gebhart/patrepeval huggingface dataset:
Mono- and multisite phosphorylation enhances Bcl2's antiapoptotic function and inhibition of cell cycle entry functions (2003)

Bcl2 functions to suppress apoptosis and retard cell cycle entry. Single-site phosphorylation at serine 70 (S70) is required for Bcl2's antiapoptotic function, and multisite phosphorylation at threonine 69 (T69), S70, and S87 has been reported to inactivate Bcl2. To address this apparent conflict and identify the regulatory role for Bcl2 phosphorylation in cell death and cell cycle control, a series of serine/threonine (S/T) --> glutamate/alanine (E/A) mutants including T69E/A, S70E/A, S87E/A, T69E/S70A/S87A (EAA), T69A/S70E/S87A (AEA), T69A/S70A/S87E (AAE), T69E/S70E/S87E (EEE), and T69A/S70A/S87A (AAA) was created to mimic or abrogate, respectively, either single-site or multisite phosphorylation. The survival and cell cycle status of cells expressing the phosphomimetic or nonphosphorylatable Bcl2 mutants were compared. Surprisingly, all of the E but not the A Bcl2 mutants potently enhance cell survival after stress and retard G(1)/S cell cycle transition. The EEE Bcl2 mutant is the most potent, indicating a possible cumulative advantage for multisite phosphorylation of Bcl2 in survival and retardation of G(1)/S transition functions. Because the E-containing Bcl2 mutants, but not the A-containing mutants, can more potently block cytochrome c release from mitochondria during apoptotic stress, even at times when steady-state expression levels are similar for all mutants, we conclude that phosphorylation at one or multiple sites within the flexible loop domain of Bcl2 not only stimulates antiapoptotic activity but also can regulate cell cycle entry.
Interaction of SeqA and Dam Methylase on the Hemimethylated Origin of Escherichia coli Chromosomal DNA Replication (1999)

Preferential binding of SeqA protein to hemimethylated oriC, the origin of Escherichia coli chromosomal replication, delays methylation by Dam methylase. Because the SeqA-oriC interaction appears to be essential in timing of chromosomal replication initiation, the biochemical functions of SeqA protein and Dam methylase at the 13-mer L, M, and R region containing 4 GATC sequences at the left end of oriC were examined. We found that SeqA protein preferentially bound hemimethylated 13-mers but not fully nor unmethylated 13-mers. Regardless of strand methylation, the binding of SeqA protein to the hemimethylated GATC sequence of 13-mer L was followed by additional binding to other hemimethylated GATC sequences of 13-mer M and R. On the other hand, Dam methylase did not discriminate binding of 13-mers in different methylation patterns and was not specific to GATC sequences. The binding specificity and higher affinity of SeqA protein over Dam methylase to the hemimethylated 13-mers along with the reported cellular abundance of this protein explains the dominant action of SeqA protein over Dam methylase to the newly replicated oriC for the sequestration of chromosomal replication. Furthermore, SeqA protein bound to hemimethylated 13-mers was not dissociated by Dam methylase, and most SeqA protein spontaneously dissociated 10 min after binding. Also, SeqA protein delayed the in vitro methylation of hemimethylated 13-mers by Dam methylase. These in vitro results suggest that the intrinsic binding instability of SeqA protein results in release of sequestrated hemimethylated oriC.
The Lipid Body Protein, PpoA, Coordinates Sexual and Asexual Sporulation in Aspergillus nidulans (2004)

The coexistence of sexual and asexual reproductive cycles within the same individual is a striking phenomenon in numerous fungi. In the fungus Aspergillus nidulans (teleomorph: Emericella nidulans) endogenous oxylipins, called psi factor, serve as hormone-like signals that modulate the timing and balance between sexual and asexual spore development. Here, we report the identification of A. nidulans ppoA, encoding a putative fatty acid dioxygenase, involved in the biosynthesis of the linoleic acid derived oxylipin psiBalpha. PpoA is required for balancing anamorph and teleomorph development. Deletion of ppoA significantly reduced the level of psiBalpha and increased the ratio of asexual to sexual spore numbers 4-fold. In contrast, forced expression of ppoA resulted in elevated levels of psiBalpha and decreased the ratio of asexual to sexual spore numbers 6-fold. ppoA expression is mediated by two developmental regulators, VeA and the COP9 signalosome, such that ppoA transcript levels are correlated with the initiation of asexual and sexual fruiting body formation. PpoA localizes in lipid bodies in these tissues. These data support an important role for oxylipins in integrating mitotic and meiotic spore development.
Cytotoxic T cells directed to tumor antigens not expressed on normal melanocytes dominate HLA-A2.1-restricted immune repertoire to melanoma. (1996)

To determine whether HLA-A21 restricted melanoma Ags exist that are not expressed on normal melanocytes, a panel of 478 T cell clones from six HLA-A21+ patients was selected for HLA-A2 restricted lysis of autologous tumor and then tested for differential recognition of HLA-A2.1+ melanomas and normal melanocytes. Four subsets of clones were identified in the panel of 107 HLA-A2-restricted CTL clones. CTL clones from three of the four subsets did not lyse melanocytes, but recognized fresh HLA-A2.1+ melanomas and defined three classes of epitopes, including unique Ags, common melanoma Ags, and Ags shared with neoplastic cells of different histologic origin. These CTL clones did not recognize any of the 10 peptides selected for specific association to HLA-A2.1 and derived from Melan-A/Mart-1, tyrosinase, gp100, or MAGE-3 proteins. By contrast, the fourth subset of HLA-A2.1-restricted CTl clones recognized both melanoma and melanocytes. These CTL clones were directed to a peptide from either Melan-A/Mart-1, tyronise, or gp100. By a limiting dilution assay, designed to evaluate the frequency of HLA-A2-restricted CTL precursors (CTLp) directed to melanoma but not to melanocytes, such precursors were found in the peripheral blood or tumor site of five of six HLA-A2.1+ melanoma patients, and their frequency was much higher than the frequency of CTLp recognizing both tumor cells and the melanocytes. These results suggest that in melanoma patients most of the HLA-A2.1-restricted immune repertoire to melanoma is directly to epitopes expressed in the neoplastic but not in the normal cells of the melanocyte lineage.
The Army and Politics in Turkey: A Collateralized Democracy (2005)

For more than forty years, politics in Turkey has been characterized by repeated interventions of the military and a strict supervision of democratic institutions. The political power of the army can be explained by the malfunctioning of a pluralist democracy that it has never considered as a major necessity of the Kemalist modernization process. It also has historical roots firmly established in collective memory and it benefits from a strong social legitimacy. The growing tension between a centralized state and a civil society more and more reluctant to accept any ideological control, may find a solution in the changes produced by the European membership candidacy. The redefinition of the relationship between the army and civil power is well under way, but the military will retain a major influence in the country.
Effect of fiber optic probe geometry on depth-resolved fluorescence measurements from epithelial tissues: a Monte Carlo simulation (2003)

Developing fiber optic probe geometries to selectively measure fluorescence spectra from different sublayers within human epithelial tissues will potentially improve the endogenous fluorescence contrast between neoplastic and nonneoplastic tissues. In this study, two basic fiber optic probe geometries, which are called the variable aperture (VA) and multidistance (MD) approaches, are compared for depth-resolved fluorescence measurements from human cervical epithelial tissues. The VA probe has completely overlapping illumination and collection areas with variable diameters, while the MD probe employs separate illumination and collection fibers with a fixed separation between them. Monte Carlo simulation results show that the total fluorescence detected is significantly higher for the VA probe geometry, while the probing depth is significantly greater for the MD probe geometry. An important observation is that the VA probe is more sensitive to the epithelial layer, while the MD probe is more sensitive to the stromal layer. The effect of other factors, including numerical aperture (NA) and tissue optical properties on the fluorescence measurements with VA and MD probe geometries, are also evaluated. The total fluorescence detected with both probe geometries significantly increases when the fiber NA is changed from 0.22 to 0.37. The sensitivity to different sublayers is found to be strongly dependent on the tissue optical properties. The simulation results are used to design a simple fiber optic probe that combines both the VA and MD geometries to enable fluorescence measurements from the different sublayers within human epithelial tissues.
Specificity and Mechanism of Action of EHT 1864, a Novel Small Molecule Inhibitor of Rac Family Small GTPases (2007)

There is now considerable experimental evidence that aberrant activation of Rho family small GTPases promotes the uncontrolled proliferation, invasion, and metastatic properties of human cancer cells. Therefore, there is considerable interest in the development of small molecule inhibitors of Rho GTPase function. However, to date, most efforts have focused on inhibitors that indirectly block Rho GTPase function, by targeting either enzymes involved in post-translational processing or downstream protein kinase effectors. We recently determined that the EHT 1864 small molecule can inhibit Rac function in vivo. In this study, we evaluated the biological and biochemical specificities and biochemical mechanism of action of EHT 1864. We determined that EHT 1864 specifically inhibited Rac1-dependent platelet-derived growth factor-induced lamellipodia formation. Furthermore, our biochemical analyses with recombinant Rac proteins found that EHT 1864 possesses high affinity binding to Rac1, as well as the related Rac1b, Rac2, and Rac3 isoforms, and this association promoted the loss of bound nucleotide, inhibiting both guanine nucleotide association and Tiam1 Rac guanine nucleotide exchange factor-stimulated exchange factor activity in vitro. EHT 1864 therefore places Rac in an inert and inactive state, preventing its engagement with downstream effectors. Finally, we evaluated the ability of EHT 1864 to block Rac-dependent growth transformation, and we determined that EHT 1864 potently blocked transformation caused by constitutively activated Rac1, as well as Rac-dependent transformation caused by Tiam1 or Ras. Taken together, our results suggest that EHT 1864 selectively inhibits Rac downstream signaling and transformation by a novel mechanism involving guanine nucleotide displacement.
Analyses of the Redistribution of Work following Cardiac Resynchronisation Therapy in a Patient Specific Model (2012)

Regulation of regional work is essential for efficient cardiac function. In patients with heart failure and electrical dysfunction such as left branch bundle block regional work is often depressed in the septum. Following cardiac resynchronisation therapy (CRT) this heterogeneous distribution of work can be rebalanced by altering the pattern of electrical activation. To investigate the changes in regional work in these patients and the mechanisms underpinning the improved function following CRT we have developed a personalised computational model. Simulations of electromechanical cardiac function in the model estimate the regional stress, strain and work pre- and post-CRT. These simulations predict that the increase in observed work performed by the septum following CRT is not due to an increase in the volume of myocardial tissue recruited during contraction but rather that the volume of recruited myocardium remains the same and the average peak work rate per unit volume increases. These increases in the peak average rate of work is is attributed to slower and more effective contraction in the septum, as opposed to a change in active tension. Model results predict that this improved septal work rate following CRT is a result of resistance to septal contraction provided by the LV free wall. This resistance results in septal shortening over a longer period which, in turn, allows the septum to contract while generating higher levels of active tension to produce a higher work rate.
Electronic Properties of N-Heterocyclic Carbene (NHC) Ligands:  Synthetic, Structural, and Spectroscopic Studies of (NHC)Platinum(II) Complexes (2007)

N-Heterocyclic carbene complexes of platinum(II) have been synthesized, notably monocarbene complexes cis-[(IPr)Pt(dmso)(Cl)2], 6, cis-[(IMes)Pt(dmso)(Cl)2], 7, cis-[(SIPr)Pt(dmso)(Cl)2], 8, cis-[(SIMes)Pt(dmso)(Cl)2], 9, and cis-[(TTP)Pt(dmso)(Cl)2], 10. All complexes have been fully characterized by multinuclear NMR spectroscopy. Complex 7, 9, and 10 have been characterized by X-ray crystallography. The data obtained have allowed for the differentiation between electronic contributions (σ and π) present in the Pt−NHC bond. Supported by computational analyses, the percentage of π back-donation from the metal to the NHC is found to be on the order of 10%. More interestingly, we find that saturated NHC (SIPr and SIMes) are more efficient π back-acceptors than their unsaturated NHC congeners (IPr and IMes). The synergistic effect between π back-donation and σ donation present in the saturated NHC systems results in increased electron density at the platinum center compared to the bonding situation in the unsaturated NHC examples.
Physics and chemistry of spin labels (1970)

Biological systems provide the physical chemist with an abundance of interesting, challenging and significant problems. One example is the problem of the molecular basis of co-operative or allosteric interactions between distant ligand or substrate binding sites in hemoglobin and in enzymes. This problem has been discussed recently in This Journal by Eigen (1968) and by Wyman (1968). Another particularly challenging problem is the molecular organization of biological membranes. Such problems tend to be particularly resistant to solution by the straight-forward application of most spectroscopic techniques, in large part because of the enormous chemical and spectroscopic complexity of biological macromolecules. This spectroscopic complexity has stimulated the use of various ‘probes’ that can be introduced into selected sites in complex systems to provide spectroscopic signals that are comparatively free from interference. The use of heavy metal atoms (‘isomorphous replacement’) in X-ray studies of protein crystals (Green, Ingram &amp; Perutz, 1954), and fluorescent dyes in the study of proteins in solutions (Weber, 1953; Steiner &amp; Edelhoch, 1962) are early examples. Spin labels represent a new member of the family of spectroscopic structural probes. A spin label is a synthetic paramagnetic organic free radical, usually having a molecular structure and/or chemical reactivity that results in its attachment or incorporation at some particular target site in a biological macromolecule, or assemblage of macromolecules (Ohnishi &amp; McConnell, 1965; Stone et al. 1965). This type of probe is being used in our laboratory to study allosteric interactions in proteins, and molecular dynamics and organization in membranes.
Alignment of Carbon Nanotubes under Low Magnetic Fields through Attachment of Magnetic Nanoparticles (2005)

The alignment of multiwalled carbon nanotubes (MWNTs) has been accomplished through deposition of uniform layers of magnetite/maghemite nanoparticles (diameter = 6-10 nm) and use of an external magnetic field. The coating of CNTs with magnetic nanoparticles was performed by combining the polymer wrapping and layer-by-layer (LbL) assembly techniques. The particle-coated MWNTs are superparamagnetic and can be aligned at room temperature on any substrate by deposition from an aqueous solution in an external field B = 0.2 T. The volume magnetization of the particle coated MWNTs is found to be enhanced by 17% compared to the pure particles in a powder indicating that either the adsorption process onto the CNTs changes the particle magnetization, or the MWNTs carry an intrinsic magnetization due to remaining Ni used as a catalyst for the growth process.
Schistosoma mansoni surface antigen defined by a rat monoclonal IgG2a. (1982)

A schistosomula surface antigen of 38,000 daltons has been isolated by using a rat monoclonal IgG2a that has been shown to confer protection against S. mansoni infection by passive transfer in rats. This antigen is one of the previously characterized surface proteins reacting with sera from various infected hosts, including rat, mouse, monkey, and human. Studies on parasites of different developmental stages indicated the presence of this antigen on cercariae and skin-derived or mechanically transformed schistosomula.
The inhibition of in vivo tumorigenesis of osteosarcoma (OS)-732 cells by antisense human osteopontin RNA (2007)

Osteopontin (OPN) is a secreted, non-collagenous, sialic acid-rich protein which functions by mediating cell-matrix interactions and cellular signaling via binding with integrins and CD44 receptors. An increasing number of studies have shown that OPN plays an important role in controlling cancer progression and metastasis. OPN was found to be expressed in many human cancer types, and in some cases, its over-expression was shown to be directly associated with poor patient prognosis. In vitro cancer cell line and animal model studies have clearly indicated that OPN can function in regulating the cell signaling that ultimately controls the oncogenic potential of various cancers. Previous studies in our laboratory demonstrated that OPN is highly expressed in human osteosarcoma (OS) cell line OS-732. In this study, we successfully reduced the tumorigenecity of OS-732 cells xenotransplanted into nude mice, using the antisense human OPN (hOPN) RNA expression vector.
Distribution of adenosine deaminase complexing protein (ADCP) in human tissues. (1989)

The normal distribution of adenosine deaminase complexing protein (ADCP) in the human body was investigated quantitatively by ADCP-specific radioimmunoassay (RIA) and qualitatively by immunohistochemistry. In these studies we used a specific rabbit anti-human ADCP antiserum. In all 19 investigated tissues, except erythrocytes, ADCP was found by RIA in the soluble and membrane fractions. From all tissues the membrane fractions contained more ADCP (expressed per mg protein) than the soluble fractions. High membrane ADCP concentrations were found in skin, renal cortex, gastrointestinal tract, and prostate. Immunoperoxidase staining confirmed the predominant membrane-associated localization of the protein. In serous sweat glands, convoluted tubules of renal cortex, bile canaliculi, gastrointestinal tract, lung, pancreas, prostate gland, salivary gland, gallbladder, mammary gland, and uterus, ADCP immunoreactivity was found confined to the luminal membranes of the epithelial cells. These data demonstrate that ADCP is present predominantly in exocrine glands and absorptive epithelia. The localization of ADCP at the secretory or absorptive apex of the cells suggests that the function of ADCP is related to the secretory and/or absorptive process.
Expression and Regulation Profile of Mature MicroRNA in the Pig: Relevance to Xenotransplantation (2017)

The pig is an important source of meat production and provides a valuable model for certain human diseases. MicroRNA (miRNA), which is non-coding RNA and regulates gene expression at the posttranscriptional level, plays a critical role in various biological processes. Studies on identification and function of mature miRNAs in multiple pig tissues are increasing, yet the literature is limited. Therefore, we reviewed current research to determine the miRNAs expressed in specific pig tissues that are involved in carcass values (including muscle and adipocytes), reproduction (including pituitary, testis, and ovary), and development of some solid organs (e.g., brain, lung, kidney, and liver). We also discuss the possible regulating mechanisms of miRNA. Finally, as pig organs are suitable candidates for xenotransplantation, biomarkers of their miRNA in xenotransplantation were evaluated.
Progress towards a generalized solvent polarity scale: The solvatochromism of 2‐(dimethylamino)‐7‐nitrofluorene and its homomorph 2‐fluoro‐7‐nitrofluorene (1995)

Abstract More than 100 solvents and the gas phase were used to develop a solvent dipolarity‐polarizability scale that combines the medium dipolarity and polarizability into a single parameter (SPP) calculated from the UV‐visible spectra of 2‐(dimethyl‐amino)‐7‐nitrofluorene (DMANF) and its homomorph 2‐fluoro‐7‐nitrofuorene (FNF). The proposed scale compares favourably for nonprotic solvents with existing solvent polarity scales including Kosower's Z, Dimroth and Reichardt's E T (30), Brooker's χ R , Dong and Winnick's Py ; Kamlet, Abboud, and Taft's π*, and Drago's S ′ scale. When data are derived from electronic transitions, they provide an accurate description for the solvent effect in UV‐Vis, IR, NMR, and fluorescence spectroscopy as well as in other chemical areas including thermodynamics and kinetics.
Bcl-2 and Bax Expression Predict Prostate Cancer Outcome in Men Treated with Androgen Deprivation and Radiotherapy on Radiation Therapy Oncology Group Protocol 92-02 (2007)

Normal Bax expression was associated with significantly more favorable outcome. The combination of negative Bcl-2 and normal Bax was more consistently significant, particularly when STAD+RT was the treatment administered. These data suggest that LTAD+RT should be used when either Bcl-2 or Bax is abnormally expressed.
Participatory Forest Management in Andhra Pradesh: A Review of Its Working (2005)

This paper traces the emergence of Participatory Forest Management (PFM) regime in Andhra Pradesh in the form of Joint Forest Management (JFM) and Community Forest Management (CFM). The paper is based on the existing literature on forest policies. It considers the role of contemporary developments in India in shaping the forest policies in Andhra Pradesh. It also examines the process and quality of implementation and the impact of the programme on local communities and resources in Andhra Pradesh. JFM is a different concept from many earlier attempts to promote forestry needs of the people, simply because it builds from the roles played by both local forest users and the professionals employed by the state to act as custodians. The combined effort of community and government is the ultimate solution under prevailing circumstances. Therefore, the government intervention is expected to address the equity and transparency aspects to strengthen the voice of the poor. In the same way, participation of the people will warrant a constant vigil against all odds to protect the forests. Hence, Vana Samrakshana Samithis (VSSs) should be viewed as an entity for an overall development of the village resources and its people, and not merely an instrument of developing the degraded forests, more so with the new initiative of graduation from JFM to CFM focusing on alleviating rural poverty.