gebhart/patrepeval huggingface dataset:
Isolation of a cDNA encoding a murine UDPgalactose:beta-D-galactosyl- 1,4-N-acetyl-D-glucosaminide alpha-1,3-galactosyltransferase: expression cloning by gene transfer. (1989)

We have developed a genetic approach to isolate cloned cDNA sequences that determine expression of cell surface oligosaccharide structures and their cognate glycosyltransferases. A cDNA library was constructed in a mammalian expression vector by using mRNA from a murine cell line known to express a UDPgalactose:beta-D-galactosyl-1,4-N-acetyl-D-glucosaminide alpha-1,3-galactosyltransferase [(alpha 1-3)GT; EC 2.4.1.151]. This library was transfected into COS-1 cells, which lack expression of (alpha 1-3)GT. Transfected cells containing functional (alpha 1-3)GT cDNAs were detected and isolated with a lectin that recognizes the surface-expressed glycoconjugate product of the (alpha 1-3)GT enzyme. One cloned (alpha 1-3)GT cDNA was rescued from lectin-positive transfected cells. This cDNA contains a single long open reading frame that predicts a 394-amino-acid protein. No significant primary structure similarities were identified between this protein and other known sequences. However, the protein predicts a type II transmembrane topology similar to two other mammalian glycosyltransferases. This topology places the large COOH-terminal domain within the Golgi lumen; this domain was shown to be catalytically active when expressed in COS-1 cells as a portion of a secreted protein A fusion peptide. Biochemical analysis confirmed that this enzyme catalyzes a transglycosylation reaction between UDP-Gal and Gal(beta 1-4)GlcNAc to form Gal(alpha 1-3)Gal(beta 1-4)GlcNAc. This cloning approach may be generally applicable to the isolation of cDNAs encoding other mammalian glycosyltransferases.
Proposal for an Interactive Environment for Information Extraction (1998)

Information extraction systems have been successfully deployed for domains ranging from terrorist activities to medical records. However, building these systems remains costly for users who lack annotated training corpora or knowledge engineering expertise. This paper proposes a framework for an interactive information extraction environment in which the user trains the system by example and by feedback about performance. If successful, this will be the first system that allows end-users to create information extraction systems without the aid of computational linguists and NLP system designers.
Theory of the Variations in Paramagnetic Anisotropy Among Different Salts of the Iron Group (1932)

A theoretical explanation is given of why nickel salts are nearly isotropic magnetically, while those of cobalt exhibit over 25 percent anisotropy even though the ${\mathrm{Ni}}^{++}$ and ${\mathrm{Co}}^{++}$ ions are both in $F$ states and are adjacent in the periodic table. The cause is an inversion of the levels in the crystalline Stark effect in passing from the configuration ${d}^{8}^{3}F({\mathrm{Ni}}^{++})$ to ${d}^{7}^{4}F({\mathrm{Co}}^{++})$. If the crystalline field has only rhombic symmetry, but with the deviations from cubic symmetry comparatively small, extension of the methods in Penney and Schlapp's preceding paper shows that a nearly isotropic level will be the ground level in ${\mathrm{Ni}}^{++}$, but an anisotropic one in ${\mathrm{Co}}^{++}$. It is to be particularly noted that the inversion exists purely in virtue of the difference between the configurations ${d}^{7}$ and ${d}^{8}$, and does not require different crystalline fields in Ni and Co compounds. The theory predicts that hydrated Ni salts conform closer to Curie's law than those of Co, and have a Curie constant more nearly equal to the "spin only" value $\frac{4NS(\mathrm{S}+1){(\frac{\mathrm{he}}{4\ensuremath{\pi}\mathrm{mc}})}^{2}}{3k}$. This agrees with experiment. Other pairs of ions are cited in the iron group in which the inversion phenomenon is encountered, with attendant diversity in magnetic behavior. The nearly perfect magnetic isotropy of manganous salts is trivial, as the ground state of ${\mathrm{Mn}}^{++}$ is $^{6}S$; the slight anisotropy may be due to a small amount of incipient $j\ensuremath{-}j$ coupling or to distortion of the constancy of orbital angular momentum by the crystalline field, so that the orbital magnetic moment does not vanish completely in $S$ states.
Diagnosis of Distributed Denial of Service Attacks using the Combination Method of Fuzzy Neural Network and Evolutionary Algorithm (2015)

Availability, integrity and confidentiality are the key concepts of cyber security. Distributed denial of service attacks affecting the availability of information sources. This type of attack when be successful which led to the non-availability to the information sources. The success and impact of service denial attacks will be identified based on the victims and the risk level, threat and consequences of this attack, according to each case is different. The aim of this study is DDOS attack detection with differential evolutionary algorithm combination method and the fuzzy neural network ANFIS. For this purpose will pay to simulate and evaluate the proposed approach. In order to simulate in this research which is used MATLAB 2013b software which is a programming language and environment for scientific computing. The result of comparison showed that the ANFIS combination algorithm and differential evolution than to the ANFIS algorithm has more accuracy. Keywords: ANFIS, Cyber Security, DDOS Attacks, Differential Evolution
Neuropeptide Y Suppresses Epileptiform Activity in Rat Hippocampus In Vitro (1997)

Neuropeptide Y (NPY) potently inhibits glutamate-mediated synaptic transmission in areas CA1 and CA3 of the rat hippocampus without affecting other synaptic inputs onto principal cells of the hippocampal formation, suggesting that its biological role may include the regulation of excitability within the hippocampus. Here we examine NPY's actions in three in vitro models of epilepsy [0 Mg2+-, picrotoxin-, and stimulus-train-induced bursting (STIB)] with the use of extracellular and whole cell patch-clamp recordings from rat hippocampal-entorhinal cortex slices. Perfusion of the slice with saline that had Mg2+ omitted (0 Mg2+) or that had picrotoxin (100 microM) added resulted in brief spontaneous bursts (SBs) resembling interictal discharges. SB frequency is significantly reduced in both models by 1 microM NPY and by the Y2-preferring agonists peptide (P)YY(3-36) (1 microM) and 1-4-(6-aminohexanoic acid)-25-36 ([ahx(5-24)] NPY; 3 microM). The Y1-preferring agonist Leu31-Pro34NPY (1 microM) is considerably less potent, but also reduces burst frequency, even in the presence of the selective Y1 receptor antagonist GR231118, suggesting the involvement of a different receptor. In STIB, high-frequency stimulus trains to stratum radiatum of area CA2/CA3 result in clonic or tonic-clonic ictaform primary afterdischarges (primary ADs) as well as longer, spontaneous secondary ictaform discharges and SBs similar to those in the other models. Primary AD duration is greatly reduced or abolished by Y2- but not Y1-preferring agonists. SBs, although variable, were inhibited by both Y1 and Y2 agonists. In single and dual whole cell recordings from CA3 pyramidal cells, we frequently observed spontaneous, rhythmic synchronous events (SRSEs) arising after several STIB stimuli. Once established, SRSEs persist in the absence of further stimuli and are insensitive to the application of NPY. SRSEs in pyramidal cells typically occur at 2-4 Hz, are outward currents when cells are clamped near rest (>100 pA at a holding potential of -55 mV), reverse between -60 and -70 mV, and are inhibited by 100 microM picrotoxin, indicating involvement of gamma-aminobutyric acid-A receptors. They are inhibited by blockers of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) but not N-methyl-D-aspartate receptors. Whole cell patch-clamp recordings from interneurons in CA3 after STIB reveal NPY-insensitive, rhythmic, inward AMPA-receptor-mediated currents that are similar in frequency to SRSEs seen in pyramidal cells. We conclude that NPY, acting predominantly via Y2 receptors, can dramatically inhibit epileptiform activity in three fundamentally different in vitro models of epilepsy without affecting endogenous inhibitory activity. The results also provide support for the hypothesis that endogenous NPY may normally control excitability in the hippocampus and suggest the potential for NPY receptors as targets for anticonvulsant therapy.
Novel electrophoresis mechanism based on synchronous alternating drag perturbation (2004)

We present a novel means of transporting molecules in solution by applying a zero-time-average alternating motive force to the molecules, and perturbing the molecular drag coefficient synchronously with the applied force, thus causing a net drift in a direction determined by the phase of the alternating drag perturbation relative to the alternating force. We apply an electrophoretic form of the method to transport and concentrate DNA in a gel, such that all molecules migrate on average away from the nearest electrode and toward a central region. Since an electrode does not occupy this central region, this method presents the possibility of transporting and focusing DNA and other charged molecules in regions free from electrodes and the associated electrochemistry.
Cloning of a human parvovirus by molecular screening of respiratory tract samples (2005)

The identification of new virus species is a key issue for the study of infectious disease but is technically very difficult. We developed a system for large-scale molecular virus screening of clinical samples based on host DNA depletion, random PCR amplification, large-scale sequencing, and bioinformatics. The technology was applied to pooled human respiratory tract samples. The first experiments detected seven human virus species without the use of any specific reagent. Among the detected viruses were one coronavirus and one parvovirus, both of which were at that time uncharacterized. The parvovirus, provisionally named human bocavirus, was in a retrospective clinical study detected in 17 additional patients and associated with lower respiratory tract infections in children. The molecular virus screening procedure provides a general culture-independent solution to the problem of detecting unknown virus species in single or pooled samples. We suggest that a systematic exploration of the viruses that infect humans, "the human virome," can be initiated.
Neoantigen-specific immunity in low mutation burden colorectal cancers of the consensus molecular subtype 4 (2019)

We have detected neoantigen-targeted reactivity by autologous T cells in mismatch repair-proficient colorectal cancers of the CMS4 subtype. These findings warrant the development of specific immunotherapeutic strategies that selectively boost the activity of neoantigen-specific T cells and target the TGF-β pathway to reinforce T cell reactivity in this patient group.
Novel Inhibitors of Fatty Acid Synthase with Anticancer Activity (2009)

PURPOSE: Fatty acid synthase (FASN) is overexpressed in human breast carcinoma. The natural polyphenol (-)-epigallocatechin-3-gallate blocks in vitro FASN activity and leads to apoptosis in breast cancer cells without any effects on carnitine palmitoyltransferase-1 (CPT-1) activity, and in vivo, does not decrease body weight. We synthesized a panel of new polyphenolic compounds and tested their effects on breast cancer models. EXPERIMENTAL DESIGN: We evaluated the in vitro effects of the compounds on breast cancer cell growth (SK-Br3, MCF-7, and MDA-MB-231), apoptosis [as assessed by cleavage of poly(ADP-ribose) polymerase], cell signaling (HER2, ERK1/2, and AKT), and fatty acid metabolism enzymes (FASN and CPT-1). In vivo, we have evaluated their antitumor activity and their effect on body weight in a mice model of BT474 breast cancer cells. RESULTS: Two compounds potently inhibited FASN activity and showed high cytotoxicity. Moreover, the compounds induced apoptosis and caused a marked decrease in the active forms of HER2, AKT, and ERK1/2 proteins. Interestingly, the compounds did not stimulate CPT-1 activity in vitro. We show evidence that one of the FASN inhibitors blocked the growth of BT474 breast cancer xenografts and did not induce weight loss in vivo. CONCLUSIONS: The synthesized polyphenolic compounds represent a novel class of FASN inhibitors, with in vitro and in vivo anticancer activity, that do not exhibit cross-activation of beta-oxidation and do not induce weight loss in animals. One of the compounds blocked the growth of breast cancer xenografts. These FASN inhibitors may represent new agents for breast cancer treatment. (Clin Cancer Res 2009;15(24):7608-15).
The clinical potential of microRNAs (2010)

MicroRNAs are small noncoding RNAs that function to control gene expression. These small RNAs have been shown to contribute to the control of cell growth, differentiation and apoptosis, important features related to cancer development and progression. In fact, recent studies have shown the utility of microRNAs as cancer-related biomarkers. This is due to the finding that microRNAs display altered expression profiles in cancers versus normal tissue. In addition, microRNAs have been associated with cancer progression. In this review, the mechanisms to alter microRNA expression and their relation to cancer will be addressed. Moreover, the potential application of microRNAs in clinical settings will also be highlighted. Finally, the challenges regarding the translation of research involving microRNAs to the clinical realm will be discussed.
Hydroxyurea-induced augmentation of fetal hemoglobin production in patients with sickle cell anemia (1987)

Five patients with sickle cell anemia were treated with hydroxyurea (HU), in hopes of augmenting their production of fetal hemoglobin. Laboratory responses in two patients treated for more than 2 years were encouraging and there were suggestions of clinical improvement. Long-term HU therapy should be considered for severely affected adults with sickle cell anemia who are willing to accept what is probably a small risk of carcinogenesis. Preliminary chromosomal analysis and knowledge of the clastogenic properties of HU suggest that conception and pregnancy should be avoided. Pharmacokinetic studies will probably be necessary to adjust individual dosage schedules so that cytotoxicity is avoided. F cell responses can be seen in 2 to 3 weeks if the HU dose is optimal, but establishment of a large number of F cells in the circulation may take a month or longer.
An alternative, Nonkinase Product of the Brain-Specifically Expressed Ca 2+ /Calmodulin-Dependent Kinase II α Isoform Gene in Skeletal muscle (1996)

The gene for the alpha isoform of Ca2+/calmodulin-dependent kinase II (alpha CaMKII) codes for a multifunctional protein kinase that is found exclusively in the brain. Here we show that in skeletal muscle, an alternative nonkinase product, hereafter referred to as alpha KAP (alpha CaMKII association protein), is expressed from the same gene. alpha KAP consists of a C-terminal region that is identical to the association domain of alpha CaMKII, with the exception of 11 amino acids inserted in the variable region. The N-terminal sequence of alpha KAP is highly hydrophobic and not present in any known CaMKII protein. The catalytic and regulatory domains of alpha CaMKII are missing in alpha KAP. Analysis of the exon-intron structure revealed that the alpha KAP transcript is derived from the alpha CaMKII gene by alternative promoter usage and RNA splicing. The transcriptional start site of alpha KAP mRNA is located within an intron of the alpha CaMKII gene. Therefore, the relationship between alpha KAP and alpha CaMKII is that of a gene within a gene. Immunostaining using anti-alpha KAP antibodies suggests that alpha KAP is associated with sarcomeres of skeletal muscle fibers. On the basis of its primary structure and specific location, the possible function of alpha KAP as an anchoring protein for CaMKII is discussed.
Scalable QoS-based IP multicast over label-switching wireless ATM networks (2000)

A Mobile IP multicast prototype that integrates a label-switching wireless asynchronous transfer mode, the mobile core-based multicast architecture, and an Internet multicast infrastructure is presented. MCOM creates multiple core-based layer 2 multicast trees that are independently established in member networks. They are interconnected via the Internet using layer 3 multicast routing. Gateways on the border of the Internet and wireless ATM networks convert ATM multicast traffic to suitable IP packets as well as converting from IP packets to ATM cells for MCOM. To solve the cell interleaving problem that results, ATM block transfer/immediate transmission capability is reasonably modified. Additionally, class-based block buffer management for ATM multicast connections is built into wireless ATM switches for soft quality of service control. Dynamic group management, multicast channel rerouting, and reliable multicasting are also studied in relation to existing Internet protocols like Mobile IP, Internet group management protocols, and multicast routing protocols.
Programmed cell death during Drosophila embryogenesis (1993)

The deliberate and orderly removal of cells by programmed cell death is a common phenomenon during the development of metazoan animals. We have examined the distribution and ultrastructural appearance of cell deaths that occur during embryogenesis in Drosophila melanogaster. A large number of cells die during embryonic development in Drosophila. These cells display ultrastructural features that resemble apoptosis observed in vertebrate systems, including nuclear condensation, fragmentation and engulfment by macrophages. Programmed cell deaths can be rapidly and reliably visualized in living wild-type and mutant Drosophila embryos using the vital dyes acridine orange or nile blue. Acridine orange appears to selectively stain apoptotic forms of death in these preparations, since cells undergoing necrotic deaths were not significantly labelled. Likewise, toluidine blue staining of fixed tissues resulted in highly specific labelling of apoptotic cells, indicating that apoptosis leads to specific biochemical changes responsible for the selective affinity to these dyes. Cell death begins at stage 11 (approximately 7 hours) of embryogenesis and thereafter becomes widespread, affecting many different tissues and regions of the embryo. Although the distribution of dying cells changes drastically over time, the overall pattern of cell death is highly reproducible for any given developmental stage. Detailed analysis of cell death in the central nervous system of stage 16 embryos (13-16 hours) revealed asymmetries in the exact number and position of dying cells on either side of the midline, suggesting that the decision to die may not be strictly predetermined at this stage. This work provides the basis for further molecular genetic studies on the control and execution of programmed cell death in Drosophila.
The Shedding of Betaglycan Is Regulated by Pervanadate and Mediated by Membrane Type Matrix Metalloprotease-1 (2004)

Betaglycan is a membrane-anchored proteoglycan that binds transforming growth factor-beta (TGF-beta) via its core protein. A soluble form of betaglycan can be released by proteolytic cleavage (also known as shedding) of the membrane-bound form, yielding soluble betaglycan. The mechanism leading to the generation of soluble betaglycan is poorly understood. Because the membrane and soluble forms of betaglycan have opposite effects regulating the availability of TGF-beta, it is important to characterize the shedding of betaglycan further. Here we present evidence showing that in certain cell types, pervanadate, a general tyrosine phosphatase inhibitor, induces the release of the previously described fragment that encompasses almost the entire extracellular domain of betaglycan (sBG-120). In addition, treatment with pervanadate unveils the existence of a novel 90-kDa fragment (sBG-90). Noticeably, the cleavage that generates sBG-90 is mediated by a tissue inhibitor of metalloprotease-2-sensitive protease. Overexpression of all membrane type matrix metalloproteases (MT-MMPs) described to date indicates that MT1-MMP and MT3-MMP are endowed with ability to generate sBG-90. Furthermore, the patterns of expression of different MT-MMPs in the cell lines used in this study suggest that MT1-MMP is the protease involved in the shedding of sBG-90. Overexpression of MT1-MMP in COS-1 cells, which do not express detectable levels of this metalloprotease, confirms the feasibility of this hypothesis. Unexpectedly, during the course of these experiments, we observed that MT2-MMP decreases the levels of MT1-MMP and betaglycan. Finally, binding competition experiments indicate that, similar to the wild type membrane betaglycan, sBG-90 binds the TGF-beta2 isoform with greater affinity than TGF-beta1, suggesting that once released, it could affect the cellular availability of TGF-beta.
Evidence for anticipation in schizophrenia. (1994)

Anticipation, or increasing severity of a disorder across successive generations, is a genetic phenomenon with an identified molecular mechanism: expansion of unstable trinucleotide repeat sequences. This study examined anticipation in familial schizophrenia. Three generations of siblines from the affected side of families selected for unilineal, autosomal dominant-like inheritance of schizophrenia were studied (n = 186). Across generations more subjects were hospitalized with psychotic illness (P < .001), at progressively earlier ages (P < .0001), and with increasing severity of illness (P < .0003). The results indicate that anticipation is present in familial schizophrenia. These findings support both an active search for unstable trinucleotide repeat sequences in schizophrenia and reconsideration of the genetic model used for linkage studies in this disorder.
Defining order and timing of mutations during cancer progression: the TO-DAG probabilistic graphical model (2015)

Somatic mutations arise and accumulate both during tumor genesis and progression. However, the order in which mutations occur is an open question and the inference of the temporal ordering at the gene level could potentially impact on patient treatment. Thus, exploiting recent observations suggesting that the occurrence of mutations is a non-memoryless process, we developed a computational approach to infer timed oncogenetic directed acyclic graphs (TO-DAGs) from human tumor mutation data. Such graphs represent the path and the waiting times of alterations during tumor evolution. The probability of occurrence of each alteration in a path is the probability that the alteration occurs when all alterations prior to it have occurred. The waiting time between an alteration and the subsequent is modeled as a stochastic function of the conditional probability of the event given the occurrence of the previous one. TO-DAG performances have been evaluated both on synthetic data and on somatic non-silent mutations from prostate cancer and melanoma patients and then compared with those of current well-established approaches. TO-DAG shows high performance scores on synthetic data and recognizes mutations in gatekeeper tumor suppressor genes as trigger for several downstream mutational events in the human tumor data.
Differentiation and Numerical Integral of the Cubic Spline Interpolation (2011)

Based on analysis of cubic spline interpolation, the differentiation formulas of the cubic spline interpolation on the three boundary conditions are put up forward in this paper. At last, this calculation method is illustrated through an example. The numerical results show that the spline numerical differentiations are quite effective for estimating first and higher derivatives of equally and unequally spaced data. The formulas based on cubic spline interpolation solving numerical integral of discrete function are deduced. The degree of integral formula is n=3.The formulas has high accuracy. At last, these calculation methods are illustrated through examples.