gebhart/patrepeval huggingface dataset:
Amygdala infusions of an NR2B-selective or an NR2A-preferring NMDA receptor antagonist differentially influence fear conditioning and expression in the fear-potentiated startle test (2008)

Within the amygdala, most N-methyl-D-aspartic acid (NMDA) receptors consist of NR1 subunits in combination with either NR2A or NR2B subunits. Because the particular subunit composition greatly influences the receptors' properties, we investigated the contribution of both subtypes to fear conditioning and expression. To do so, we infused the NR1/NR2B receptor antagonist CP101,606 (0.5, 1.5, or 4.5 microg/amygdala) or the NR1/NR2A-preferring antagonist NVP-AAM077 (0.075, 0.25, 0.75, or 2.5 microg/amygdala) into the amygdala prior to either fear conditioning (i.e., light-shock pairings) or fear-potentiated startle testing. CP101,606 nonmonotonically disrupted fear conditioning but did not disrupt fear expression. NVP-AAM077 dose-dependently disrupted fear conditioning as well as fear expression. The results suggest that amygdala NR1/NR2B receptors play a special role in fear memory formation, whereas NR1/NR2A receptors participate more generally in synaptic transmission.
Progress in Antisense Technology (2004)

Antisense technology exploits oligonucleotide analogs to bind to target RNAs via Watson-Crick hybridization. Once bound, the antisense agent either disables or induces the degradation of the target RNA. Antisense agents can also alter splicing. During the past decade, much has been learned about the basic mechanisms of antisense, the medicinal chemistry, and the pharmacologic, pharmacokinetic, and toxicologic properties of antisense molecules. Antisense technology has proven valuable in gene functionalization and target validation. With one drug marketed, Vitravenetm, and approximately 20 antisense drugs in clinical development, it appears that antisense drugs may prove important in the treatment of a wide range of diseases.
Titanocene-Catalyzed Asymmetric Ketone Hydrosilylation:  The Effect of Catalyst Activation Protocol and Additives on the Reaction Rate and Enantioselectivity (1999)

The efficient asymmetric hydrosilylation of ketones with a chiral titanocene catalyst has been realized. In this procedure, (R,R)-ethylenebis(tetrahydroindenyl) titanium difluoride (1) was used as the precatalyst, and alcohol additives were employed. Aromatic and α,β-unsaturated ketones were reduced to the corresponding alcohols with a high level of enantioselectivity.
Potential Role of Peptidylarginine Deiminase Enzymes and Protein Citrullination in Cancer Pathogenesis (2012)

The peptidylarginine deiminases (PADs) are a family of posttranslational modification enzymes that catalyze the conversion of positively charged protein-bound arginine and methylarginine residues to the uncharged, nonstandard amino acid citrulline. This enzymatic activity is referred to as citrullination or, alternatively, deimination. Citrullination can significantly affect biochemical pathways by altering the structure and function of target proteins. Five mammalian PAD family members (PADs 1-4 and 6) have been described and show tissue-specific distribution. Recent reviews on PADs have focused on their role in autoimmune diseases. Here, we will discuss the potential role of PADs in tumor progression and tumor-associated inflammation. In the context of cancer, increasing clinical evidence suggests that PAD4 (and possibly PAD2) has important roles in tumor progression. The link between PADs and cancer is strengthened by recent findings showing that treatment of cell lines and mice with PAD inhibitors significantly suppresses tumor growth and, interestingly, inflammatory symptoms. At the molecular level, transcription factors, coregulators, and histones are functional targets for citrullination by PADs, and citrullination of these targets can affect gene expression in multiple tumor cell lines. Next generation isozyme-specific PAD inhibitors may have therapeutic potential to regulate both the inflammatory tumor microenvironment and tumor cell growth.
p28, A first in class peptide inhibitor of cop1 binding to p53 (2013)

These data identify the specific motifs within the DBD of p53 that bind p28 and suggest that p28 inhibition of COP1 binding results in the sustained, post-translational increase in p53 levels and subsequent inhibition of cancer cell growth independent of an HDM2 pathway.
Scalable lock-free dynamic memory allocation (2004)

Dynamic memory allocators (malloc/free) rely on mutual exclusion locks for protecting the consistency of their shared data structures under multithreading. The use of locking has many disadvantages with respect to performance, availability, robustness, and programming flexibility. A lock-free memory allocator guarantees progress regardless of whether some threads are delayed or even killed and regardless of scheduling policies. This paper presents a completely lock-free memory allocator. It uses only widely-available operating system support and hardware atomic instructions. It offers guaranteed availability even under arbitrary thread termination and crash-failure, and it is immune to deadlock regardless of scheduling policies, and hence it can be used even in interrupt handlers and real-time applications without requiring special scheduler support. Also, by leveraging some high-level structures from Hoard, our allocator is highly scalable, limits space blowup to a constant factor, and is capable of avoiding false sharing. In addition, our allocator allows finer concurrency and much lower latency than Hoard. We use PowerPC shared memory multiprocessor systems to compare the performance of our allocator with the default AIX 5.1 libc malloc, and two widely-used multithread allocators, Hoard and Ptmalloc. Our allocator outperforms the other allocators in virtually all cases and often by substantial margins, under various levels of parallelism and allocation patterns. Furthermore, our allocator also offers the lowest contention-free latency among the allocators by significant margins.
Coexpression of epidermal growth factor receptor protein and c-erbB-2 oncoprotein in human astrocytic tumors. An immunohistochemical study. (1994)

C-erbB-2-oncoprotein and the epidermal growth factor receptor (EGFR) protein are transmembrane glycoproteins with an external ligand-binding domain and a nearly homologous internal tyrosine kinase domain. In the present study it was investigated in 63 astrocytic tumors (9 astrocytomas G1, 18 astrocytomas G2, 17 anaplastic astrocytomas G3 and 19 glioblastomas G4) whether the structural homology of both glycoproteins correlated with the coexpression in astrocytic tumor cells. The immunoreactive products were identified by a computerized image analysis. There was no expression of the EGFR-protein in low grade astrocytomas (G1, G2) measured by density of gray level. The immunoreactivity increased remarkably in anaplastic and malignant gliomas. The number of the c-erbB2-oncoprotein-reactive tumor cells increased with the progression and dedifferentiation of tumors. Significant differences could be found between low grade anaplastic astrocytoma as well as glioblastoma. The correlative analysis resulted in a significant positive homology with increasing grading level between the expression of EGFR- and c-erbB-2 protein. The trend goes in the same direction. The results emphasize that EGFR- and c-erbB-2 protein were expressed in astrocytic tumors with increased malignancy and dedifferentiation.
Synthesis of Titanium, Zirconium, and Hafnium Complexes That Contain the [(MesitylN-o-C6H4)2O]2- Ligand (2000)

(MesitylNH-o-C6H4)2O (H2[MesNON]) has been synthesized in ∼70% yield, and several [MesNON]2- complexes of Ti, Zr, and Hf have been prepared, in particular a variety of dialkyl complexes, [MesNON]MR2 (M = Zr, R = Me, CH2CMe3, Ph; M = Hf, R = Me, Et, CH2CHMe2, CH2CMe3, Ph). [MesNON]ZrMe2 can be activated with [Ph3C][B(C6F5)4] or [PhNMe2H][B(C6F5)4], but the resulting cationic species will only oligomerize 1-hexene. We conclude that the sterically bulky tert-butyl groups in [(R‘N-o-C6H4)2O]2- systems are necessary for the success of [R‘NON]2- Zr catalyst systems for the living polymerization of 1-hexene.
Familial hypercholesterolemia: pathogenesis of a receptor disease. (1978)

Familial hypercholesterolemia is a prototype for a class of diseases that result from defects in receptor molecules. The three cardinal features of familial hypercholesterolemia are: 1) a selective elevation in the plasma level of one cholesterol-carrying lipoprotein, low density lipoprotein (LDL); 2) a selective deposition of LDL-derived cholesterol in macrophage-like scavenger cells throughout the body, but not in parenchymal cells; and 3) inheritance as an autosomal dominant trait with gene dosage effect, i.e., the disease is more serious in patients with the homozygous than with the heterozygous state. In this article, we review the evidence that each of these cardinal features of familial hypercholesterolemia can be explained by a genetic defect in a cell surface receptor for plasma LDL.
The role of anti-DNA idiotype antibodies in systemic lupus erythematosus. (1990)

In this article, we review mainly the major characteristics of anti-DNA antibodies and idiotypes found in either murine or human SLE. We shall refer to the pathogenic role of these antibodies and idiotypes in SLE, and especially to their importance in the early induction of the disease
Alpha melanocyte stimulating hormone inhibits immunostimulatory and inflammatory actions of interleukin 1. (1986)

The ability of interleukin 1 (IL 1) to augment the proliferation of murine thymocytes in vitro was inhibited in a dose-dependent manner by the neuropeptide alpha-melanocyte-stimulating hormone (alpha MSH). The minimal effective concentration of alpha MSH was 10(-11) M. Maximal effect occurred between 10(-8) and 10(-7) M, with diminishing effectiveness at higher concentrations. IL 1-induced production of prostaglandin E (PGE) by fibroblasts was also inhibited by alpha MSH with a biphasic dose response. The minimal effective concentration was 10(-11) M, and maximum effect was achieved at 10(-10) M. alpha MSH appeared to affect the interaction of IL 1 with its target cells in a specific manner, because it did not inhibit basal mitogen-induced thymocyte proliferation or IL 2-induced proliferation of a cytotoxic T lymphocyte line. Furthermore, production of IL 1 by endotoxin-stimulated monocytes was not affected by alpha MSH. An analog of alpha MSH (Nle4, D-Phe7 alpha MSH), which is highly potent in other melanotropin-sensitive systems, did not affect the action of IL 1 on thymocytes, suggesting that the immunomodulatory effects of alpha MSH may not be mediated by the classic melanocyte alpha MSH receptor. The influence of alpha MSH on thymocytes and fibroblasts suggests that alpha MSH is an endogenous antagonist of IL 1, perhaps important for limiting inflammatory damage to host tissues.
A Versatile Total Synthesis of Benzo[c]phenanthridine and Protoberberine Alkaloids Using Lithiated Toluamide−Benzonitrile Cycloaddition (2004)

A new versatile synthesis of benzo[c]phenanthridine and protoberberine alkaloids using lithiated toluamide-benzonitrile cycloaddition was carried out. The coupling reaction between benzonitrile 6 with o-toluamides (8a-c) afforded 3-arylisoquinolines (9a-c) that were transformed to the protoberberines (11a-c) or benzo[c]phenanthridines (14a-c). These compounds were synthesized by ring closure of the two-carbon chain on either position 2 or 4 of the 3-arylisoquinolinone (9a-c). Several kinds of substituted benzo[c]phenanthridine alkaloids such as oxysanguinarine, oxyavicine, and oxynitidine as well as protoberberines such as 8-oxocoptisine, 8-oxopseudoberberine, and 8-oxopseudocoptisine were synthesized.
Protein Purification (1990)

Large scale protein purification is the final production step, prior to product packaging, in the manufacture of therapeutic proteins, specialty enzymes, and diagnostic products. The art and science of protein purification evolves from laboratory scale techniques which are often adapted and scaled up to satisfy the need for larger amounts of extremely pure test quantities of the product for analysis, characterization, testing of efficacy, clinical or field trials, and, finally, full scale commercialization. Development of appropriate strategies for protein recovery and purification differs from development of separation techniques for more traditional chemical or agricultural processing technologies by the broadness of cross-disciplinary interactions required to achieve scale-up. The uncompromising standards for product quality, as well as rigorous quality control of manufacturing practices embodied in current good manufacturing practices (cGMP's), provide further challenges to the scale-up of protein purification. Analysis of electrokinetic, chromatographic, adsorptive, and membrane separation techniques suggests that if yield recovery is paramount, documented purity is critical, and both must ultimately be attained within certain cost constraints. Examples of purification of insulin and proinsulin, IgM, recombinant interferon-alpha, interleukins, histidine containing peptides, lutenizing hormone releasing hormone, and bovine growth hormone illustrate conceptual approaches used in successful industrial processes.
Influence of preparation methods on the texture and structure of titania supported on silica (1994)

Deposition of titanium over a silica support was performed by three methods: precipitation with TiCl4 and ammonium hydroxide in aqueous solution; impregnation with titanium(IV) isopropoxide in isopropyl alcohol; grafting with a solution of TiCl4 in hexane. Samples were characterized by BET, XPS, zeta potential, DBS, XRD, SEM and EPMA. The method of deposition influences deeply the morphology and dispersion of the coated oxide. With the precipitation method, TiO2 is deposited at the external surface of the silica. Impregnation provides the best external superficial dispersion of titania allowing the formation of small crystallites at its surface. The grafting method gives the best internal TiO2 dispersion with formation of large crystallites at the external surface of silica. A strong interaction is found between titanium and silicon. This work also draws attention to the many analytical techniques needed to characterize the TiO2-coated supports.
Assessment and follow-up of intercostal nerve damage after video-assisted thoracic surgery (2010)

This is the first study that objectively evaluated pain after video-assisted thoracic surgery. The results suggest that the Aβ and Aδ fibers play a significant role in the development of intercostal nerve damage. The current perception threshold values clearly demonstrated that video-assisted thoracic surgery is a less-invasive procedure resulting in less post-thoracotomy pain and, they have some possibilities to objectively evaluate the ongoing pain after surgery.
In Situ Vaccination for the Treatment of Cancer (2016)

Vaccination has had a tremendous impact on human health by harnessing the immune system to prevent and eradicate infectious diseases and this same approach might be used in cancer therapy. Cancer vaccine development has been slowed hindered by the paucity of universal tumor-associated antigens and the difficulty in isolating and preparing individualized vaccines ex vivo. Another approach has been to initiate or stimulate an immune response in situ (at the tumor site) and thus exploit the potentially numerous tumor-associated antigens there. Here, we review the many approaches that have attempted to accomplish effective in situ vaccination, using intratumoral administration of immunomodulators to increase the numbers or activation state of either antigen present cells or T cells within the tumor.
Amylin and insulin in rat soleus muscle: dose responses for cosecreted noncompetitive antagonists (1992)

Increasing concentrations of amylin progressively depressed the maximal insulin-stimulated radioglucose incorporation into soleus muscle glycogen, but did not substantively change the EC50 (range 0.78 to 1.52 nM); these findings show noncompetitive, insurmountable antagonism of insulin action by amylin. The results from 36 combinations of different insulin and amylin concentrations were used to construct a response surface that can be used to predict the response for any combination of insulin and amylin concentration. The predicted response to a constant ratio of insulin and amylin concentration is a bell-shaped curve. The experimentally determined response to increasing amounts of an amylin-insulin mixture (molar ratio of 0.14:1, within the range measured for pancreatic secretion and plasma levels) gave a bell-shaped response rather than the sigmoidal response seen with insulin alone. The amylin dose-response relation in the soleus system provides a useful bioassay for amylin agonists. The dose response for highly purified, synthetic human amylin obtained by measuring amylin concentrations by radioimmunoassay in the incubation medium gave an EC50 of 456 pM (+/- 0.18 log units). Human amylin had a potency greater than or equal to that of human insulin in this highly insulin-sensitive preparation.
Estudio comparativo de tres pruebas para evaluar el comportamiento higiénico en colonias de abejas (Apis mellifera L.)* Comparative study of three assays to evaluate hygienic behavior in honey bee (Apis mellifera L.) colonies (2008)

The discriminatory capacity, cost and practicality of three assays to measure hygienic behavior in 60 honey bee colonies were compared in a fi rst experiment. Capped worker brood of these colonies were killed with an insect pin (P), frozen in a freezer at ‐18oC (CC) and with liquid nitrogen at ‐195oC (CN2). The percentage of brood removed by the bees was recorded 24 h after being killed. Since the P assay showed a low discriminatory capacity, an additional experiment with 50 colonies was performed, reducing the evaluation time to 8 h and verifying the infl uence of body fl uids and odors released by the pin-killed brood. Colonies were signifi cantly more hygienic (P 0.54, P 0.37, P < 0.01). Variation among colonies was greater with the CN2 and CC assays than with the P assay. The P assay was the least expensive and easiest to apply (6.59 pesos, 0.58 dollars per colony), but showed the lowest discriminatory capacity, that could not be enhanced even though the time of evaluation was reduced. This could have been caused by the strong stimulus from odors and haemolymph released from the pinkilled brood. The CN2 and the CC assays showed a high discriminatory capacity, but the former was more expensive (14.80 pesos, 1.31 dollars) and the least practical. The CC assay was the second least expensive (10.15 pesos, 0.90 dollars) and practical. The application of either freeze assays is recommended for screening hygienic behavior in honey bees because of their reliability.
Studies on the Tolerance of Crops to Soil Acidity : (II) Relation between the pH value of soil and the growth of some crop plants with special reference to the response to calcium cyanamide. (1964)

5 crop species were grown to know the most suitable pH value of soils for those plants modified by adding lime or nitro-lime to high-acidic volcanic ash soils of high cation exchange capacity and low base saturation. Results obtained are summarized as follows: (1) Germination and the following early growth were arrested comparatively little by soil scidity. Tolerant plants in their earlier stages of development seemed to be strongly influenced by N concentration and also quite susceptible to excessive Ca applied. (2) As the plants grew, the highest growth was seen in the plots of high pH values owing primarily to Al toxicity; this seems to be due to gradual acidification of soils by raising the intolerant plants to soil acidtiy and also possibly to the decreased susceptibility of the plants themselves to excessive Ca. (3) The highest yield of maize was gained at pH 5, and others at pH 6.4, however, as for sugar beet, yield could not be increased on soils of higher pH any more. These results show that the pH value giving the most promising yield on this soil seems to be those which are least susceptible to excessive Ca and also give least Al toxicity.
Computing Dirichlet tessellations (1981)

An efficient algorithm is proposed for computing the Dirichlet tessellation and Delaunay triangulation in a k dimensional Euclidean space (k≥2). The algorithm is designed in a way that should allow it to be extended to some of the simpler non-Euclidean metric spaces as well. The algorithm has been implemented in ISO FORTRAN by the author and execution time and stereoscopic pictures of the tessellation and triangulation are presented at the end of this paper.
Capillary electrophoresis of proteins for proteomic studies (1999)

Analyses of proteins in complex mixtures such as cell lyzates are presently performed mainly by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. For structural analysis, each protein in a spot is digested with proteases and the fragment peptides are subjected to Edman sequencing and/or mass spectrometry. These works aim at the total analysis of proteins in a complex mixture and reconstruction of their cooperative functions. Genomic studies are now being combined with these proteomic studies. This review article focuses on the application of capillary electrophoresis aiming at the total analysis of complex protein systems or structural analysis of each separated protein. From this viewpoint, articles on capillary zone electrophoresis, capillary isoelectric focusing, and sieving SDS capillary electrophoresis are reviewed. Since these techniques of capillary electrophoresis have been thoroughly reviewed previously, papers published in 1997 and 1998 are mainly covered.
Projection Onto A Simplex (2011)

This mini-paper presents a fast and simple algorithm to compute the projection onto the canonical simplex $\triangle^n$. Utilizing the Moreau's identity, we show that the problem is essentially a univariate minimization and the objective function is strictly convex and continuously differentiable. Moreover, it is shown that there are at most n candidates which can be computed explicitly, and the minimizer is the only one that falls into the correct interval.
A Novel Function for the Second C2 Domain of Synaptotagmin (1996)

Synaptotagmin serves as the major Ca2+ sensor for regulated exocytosis from neurons. While the mechanism by which synaptotagmin regulates membrane fusion remains unknown, studies using Drosophila indicate that the molecule functions as a multimeric complex and that its second C2 domain is essential for efficient excitation-secretion coupling. Here we describe biochemical data that may account for these phenomena. We report that Ca2+ causes synaptotagmin to oligomerize, primarily forming dimers, via its second C2 domain. This effect is specific for divalent cations that can stimulate exocytosis of synaptic vesicles (Ca2+ >> Ba2+, Sr2+ >> Mg2+) and occurs with an EC50 value of 3-10 microM Ca2+. In contrast, a separate Ca2+-dependent interaction between synaptotagmin and syntaxin, a component of the fusion apparatus, occurs with an EC50 value of approximately 100 microM Ca2+ and involves the synergistic action of both C2 domains of synaptotagmin. We propose that Ca2+ triggers two consecutive protein-protein interactions: the formation of synaptotagmin dimers at low Ca2+ concentrations followed by the association of synaptotagmin dimers with syntaxin at higher Ca2+-concentrations. Our findings, in conjunction with physiological studies, indicate that the Ca2+-induced dimerization of synaptotagmin is important for the efficient regulation of exocytosis by Ca2+.