gebhart/patrepeval huggingface dataset:
The A53T alpha-synuclein mutation increases iron-dependent aggregation and toxicity. (2000)

Parkinson's disease (PD) is the most common motor disorder affecting the elderly. PD is characterized by the formation of Lewy bodies and death of dopaminergic neurons. The mechanisms underlying PD are unknown, but the discoveries that mutations in alpha-synuclein can cause familial PD and that alpha-synuclein accumulates in Lewy bodies suggest that alpha-synuclein participates in the pathophysiology of PD. Using human BE-M17 neuroblastoma cells overexpressing wild-type, A53T, or A30P alpha-synuclein, we now show that iron and free radical generators, such as dopamine or hydrogen peroxide, stimulate the production of intracellular aggregates that contain alpha-synuclein and ubiquitin. The aggregates can be identified by immunocytochemistry, electron microscopy, or the histochemical stain thioflavine S. The amount of aggregation occurring in the cells is dependent on the amount of alpha-synuclein expressed and the type of alpha-synuclein expressed, with the amount of alpha-synuclein aggregation following a rank order of A53T > A30P > wild-type > untransfected. In addition to stimulating aggregate formation, alpha-synuclein also appears to induce toxicity. BE-M17 neuroblastoma cells overexpressing alpha-synuclein show up to a fourfold increase in vulnerability to toxicity induced by iron. The vulnerability follows the same rank order as for aggregation. These data raise the possibility that alpha-synuclein acts in concert with iron and dopamine to induce formation of Lewy body pathology in PD and cell death in PD.
Peptides from Peptic Hydrolyzate of Heated Sardine Meat That Inhibit Angiotensin I Converting Enzyme. (1992)

加熱処理を行ったイワシすり身をペプシンで加水分解し,その分解液(P-1)に含まれるACE阻害ペプチドの単離と配列決定を行って,以下の結果を得た. (1) P-1をODS充填カラムに通し,25%エタノールで溶出した画分F-3にはSP-Sephadexによるイオン交換クロマトグラフィーの結果,4つの主要な活性画分が含まれていた. (2) SP-Sephadexから0.1M蟻酸アンモニウムで二番目に溶出したB画分を逆相HPLCで分離した結果,多くのACE阻害活性を有するペプチドが含まれていた. (3) 逆相HPLCで高い活性を有していた画分をB-1, B-2, B-3としてサイズ排除クロマトグラフィーと逆相HPLCのリクロマトを行い,それぞれを単離し,以下のアミノ酸配列とIC50を有することを明らかにした.これらのペプチドは新規なACE阻害ペプチドであった. B-1: Val-Lys-Ala-Gly-Phe (IC50=83μM) B-2: Lys-Val-Leu-Ala-Gly-Met (IC50=30μM) B-3: Leu-Lys-Leu (IC50=188μM) (4) ホモロジー検索の結果, B-1は種々の起源のアクチンにおける17から21番目のアミノ酸配列と完全に一致することが明らかとなった.
Immunochemical detection of multiple conformations within a 36 base pair oligonucleotide (1988)

A 36 base pair chimeric oligonucleotide containing a central core of DNA duplex flanked by RNA/DNA hybrid at each end was synthesized. These distinct regions of the oligonucleotide adopt different conformations which were detected with antibody probes. Enzyme linked immunosorbent assays (ELISA) and a gel electrophoresis retardation assay were used to demonstrate the binding of antibodies which recognize B-DNA, Z-DNA and RNA/DNA hybrid. The DNA duplex core of this oligonucleotide adopts the B-conformation in 0.14 M NaCl. In high salt solution (4 M NaCl) the DNA core adopts the Z-conformation. The RNA/DNA hybrid at the ends of the oligomer adopt a conformation which is distinct from both B-DNA and A-RNA.
Introduction (2008)

Agrarianism is a way of thinking and ordering life in community that is based on the health of the land and of living creatures. Often out of step with the prevailing values of wealth, technology, and political and military domination, the mind-set and practices that constitute agrarianism have been marginalized by the powerful within most “history-making” cultures across time, including that of ancient Israel. Yet, agrarianism is the way of thinking predominant among the biblical writers, who very often do not represent the interests of the powerful. The sheer pervasiveness of their appreciation and concern for the health of the land is the single most important point of this study.
Using the domestic chicken (Gallus gallus) as an in vivo model for iron bioavailability (2010)

Iron fortification of foods and biofortification of staple food crops are strategies that can help to alleviate Fe deficiency. The broiler chicken may be a useful model for initial in vivo screening of Fe bioavailability in foods due to its growth rate, anatomy, size, and low cost. In this study, we assess the broiler as a model for hemoglobin (Hb) maintenance studies and present a unique duodenal loop technique for direct measurement of intestinal Fe absorption. One-week-old chicks were allocated into Fe-deficient versus Fe-adequate treatment groups. For 6 wk, blood Hb, feed consumption, and BW were measured. At wk 7, birds were anesthetized and their duodenal loops were exposed. The loop was isolated and a nonocclusive catheter was inserted into the duodenal vein for blood sampling. A stable isotope solution containing (58)Fe (1 mg of Fe in 10 mM ascorbic acid) was injected into the loop. Blood samples were collected every 5 min and for 120 min postinjection and analyzed by inductively coupled argon-plasma mass spectrometry for (58)Fe concentrations. In the low-Fe group, Hb concentrations, total body Hb Fe, and BW were lower and Hb maintenance efficiency (indicator for dietary Fe availability) was higher than in the high-Fe group (P < 0.05). Iron absorption was higher in the Fe-deficient birds (P < 0.05). In addition, expression of proteins involved in Fe uptake and transfer [i.e., divalent metal transporter 1 (Fe uptake transporter), ferroportin (involved in Fe transport across the enterocyte), and duodenal cytochrome B reductase (reduces Fe at brush border membrane)] were elevated in the low-Fe group. These results indicate that this model exhibits the appropriate responses to Fe deficiency and has potential to serve as a model for Fe bioavailability. Such a model should be most useful as an intermediate test of in vivo Fe bioavailability observations in preparation for subsequent human studies.
Performance Improvement of InP-based Differential HBT VCO using the Resonant Tunneling Diode (2006)

A new InP-based RTD/HBT VCO, which has two RTDs at the nodes of resonators to increase the total negative gm in the conventional HBT VCO circuit, has been proposed for the first time. The output power and phase noise of the proposed VCO have been found to be enhanced by 3.3 dBm and 8.7 dBc/Hz, respectively, compared to the conventional one.
Mortality rates after heart transplantation: How to compare center-specific outcome data? (2003)

EB methods, because they are known to incorporate more information from the data, enable a more precise and realistic portrayal of heart transplant centers' performances, compared with other risk-adjusted center effect methods. In the context of auditing procedures, EB methods should preferably be used for the identification of centers that deviate significantly from quality standards.
Interleukin-1-inducible tumor growth arrest is characterized by activation of cell type-specific “early” gene expression programs. (1992)

Human melanoma cells, A375-C6, were "committed" to growth arrest within a few hours of exposure to interleukin-1 (IL-1). Co-treatment with actinomycin D rescued the cells from the "commitment," suggesting that "early" gene activation events may be crucial for growth arrest. To understand the mechanism of IL-1 action, we are studying early genes whose expression is induced by the cytokine. Five early genes associated with IL-1 action in the melanoma cells were isolated by differential screening of a cDNA library, which was enriched for sequences representing IL-1 responsive genes (IRGs). Nucleotide sequencing identified four of the genes as gro-alpha, gro-beta, c-jun and nur77/NGF1-B/NAK1, respectively, while the fifth was judged as novel by GenBank search and designated IRG-9. None of the early genes was uniquely associated with the antiproliferative action of IL-1: other growth-inhibitory as well as growth-stimulatory signals induced these genes in diverse cell types. However, analysis of the induction patterns of the IRGs and other well known early genes revealed that IL-1 action in the melanoma cells is characterized by activation of a unique primary gene expression program. This program was defined by the magnitude and temporal pattern of induction of the five IRGs, feeble induction of c-fos, and lack of induction of Egr-1 and c-myc. We present evidence that this program is growth arrest-specific in the melanoma cells and that distinct cell type-specific programs are associated with IL-1 growth-regulatory actions in other tumor cells. Based on these data, we propose that early genes may play multifunctional roles in tumor growth control, but specificity for the growth arrest action of IL-1 is determined by the composite early gene induction program.
Postnatal NG2 proteoglycan–expressing progenitor cells are intrinsically multipotent and generate functional neurons (2003)

Neurogenesis is known to persist in the adult mammalian central nervous system (CNS). The identity of the cells that generate new neurons in the postnatal CNS has become a crucial but elusive issue. Using a transgenic mouse, we show that NG2 proteoglycan-positive progenitor cells that express the 2',3'-cyclic nucleotide 3'-phosphodiesterase gene display a multipotent phenotype in vitro and generate electrically excitable neurons, as well as astrocytes and oligodendrocytes. The fast kinetics and the high rate of multipotent fate of these NG2+ progenitors in vitro reflect an intrinsic property, rather than reprogramming. We demonstrate in the hippocampus in vivo that a sizeable fraction of postnatal NG2+ progenitor cells are proliferative precursors whose progeny appears to differentiate into GABAergic neurons capable of propagating action potentials and displaying functional synaptic inputs. These data show that at least a subpopulation of postnatal NG2-expressing cells are CNS multipotent precursors that may underlie adult hippocampal neurogenesis.
Regulation of Vascular Smooth Muscle Cell Proliferation by Nuclear Factor-κB and Its Inhibitor, I-κB (2000)

Proliferation of vascular smooth muscle cells (SMC) is a crucial event in the formation of atherosclerotic tissues and is regulated by nuclear transcriptional factors including nuclear factor-kappaB (NF-kappaB). We constructed a reporter gene assay to measure NF-kappaB-dependent transcriptional activity in SMC. Thrombin receptor-activating peptide (TRAP) and basic fibroblast growth factor (bFGF) stimulated SMC proliferation and rapidly enhanced the NF-kappaB transcriptional activity in a dose-dependent manner. 4-Cyano-5,5-bis-(methoxyphenyl)4-pentenoic acid (E5510) significantly inhibited SMC proliferation and also suppressed NF-kappaB transcription stimulated by TRAP and bFGF. In contrast, although tumor necrosis factor (TNF)-alpha activated NF-kappaB transcription, E5510 had no effect on TNF-alpha-induced activation. NF-kappaB was activated after the stimulation of TRAP, bFGF, and TNF-alpha in electrophoretic mobility shift assay, and E5510 suppressed the NF-kappaB activation induced by TRAP and bFGF but not the activation by TNF-alpha. Western blot analysis of I-kappaBalpha and I-kappaBbeta, inhibitors of NF-kappaB, indicated that I-kappaBalpha degradation, rather than I-kappaBbeta degradation, was important in NF-kappaB activation after the stimulation of TRAP and bFGF. PD98059, an inhibitor of extracellular signal-regulated kinase (ERK) kinase, suppressed NF-kappaB transcriptional activity and SMC proliferation. The phosphorylation of ERK1/2 was rapidly induced by TRAP and bFGF but not by TNF-alpha. These results indicate that TRAP and bFGF induced I-kappaB degradation and NF-kappaB activation through a distinct pathway from TNF-alpha and that ERK1/2 may play an important role in NF-kappaB activation induced by TRAP and bFGF.
Regulation and function of interleukin-36 cytokines in homeostasis and pathological conditions (2015)

IL-36α, IL-36β, and IL-36γ are members of the IL-1 family of cytokines that signal through a common receptor composed of IL-36R and IL-1R/AcP to activate NF-κB and MAPKs, such as p38 and JNK, and promote inflammatory responses. IL-36Ra is a natural antagonist of the 3 IL-36 agonists that binds to IL-36R and inhibits binding of the agonistic ligands. These cytokines are expressed predominantly by epithelial cells and act on a number of cells, including immune cells, epithelial cells, and fibroblasts. Processing of the N terminus is required for full agonist or antagonist activity for all IL-36 members. The role of IL-36 has been demonstrated extensively in the skin, where it can act on keratinocytes and immune cells to induce a robust inflammatory response and is implicated strongly through functional and genetic evidence in the pathology of psoriatic disorders. Emerging data also suggest a role for this cytokine family in pulmonary physiology and pathology. Although much has been learned about the biochemistry of IL-36 and its role in various tissues, it is clear that we are at an early stage in our understanding of the full biology of these cytokines.
An Analysis of Mek1 Signaling in Cell Proliferation and Transformation (1998)

The Mek1 dual specificity protein kinase phosphorylates and activates the mitogen-activated protein kinases Erk1 and Erk2 in response to mitogenic stimulation. The molecular events downstream of Mek and Erk necessary to promote cell cycle entry are largely undefined. In order to study signals emanating from Mek independent of upstream proteins capable of activating multiple signaling pathways, we fused the hormone-binding domain of the estrogen receptor (ER) to the C terminus of constitutively activated Mek1 phosphorylation site mutants. Although 4-OH-tamoxifen stimulation of NIH-3T3 cells expressing constitutively activated Mek-ER resulted in only a small increase in specific activity of the fusion protein, a 5-10 fold increase in total cellular Mek activity was observed over a period of 1-2 days due to an accumulation of fusion protein. Induction of constitutively activated Mek-ER in NIH-3T3 cells resulted in accelerated S phase entry, proliferation in low serum, morphological transformation, and anchorage independent growth. Endogenous Erk1 and Erk2 were phosphorylated with kinetics similar to the elevation of Mek-ER activity. However, elevated Mek-ER activity attenuated subsequent stimulation of Erk1 and Erk2 by serum. 4-OH-tamoxifen stimulation of Mek-ER-expressing fibroblasts also resulted in up-regulation of cyclin D1 expression and down-regulation of p27(Kip1) expression, establishing a direct link between Mek1 and the cell cycle machinery.
Doxycycline (1982)

The chemistry, mode of action, antimicrobial activity, pharmacokinetics, and therapeutic efficacy of doxycycline are reviewed. Doxycycline displays excellent activity against gram-positive and gram-negative aerobic and anaerobic pathogens. The oral absorption of doxycycline is rapid and virtually complete and is not significantly decreased by food. Moreover, serum concentrations of doxycycline following oral and intravenous (i.v.) administration are comparable. Because of the prolonged half-life of doxycycline, once daily administration is possible. Tissue penetration of doxycycline is excellent. Levels within the therapeutic range have been found in most organs and tissues, including kidney, lung, gallbladder, prostate, intestinal tract, myocardium, sinus secretions, tonsil, aqueous humor, and female reproductive tissue. Doxycycline does not accumulate in patients with renal insufficiency and is not removed from the blood to any great extent during hemodialysis. Extensive clinical investigation has shown doxycycline to be highly effective in infections of the respiratory tract, including atypical pneumonias; skin and soft tissue; genitourinary infection including gonorrhea, syphilis, nonspecific urethritis, and prostatitis; intraabdominal infection due to trauma, sepsis, or surgery; and cholera. Evidence also suggests that doxycycline will prove effective in the treatment of Legionnaires' disease. In addition, placebo-controlled clinical trials suggest doxycycline is effective in the prevention of traveler's diarrhea.
Design of an adenosine phosphorylase by active-site modification of murine purine nucleoside phosphorylase: Enzyme kinetics and molecular dynamics simulation of Asn-243 and Lys-244 substitutions of purine nucleoside phosphorylase (1999)

Our objective was to alter the substrate specificity of purine nucleoside phosphorylase such that it would catalyse the phosphorolysis of 6-aminopurine nucleosides. We modified both Asn-243 and Lys-244 in order to promote the acceptance of the C6-amino group of adenosine. The Asn-243-Asp substitution resulted in an 8-fold increase in K(m) for inosine from 58 to 484 microM and a 1000-fold decrease in k(cat)/K(m). The Asn-243-Asp construct catalysed the phosphorolysis of adenosine with a K(m) of 45 microM and a k(cat)/K(m) 8-fold that with inosine. The Lys-244-Gln construct showed only marginal reduction in k(cat)/K(m), 83% of wild type, but had no activity with adenosine. The Asn-243-Asp;Lys-244-Gln construct had a 14-fold increase in K(m) with inosine and 7-fold decrease in k(cat)/K(m) as compared to wild type. This double substitution catalysed the phosphorolysis of adenosine with a K(m) of 42 microM and a k(cat)/K(m) twice that of the single Asn-243-Asp substitution. Molecular dynamics simulation of the engineered proteins with adenine as substrate revealed favourable hydrogen bond distances between N7 of the purine ring and the Asp-243 carboxylate at 2.93 and 2.88 A, for Asn-243-Asp and the Asn-243-Asp;Lys-244-Gln constructs respectively. Simulation also supported a favourable hydrogen bond distance between the purine C6-amino group and Asp-243 at 2.83 and 2.88 A for each construct respectively. The Asn-243-Thr substitution did not yield activity with adenosine and simulation gave unfavourable hydrogen bond distances between Thr-243 and both the C6-amino group and N7 of the purine ring. The substitutions were not in the region of phosphate binding and the apparent S(0.5) for phosphate with wild type and the Asn-243-Asp enzymes were 1.35+/-0.01 and 1.84+/-0.06 mM, respectively. Both proteins exhibited positive co-operativity with phosphate giving Hill coefficients of 7.9 and 3.8 respectively.
Fabrication of individual vertically aligned carbon nanofibres on metal substrates from prefabricated catalyst dots (2006)

Carbon nanofibres (CNFs) of controlled diameter and length were grown on different metal substrates using plasma-enhanced chemical vapour deposition (PECVD). The diameter control of catalyst dots (and hence CNF diameter) was obtained by using the shot modulation technique in electron beam lithography. Catalyst dots of different sizes within arrays of different pitch were prepared and the dependence of the growth of vertically aligned CNFs on these parameters was studied for different metal underlayers. Good quality vertically aligned CNFs with a narrow length distribution were grown on Mo and W substrates. The structures grown on Nb substrates were significantly shorter for identical growth conditions and showed a lower nucleation rate. We demonstrate that through the shot modulation technique it is possible to control the diameter variation of CNFs from a single design geometry for the catalyst deposition. Individual VACNFs can be grown down to a pitch within the range 100–500 nm.
Model-based feedback control of autonomous underwater gliders (2001)

We describe the development of feedback control for autonomous underwater gliders. Feedback is introduced to make the glider motion robust to disturbances and uncertainty. Our focus is on buoyancy-propelled, fixed-wing gliders with attitude controlled by means of active internal mass redistribution. We derive a nonlinear dynamic model of a nominal glider complete with hydrodynamic forces and coupling between the vehicle and the movable internal mass. We use this model to study stability and controllability of glide paths and to derive feedback control laws. For our analysis, we restrict to motion in the vertical plane and consider linear control laws. For illustration, we apply our methodology to a model of our own laboratory-scale underwater glider.
Improving the performance of PHOLEDs by using dual doping (2008)

Phosphorescent organic light emitting device (PHOLED<sup>TM</sup>) technology has demonstrated record high efficiencies and long operational stability. Here we report on the introduction of an additional charge transporting dopant into the device emissive layer to further improve the luminous efficiency and device lifetime. The performance enhancement is attributed to the separation of polarons and excitons in the device emissive layer, which results in reduced triplet-triplet and triplet-polaron interactions as well as minimizing self quenching and reabsorption. Specifically we report a 50% improvement in the luminous efficiency of a red PHOLED and a 3 fold improvement of the device lifetime due to the use of dual doping. A dual doped sRGB red device with 28 cd/A and the lifetime over 300,000h at 1,000 nits is demonstrated.
Neurogenic bladder in spinal cord injury patients (2015)

Neurogenic bladder dysfunction due to spinal cord injury poses a significant threat to the well-being of patients. Incontinence, renal impairment, urinary tract infection, stones, and poor quality of life are some complications of this condition. The majority of patients will require management to ensure low pressure reservoir function of the bladder, complete emptying, and dryness. Management typically begins with anticholinergic medications and clean intermittent catheterization. Patients who fail this treatment because of inefficacy or intolerability are candidates for a spectrum of more invasive procedures. Endoscopic managements to relieve the bladder outlet resistance include sphincterotomy, botulinum toxin injection, and stent insertion. In contrast, patients with incompetent sphincters are candidates for transobturator tape insertion, sling surgery, or artificial sphincter implantation. Coordinated bladder emptying is possible with neuromodulation in selected patients. Bladder augmentation, usually with an intestinal segment, and urinary diversion are the last resort. Tissue engineering is promising in experimental settings; however, its role in clinical bladder management is still evolving. In this review, we summarize the current literature pertaining to the pathology and management of neurogenic bladder dysfunction in patients with spinal cord injury.
Characterization of the Light-Responsive Promoter of Rice Chloroplast psbD-C Operon and the Sequence-Specific DNA Binding Factor (1996)

The transcription of rice plastid psbD-psbC genes encoding photosystem II reaction center protein D2 and chlorophyll alpha-binding protein CP43 is closely regulated by light. To elucidate the sequence requirement for the light-responsive promoter of psbD-psbC operon, transcriptional analysis of the rice promoter was performed with deleted mutants and site-directed mutants in vitro. Deletion of -546 approximately -100 upstream sequences resulted in 4- to 5-fold decrease in the transcription rate. Further deletion of -99 approximately -40 conserved region of repeated sequences resulted in 2-fold decrease in the transcription rate. The core light-responsive promoter requires "-10" element but not "-35" element for accurate initiation of basal transcription. No downstream promoter element was found in the +4 approximately +111 region. The competitive gel-retardation experiments revealed the presence of DNA-binding protein in the rice chloroplasts, which interacts specifically with the -60 approximately -37 repeated sequences. Southwestern blot analysis further demonstrated that the binding factor is composed of 36-kDa polypeptide(s).