gebhart/patrepeval huggingface dataset:
Alternating Ring-Opening Polymerization of Cyclohexene Oxide and Anhydrides: Effect of Catalyst, Cocatalyst, and Anhydride Structure (2012)

Ring-opening copolymerization of cyclohexene oxide with alicyclic anhydrides containing different ring strain (succinic anhydride, cyclopropane-1,2-dicarboxylic acid anhydride, and phthalic anhydride) was performed applying metal salen chloride complexes, (salen)MCl (M = Al, Cr, Co; salen = N,N-bis(3,5-di-tert-butylsalicylidene)diimine) with different metals and ligand–diimine backbones. While some of the bulk copolymerizations afforded poly(ester-co-ether)s, all solution polymerizations produced perfect alternating copolymers. The chromium catalysts performed best while the aluminum catalysts were the least active ones. For each metal, the salophen complexes yielded the best performing catalyst. A variety of cocatalysts have been employed: bis(triphenylphosphoranylidene)ammonium chloride, N-heterocyclic nucleophiles including 4-(dimethylamino)pyridine, N-methylimidazole, and 1,5,7-triazabicyclododecene and the phosphines trimesitylphosphine, tris(2,4,6-trimethoxyphenyl)phosphine, tricyclohexylphosphine to triphenylphsophine. Of all cocatalysts, bis(triphenylphosphoranylidene)ammonium chloride was found to be the most efficient cocatalyst in combination with salophenCrCl for the copolymerization of cyclohexene oxide with phthalic anhydride, and 1 equiv was enough to reach optimum activity. N-Heterocyclic nucleophiles showed the lowest activity. Of the three anhydrides used, phthalic anhydride is the most reactive giving the highest conversions and the highest molecular weight products.
FRET from single to multiplexed signaling events (2017)

Förster resonance energy transfer (FRET) is a powerful tool for the visualization of molecular signaling events such as protein activities and interactions in cells. In its different implementations, FRET microscopy has been mainly used for monitoring single events. Recently, there has been a trend of extending FRET imaging towards the simultaneous detection of multiple events and interactions. The concomitant increase in experimental complexity requires a deeper understanding of the biophysical background of FRET. The presence of multiple acceptors for one donor affects the well-known formalism for FRET between two molecules, increasing distance sensitivity through mechanisms that have become known as the 'antenna' and 'surplus' effect. We will discuss the nature of these effects and present the imaging methods that have been used to unravel the combined transfer rates in the multi-protein interactions of multiplexed FRET experiments. Multiplexing strategies are becoming invaluable analytical tools for the elucidation of biological complexes and for the visualization of decision points in cellular signaling networks in physiological and pathological conditions.
The importance of 5-HT1A receptor agonism in antipsychotic drug action: rationale and perspectives. (2010)

Serotonin 5-HT1A receptors are attractive targets for the development of improved antipsychotics. Indeed, extensive evidence in rodent models indicates that the activation of these receptors prevents extrapyramidal symptoms (EPS) induced by dopamine D2 receptor blockade, favors dopaminergic neurotransmission in the frontal cortex, has a positive influence on mood, and opposes NMDA receptor antagonist-induced cognitive and social interaction deficits. Therefore, 'third-generation' antipsychotics that combine partial agonism at 5-HT1A receptors with antagonism (or partial agonism) at D2 receptors have been investigated, including aripiprazole, perospirone, lurasidone (Dainippon Sumitomo Pharma Co Ltd), cariprazine (Gedeon Richter Ltd/Forest Laboratories Inc/Mitsubishi Tanabe Pharma Corp), PF-217830 (Pfizer Inc), F-97013-GD, F-15063 and bifeprunox. Such compounds appear to provide therapeutic benefits against a broader range of symptoms of schizophrenia, including negative symptoms and cognitive deficits that are poorly controlled by established antipsychotics. Recently developed compounds are essentially free of EPS liability, and exhibit little or no interaction at sites that are potentially involved in causing side effects such as weight gain, metabolic disorders or autonomic disturbance. These compounds differ in their balance of 5-HT1A/D2 receptor affinity and agonist or antagonist properties; such differences are likely to translate into distinct therapeutic profiles. The balance of 5-HT1A/D2 receptor properties should therefore be considered when selecting compounds as antipsychotic development candidates.
Differential Vulnerability of Calbindin-immunoreactive Neurons in HIV Encephalitis (1995)

Recent studies have suggested that the neuronal damage during human immunodeficiency virus encephalitis (HIVE) might be mediated by increased intracellular calcium. Since in vitro studies have shown that calcium-binding proteins protect neurons from calcium-mediated toxicity, we hypothesized that calbindin-expressing neurons might be resistant to HIV1-mediated damage. We compared patterns of calbindin immunoreactivity in the cortex and subcortex of autopsied AIDS cases with and without HIVE. Calbindin-immunoreactive neurons in the neocortex were significantly reduced in HIVE (one-way ANOVA, p < 0.001), while these neurons in the basal ganglia and hippocampus were unaffected. The loss of calbindin-immunolabeled neurons in the neocortex was correlated with viral burden (r = -0.45, p < 0.001). Differential loss of calbindin-immunoreactive neurons in HIVE suggests that neuronal damage in different regions of the CNS may be mediated by different pathogenic mechanisms.
Anergy in immature B lymphocytes. Differential responses to receptor-mediated stimulation and T helper cells (1991)

We have compared the responses of purified neonatal and adult B lymphocytes to stimulation by anti-Ig antibodies, which are functional analogues of Ag, and by Th cells. Neonatal B cells are markedly deficient in proliferative responses to anti-Ig antibodies + IL-4 or to anti-Ig conjugated to dextran, both of which induce strong proliferation of adult B cells in the absence of T lymphocytes. Anti-Ig antibodies actually inhibit the functional responses of neonatal B cells, even to polyclonal stimuli such as LPS. However, Th cells induce both proliferation and Ig secretion by neonatal B cells in the presence of Ag that bind to B cell Ig and are subsequently presented by the B cells. Thus, in neonatal B lymphocytes, cross-linking of membrane Ig in the absence of Th cells has a net inhibitory effect, and this inhibition is overcome by T cell help. These results also suggest that unresponsiveness or tolerance to thymus-independent Ag is induced in the B cells themselves, but tolerance to thymus-dependent proteins resides primarily in the T cell compartment.
Growing human organs in pigs—A dream or reality? (2016)

Organ transplantation has been the last line of therapy for saving patients experiencing end-stage organ failure. However, the success of organ transplantation is critically dependent on the availability of donor organs. There are high expectations for research on organ regeneration as a solution to the donor shortage issue faced by transplantation medicine. Thus, generation of human organs from pluripotent stem cells is now one of the ultimate goals of regenerative medicine. In recent years, several approaches to using pluripotent stem cells to generate organs of complex structure and function have been developed. Reproductive biology plays an indispensable role in the development of innovative organ regeneration researches. In this review, we discuss the potential of the animal biotechnology aiming at making human organs using pigs as a platform.
The chromatin accessibility landscape of primary human cancers (2018)

We present the genome-wide chromatin accessibility profiles of 410 tumor samples spanning 23 cancer types from The Cancer Genome Atlas (TCGA). We identify 562,709 transposase-accessible DNA elements that substantially extend the compendium of known cis-regulatory elements. Integration of ATAC-seq (the assay for transposase-accessible chromatin using sequencing) with TCGA multi-omic data identifies a large number of putative distal enhancers that distinguish molecular subtypes of cancers, uncovers specific driving transcription factors via protein-DNA footprints, and nominates long-range gene-regulatory interactions in cancer. These data reveal genetic risk loci of cancer predisposition as active DNA regulatory elements in cancer, identify gene-regulatory interactions underlying cancer immune evasion, and pinpoint noncoding mutations that drive enhancer activation and may affect patient survival. These results suggest a systematic approach to understanding the noncoding genome in cancer to advance diagnosis and therapy.
Compliance defects in public-key cryptography (1996)

Abstract Public-key cryptography has low infrastructural overhead because public-key users bear a substantial but hidden administrative burden. A public-key security system trusts its users to validate each others &amp;apos; public keys rigorously and to manage their own private keys securely. Both tasks are hard to do well, but publickey security systems lack a centralized infrastructure for enforcing users &amp;apos; discipline. A compliance defect in a cryptosystem is such a rule of operation that is both difficult to follow and unenforceable. This paper presents five compliance defects that are inherent in public-key cryptography; these defects make publickey cryptography more suitable for server-to-server security than for desktop applications. 1 Introduction Public-key cryptography is uniquely well-suited to certain parts of a secure global network. It is widely accepted that public-key security systems are easier to administer, more secure, less trustful, and have better geographical reach, than symmetric-key security systems. However, it is not widely appreciated that these advantages rely excessively on end-users &amp;apos; security discipline. In fact, the reason public-key security doesn&amp;apos;t need a trusted key-management infrastructure is that the burden of key-management falls to public-key clients. With public-key cryptography, clients must constantly be careful to validate rigorously every public key they use, and they must husband the secrecy of their long-lived private keys. It turns out that these tasks are harder than they seem.
Androgen receptor: A key molecule in the progression of prostate cancer to hormone independence (2003)

Despite earlier detection and recent advances in surgery and radiation, prostate cancer is second only to lung cancer in male cancer deaths in the United States. Hormone therapy in the form of medical or surgical castration remains the mainstay of systemic treatment in prostate cancer. Over the last 15 years with the clinical use of prostate specific antigen (PSA), there has been a shift to using hormone therapy earlier in the disease course and for longer duration. Despite initial favorable response to hormone therapy, over a period of time these tumors will develop androgen-independence that results in death. The androgen receptor (AR) is central to the initiation and growth of prostate cancer and to its response to hormone therapy. Analyses have shown that AR continues to be expressed in androgen-independent tumors and AR signaling remains intact as demonstrated by the expression of the AR regulated gene, PSA. Androgen-independent prostate cancers have demonstrated a variety of AR alterations that are either not found in hormone naïve tumors or found at lower frequency. These changes include AR amplification, AR point mutation, and changes in expression of AR co-regulatory proteins. These AR changes result in a "super AR" that can respond to lower concentrations of androgens or to a wider variety of agonistic ligands. There is also mounting evidence that AR can be activated in a ligand independent fashion by compounds such as growth factors or cytokines working independently or in combination. These growth factors working through receptor tyrosine kinase pathways may promote AR activation and growth in low androgen environments. The clinical significance of these AR alterations in the development and progression of androgen-independent prostate cancer remains to be determined. Understanding the changes in AR signaling in the evolution of androgen-independent prostate cancer will be key to the development of more effective hormone therapy.
Topological Quantum Buses: Coherent Quantum Information Transfer between Topological and Conventional Qubits (2011)

We propose computing bus devices that enable quantum information to be coherently transferred between topological and conventional qubits. We describe a concrete realization of such a topological quantum bus acting between a topological qubit in a Majorana wire network and a conventional semiconductor double quantum dot qubit. Specifically, this device measures the joint (fermion) parity of these two different qubits by using the Aharonov-Casher effect in conjunction with an ancilliary superconducting flux qubit that facilitates the measurement. Such a parity measurement, together with the ability to apply Hadamard gates to the two qubits, allows one to produce states in which the topological and conventional qubits are maximally entangled and to teleport quantum states between the topological and conventional quantum systems.
Optimization of Activity-Based Probes for Proteomic Profiling of Histone Deacetylase Complexes (2008)

Histone deacetylases (HDACs) are key enzymatic regulators of the epigenome and serve as promising targets for anticancer therapeutics. Recently, we developed a photoreactive "clickable" probe, SAHA-BPyne, to report on HDAC activity and complex formation in native biological systems. Here, we investigate the selectivity, sensitivity, and inhibitory properties of SAHA-BPyne and related potential activity-based probes for HDACs. While we identified several probes that are potent HDAC inhibitors and label HDAC complex components in native proteomic preparations, SAHA-BPyne was markedly superior for profiling HDAC activities in live cells. Interestingly, the enhanced performance of SAHA-BPyne as an in situ activity-based probe could not be solely ascribed to potency in HDAC binding, implying that other features of the molecule were key to efficient active site-directed labeling in living systems. Finally, we demonstrate the value of in situ profiling of HDACs by comparing the activity and expression of HDAC1 in cancer cells treated with the cytotoxic agent parthenolide. These results underscore the utility of activity-based protein profiling for studying HDAC function and may provide insight for the future development of click chemistry-based photoreactive probes for the in situ analysis of additional enzyme activities.
Enhanced Exon-skipping Induced by U7 snRNA Carrying a Splicing Silencer Sequence: Promising Tool for DMD Therapy (2009)

Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disorder caused by mutations in the dystrophin gene. In most cases, the open-reading frame is disrupted which results in the absence of functional protein. Antisense-mediated exon skipping is one of the most promising approaches for the treatment of DMD and has recently been shown to correct the reading frame and restore dystrophin expression in vitro and in vivo. Specific exon skipping can be achieved using synthetic oligonucleotides or viral vectors encoding modified small nuclear RNAs (snRNAs), by masking important splicing sites. In this study, we demonstrate that enhanced exon skipping can be induced by a U7 snRNA carrying binding sites for the heterogeneous ribonucleoprotein A1 (hnRNPA1). In DMD patient cells, bifunctional U7 snRNAs harboring silencer motifs induce complete skipping of exon 51, and thus restore dystrophin expression to near wild-type levels. Furthermore, we show the efficacy of these constructs in vivo in transgenic mice carrying the entire human DMD locus after intramuscular injection of adeno-associated virus (AAV) vectors encoding the bifunctional U7 snRNA. These new constructs are very promising for the optimization of therapeutic exon skipping for DMD, but also offer powerful and versatile tools to modulate pre-mRNA splicing in a wide range of applications.
Effects of two venotropic drugs on inactivation and O-methylation of catecholamines in an isolated canine vein. (1985)

Clobenoside (1-O-ethyl-3-O-propyl-5,6-di-O-chlorbenzyl-D-glucofuranose, CL) and Venoruton [O-(beta-hydroxyethyl)-rutosides, HR] did not cause supersensitivity to either exogenous or endogenous (stimulation-released) noradrenaline, in strips of the saphenous vein of the dog. Both drugs caused a significant blockade of the inactivation of noradrenaline, in oil immersion experiments. In incubation experiments with 3H-isoprenaline, CL and HR (100 to 900 mumol/l) caused a dose-dependent inhibition of O-methylation; they had additive effects with the COMT inhibitor, U-0521 and their effects were abolished in the presence of hydrocortisone. In incubation experiments with 3H-adrenaline, formation of metanephrine was inhibited, neuronal uptake and oxidative deamination remaining unaffected. After intravenous administration of HR (100 mg/kg), the O-methylating capacity of blood vessels was similarly reduced. It is concluded that CL and HR affected exclusively the extraneuronal O-methylating system (probably both by inhibiting COMT and depressing uptake) and that this effect may contribute to their therapeutic actions.
Nigeria : le Projet national de Developpement des Fadama (2002)

The objectives of the loan (1993-1999) were to build on the achievements of some of the Northern agricultural development projects (ADPs) in developing small-scale irrigation through the extraction of shallow groundwater with low-cost petrol-driven pumps. By making agricultural production less dependent on erratic rainfall, farmers' incomes were expected to be raised and food security augmented. this article, largely excerpted from the Implementation Completion Report no. 19730 describes the project's impact, lists the lessons learned, and underscores the aims of the follow-up project in preparation.
Model for studying virus attachment. II. Binding of biotinylated human T cell leukemia virus type I to human blood mononuclear cells potential targets for human T cell leukemia virus type I infection (1991)

Purified human T cell leukemia virus type I (HTLV-I) was biotinylated and used to study its attachment to human PBMC. The use of biotinylated HTLV-I (biot-HTLV-I) in conjunction with mouse mAb specific for selected cell-surface molecules and flow cytometric analysis allowed us to positively identify virus-binding cells among a heterogeneous blood mononuclear cell population. Biot-HTLV-I efficiently bound not only to T cells, but also to B cells and monocytes. Preincubation of monocytes with excess of unlabeled HTLV-I significantly reduced the attachment of biot-HTLV-I. HTLV-I not only bound to, but also infected, B cells, as suggested by: i) in situ hybridization of a 35S-labeled full length HTLV-I DNA probe with EBV-transformed B cells, previously cocultured with HTLV-I-producing (G11MJ) T cells, and ii) hybridization of the same nick-translated 32P-labeled DNA probe with blotted DNA from similar HTLV-I-infected EBV-transformed B cells. HTLV-I infection did not affect the ability of B cells to secrete IgG. These findings suggest that HTLV-I cannot only infect cells of the T lineage, but can also infect B cells.
Innovative PV Micro-Inverter Topology Eliminates Electrolytic Capacitors for Longer Lifetime (2006)

An extremely reliable micro-inverter is critical to the success of the AC PV building block and the AC PV module concepts. [1,2,3,4]. An innovative inverter design has been developed and prototyped in order to address some of the most critical issues associated with extending the mean time between failure (MTBF) and the total lifetime of the micro-inverter when it is integrated onto a PV module. The innovative micro-inverter addressed in this paper uses a unique proprietary circuit topology to reduce the numbers and sizes of capacitors, is currently rated at 150 W, and has been shown to be thermally robust and feasible. Additionally, the smaller capacitors used in the design use advanced technology exhibiting much longer lifetime (30-year) in the anticipated thermal environment. The unconventional micro-inverter design considerations, layout, early findings from modeling and evaluation results are presented. Preliminary findings for proposed redesign to increase the rating to 300 W are presented. An initial assessment of a reliability requirement study for micro-inverters is also discussed
The effect of sheared axial flow on the linear stability of the Z-pinch (1996)

A linear analysis of the ideal magnetohydrodynamic (MHD) stability of the Z-pinch is presented in which plasma flows are included in the equilibrium. With sheared axial flows it is found that substantial stabilization of internal modes is possible for some equilibrium profiles. For this to occur equilibria with a change in fluid velocity across the pinch radius of about Mach 2 are required. However, this ignores the surrounding vacuum and for the more realistic free boundary modes flows of about Mach 4 are required to stabilize all global MHD modes. This stabilization of MHD modes is not observed for all equilibria however. This fact, combined with the supersonic flow speeds required for stability, make it unlikely that a Z-pinch could in practice be stabilized by the introduction of sheared flow.
Further Studies on Facility of Flow Through the Trabecular Meshwork (1958)

In 1954 and 1955 preliminary results were reported on attempts at measuring directly how much of the normal resistance to outflow of aqueous humor is attributable to the trabecular meshwork in human eyes.<sup>1,2</sup>In the more recent of these experiments enucleated human eyes were perfused with sodium chloride solution through a needle which entered the anterior chamber through the cornea and communicated with both anterior and posterior chambers. The facility of outflow was determined by measuring both the rate of flow and the intraocular pressure after a steady state was attained. Then, the trabecular meshwork in one quadrant was curetted with the point of the transcorneal needle, and the facility of outflow was redetermined. In experiments on 19 eyes, no change in facility of outflow was found in 12, but an increase occurred in 6, and a small decrease, in only 1. Microscopic examination of sections of all eyes
LIS1 Missense Mutations (2003)

Mutations in one allele of the human LIS1 gene cause a severe brain malformation, lissencephaly. Although most LIS1 mutations involve deletions, several point mutations with a single amino acid alteration were described. Patients carrying these mutations reveal variable phenotypic manifestations. We have analyzed the functional importance of these point mutations by examining protein stability, folding, intracellular localization, and protein-protein interactions. Our data suggest that the mutated proteins were affected at different levels, and no single assay could be used to predict the lissencephaly phenotype. Most interesting are those mutant proteins that retain partial folding and interactions. In the case of LIS1 mutated in F31S, the cellular phenotype may be modified by overexpression of specific interacting proteins. Overexpression of the PAF-AH alpha1 subunit dissolved aggregates induced by this mutant protein and increased its half-life. Overexpression of NudE or NudEL localized this mutant protein to spindle poles and kinetochores but had no effect on protein stability. Our results implicate that there are probably different biochemical and cellular mechanisms obstructed in each patient yielding the varied lissencephaly phenotypes.