gebhart/patrepeval huggingface dataset:
The chemistry and antioxidant properties of tocopherols and tocotrienols (1996)

This article is a review of the fundamental chemistry of the tocopherols and tocotrienols relevant to their antioxidant action. Despite the general agreement that alpha-tocopherol is the most efficient antioxidant and vitamin E homologue in vivo, there was always a considerable discrepancy in its "absolute" and "relative" antioxidant effectiveness in vitro, especially when compared to gamma-tocopherol. Many chemical, physical, biochemical, physicochemical, and other factors seem responsible for the observed discrepancy between the relative antioxidant potencies of the tocopherols in vivo and in vitro. This paper aims at highlighting some possible reasons for the observed differences between the tocopherols (alpha-, beta-, gamma-, and delta-) in relation to their interactions with the important chemical species involved in lipid peroxidation, specifically trace metal ions, singlet oxygen, nitrogen oxides, and antioxidant synergists. Although literature reports related to the chemistry of the tocotrienols are quite meager, they also were included in the discussion in virtue of their structural and functional resemblance to the tocopherols.
Saving Death: Apoptosis for Intervention in Transplantation and Autoimmunity (2006)

Long considered immunologically "bland," apoptotic cells are now recognized as important modulators of immune responses. The role of apoptosis in immunological homeostasis has been inferred from several findings, for example, induction of tolerance after injection of apoptotic cells and the capacity of APCs like macrophages and DCs to induce and maintain tolerance after phagocytosis of dead cells. Processing of apoptotic cells by DCs is of particular interest, because DCs are the only known APCs capable of activating naïve T lymphocytes to become effector or regulatory cells. In that regard, recent evidence suggests that phagocytosis of apoptotic cells by DCs can induce Tregs, a finding that has significant implications for the treatment of a variety of immune-mediated inflammatory disorders. Here, we review the relationship between apoptotic cells, DCs, and Tregs, and its impact on prevention of transplant rejection and treatment of autoimmune diseases.
Characterization and optimization of lyophilization and storage conditions of Leech saliva extract from the tropical leech Hirudinaria manillensis. (2013)

The medicinal Malaysian leeches have been used in traditional medicine to treat many different ailments. In this study, leech saliva extract (LSE) was collected from the medicinal Malaysian leech Hirudinaria manillensis. Gel electrophoresis of LSE was carried out to estimate the peptide and protein molecular weights of its content. Results showed that LSE contains more than 60 peptides and proteins with molecular masses ranging from 1.9-250kDa. Thrombin time assay in vitro was employed to assess the collected LSE antithrombin activity. First, to study its stability, LSE was lyophilized under the following different conditions: pre-freezing temperature, type of container and lyophilization cycle. Pre-freezed LSE sample at -20°C and lyophilized for 24 hours retained about 100-95% of its original biological activities. Second, the LSE antithrombin activity was monitored for a period of six months. Storage temperature, type of the container and photosensitivity effects on antithrombin activity of the lyophilized (solid state) and non-lyophilized (liquid state) were investigated. Results showed that storage temperature drastically affected the biological activity of LSE with -20 °C as the optimum temperature. Samples stored at ambient temperature and +4 °C were light photosensitive and adversely affected when stored in polypropylene tubes. Lyophilized samples were more stable than non-lyophilized ones over the period of study. To sum up, in order to have a biologically active stock of LSE, it has to be lyophilized for no more than 24 hours following freezing at -20°C and has to be stored at -20°C in glass tubes protected from light.
Involvement of Calcium in Pineal Gland Function (1991)

The pineal gland functions as a neurohumoral transducer, accepting photic information from the retinae and converting this neural message into chemical mediators, the best documented of which is melatonin (N-acetyl-5-methoxytryptamine) (1). The onset of darkness causes information to travel from the suprachiasmatic nuclei of the hypothalamus via the superior cervical ganglia to postganglionic sympathetic nerves that end in the pineal, where they release norepinephrine. The resultant stimulation of β-adrenergic receptors, possibly augmented by α-adrenergic stimulation, leads to an increased activity of N-acetyltransferase (NAT) (2), the rate-limiting enzyme involved in synthesis of melatonin (3). Serotonin, derived from dietary tryptophan taken up by pinealocytes from the blood, is N-acetylated by NAT, which is subsequently O-methylated by hydroxyindole-O-methyltransferase (HIOMT) to form melatonin, which is then released into the general circulation. Being a small lipophilic molecule, melatonin is generally considered to be released rapidly and passively following synthesis, although there is some evidence that short-term storage of melatonin by the pineal gland might occur (4). Melatonin's lipophilicity also ensures that it distributes widely to target tissues, which, therefore, receive photoperiodic information and can subsequently act with appropriate physiological responses (5). The multiplicity of extracellular and intracellular events that interact to produce the melatonin message are not fully understood, although certain aspects have been reasonably well characterized. For example, it is well-known that β-adrenergic stimulation leads to activation of adenylate cyclase, and that the resultant increase in CAMP stimulates mRNA synthesis, leading to increased NAT activity (3). The α-adrenergic augmentation of this process results from activation of protein kinase C. A number of stimulatory/regulatory processes involved in melatonin production have been associated with calcium, and the following discussion serves to review current understanding of the relationship between calcium and pineal gland function.
Top Value Added Chemicals From Biomass: I. Results of Screening for Potential Candidates from Sugars and Synthesis Gas (2004)

This report identifies twelve building block chemicals that can be produced from sugars via biological or chemical conversions. The twelve building blocks can be subsequently converted to a number of high-value bio-based chemicals or materials. Building block chemicals, as considered for this analysis, are molecules with multiple functional groups that possess the potential to be transformed into new families of useful molecules. The twelve sugar-based building blocks are 1,4-diacids (succinic, fumaric and malic), 2,5-furan dicarboxylic acid, 3-hydroxy propionic acid, aspartic acid, glucaric acid, glutamic acid, itaconic acid, levulinic acid, 3-hydroxybutyrolactone, glycerol, sorbitol, and xylitol/arabinitol. In addition to building blocks, the report outlines the central technical barriers that are preventing the widespread use of biomass for products and chemicals.
Clearance of apoptotic cells: implications in health and disease (2010)

Recent advances in defining the molecular signaling pathways that regulate the phagocytosis of apoptotic cells have improved our understanding of this complex and evolutionarily conserved process. Studies in mice and humans suggest that the prompt removal of dying cells is crucial for immune tolerance and tissue homeostasis. Failed or defective clearance has emerged as an important contributing factor to a range of disease processes. This review addresses how specific molecular alterations of engulfment pathways are linked to pathogenic states. A better understanding of the apoptotic cell clearance process in healthy and diseased states could offer new therapeutic strategies.
N-Acetylcysteine Inhibits Post-Impact Chondrocyte Death in Osteochondral Explants (2009)

Treatment with N-acetylcysteine soon after a blunt impact injury can reduce chondrocyte death and proteoglycan loss measured seven to fourteen days after injury.
To tune or not to tune?: a lightweight physical design alerter (2006)

In recent years there has been considerable research on automating the physical design in database systems. Current techniques provide good recommendations, but are resource intensive. This makes DBAs somewhat conservative when deciding to launch a resource-intensive tuning session. In this paper, we introduce an alerter that helps determining when a physical design tool should be invoked. The alerter is a lightweight mechanism that provides guaranteed lower (and upper bounds) on the improvement that a DBA could expect by invoking a comprehensive physical design tool. Moreover, it produces an accompanying recommendation that serves as a proof for the lower bound. We show experimentally that the alerter handles large workloads with little overhead, and help judiciously decide on launching subsequent tuning sessions.
RAPID AND EFFICIENT SYNTHESIS OF 2-[3-CYANO-4-(2-ARYLIDEN)-5, 5-DIMETHYL-5H-FURAN-2-YLIDENE]-MALONONITRILE UNDER FOCUSED MICROWAVE IRRADIATION (2001)

New biological potential furan-2-ylidenemalononitriles (IIIa-j) were synthetised efficiently by one-pot condensation under focused microwave from starting and easy available compounds.
8-Aza-analogues of PMEA and PMEG: Synthesis andIn VitroAnti-HIV Activity (1994)

Abstract 8-Aza-analogues of the potent antiviral nucleotide analogues 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) and 9-[2-(phosphonomethoxy)-ethyl]guanine (PMEG) were prepared and evaluated for activity against human immunodeficiency viruses. When compared to the parent compounds, 8-aza-PMEA (1) and -PMEG (2) were less cytotoxic for MT-4 cells, but also less potent against HIV-1 and HIV-2. A new synthesis of PMEG starting from guanine is also reported.
The Tec Kinases Itk and Rlk Regulate NKT Cell Maturation, Cytokine Production, and Survival (2008)

The Tec kinases Itk and Rlk are required for efficient positive selection of conventional CD4+ and CD8+ T cells in the thymus. In contrast, recent studies have shown that these Tec kinases are dispensable for the development of CD8+ T cells with characteristics of innate T cells. These findings raise questions about the potential role of Itk and Rlk in NKT cell development, because NKT cells represent a subset of innate T cells. To address this issue, we examined invariant NKT cells in Itk-/- and Itk/Rlk-/- mice. We find, as has been reported previously, that Itk-/- mice have reduced numbers of NKT cells with a predominantly immature phenotype. We further show that this defect is greatly exacerbated in the absence of both Itk and Rlk, leading to a 7-fold reduction in invariant NKT cell numbers in the thymus of Itk/Rlk-/- mice and a more severe block in NKT cell maturation. Splenic Itk-/- and Itk/Rlk-/- NKT cells are also functionally defective, because they produce little to no cytokine following in vivo activation. Tec kinase-deficient NKT cells also show enhanced cell death in the spleen. These defects correlate with greatly diminished expression of CD122, the IL-2R/IL-15R beta-chain, and impaired expression of the T-box transcription factor, T-bet. These data indicate that the Tec kinases Itk and Rlk provide important signals for terminal maturation, efficient cytokine production, and peripheral survival of NKT cells.
Photorhabdus: towards a functional genomic analysis of a symbiont and pathogen (2003)

Pathogenicity and symbiosis are central to bacteria^host interactions. Although several human pathogens have been subjected to functional genomic analysis, we still understand little about bacteria^invertebrate interactions despite their ecological prevalence. Advances in our knowledge of this area are often hindered by the difficulty of isolating and working with invertebrate pathogenic bacteria and their hosts. Here we review studies on pathogenicity and symbiosis in an insect pathogenic bacterium Photorhabdus and its entomopathogenic nematode vector and model insect hosts. Whilst switching between these hosts, Photorhabdus changes from a state of symbiosis with its nematode vector to one of pathogenicity towards its new insect host and both the bacteria and the nematode then cooperatively exploit the dying insect. We examine candidate genes involved in symbiosis and pathogenicity, their secretion and expression patterns in culture and in the host, and begin to dissect the extent of their genetic coregulation. We describe the presence of several large genomic islands, putatively involved in pathogenicity or symbiosis, within the otherwise Yersinia-like backbone of the Photorhabdus genome. Finally, we examine the emerging comparative genomics of the Photorhabdus group and begin to describe the interrelationship between anti-invertebrate virulence factors and those used against vertebrates.
Cytokine function of heat shock proteins (2004)

Extensive work in the last 10 years has suggested that heat shock proteins (HSPs) may be potent activators of the innate immune system. It has been reported that Hsp60, Hsp70, Hsp90, and gp96 are capable of inducing the production of proinflammatory cytokines by the monocyte-macrophage system and the activation and maturation of dendritic cells (antigen-presenting cells) in a manner similar to the effects of lipopolysaccharide (LPS) and bacterial lipoprotein, e.g., via CD14/Toll-like receptor2 (TLR2) and CD14/TLR4 receptor complex-mediated signal transduction pathways. However, recent evidence suggests that the reported cytokine effects of HSPs may be due to the contaminating LPS and LPS-associated molecules. The reasons for previous failure to recognize the contaminant(s) as being responsible for the reported HSP cytokine effects include failure to use highly purified, low-LPS preparations of HSPs; failure to recognize the heat sensitivity of LPS; and failure to consider contaminant(s) other than LPS. Thus it is essential that efforts should be directed to conclusively determine whether the reported HSP cytokine effects are due to HSPs or to contaminant(s) present in the HSP preparations before further exploring the implication and therapeutic potential of the putative cytokine function of HSPs.
pH and cation-responsive supramolecular gels formed by cyclodextrin amines in DMSO (2010)

Amine-modified cyclodextrins are capable of forming pH and cation-responsive organogels in DMSO at low molar fractions.
The Role of Cholesterol and Statins in Alzheimer's Disease (2003)

Preliminary evidence suggests that statins may offer a protective effect against the development of AD. However, review of the literature does not lend credence to the use of statins in the general nondemented population without hyperlipidemia. Potential confounding variables have not been considered in the majority of trials. Placebo-controlled clinical trials are ongoing and should yield more definitive results.
Identification of gene expression profiles that predict the aggressive behavior of breast cancer cells. (2001)

With the goal of identifying genes that have an expression pattern that can facilitate the diagnosis of primary breast cancers (BCs) as well as the discovery of novel drug leads for BC treatment, we used cDNA hybridization arrays to analyze the gene expression profiles (GEPs) of nine weakly invasive and four highly invasive BC cell lines. Differences in gene expression between weakly and highly invasive BC cells were identified that enabled the definition of consensus GEPs for each invasive phenotype. To determine whether the consensus GEPs, comprising 24 genes, could be used to predict the aggressiveness of previously uncharacterized cells, gene expression levels and comparative invasive and migratory characteristics of nine additional human mammary epithelial cell strains/lines were determined. The results demonstrated that the GEP of a cell line is predictive of its invasive and migratory behavior, as manifest by the morphology of its colonies when cultured on a matrix of basement membrane constituents (i.e., Matrigel). We found that the expression of keratin 19 was consistently elevated in the less aggressive BC cell lines and that vimentin and fos-related antigen-1 (FRA-1) were consistently overexpressed in the more highly aggressive BC cells. Moreover, even without these three genes, the GEP of a cell line still accurately predicted the aggressiveness of the BC cell, indicating that the expression pattern of multiple genes may be used as BC prognosticators because single markers often fail to be predictive in clinical specimens.
BET bromodomain proteins are required for glioblastoma cell proliferation (2014)

Epigenetic proteins have recently emerged as novel anticancer targets. Among these, bromodomain and extra terminal domain (BET) proteins recognize lysine-acetylated histones, thereby regulating gene expression. Newly described small molecules that inhibit BET proteins BRD2, BRD3, and BRD4 reduce proliferation of NUT (nuclear protein in testis)-midline carcinoma, multiple myeloma, and leukemia cells in vitro and in vivo. These findings prompted us to determine whether BET proteins may be therapeutic targets in the most common primary adult brain tumor, glioblastoma (GBM). We performed NanoString analysis of GBM tumor samples and controls to identify novel therapeutic targets. Several cell proliferation assays of GBM cell lines and stem cells were used to analyze the efficacy of the drug I-BET151 relative to temozolomide (TMZ) or cell cycle inhibitors. Lastly, we performed xenograft experiments to determine the efficacy of I-BET151 in vivo. We demonstrate that BRD2 and BRD4 RNA are significantly overexpressed in GBM, suggesting that BET protein inhibition may be an effective means of reducing GBM cell proliferation. Disruption of BRD4 expression in glioblastoma cells reduced cell cycle progression. Similarly, treatment with the BET protein inhibitor I-BET151 reduced GBM cell proliferation in vitro and in vivo. I-BET151 treatment enriched cells at the G1/S cell cycle transition. Importantly, I-BET151 is as potent at inhibiting GBM cell proliferation as TMZ, the current chemotherapy treatment administered to GBM patients. Since I-BET151 inhibits GBM cell proliferation by arresting cell cycle progression, we propose that BET protein inhibition may be a viable therapeutic option for GBM patients suffering from TMZ resistant tumors.
Minor Groove Binding DNA Ligands with Expanded A/T Sequence Length Recognition, Selective Binding to Bent DNA Regions and Enhanced Fluorescent Properties (2003)

DNA minor groove ligands provide a paradigm for double-stranded DNA recognition, where common structural motifs provide a crescent shape that matches the helix turn. Since minor groove ligands are useful in medicine, new ligands with improved binding properties based on the structural information about DNA-ligand complexes could be useful in developing new drugs. Here, two new synthetic analogues of AT specific Hoechst 33258 5-(4-methylpiperazin-1-yl)-2-[2'-(3,4-dimethoxyphenyl)-5'-benzimidazolyl] benzimidazole (DMA) and 5-(4-methylpiperazin-1-yl)-2-[2'[2''-(4-hydroxy-3-methoxyphenyl)-5' '-benzimidazolyl]-5'-benzimidazolyl] benzimidazole (TBZ) were evaluated for their DNA binding properties. Both analogues are bisubstituted on the phenyl ring. DMA contains two ortho positioned methoxy groups, and TBZ contains a phenolic group at C-4 and a methoxy group at C-3. Fluorescence yield upon DNA binding increased 100-fold for TBZ and 16-fold for DMA. Like the parent compound, the new ligands showed low affinity to GC-rich (K approximately 4 x 10(7) M(-1)) relative to AT-rich sequences (K approximately 5 x 10(8) M(-1)), and fluorescence lifetime and anisotropy studies suggest two distinct DNA-ligand complexes. Binding studies indicate expanded sequence recognition for TBZ (8-10 AT base pairs) and tighter binding (DeltaT(m) of 23 degrees C for d (GA(5)T(5)C). Finally, EMSA and equilibrium binding titration studies indicate that TBZ preferentially binds highly hydrated duplex domains with altered A-tract conformations d (GA(4)T(4)C)(2) (K= 3.55 x 10(9) M(-1)) and alters its structure over d (GT(4)A(4)C)(2) (K = 3.3 x 10(8) M(-1)) sequences. Altered DNA structure and higher fluorescence output for the bound fluorophore are consistent with adaptive binding and a constrained final complex. Therefore, the new ligands provide increased sequence and structure selective recognition and enhanced fluorescence upon minor groove binding, features that can be useful for further development as probes for chromatin structure stability.
Frequency Response of Top-Gated Carbon Nanotube Field-Effect Transistors (2004)

The ac performance of carbon nanotube field-effect transistors (CNFETs) has been characterized using two approaches involving: 1) time- and 2) frequency-domain measurements. A high input impedance measurement system was used to demonstrate time-domain switching of CNFETs at frequencies up to 100 kHz. The low level of signal crosstalk in CNFETs fabricated on quartz substrates enabled frequency-domain measurements of the ac response of CNFETs in the megahertz range, over five orders of magnitude higher in frequency than previously reported ac measurements of CNFET devices.
Detecting computer and network misuse through the production-based expert system toolset (P-BEST) (2003)

The paper describes an expert system development toolset called the Production-Based Expert System Toolset (P-BEST) and how it is employed in the development of a modern generic signature analysis engine for computer and network misuse detection. For more than a decade, earlier versions of P-BEST have been used in intrusion detection research and in the development of some of the most well known intrusion detection systems, but this is the first time the principles and language of P-BEST are described to a wide audience. We present rule sets for detecting subversion methods against which there are few defenses-specifically, SYN flooding and buffer overruns-and provide performance measurements. Together, these examples and performance measurements indicate that P-BEST based expert systems are well suited for real time misuse detection in contemporary computing environments. In addition, the simplicity of the P-BEST language and its close integration with the C programming language makes it easy to use while still being very powerful and flexible.
An algorithm for automatic formant extraction using linear prediction spectra (1974)

An algorithm is presented which finds the frequency and amplitude of the first three formants during all vowel-like segments of continuous speech. It uses as input the peaks of the linear prediction spectra and a segmentation parameter to indicate energy and voicing. Ideally, the first three peaks are the first three formants. Frequently, however, two peaks merge, or spurious peaks appear, and the difficult part is to recognize such situations and deal with them. The general method is to fill formant slots with the available peaks at each frame, based on frequency position relative to an educated guess. Then, if a peak is left over and/or a slot is unfilled, special routines are called to decide how to deal with them. Included is a formant enhancement technique, analogous to a similar technique which has been implemented via the chirp-z transform [8], which usually succeeds in separating two merged formants. Processing begins at the middle of each high volume voiced segment, where formants are most likely to be correct, and branches outward from there in both directions in time, using the most recently found formant frequencies as the educated guess for the current frame. The algorithm has been implemented at Lincoln Laboratory on the Univac 1219 and the Fast Digital Processor, a programmable processor [9], and has been tested on a large number of unrestricted sentences.