gebhart/patrepeval huggingface dataset:
D4.2 Final report on trade-off investigations (2014)

Research activities in METIS WP4 include several as&#13;\npects related to the network-level of &#13;\nfuture wireless communication networks. Thereby, a &#13;\nlarge variety of scenarios is considered &#13;\nand solutions are proposed to serve the needs envis&#13;\nioned for the year 2020 and beyond. &#13;\nThis document provides vital findings about several trade-offs that need to be leveraged when &#13;\ndesigning future network-level solutions. In more detail, it elaborates on the following trade-&#13;\noffs: &#13;\n• Complexity vs. Performance improvement &#13;\n• Centralized vs. Decentralized &#13;\n• Long time-scale vs. Short time-scale &#13;\n• Information Interflow vs. Throughput/Mobility enha&#13;\nncement &#13;\n• Energy Efficiency vs. Network Coverage and Capacity &#13;\nOutlining the advantages and disadvantages in each trade-off, this document serves as a &#13;\nguideline for the application of different network-level solutions in different situations and &#13;\ntherefore greatly assists in the design of future communication network architectures.
Structural basis of androgen receptor binding to selective androgen response elements (2004)

Steroid receptors bind as dimers to a degenerate set of response elements containing inverted repeats of a hexameric half-site separated by 3 bp of spacer (IR3). Naturally occurring selective androgen response elements have recently been identified that resemble direct repeats of the hexameric half-site (ADR3). The 3D crystal structure of the androgen receptor (AR) DNA-binding domain bound to a selective ADR3 reveals an unexpected head-to-head arrangement of the two protomers rather than the expected head-to-tail arrangement seen in nuclear receptors bound to response elements of similar geometry. Compared with the glucocorticoid receptor, the DNA-binding domain dimer interface of the AR has additional interactions that stabilize the AR dimer and increase the affinity for nonconsensus response elements. This increased interfacial stability compared with the other steroid receptors may account for the selective binding of AR to ADR3 response elements.
HtrA1 is upregulated during RANKL‐induced osteoclastogenesis, and negatively regulates osteoblast differentiation and BMP2‐induced Smad1/5/8, ERK and p38 phosphorylation (2013)

Bone remodeling is regulated by secreted factors in the bone microenvironment. However, data regarding osteoclast-derived factors that influence osteoblast differentiation are lacking. Here, we show that HtrA1 is produced as a secreted protein during osteoclastogenesis, and negatively regulates osteoblast differentiation. Exogenous addition of recombinant HtrA1 attenuates osteoblast differentiation and BMP2-induced Smad1/5/8, ERK1/2 and p38 phosphorylation in pre-osteoblasts. Our studies imply a unique mode of crosstalk in which HtrA1 is produced by both osteoclasts and osteoblasts and negatively regulates osteoblast differentiation, suggesting that HtrA1 may mediate the fine tuning of paracrine and autocrine regulations during bone remodeling processes.
Historical and Current Adenosine Receptor Agonists in Preclinical and Clinical Development (2019)

Adenosine receptors (ARs) function in the body's response to conditions of pathology and stress associated with a functional imbalance, such as in the supply and demand of energy/oxygen/nutrients. Extracellular adenosine concentrations vary widely to raise or lower the basal activation of four subtypes of ARs. Endogenous adenosine can correct an energy imbalance during hypoxia and other stress, for example, by slowing the heart rate by A<sub>1</sub>AR activation or increasing the blood supply to heart muscle by the A<sub>2A</sub>AR. Moreover, exogenous AR agonists, antagonists, or allosteric modulators can be applied for therapeutic benefit, and medicinal chemists working toward that goal have reported thousands of such agents. Thus, numerous clinical trials have ensued, using promising agents to modulate adenosinergic signaling, most of which have not succeeded. Currently, short-acting, parenteral agonists, adenosine and Regadenoson, are the only AR agonists approved for human use. However, new concepts and compounds are currently being developed and applied toward preclinical and clinical evaluation, and initial results are encouraging. This review focuses on key compounds as AR agonists and positive allosteric modulators (PAMs) for disease treatment or diagnosis. AR agonists for treating inflammation, pain, cancer, non-alcoholic steatohepatitis, angina, sickle cell disease, ischemic conditions and diabetes have been under development. Multiple clinical trials with two A<sub>3</sub>AR agonists are ongoing.
Construction and characterization of attenuated delta aroA delta virG Shigella flexneri 2a strain CVD 1203, a prototype live oral vaccine (1994)

We engineered an oral Shigella vaccine prototype that can invade intestinal epithelial cells but cannot undergo extensive intracellular replication or extend to adjacent epithelial cells. Strain CVD 1203, derived from wild-type Shigella flexneri 2a by introducing deletions in chromosomal aroA and invasion plasmid virG, was highly attenuated in the Sereny test. Two 10(9)-CFU orogastric doses (2 weeks apart) stimulated production of secretory immunoglobulin A antibodies to S. flexneri 2a and protected against conjunctival sac challenge with virulent S. flexneri 2a.
Legal Basis for the Use of Armed Force (2014)

Abstract This chapter addresses how the international legal authority for nations to resort to military force to protect their security interests—generally known as the jus ad bellum —impacts use of force against al-Qaeda and associated forces. The chapter explains how traditional notions of national and collective self-defense focused on threats posed by other States evolved to address the threat posed by transnational nonstate groups. The chapter reviews U.S. interpretations of this law and explains how these interpretations frame the legal authority for contemporary counter-terror military operations in various locations around the world. It also discusses the role of the United Nations, specifically its Charter prohibiting the use of force by States and the exceptions to that prohibition.
Biological Applications of Anti-Stokes Raman Spectroscopy: Quantitative Analysis of Glucose in Plasma and Serum by a Highly Sensitive Multichannel Raman Spectrometer (1996)

This study demonstrates the potential of anti-Stokes Raman spectroscopy in investigating biological samples in a nondestructive manner; quantitative analysis of glucose in plasma and serum has been studied as an example. The efficient collection of anti-Stokes Raman scattering by use of chromatic aberration of a lens has allowed us to obtain high-quality anti-Stokes Raman spectra from glucose in plasma and serum, which is a strongly fluorescent biological sample. The concentration of glucose in these materials can be estimated by the anti-Stokes Raman intensity of the band at 1130 cm −1 due to the C–O stretching mode. The correlation coefficient between the concentration and the intensity has been calculated to be 0.993 and 0.991 for glucose in plasma and serum, respectively. The detection limits for these materials have been found to be 45 mg/dL and 50 mg/dL, respectively.
Verification of 50- to 100-mer DNA and RNA sequences with high-resolution mass spectrometry. (1995)

Electrospray ionization with Fourier-transform mass spectrometry achieves accurate (< 50-ppm) determination of molecular weights of nucleotides, verifying structures of biological RNA and synthetic single-stranded DNA. High (1o(5)) resolving power makes possible detection of subpicomole impurities and adducts that confuse lower-resolution measurements. Molecular ions in a spectrum of 76-mer tRNA(Phe) had 34-55 Na adducts; when desalted, these show a molecular mass of 24,950.5 Da (expected, 24,950.3 Da) and minor variants at approximately -15 and +15 Da. A 50-mer DNA is characterized with < 10-ppm mass error, with detection of both N + 1 and N - 1 failure sequences. Special electrospray ionization conditions are necessary for a 72-mer to minimize fragmentation in the ion source. Despite the chemical noise from this, as well as failed sequences from automated synthesis, the spectrum of a 100-mer single-stranded DNA yielded a molecular mass of 30,702.4 +/- 1 Da, in good agreement with the expected value, 30,702.1 Da.
Synergistic effects of methylnaltrexone with 5-fluorouracil and bevacizumab on inhibition of vascular endothelial growth factor–induced angiogenesis (2008)

Many patients with cancer receive combinations of drug treatments that include 5-fluorouracil (5-FU) and bevacizumab. Therapeutic doses of 5-FU are often associated with unwanted side effects, and bevacizumab is costly. Therefore, we explored potential agents that can reduce the therapeutic concentration of these drugs. Our data indicate that methylnaltrexone (MNTX), a peripheral antagonist of the mu-opioid receptor, exerts a synergistic effect with 5-FU and bevacizumab on inhibition of vascular endothelial growth factor (VEGF)-induced human pulmonary microvascular endothelial cell (EC) proliferation and migration, two key components in cancer-associated angiogenesis. MNTX inhibited EC proliferation with an IC(50) of approximately 100 nmol/L. Adding 100 nmol/L MNTX to EC shifted the IC(50) of 5-FU from approximately 5 micromol/L to approximately 7 nmol/L. Further, adding 50 ng/mL MNTX shifted the IC(50) of bevacizumab on inhibition of EC migration from approximately 25 to approximately 6 ng/mL. These synergistic effects were not observed with naltrexone, a tertiary mu-opioid receptor antagonist. On a mechanistic level, we observed that treatment of human EC with MNTX, but not naltrexone, increased receptor protein tyrosine phosphatase mu activity, which was independent of mu-opioid receptor expression. Silencing receptor protein tyrosine phosphatase mu expression (small interfering RNA) in human EC inhibited both synergy between MNTX and bevacizumab or 5-FU and increased VEGF-induced tyrosine phosphorylation of Src and p190 RhoGAP with enhanced activation of Akt and the actin cytoskeletal regulatory protein, RhoA, whereas silencing Src, Akt, or RhoA blocked VEGF-induced angiogenic events. Therefore, addition of MNTX could potentially lower the therapeutic doses of 5-FU and bevacizumab, which could improve index.
Generation or large numbers of immature and mature dendritic cells from rat bone marrow cultures (1998)

We have defined conditions for generating large numbers of dendritic cells (DC) in marrow cultures from 10-12-week-old ACI or WF rats. The combination of granulocyte-macrophage colony-stimulating factor (GM-CSF) and TNF-alpha, known to induce DC from human CD34+ progenitors, was not effective with rat. In contrast, GM-CSF plus IL-4 generated DC in high yield, corresponding to 30-40% of the initial number of plated marrow cells. The DC proliferated in distinctive aggregates, in which most cells had an immature phenotype marked by undetectable surface B7 and high levels of MHC class II products within intracellular lysosomes. When dislodged and dispersed, the aggregates gave rise to mature stellate DC with abundant surface MHC class II and B7, sparse MHC class II- lysosomes, and strong T cell-stimulating capacity. Therefore, rat marrow progenitors can generate large numbers of immature DC, with abundant intracellular MHC class II compartments, and potent, stimulatory, mature DC.
From Nicotine to Breast Cancer, Implications of Cholinergic Receptor Pathway (2010)

Nicotine is the most important pharmacologically active compound in all forms of tobacco smoke because of its interaction with cholinergic receptors. In the current issue of the Journal, a research article by Lee et al. (1) and a brief communication by Falvella et al. (2) use different approaches to contribute to a better understanding of the roles of nicotine receptors and the biological basis that underlies the environmental and genetic components of smoking-related cancer risk. Two types of acetylcholine receptors (AChRs) exist: the nicotinic AChRs (nAChRs) and muscarinic AChRs (mAChRs). The nAChRs are ligand-gated ion channels and form pentameric complexes that consist of four related but genetically and immunologically distinct subunits: a, b, g, and d (3). The a9-nAChR, a known homopentamer that plays a central role in coordinating keratinocyte adhesion and motility during wound healing (4), is encoded by a gene (CHRNA9) on human chromosome 4p (5). Lee et al. (1) showed that a9-nAChRs were ubiquitously expressed in many epithelial and cancer cell lines from lung and breast and that most of the same cell lines also expressed a5- and a10-nAChRs. The a9-nAChRs were also present in primary tumors and nonmalignant breast tissue obtained from patients; however, cancers had increased a9-nAChR expression compared with the surrounding
Meso/Macroporous Inorganic Oxide Monoliths from Polymer Foams (2003)

Low‐density bimodal inorganic oxide monoliths (see Figure) have been prepared via a two‐step procedure using macroporous polystyrene foams and amphiphilic block copolymer structure‐directing agents. The resulting meso/macroporous inorganic framework structures could be obtained with different 3D bulk shapes and for a range of inorganic oxides, as demonstrated here for silica, zirconia, and titania.
[Effects of lidocaine on stimulation-coupled responses of neutrophils and protein kinase C activity]. (1992)

The effects of lidocaine on superoxide generation and other stimulation-coupled responses of neutrophils induced by 12-phorbol myristate 13-acetate (PMA) were studied. Depolarization of membrane potential, superoxide generation and chemiluminescence response were inhibited by lidocaine in a concentration dependent manner. Lidocaine inhibited protein kinase C (PKC) activity in a manner competitive with phosphatidylserine. Lidocaine also inhibited the phosphorylation of 47 kDa neutrophil cytoplasmic protein, a phosphorylated protein required for activation of NADPH oxidase. The inhibitory action of lidocaine on PKC activity may correlate with the inhibition of superoxide generation induced by PMA.
Role of Heat Shock Proteins in Protection from and Pathogenesis of Infectious Diseases (1999)

Increased synthesis of heat shock proteins (hsp) occurs in prokaryotic and eukaryotic cells when they are exposed to stress. By increasing their hsp content, cells protect themselves from lethal assaults, primarily because hsp interfere with the uncontrolled protein unfolding that occurs under stress. However, hsp are not produced only by stressed cells; some hsp are synthesized constitutively and perform important housekeeping functions. Accordingly, hsp are involved in the assembly of molecules which play important roles in the immune system. It is not surprising that due to their wide distribution and their homology among different species, hsp represent target antigens of the immune response. Frequent confrontation of the immune system with conserved regions of hsp which are shared by various microbial pathogens can potentiate antimicrobial immunity. However, long-term confrontation of the immune system with hsp antigens which are similar in the host and invaders may convert the immune response against these host antigens and promote autoimmune disease. This review provides an overview of the role of hsp in immunity with a focus on infectious and autoimmune diseases.
Evaluation of flow injection analysis for determination of urea in sheep's and cow's milk (2002)

Difficulties in measuring the urea content in sheep's milk often occur with spectral photometry due to the high protein and fat concentrations of the milk. In this study an enzymatic flow procedure (QuickChem 8000 Ion Analyser, Lachat Instruments, Milwaukee, USA) to determine the urea content in ovine and bovine milk was evaluated. Urea content is determined by the Berthelot reaction after splitting it enzymatically with urease. The free ammonia diffuses through a teflon membrane into a stream of reagent solutions. Detection takes place by means of a reaction between the ammonium ions with hypochlorite and salicylate producing a green colour, which is measured spectrometrically in a flow meter at 660 nm. By using a diffusion cell chemical deproteinisation of milk is not necessary and capacity is high. The assessed procedure exhibited high accuracy and precision and reached a sample capacity of 55 samples an hour. Storage of the milk samples for several days as well as chemical preservation with bronopol had no effect on the measurement procedure. Due to the complexity of the apparatus and the costs associated therewith, the device proves less suitable for routine diagnostics but rather serves as a reference method for the measurement of urea concentration in milk.
Differentiation enhances aminolevulinic acid-dependent photodynamic treatment of LNCaP prostate cancer cells (2002)

Photodynamic therapy using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) may be applied to the treatment of neoplasms in a variety of organs. In order to enhance existing regimens of photodynamic therapy, we investigated the effects of adding differentiation therapy to photodynamic therapy in human prostate cancer cells in vitro. The objective of differentiation therapy per se is to reverse the lack of differentiation in cancer cells using pharmacological agents. The motivation for this study was to exploit the differentiation-dependent expression of some heme enzymes to enhance tumour cell toxicity of ALA-photodynamic therapy. A short course of differentiation therapy was applied to increase PpIX formation during subsequent ALA exposure. Using the synthetic androgen R1881, isomers of retinoic acid, and analogues of vitamin D for 3 to 4 days, exogenous ALA-dependent PpIX formation in LNCaP cells was increased, along with markers for growth arrest and for differentiation. As a consequence of higher PpIX levels, cytotoxic effects of visible light exposure were also enhanced. Short-term differentiation therapy increased not only the overall PpIX production but also reduced that fraction of cells that contained low PpIX levels as demonstrated by flow cytometry and fluorescence microscopy. This study suggests that it will be feasible to develop protocols combining short-term differentiation therapy with photodynamic therapy for enhanced photosensitisation.
Synthesis, Characterization and Electrochemistry of Lithium Battery Electrodes: xLi2MnO3·(1 − x)LiMn0.333Ni0.333Co0.333O2 (0 ≤ x ≤ 0.7) (2008)

Lithium- and manganese-rich layered electrode materials, represented by the general formula xLi2MnO3·(1 − x)LiMO2 in which M is Mn, Ni, and Co, are of interest for both high-power and high-capacity lithium ion cells. In this paper, the synthesis, structural and electrochemical characterization of xLi2MnO3·(1 − x)LiMn0.333Ni0.333Co0.333O2 electrodes over a wide compositional range (0 ≤ x ≤ 0.7) is explored. Changes that occur to the compositional, structural, and electrochemical properties of the electrodes as a function of x and the importance of using a relatively high manganese content and a high charging potential (>4.4 V) to generate high capacity (>200 mAh/g) electrodes are highlighted. Particular attention is given to the electrode composition 0.3Li2MnO3·0.7LiMn0.333Ni0.333Co0.333O2 (x = 0.3) which, if completely delithiated during charge, yields Mn0.533Ni0.233Co0.233O2, in which the manganese ions are tetravalent and, when fully discharged, LiMn0.533Ni0.233Co0.233O2, in which the average manganese oxidation state (3.44) is marginally below that expected for a potentially damaging Jahn−Teller distortion (3.5). Acid treatment of 0.3Li2MnO3·0.7LiMn0.333Ni0.333Co0.333O2 composite electrode structures with 0.1 M HNO3 chemically activates the Li2MnO3 component and essentially eliminates the first cycle capacity loss but damages electrochemical behavior, consistent with earlier reports for Li2MnO3-stabilized electrodes. Differences between electrochemical and chemical activation of the Li2MnO3 component are discussed. Electrochemical charge/discharge profiles and cyclic voltammogram data suggest that small spinel-like regions, generated in cycled manganese-rich electrodes, serve to stabilize the electrodes, particularly at low lithium loadings (high potentials). The study emphasizes that, for high values of x, a relatively small LiMO2 concentration stabilizes a layered Li2MnO3 electrode to reversible lithium insertion and extraction when charged to a high potential.
Toxicity from different SOD1 mutants dysregulates the complement system and the neuronal regenerative response in ALS motor neurons (2007)

Global, age-dependent changes in gene expression from rodent models of inherited ALS caused by dominant mutations in superoxide-dismutase 1 (SOD1) were identified by using gene arrays and RNAs isolated from purified embryonic and adult motor neurons. Comparison of embryonic motor neurons expressing a dismutase active ALS-linked mutant SOD1 with those expressing comparable levels of wild-type SOD1 revealed the absence of mutant-induced mRNA changes. An age-dependent mRNA change that developed presymptomatically in adult motor neurons collected by laser microdissection from mice expressing dismutase active ALS-linked mutants was dysregulation of the d/l-serine biosynthetic pathway, previously linked to both excitotoxic and neurotrophic effects. An unexpected dysregulation common to motor neurons expressing either dismutase active or inactive mutants was induction of neuronally derived components of the classic complement system and the regenerative/injury response. Alteration of these mutant SOD1-induced pathways identified a set of targets for therapies for inherited ALS.
RNA viruses. A practical approach. (2000)

Preface 1. Extraction, purification and characterization of virus DNA 2. Investigation of DNA virus genome structure 3. Mutagenesis of DNA virus genomes 4. Interactions between viral and cellular proteins during DNA virus replication 5. Analysis of transcriptional control in DNA virus infections 6. Identification and analysis of trans-acting proteins involved in regulation of DNA virus gene expression 7. Interaction of DNA virus proteins with host cytokines 8. Analysis of DNA virus proteins involved in neoplastic cell transformation 9. Chemotherapy of DNA virus infections 10. Herpes simplex virus and adenovirus vectors
The etiology of antisocial personality disorder: The differential roles of adverse childhood experiences and childhood psychopathology (2019)

Antisocial Personality Disorder (ASPD) is a severe personality disorder with robust associations with crime and violence, but its precise etiology is unknown. Drawing on near-population of federal correctional clients in the Midwestern United States, the current study examined antecedent background factors spanning adverse childhood experiences and childhood psychopathology. Greater adverse childhood experiences were associated with ASPD diagnosis with physical abuse showing associations with ASPD symptoms and sexual abuse with lifetime diagnosis for ASPD. Conduct Disorder was strongly linked to ASPD; however, Oppositional Defiant Disorder and ADHD had null associations. Given the role of environmental factors in the development of ASPD, greater criminological attention should be devoted to understanding how assorted forms of abuse and neglect coupled with childhood psychopathology contribute to ASPD especially given its linkages to severe criminal offending.