerical results of the grid distortions of four typical star tracker lens systems have been investigated, and then data fitting is done with combined multinomial of different number of terms and powers of radial radius. The results indicate that the expression of relative distortion including terms of the one, two, three and four powers of the radial distortion is beneficial in terms of accuracy, and the fitting function with high-order is not quite helpful in providing a more accurate expansion. In order to further validate this distortion model, a star tracker camera calibration approach has been simulated with the data obtained by ray tracing via the Non-Sequential Components of ZEMAX, with imperfect alignment and assembly taken into account. Simulation results also indicate that the four-order of the radial distortion is beneficial.
HIGH AFFINITY TRANSPORT OF CHOLINE INTO SYNAPTOSOMES OF RAT BRAIN1 (1973)

Abstract —The accumulation of [ 3 H]choline into synaptosome‐enriched homogenates of rat corpus striatum, cerebral cortex and cerebellum was studied at [ 3 H]choline concentrations varying from 0.5 to 100 μ m . The accumulation of [ 3 H]choline in these brain regions was saturable. Kinetic analysis of the accumulation of the radiolabel was performed by double‐reciprocal plots and by least squares iterative fitting of a substrate‐velocity curve to the data. With both of these techniques, the data were best satisfied by two transport components, a high affinity uptake system with K m . values of 1.4 μM (corpus striatum), and 3.1 μM (ceμ(cerebral cortex) and a low affinity uptake system with respective K m . values of 93 and 33 μM for these two brain regions. In the cerebellum choline was accumulated only by the low affinity system. When striatal homogenates were fractionated further into synaptosomes and mitochondria and incubated with varying concentrations of [ 3 H]choline, the high affinity component of choline uptake was localized to the synaptosomal fraction. The high affinity uptake system required sodium, was sensitive to various metabolic inhibitors and was associated with considerable formation of [ 3 H]acetylcholine. The low affinity uptake system was much less dependent on sodium, and was not associated with a marked degree of [ 3 H]acetylcholine formation. Hemicholinium‐3 and acetylcholine were potent inhibitors of the high affinity uptake system. A variety of evidence suggests that the high affinity transport represents a selective accumulation of choline by cholinergic neurons, while the low affinity uptake system has some less specific function.
A programmable co-processor for profiling (2002)

Aggressive program optimization requires accurate profile information, but such accuracy requires many samples to be collected. We explore a novel profiling architecture that reduces the overhead of collecting each sample by including a programmable co-processor that analyzes a stream of profile samples generated by a microprocessor. From this stream of samples, the co-processor can detect correlations between instructions (e.g., memory dependence profiling) as well as those between different dynamic instances of the same instruction (e.g., value profiling). The profiler's programmable nature allows a broad range of data to be extracted, post-processed, and formatted, as well as provides the flexibility to tailor the profiling application to the program under test. Because the co-processor is specialized for profiling, it can execute profiling applications more efficiently than a general-purpose processor. The co-processor should not significantly impact the cost or performance of the main processor because it can be implemented using a small number of transistors at the chip's periphery We demonstrate the proposed design through a detailed evaluation of load value profiling. Our implementation quickly and accurately estimates the value invariance of loads, with time overhead roughly proportional to the size of the instruction working set of the program. This algorithm demonstrates a number of general techniques for profiling, including: estimating the completeness of a profile, a means to focus profiling on particular instructions, management of profiling resources.
The emergence of pandemic influenza viruses (2010)

Pandemic influenza has posed an increasing threat to public health worldwide in the last decade. In the 20th century, three human pandemic influenza outbreaks occurred in 1918, 1957 and 1968, causing significant mortality. A number of hypotheses have been proposed for the emergence and development of pandemic viruses, including direct introduction into humans from an avian origin and reassortment between avian and previously circulating human viruses, either directly in humans or via an intermediate mammalian host. However, the evolutionary history of the pandemic viruses has been controversial, largely due to the lack of background genetic information and rigorous phylogenetic analyses. The pandemic that emerged in early April 2009 in North America provides a unique opportunity to investigate its emergence and development both in human and animal aspects. Recent genetic analyses of data accumulated through long-term influenza surveillance provided insights into the emergence of this novel pandemic virus. In this review, we summarise the recent literature that describes the evolutionary pathway of the pandemic viruses. We also discuss the implications of these findings on the early detection and control of future pandemics.
Discovery of Novel Potent and Selective Agonists at the Melanocortin-3 Receptor (2015)

The melanocortin receptors 3 and 4 control energy homeostasis, food-intake behavior, and correlated pathophysiological conditions. The melanocortin-4 receptor (MC4R) has been broadly investigated. In contrast, the knowledge related to physiological roles of the melanocortin-3 receptor (MC3R) is lacking because of the limited number of known MC3R selective ligands. Here, we report the design, synthesis, biological activity, conformational analysis, and docking with receptors of two potent and selective agonists at the human MC3 receptor.
An articulated antibiotic spacer used for infected total knee arthroplasty: A comparative in vitro elution study of Simplex® and Palacos® bone cements (2004)

For the staged management of infected total knee arthroplasty (TKA), antibiotic laden polymethylmethacrylate (PMMA) spacers have been recommended. Antibiotic-impregnated PMMA spacers target drug delivery, achieving high local levels while limiting the potential for host toxicity associated with parenteral antimicrobial therapy. This study examined the elution characteristics of an articulating PMMA TKA spacer that has been useful clinically. Tobramycin and vancomycin are both active against many organisms leading to joint infections. We used various combined antibiotic concentrations (maintaining a relative ratio of 55% tobramycin to 45% vancomycin w/w), and then assayed the elution profile of the TKA spacer in vitro. Additionally, the elution qualities of two brands of bone cement, Simplex and Palacos, were compared. Briefly, three groups of PMMA spacers, impregnated with different antibiotic loads, were fashioned from a mold replicating a femoral TKA component. The entire spacer surface area was immersed in sterile phosphate buffered saline (PBS) in a 1:6 ratio of grams of cement to milliliters of PBS and incubated at 37 degrees C for 24 h. After 24 h, aliquot eluates were taken, the PBS discarded, and replaced with fresh, sterile PBS. PBS was changed daily and an aliquot was taken at least weekly for nine weeks. Eluate samples were stored at -70 degrees C until assayed. Each spacer eluate sample's antibiotic concentration was determined by disc diffusion bioassay against Bacillus subtilis. Mean zone inhibition diameters were extrapolated from the standard curve to yield micrograms per milliliter of antibiotic in PBS. In all groups the Palacos spacers demonstrated higher elution levels, above the MIC for the organism used, for a longer period of time than those made with Simplex. Based on the observed elution profiles, antibiotic-impregnated Palacos bone cement may offer a more effective vehicle for local drug delivery during staged treatment of infected TKA.
Host Recognition of Bacterial Muramyl Dipeptide Mediated through NOD2 (2003)

NOD2, a protein associated with susceptibility to Crohn's disease, confers responsiveness to bacterial preparations of lipopolysaccharide and peptidoglycan, but the precise moiety recognized remains elusive. Biochemical and functional analyses identified muramyl dipeptide (MurNAc-L-Ala-D-isoGln) derived from peptidoglycan as the essential structure in bacteria recognized by NOD2. Replacement of L-Ala for D-Ala or D-isoGln for L-isoGln eliminated the ability of muramyl dipeptide to stimulate NOD2, indicating stereoselective recognition. Muramyl dipeptide was recognized by NOD2 but not by TLR2 or co-expression of TLR2 with TLR1 or TLR6. NOD2 mutants associated with susceptibility to Crohn's disease were deficient in their recognition of muramyl dipeptide. Notably, peripheral blood mononuclear cells from individuals homozygous for the major disease-associated L1007fsinsC NOD2 mutation responded to lipopolysaccharide but not to synthetic muramyl dipeptide. Thus, NOD2 mediates the host response to bacterial muropeptides derived from peptidoglycan, an activity that is important for protection against Crohn's disease. Because muramyl dipeptide is the essential structure of peptidoglycan required for adjuvant activity, these results also have implications for understanding adjuvant function and effective vaccine development.
Engineered IgG1‐Fc – one fragment to bind them all (2016)

The crystallizable fragment (Fc) of the immunoglobulin class G (IgG) is a very attractive scaffold for the design of novel therapeutics due to its quality of uniting all essential antibody functions. This article reviews the functionalization of this homodimeric glycoprotein by diversification of structural loops of CH3 domains for the design of Fcabs, i.e. antigen-binding Fc proteins. It reports the design of libraries for the selection of nanomolar binders with wildtype-like in vivo half-life and correlation of Fc receptor binding and ADCC. The in vitro and preclinical biological activity of selected Fcabs is compared with that of clinically approved antibodies. Recently, the great potential of the scaffold for the development of therapeutics for clinical use has been shown when the HER2-binding Fcab FS102 entered clinical phase I. Furthermore, methods for the engineering of biophysical properties of Fcabs applicable to proteins in general are presented as well as the different approaches in the design of heterodimeric Fc-based scaffolds used in the generation of bispecific monoclonal antibodies. Finally, this work critically analyzes and compares the various efforts in the design of highly diverse and functional libraries that have been made in the engineering of IgG1-Fc and structurally similar scaffolds.
The cerebrospinal fluid production rate is reduced in dementia of the Alzheimer’s type (2001)

These results indicate that the rate of CSF production in patients with PD is normal, and that the rate of CSF production in patients with AD is markedly reduced.
Resistance of mitochondrial DNA to degradation characterizes the apoptotic but not the necrotic mode of human leukemia cell death (1993)

Cell death can occur by two basically different processes. The original term, necrosis, is now reserved for the generally destructive series of events which include the release of lysosomal enzymes and loss of cell membrane integrity. In contrast, mild treatment with cell damaging agents, or withdrawal of growth factors, may result in a characteristic form of degradation of cellular DNA which is associated with cell death that has morphology known as apoptosis. In this study human leukemia cells were exposed to agents or conditions previously reported to cause necrosis or apoptosis, monitored by detection of DNA "ladders," and the integrity of cellular DNA was determined on Southern blots. Nuclear DNA was distinguished from mitochondrial DNA by use of probes specific for nuclear genes or for mitochondrial DNA. When HL60, K562, MOLT4, or U937 cells were exposed to conditions which resulted in necrosis, mitochondrial DNA was damaged at approximately the same rate as nuclear DNA, but in apoptosis mtDNA was not degraded. Thus, the ratio of the relative (to untreated cells) abundance of mitochondrial DNA measured by a probe for 16S mitochondrial ribosomal RNA on Southern blots, to the relative abundance of DNA of any nuclear gene, was 1 or less in necrosis, but rose to values greater than 2 in apoptosis. It is concluded that the comparison of the degree of fragmentation of mitochondrial and nuclear DNA provides a quantitative way of distinguishing necrosis from apoptosis.