gebhart/patrepeval huggingface dataset:
IAR4, a Gene Required for Auxin Conjugate Sensitivity in Arabidopsis, Encodes a Pyruvate Dehydrogenase E1α Homolog (2004)

The formation and hydrolysis of indole-3-acetic acid (IAA) conjugates represent a potentially important means for plants to regulate IAA levels and thereby auxin responses. The identification and characterization of mutants defective in these processes is advancing the understanding of auxin regulation and response. Here we report the isolation and characterization of the Arabidopsis iar4 mutant, which has reduced sensitivity to several IAA-amino acid conjugates. iar4 is less sensitive to a synthetic auxin and low concentrations of an ethylene precursor but responds to free IAA and other hormones tested similarly to wild type. The gene defective in iar4 encodes a homolog of the E1alpha-subunit of mitochondrial pyruvate dehydrogenase, which converts pyruvate to acetyl-coenzyme A. We did not detect glycolysis or Krebs-cycle-related defects in the iar4 mutant, and a T-DNA insertion in the IAR4 coding sequence conferred similar phenotypes as the originally identified missense allele. In contrast, we found that disruption of the previously described mitochondrial pyruvate dehydrogenase E1alpha-subunit does not alter IAA-Ala responsiveness or confer any obvious phenotypes. It is possible that IAR4 acts in the conversion of indole-3-pyruvate to indole-3-acetyl-coenzyme A, which is a potential precursor of IAA and IAA conjugates.
Unmanned Air Vehicle/Remotely Piloted Vehicle Analysis for Lethal UAV/ RPV (1993)

An investigation was conducted to provide a comprehensive evaluation of current Unmanned Aircraft Vehicle/Remotely Piloted Vehicle (UAV/RPV) system and its applicability as a lethal weapon system. Numerous systems were evaluated while concentrating on the Department of Defense more prominent programs, the Pioneer UAV, Vertical Takeoff and Landing (VTOL) UAV and BQM-147A (EXDRONE) UAV. Israel has proven time and time again, that UAVs/RPVs, when properly integrated into the combat arena as a lethal weapon system, can contribute significantly at a lower cost with less risk to an aircrew man in a manned aircraft system. In general the thesis shows many capable UAV/RPV systems designs are available in the market place today. These systems are assessed to determine their viability in the every changing combat environment. Unmanned air vehicle/remotely piloted vehicle, UAV/RPV, Vertical takeoff and landing.
Studies of cGMP analog specificity and function of the two intrasubunit binding sites of cGMP-dependent protein kinase. (1986)

The specificity of the two intrasubunit cGMP binding sites of cGMP-dependent protein kinase was determined by measuring the ability of 46 cGMP analogs to compete with [3H]cGMP. Both sites of the enzyme exhibited high specificity for the ribose cyclic phosphate moiety, and lower specificity for the guanine moiety. Effects of modifications in the ribose cyclic phosphate moiety suggested that cGMP is bound at both sites by three hydrogen bonds at 2'-OH, 3'-O, and 5'-O. A negative charge in the cyclic phosphate is apparently required. Modifications of the pyrimidine part of guanine, particularly at C-1, generally caused selectivity for the rapidly exchanging site while modifications of the imidazole part of guanine at C-7 and C-8 caused selectivity for the slowly exchanging site. These increases in selectivity for a site were mainly due to losses in affinity of the other site. There was an apparent requirement of the intact amino group at C-2, particularly for the slowly exchanging site. Comparison of the molecular interactions of cAMP and cGMP with their specific protein kinases showed that both nucleotides are bound by similar forces in the 2', 3' and 5' region, both bases may be bound in syn conformation, but that each base moiety is bound by different molecular interaction, thus leading to the selectivity of the two enzymes. cGMP analogs which possessed strong selectivity for the rapidly exchanging site, but not those selective for the slowly exchanging site, stimulated the binding of [3H]cGMP. Only a few cGMP analogs were more potent than cGMP in stimulating protein kinase activity. The potency of cGMP analogs as stimulators of kinase activity correlated better with the mean binding affinity for both binding sites than with the affinity for either site alone. Two analogs added in combination were synergistic in kinase activation, particularly if one analog was selective for the slowly exchanging site and the other for the rapidly exchanging site. These observations are suggestive that cGMP binding at the rapidly exchanging site stimulates cGMP binding at the slowly exchanging site and that both sites are involved in the activation process.
Dengue — Quo tu et quo vadis? (2011)

Dengue viruses (DENV) are by far the most important arboviral pathogens in the tropics around the world, putting at risk of infection nearly a third of the global human population. DENV are members of the genus Flavivirus in the Family Flaviviridae and comprise four antigenically distinct serotypes (DENV-1-4). Although they share almost identical epidemiological features, they are genetically distinct. Phylogenetic analyses have revealed valuable insights into the origins, epidemiology and the forces that shape DENV evolution in nature. In this review, we examine the current status of DENV evolution, including but not limited to rates of evolution, selection pressures, population sizes and evolutionary constraints, and we discuss how these factors influence transmission, pathogenesis and emergence.
The effects of local administration of lactoferrin on inflammation in murine autoimmune and infectious arthritis (2000)

Lactoferrin may have clinical utility in reducing articular inflammation, particularly in septic arthritis, in which antiinflammatory effects may be achieved without promoting bacterial survival.
Fabrication of PLGA microvessel scaffolds with circular microchannels using soft lithography (2007)

A simple micromolding method for fabricating PLGA (poly(lactic-co-glycolic acid)) microstructures made up of microchannels with a circular cross-section is presented. The thermal reflow technique is adopted to fabricate the semi-cylindrical photoresist master. The PLGA solution is prepared by dissolving PLGA polymer in acetone and then casting the solution onto the semi-cylindrical photoresist master to produce PLGA microstructures. Two PLGA membranes are bonded together to form microstructures consisting of circular microchannels. A microvessel scaffold suitable for tissue engineering was fabricated using the proposed method, and bovine endothelial cells were cultured into the scaffold by semi-dynamic seeding. The cell stain Calcein-AM was used to overcome the problem of the PLGA scaffolds becoming opaque, which in the past had made it difficult to effectively monitor the progress of cell seeding.
Drug-induced apoptosis in hepatoma cells is mediated by the CD95 (APO-1/Fas) receptor/ligand system and involves activation of wild-type p53. (1997)

Chemotherapeutic drugs are cytotoxic by induction of apoptosis in drug-sensitive cells. We investigated the mechanism of bleomycin-induced cytotoxicity in hepatoma cells. At concentrations present in the sera of patients during therapy, bleomycin induced transient accumulation of nuclear wild-type (wt) p53 and upregulated expression of cell surface CD95 (APO-1/Fas) receptor in hepatoma cells carrying wt p53 (HepG2). Bleomycin did not increase CD95 in hepatoma cells with mutated p53 (Huh7) or in hepatoma cells which were p53-/- (Hep3B). In addition, sensitivity towards CD95-mediated apoptosis was also increased in wt p53 positive HepG2 cells. Microinjection of wt p53 cDNA into HepG2 cells had the same effect. In contrast, bleomycin did not enhance susceptibility towards CD95-mediated apoptosis in Huh7 and in Hep3B cells. Furthermore, bleomycin treatment of HepG2 cells increased CD95 ligand (CD95L) mRNA expression. Most notably, bleomycin-induced apoptosis in HepG2 cells was almost completely inhibited by antibodies which interfere with CD95 receptor/ligand interaction. These data suggest that apoptosis induced by bleomycin is mediated, at least in part, by p53-dependent stimulation of the CD95 receptor/ligand system. The same applies to other anti-cancer drugs such as cisplatin and methotrexate. These data may have major consequences for drug treatment of cancer and the explanation of drug sensitivity and resistance.
Nitric oxide regulation of cGMP production in osteoclasts (1999)

Bone resorption by osteoclasts is modified by agents that affect cyclic guanosine monophosphate (cGMP), but their relative physiological roles, and what components of the process are present in osteoclasts or require accessory cells such as osteoblasts, are unclear. We studied cGMP regulation in avian osteoclasts, and in particular the roles of nitric oxide and natriuretic peptides, to clarify the mechanisms involved. C-type natriuretic peptide drives a membrane guanylate cyclase, and increased cGMP production in mixed bone cells. However, C-type natriuretic peptide did not increase cGMP in purified osteoclasts. By contrast, osteoclasts did produce cGMP in response to nitric oxide (NO) generators, sodium nitroprusside or 1-hydroxy-2-oxo-3,3-bis(3-aminoethyl)-1-triazene. These findings indicate that C-type natriuretic peptide and NO modulate cGMP in different types of bone cells. The activity of the osteoclast centers on HCI secretion that dissolves bone mineral, and both NO generators and hydrolysis-resistant cGMP analogues reduced bone degradation, while cGMP antagonists increased activity. NO synthase agonists did not affect activity, arguing against autocrine NO production. Osteoclasts express NO-activated guanylate cyclase and cGMP-dependent protein kinase (G-kinase). G-kinase reduced membrane HCI transport activity in a concentration-dependent manner, and phosphorylated a 60-kD osteoclast membrane protein, which immunoprecipitation showed is not an H+-ATPase subunit. We conclude that cGMP is a negative regulator of osteoclast activity. cGMP is produced in response to NO made by other cells, but not in response to C-type natriuretic peptide. G-kinase modulates osteoclast membrane HCI transport via intermediate protein(s) and may mediate cGMP effects in osteoclasts.
Photochemistry of manganese porphyrins. Part 2.—Photoreduction (1979)

Both manganese(II) and (III) porphyrins exhibit low-intensity, short-lived luminescence in ethanol solution at 77 K. Manganese(II) porphyrins are stable towards photodecomposition when irradiated in fluid solution but undergo efficient photoreduction in the presence of a good hydrogen donor such as ascorbic acid. Manganese(III) porphyrins are reduced to the manganese(II) compounds when irradiated with visible light but the quantum yields are very low (≈ 10–4). In water, the quantum yield depends upon pH and excitation wavelength but is independent of the nature of the water-solubilising group. The predominant reaction pathway involves intramolecular reduction via an axially coordinated water molecule. Manganese(IV) porphyrins, which are better described as the manganese(III)π-radical cations, undergo relatively efficient photoreduction in water. Here, reduction leads to formation of hydrogen peroxide and involves attack at the ring periphery rather than at an axial position.
Interaction of a Golgi-Associated Kinesin-Like Protein with Rab6 (1998)

Rab guanosine triphosphatases regulate vesicular transport and membrane traffic within eukaryotic cells. Here, a kinesin-like protein that interacts with guanosine triphosphate (GTP)-bound forms of Rab6 was identified. This protein, termed Rabkinesin-6, was localized to the Golgi apparatus and shown to play a role in the dynamics of this organelle. The carboxyl-terminal domain of Rabkinesin-6, which contains the Rab6-interacting domain, inhibited the effects of Rab6-GTP on intracellular transport. Thus, a molecular motor is a potential effector of a Rab protein, and coordinated action between members of these two families of proteins could control membrane dynamics and directional vesicular traffic.
A Practical Total Synthesis of Globo-H for Use in Anticancer Vaccines (2009)

An improved synthesis of the hexasaccharide MBr1 antigen (globo-H) is reported. Enhanced efficiency in the synthesis was necessary for the scale-up production of globo-H, in order to advance globo-H-based anticancer vaccines to clinical trials. The key features of the improved synthesis include preactivation-based glycosylations and a revised iodosulfonimidation/rearrangement.
Abstract 14033: Hemodynamic Responses and Histological Effects of Radiofrequency Catheter Ablation to Renal Artery Sympathetic Nerve (2012)

Background: Radiofrequency (RF) catheter ablation of the renal artery is therapeutic in patients with drug-refractory essential hypertension, although details of the therapeutic mechanisms have not...
Road to New York (2005)

Subtitle: Several Greek shipowners have trodden a path to US investors to raise funds through share issues. Stephen Matthews asks whether this is astute financial management or simply short-term opportunism that will store up problems for the future.
Targeting Antioxidants to Mitochondria by Conjugation to Lipophilic Cations (2006)

Mitochondrial oxidative damage contributes to a range of degenerative diseases. Consequently, the selective inhibition of mitochondrial oxidative damage is a promising therapeutic strategy. One way to do this is to invent antioxidants that are selectively accumulated into mitochondria within patients. Such mitochondria-targeted antioxidants have been developed by conjugating the lipophilic triphenylphosphonium cation to an antioxidant moiety, such as ubiquinol or alpha-tocopherol. These compounds pass easily through all biological membranes, including the blood-brain barrier, and into muscle cells and thus reach those tissues most affected by mitochondrial oxidative damage. Furthermore, because of their positive charge they are accumulated several-hundredfold within mitochondria driven by the membrane potential, enhancing the protection of mitochondria from oxidative damage. These compounds protect mitochondria from damage following oral delivery and may therefore form the basis for mitochondria-protective therapies. Here we review the background and work to date on this class of mitochondria-targeted antioxidants.
Cerebrospinal Fluid Cytokine Dynamics Differ Between Alzheimer Disease Patients and Elderly Controls (2011)

The time courses of levels of multiple plasma and cerebrospinal fluid (CSF) cytokines in patients with Alzheimer disease (AD) and in age-matched control subjects were compared. Interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, IL-12p70, granulocyte-macrophage colony-stimulating factor, interferon-γ, and tumor necrosis factor alpha levels were measured 7 times over a 24-hour period in plasma and CSF using a lumbar catheter. Baseline plasma and CSF cytokine levels were found to be similar in AD and control subjects. However, the CSF levels of all measured cytokines, except IL-6 and IL-8, diverged over time between AD and control subjects, such that CSF cytokine levels in AD subjects were higher than in controls. This difference was greatest at 24 hours after the insertion of the lumbar catheter. In contrast, no differences in cytokine trajectories were seen in plasma. These data suggest that the neuroinflammatory response to lumbar catheter placement differs between AD and control subjects.
Osteopontin silencing by small interfering RNA suppresses in vitro and in vivo CT26 murine colon adenocarcinoma metastasis (2005)

Hepatic metastasis is a primary cause for failure of locoregional therapy in colorectal cancer. Increased expression of osteopontin (OPN), a ligand for alpha(v)beta3 integrin and CD44 receptors, is associated with metastasis in several types of cancer. However, the mechanism by which OPN mediates metastasis in colorectal cancer remains unknown. We hypothesized that OPN mediates invasion of colon cancer cells through basement membrane and migration through extracellular matrix (ECM). In this study, we used CT26 murine colon adenocarcinoma cells syngeneic to BALB/c mice to generate cell lines (pS-OPN) in which OPN expression was suppressed through small interfering RNA (siRNA) plasmids. CT26 wild-type cells (WT) and CT26 cells stably expressing murine-mismatch siRNA (pS-MM) served as controls. Western blotting quantified OPN protein levels and our most downregulated clone, pS-OPN-A4, demonstrated a mean 3.0-fold decrease in OPN protein expression versus WT. In vitro cell motility and invasiveness were decreased in pS-OPN-A4 by 3.6-fold (P = 0.004 versus WT) and 4.1-fold (P = 0.01 versus WT), but proliferation was similar amongst cell lines. We demonstrated that OPN suppression significantly correlates with MMP-2 downregulation. In vivo hepatic metastasis was assessed by quantifying liver weights and surface tumor nodules in 33 BALB/c mice (11/group) subjected to intrasplenic injection of tumor cells. pS-OPN-A4 resulted in a 50.4% decrease in mean liver weight compared with WT (3.79 +/- 1.49 g versus 1.88 +/- 1.34 g, P = 0.009). Only 18% of pS-OPN-A4 livers had >20 metastatic surface nodules compared with 89% for WT and 75% for pS-MM-V6. This study demonstrates that RNA interference stably reduces CT26 tumor expression of OPN and significantly attenuates CT26 colon cancer metastasis by diminishing tumor cell motility and invasiveness.
Diagnostic Specificity of Sucrose Hemolysis Test for Paroxysmal Nocturnal Hemoglobinuria (1970)

Abstract The diagnostic specificity of the various modifications of the sucrose hemolysis test for PNH was examined in detail. In whole blood screening tests the greatest specificity was achieved using citrated or oxalated blood and room temperature incubation (23°). Defibrinated whole blood should not be used since "false positive" hemolysis may occur in blood disorders other than PNH. Mechanisms were suggested for this phenomenon. The validity of the confirmatory sucrose hemolysis test employing normal serum was further reported. Because of the clear, colorless character of serum-sucrose mixtures, an insignificant degree of hemolysis (i.e., less than 5%) is more readily visible than in other PNH hemolytic tests employing undiluted serum. Definitive instructions and criteria for interpretation were given for both the whole blood screening test and the confirmatory sucrose hemolysis test.
TIP49b, a New RuvB-like DNA Helicase, Is Included in a Complex Together with Another RuvB-like DNA Helicase, TIP49a (1999)

We previously reported that TIP49a is a novel mammalian DNA helicase showing structural similarity with the bacterial recombination factor RuvB. In this study, we isolated a new TIP49a-related gene, termed TIP49b, from human and yeast cells. TIP49b also resembled RuvB, thus suggesting that TIP49a and TIP49b are included in a gene family. Like TIP49a, TIP49b was abundantly expressed in the testis and thymus. Enzyme assays revealed that TIP49b was an single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase. Most of the enzymatic properties of TIP49b were the same as those of TIP49a, whereas the polarity of TIP49b DNA helicase activity (5' to 3') was the opposite to that of TIP49a. TIP49b and TIP49a bound to each other and were included in the same complex of approximately 700 kDa in a cell. We found that TIP49b was an essential gene for the growth of Saccharomyces cerevisiae, as is the TIP49a gene, suggesting that TIP49b does not complement the TIP49a function and vice versa. From these observations, we suggest that TIP49b plays an essential role in the cellular processes involved in DNA metabolism.
Dose loss in phosphorus implants due to transient diffusion and interface segregation (1995)

For implanted phosphorus in the dose range of 5×1013/cm2–4×1014/cm2, up to half the implanted dose may be lost during low thermal budget anneals due to transient diffusion and anomalous segregation at the Si–SiO2 interface. The phosphorus atoms, rendered mobile by the implant damage, stick in the oxide near the interface where they are electrically inactive and can be removed by stripping the surface oxide. Such a dose loss needs to be accounted for in a typical device fabrication process.
[See symptoms and signs of six channels of feet in Huangdi's Internal Classic from medical books of bamboo slips and silk cloth]. (2007)

Some champers besides Miraculous Pivot: Channels and Vessels in Huangdi's Internal Classic are involved in diseases of channels and vessels, and most of them which mainly discuss diseases of channels and vessels are explained in the type of six channels of feet. Studies have showed that the diseases of six channels of the feet are closely related with diseases of channels and vessels in the medical books of bamboo slips and silk cloth, indicating that on the one hand, the studies on diseases of channels and vessels are not only limited in Miraculous Pivot: Channels and Vessels, and on the other hand, the influence of the literature of channels and vessels in the medical books of bamboo slips and silk cloth is quite profound and lasting. Widening the field of vision of investigating concept of diseases of channels and vessels, and looking closely at the course of history from academic development are favorable to deeply understanding diseases of channels and vessels, even early theories of channels and vessels.
Are There Limits to Running World Records? (2005)

Many of the established men's and women's endurance running world records are nearing their limits and, consequently, women's world records are unlikely to ever reach those achieved by men.
Anticancer Polymeric Nanomedicines (2007)

Polymers play important roles in the design of delivery nanocarriers for cancer therapies. Polymeric nanocarriers with anticancer drugs conjugated or encapsulated, also known as polymeric nanomedicines, form a variety of different architectures including polymer‐drug conjugates, micelles, nanospheres, nanogels, vesicles, and dendrimers. This review focuses on the current state of the preclinical and clinical investigations of polymer‐drug conjugates and polymeric micelles. Recent progress achieved in some promising fields, such as site‐specific protein conjugation, pH‐sensitive polymer‐drug conjugates, polymer nanoparticles for targeted cancer therapy, stimuli‐responsive polymeric micelles, polymeric vesicles, and dendrimer‐based anticancer nanomedicines, will be highlighted.
Nucleoside-modified VEGFC mRNA induces organ-specific lymphatic growth and reverses experimental lymphedema (2021)

Lack or dysfunction of the lymphatics leads to secondary lymphedema formation that seriously reduces the function of the affected organs and results in degradation of quality of life. Currently, there is no definitive treatment option for lymphedema. Here, we utilized nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNPs) encoding murine Vascular Endothelial Growth Factor C (VEGFC) to stimulate lymphatic growth and function and reduce experimental lymphedema in mouse models. We demonstrated that administration of a single low-dose of VEGFC mRNA-LNPs induced durable, organ-specific lymphatic growth and formation of a functional lymphatic network. Importantly, VEGFC mRNA-LNP treatment reversed experimental lymphedema by restoring lymphatic function without inducing any obvious adverse events. Collectively, we present a novel application of the nucleoside-modified mRNA-LNP platform, describe a model for identifying the organ-specific physiological and pathophysiological roles of the lymphatics, and propose an efficient and safe treatment option that may serve as a novel therapeutic tool to reduce lymphedema.