gebhart/patrepeval huggingface dataset:
Generalized Barycentric Coordinates on Irregular Polygons (2002)

Abstract In this paper we present an easy computation of a generalized form of barycentric coordinates for irregular, convex n-sided polygons. Triangular barycentric coordinates have had many classical applications in computer graphics, from texture mapping to ray tracing. Our new equations preserve many of the familiar properties of the triangular barycentric coordinates with an equally simple calculation, contrary to previous formulations. We illustrate the propert ies and behavior of these new generalized barycentric coordinates through several example applications.
Review of insulin and insulin-like growth factor expression, signaling, and malfunction in the central nervous system: Relevance to Alzheimer's disease (2005)

Interest in characterizing the role of impaired insulin actions in Alzheimer's disease (AD) and vascular dementia is growing exponentially. This review details what is currently known about insulin, insulin-like growth factor type I (IGF-I) and IGF-II proteins and their corresponding receptors in the brain, and delineates the major controversies pertaining to alterations in the expression and function of these molecules in AD. The various experimental animal models generated by over-expression, mutation, or depletion of genes that are critical to the insulin or IGF signaling cascades are summarized, noting the degrees to which they reproduce the histopathological, biochemical, molecular, or behavioral abnormalities associated with AD. Although no single model was determined to be truly representative of AD, depletion of the neuronal insulin receptor and intracerebroventricular injection of Streptozotocin reproduce a number of important aspects of AD-type neurodegeneration, and therefore provide supportive evidence that AD may be caused in part by neuronal insulin resistance, i.e. brain diabetes. The extant literature did not resolve whether the CNS insulin resistance in AD represents a local disease process, or complication/extension of peripheral insulin resistance, i.e. chronic hyperglycemia, hyperinsulinemia, and Type 2 diabetes mellitus. The available epidemiological data are largely inconclusive with regard to the contribution of Type 2 diabetes mellitus to cognitive impairment and AD-type neurodegeneration. A major conclusion drawn from this review is that there is a genuine need for thorough and comprehensive study of the neuropathological changes associated with diabetes mellitus, in the presence or absence of superimposed AD or vascular dementia. Strategies for intervention may depend entirely upon whether the CNS disease processes are mediated by peripheral, central, or both types of insulin resistance.
Antitumor Effect of bcl-2 Antisense Phosphorothioate Oligodeoxynucleotides on Human Renal-Cell Carcinoma Cells in Vitro and in Mice (2001)

Treatment of human RCC with antisense ODNs targeted to bcl-2 inhibits growth and is associated with the induction of programmed cell death. These results suggest therapeutic use of antisense bcl2 in the treatment of RCC.
Acquisition and reconstruction of undersampled radial data for myocardial perfusion magnetic resonance imaging (2009)

The new radial data acquisition and reconstruction scheme for dynamic myocardial perfusion imaging is a promising approach for obtaining significantly higher coverage and improved SNR ratios. Further testing of this approach is warranted during vasodilation in patients with coronary artery disease.
Clustered and interspersed gene families in the mouse immunoglobulin ϰ locus (1995)

Although numerous solitary germ-line V kappa genes and two small V kappa contiguously cloned gene regions (contigs) are known, no attempts to systematically elucidate the structure of the kappa locus of the mouse have been reported so far. As a first step to this aim we screened a cosmid library of C57BL/6J mouse DNA with 18 probes that are more or less specific for the different V kappa gene families. Ninety-one V kappa gene-containing cosmid clones were characterized by detailed restriction mapping and hybridizations. Several contigs were constructed from overlapping clones. The contigs and the still unlinked cosmid clones cover 1.6 Mb. Many of the cosmid clones were localized on chromosome 6 where the kappa locus is known to reside; no evidence for the existence of dispersed V kappa genes (orphons) was obtained. Eighty-five strong hybridization signals were assigned to distinct V kappa gene families, while for 11 weak signals the assignment was less definite. As to the distribution of gene families within the locus the following situation emerged: there are both, groups of genes which belong to one V kappa gene family ("clusters") and groups in which genes of different families are interspersed. The interspersion of gene families seems to be more pronounced than has been assumed so far. Additional V kappa genes which are known to exist will have to be isolated from other gene libraries of the same mouse Ig kappa haplotype.
Voltage-gated and Ca(2+)-activated K+ channels in intact human T lymphocytes. Noninvasive measurements of membrane currents, membrane potential, and intracellular calcium. (1995)

Voltage-gated n-type K(V) and Ca(2+)-activated K+ [K(Ca)] channels were studied in cell-attached patches of activated human T lymphocytes. The single-channel conductance of the K(V) channel near the resting membrane potential (Vm) was 10 pS with low K+ solution in the pipette, and 33 pS with high K+ solution in the pipette. With high K+ pipette solution, the channel showed inward rectification at positive potentials. K(V) channels in cell-attached patches of T lymphocytes inactivated more slowly than K(V) channels in the whole-cell configuration. In intact cells, steady state inactivation at the resting membrane potential was incomplete, and the threshold for activation was close to Vm. This indicates that the K(V) channel is active in the physiological Vm range. An accurate, quantitative measure for Vm was obtained from the reversal potential of the K(V) current evoked by ramp stimulation in cell-attached patches, with high K+ solution in the pipette. This method yielded an average resting Vm for activated human T lymphocytes of -59 mV. Fluctuations in Vm were detected from changes in the reversal potential. Ionomycin activates K(Ca) channels and hyperpolarizes Vm to the Nernst potential for K+. Elevating intracellular Ca2+ concentration ([Ca2+]i) by ionomycin opened a 33-50-pS channel, identified kinetically as the CTX-sensitive IK-type K(Ca) channel. The Ca2+ sensitivity of the K(Ca) channel in intact cells was determined by measuring [Ca2+]i and the activity of single K(Ca) channels simultaneously. The threshold for activation was between 100 and 200 nM; half-maximal activation occurred at 450 nM. At concentrations > 1 microM, channel activity decreased. Stimulation of the T-cell receptor/CD3 complex using the mitogenic lectin, PHA, increased [Ca2+]i, and increased channel activity and current amplitude resulting from membrane hyperpolarization.
De-intercalation of Ethidium Bromide and Acridine Orange by Xanthine Derivatives and Their Modulatory Effect on Anticancer Agents: A study of DNA-directed Toxicity Enlightened by Time Correlated Single Photon Counting (2003)

Time Correlated Single Photon Counting (TCSPC) was used for the first time to analyze the effect/changes in the mode of intercalation of ethidium bromide (EtBr) and acridine orange (AO) to calf thymus DNA brought about due to interaction of naturally occurring methylxanthines such as theophylline (X1), theobromine (X2) and caffeine (X3). UV absorption and fluorescence studies were also carried to observe the behaviour of these xanthines on the modulation of the binding mode of anticancer agents (cisplatin, novantrone, and actinomycin D) and certain intercalating dyes (EtBr and AO) to DNA. In TCSPC analysis we found that when the concentration of the drugs (X1, X2 and X3) increased from 0.025 mM to 2 mM i.e. P/D 2.4 to P/D 0.03 reduction in intercalation of EtBr and AO was observed, suggesting that xanthine derivatives could play very important role in reducing the DNA-directed toxicity in a dose dependent manner. In TCSPC, the amplitude of smaller lifetime component A(1) and higher lifetime component A(2) are attributed to free and intercalated dye concentration and their variation could indicate the process of intercalation or reduced intercalation of EtBr and AO by xanthine derivatives. We found that at the maximum drug concentration the smaller lifetime component A(1) was increased by 7-8% and 17-37% in EtBr and AO intercalated complex respectively. Also the changes in lifetime and fluorescence decay profile were observed for the DNA-intercalated dyes before and after treatment with xanthines. Especially, at maximum P/D 0.03 the lifetime of DNA-intercalated EtBr and AO reduced by 1-2 ns. The present analysis reveals that xanthines are able to interact with free dyes and also with intercalated dyes, suggesting that when they interact with free dyes they might inhibit the further intercalation of dye molecules to DNA and the interaction with intercalated dyes might lead to displacement of the dyes resulting in de-intercalation. The results obtained from UV and fluorescence spectroscopy also support the present investigation of probable interaction of xanthines with the DNA damaging agents in modulating/reducing the DNA-directed toxicity.
Design, synthesis, and duplex-stabilizing properties of conformationally constrained tricyclic analogues of LNA (2016)

The design, synthesis and biophysical evaluation of two highly-constrained tricyclic analogues of locked nucleic acid (LNA), which restrict rotation around the C4'-C5'-exocyclic bond (torsion angle γ) and enhance hydrophobicity in the minor groove and along the major groove, are reported. A structural model that provides insights into the sugar-phosphate backbone conformations required for efficient hybridization to complementary nucleic acids is also presented.
Characterization of novel and complex genomic aberrations in glioblastoma using a 32K BAC array (2009)

Glioblastomas (GBs) are malignant CNS tumors often associated with devastating symptoms. Patients with GB have a very poor prognosis, and despite treatment, most of them die within 12 months from diagnosis. Several pathways, such as the RAS, tumor protein 53 (TP53), and phosphoinositide kinase 3 (PIK3) pathways, as well as the cell cycle control pathway, have been identified to be disrupted in this tumor. However, emerging data suggest that these aberrations represent only a fraction of the genetic changes involved in gliomagenesis. In this study, we have applied a 32K clone-based genomic array, covering 99% of the current assembly of the human genome, to the detailed genetic profiling of a set of 78 GBs. Complex patterns of aberrations, including high and narrow copy number amplicons, as well as a number of homozygously deleted loci, were identified. Amplicons that varied both in number (three on average) and in size (1.4 Mb on average) were frequently detected (81% of the samples). The loci encompassed not only previously reported oncogenes (EGFR, PDGFRA, MDM2, and CDK4) but also numerous novel oncogenes as GRB10, MKLN1, PPARGC1A, HGF, NAV3, CNTN1, SYT1, and ADAMTSL3. BNC2, PTPLAD2, and PTPRE, on the other hand, represent novel candidate tumor suppressor genes encompassed within homozygously deleted loci. Many of these genes are already linked to several forms of cancer; others represent new candidate genes that may serve as prognostic markers or even as therapeutic targets in the future. The large individual variation observed between the samples demonstrates the underlying complexity of the disease and strengthens the demand for an individualized therapy based on the genetic profile of the patient.
Fast portscan detection using sequential hypothesis testing (2004)

Attackers routinely perform random portscans of IP addresses to find vulnerable servers to compromise. Network intrusion detection systems (NIDS) attempt to detect such behavior and flag these portscanners as malicious. An important need in such systems is prompt response: the sooner a NIDS detects malice, the lower the resulting damage. At the same time, a NIDS should not falsely implicate benign remote hosts as malicious. Balancing the goals of promptness and accuracy in detecting malicious scanners is a delicate and difficult task. We develop a connection between this problem and the theory of sequential hypothesis testing and show that one can model accesses to local IP addresses as a random walk on one of two stochastic processes, corresponding respectively to the access patterns of benign remote hosts and malicious ones. The detection problem then becomes one of observing a particular trajectory and inferring from it the most likely classification for the remote host. We use this insight to develop TRW (Threshold Random Walk), an online detection algorithm that identifies malicious remote hosts. Using an analysis of traces from two qualitatively different sites, we show that TRW requires a much smaller number of connection attempts (4 or 5 in practice) to detect malicious activity compared to previous schemes, while also providing theoretical bounds on the low (and configurable) probabilities of missed detection and false alarms. In summary, TRW performs significantly faster and also more accurately than other current solutions.
Micromachined silicon tunnel sensor for motion detection (1991)

We have used the extreme sensitivity of electron tunneling to variations in electrode separation to construct a novel, compact displacement transducer. Electrostatic forces are used to control the separation between the tunneling electrodes, thereby eliminating the need for piezoelectric actuators. The entire structure is composed of micromachined silicon single crystals, including a folded cantilever spring and a tip. Measurements of displacement sensitivity and noise are reported. This device offers a substantial improvement over conventional technology for applications which require compact, highly sensitive transducers.
Evidence for a direct antitumor mechanism of action of bovine lactoferricin. (2003)

Our study demonstrated that LfcinB elicits an antitumor effect mediated through a direct mechanism of action not observed with LFB or LfcinM.
Phase I Evaluation of CDP791, a PEGylated Di-Fab′ Conjugate that Binds Vascular Endothelial Growth Factor Receptor 2 (2007)

The data show that CDP791 is biologically active and well tolerated, achieving appropriate plasma concentrations when administered at 10 mg/kg or more every 3 weeks.
Microchimerism, dendritic cell progenitors and transplantation tolerance (1995)

The recent discovery of multilineage donor leukocyte microchimerism in allograft recipients up to three decades after organ transplantation implies the migration and survival of donor stem cells within the host. It has been postulated that in chimeric graft recipients, reciprocal modulation of immune responsiveness between donor and recipient leukocytes may lead, eventually, to the induction of mutual immunologic nonreactivity (tolerance). A prominent donor leukocyte, both in human organ transplant recipients and in animals, has invariably been the bone marrow-derived dendritic cell (DC). These cells have been classically perceived as the most potent antigen-presenting cells but evidence also exists for their tolerogenicity. The liver, despite its comparatively heavy leukocyte content, is the whole organ that is most capable of inducing tolerance. We have observed that DC progenitors propagated from normal mouse liver in response to GM-CSF express only low levels of major histocompatibility complex (MHC) class II antigen and little or no cell surface B7 family T cell costimulatory molecules. They fail to activate resting naive allogeneic T cells. When injected into normal allogeneic recipients, these DC progenitors migrate to T-dependent areas of host lymphoid tissue, where some at least upregulate cell surface MHC class II. These donor-derived cells persist indefinitely, recapitulating the behavior pattern of donor leukocytes after the successful transplantation of all whole organs, but most dramatically after the orthotopic (replacement) engraftment of the liver. A key finding is that in mice, progeny of these donor-derived DC progenitors can be propagated ex vivo from the bone marrow and other lymphoid tissues of nonimmunosuppressed spontaneously tolerant liver allograft recipients. In humans, donor DC can also be grown from the blood of organ allograft recipients whose organ-source chimerism is augmented with donor bone marrow infusion. DC progenitors cannot, however, be propagated from the lymphoid tissue of nonimmunosuppressed cardiac-allografted mice that reject their grafts. These findings are congruent with the possibility that bidirectional leukocyte migration and donor cell chimerism play key roles in acquired transplantation tolerance. Although the cell interactions are undoubtedly complex, a discrete role can be identified for DC under well-defined experimental conditions. Bone marrow-derived DC progenitors (MHC class II+, B7-1dim, B7-2-) induce alloantigen-specific hyporesponsiveness (anergy) in naive T cells in vitro. Moreover, costimulatory molecule-deficient DC progenitors administered systemically prolong the survival of mouse heart or pancreatic islet allografts. How the regulation of donor DC phenotype and function relates to the balance between the immunogenicity and tolerogenicity of organ allografts remains to be determined.
Variation of R1 repeated sequence present in open reading frame 11 of varicella-zoster virus strains (1988)

We molecularly cloned the tandem direct reiteration (R1) present in open reading frame (ORF) 11 from three independent strains of varicella-zoster virus. Comparison of the R1 sequences among varicella-zoster virus strains revealed that, although the portion of R1 near the 5' terminus of ORF 11 was conserved among strains, the 3'-terminal portion varied remarkably. This variation was due to the different arrangement of two elements (A and B) and a segment produced by fusion of A and B and to a single-base change in the A element. Since the difference in the size of R1 among strains was a multiple of 3 base pairs, the variation in R1 caused no frame shift in ORF 11.
The cytoplasmic domain of the interleukin-2 receptor beta chain contains both unique and functionally redundant signal transduction elements. (1994)

Binding of interleukin-2 (IL-2) to the IL-2 receptor (IL-2R) triggers a series of intracellular events culminating in lymphocyte proliferation and differentiation. A novel transient assay of signal transduction leading to proliferation is now described which allows the rapid functional assessment of wild type and mutant receptors, including the IL-2R and other members of the cytokine receptor superfamily. This assay has been used to define domains and specific residues within the IL-2R beta intracellular region that contribute to growth signal transduction. In these studies, internal deletion of either the conserved "Box 1" or "Box 2" proximal cytokine receptor homology segments significantly impaired receptor function. Similarly, mutation of specific key residues within or between Box 1 and Box 2, or deletion of the C-terminal 94 residues of the IL-2R beta chain, impaired growth signaling. In contrast, either replacement of the transmembrane domain with that of the CD4 molecule or internal deletion of the 119 amino acids immediately downstream of Box 2 had no impact on growth signaling competence. These studies thus further define the functional architecture of the intracellular region of IL-2R beta, and reveal specific receptor domains that are dispensable, unique, or functionally redundant.
Simple and fast electrochemical detection of sequence-specific DNA via click chemistry-mediated labeling of hairpin DNA probes with ethynylferrocene (2015)

A universal and straightforward electrochemical biosensing strategy for the detection and identification of sequence-specific DNA via click chemistry-mediated labeling of hairpin DNA probes (hairpins) with ethynylferrocene was reported. In the target-unbound form, the immobilized hairpins were kept in the folded stem-loop configuration with their azido terminals held in close proximity of the electrode surface, making them difficult to be labeled with ethynylferrocene due to the remarkable steric hindrance of the densely packed hairpins. Upon hybridization, they were unfolded and underwent a large conformational change, thus enabling the azido terminals to become available for its subsequent conjugation with ethynylferrocene via the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). After that, the quantitatively labeled ethynylferrocene could be exploited as the electroactive probes to monitor the DNA hybridization. As the unfolded hairpins were labeled in a stoichiometric ratio of 1 : 1, the electrochemical measurement based on differential pulse voltammetry enabled a reliable quantification of sequence-specific DNA. Under optimal conditions, the strategy could detect target single-stranded DNA (ssDNA) down to 0.296 pM with a good linear response over the range from 1 pM to 1 nM, and had excellent specificity in the genotyping of single-nucleotide polymorphisms. Furthermore, it also exhibited good detection reliability in serum samples and required no complicated protocols. More importantly, the simplicity of this strategy together with its compatibility with microfluidic chips makes it show great potential in clinical applications, where simple procedures are generally preferred.
Preoperative/Neoadjuvant Therapy in Pancreatic Cancer: A Systematic Review and Meta-analysis of Response and Resection Percentages (2010)

In patients with initially resectable tumors ("resectable tumor patients"), resection frequencies and survival after neoadjuvant therapy are similar to those of patients with primarily resected tumors and adjuvant therapy. Approximately one-third of initially staged non-resectable tumor patients would be expected to have resectable tumors following neoadjuvant therapy, with comparable survival as initially resectable tumor patients. Thus, patients with locally non-resectable tumors should be included in neoadjuvant protocols and subsequently re-evaluated for resection.
Agricultural uses of plant biostimulants (2014)

Plant biostimulants are diverse substances and microorganisms used to enhance plant growth. The global market for biostimulants is projected to increase 12 % per year and reach over $2,200 million by 2018. Despite the growing use of biostimulants in agriculture, many in the scientific community consider biostimulants to be lacking peer-reviewed scientific evaluation. This article describes the emerging definitions of biostimulants and reviews the literature on five categories of biostimulants: i. microbial inoculants, ii. humic acids, iii. fulvic acids, iv. protein hydrolysates and amino acids, and v. seaweed extracts. The large number of publications cited for each category of biostimulants demonstrates that there is growing scientific evidence supporting the use of biostimulants as agricultural inputs on diverse plant species. The cited literature also reveals some commonalities in plant responses to different biostimulants, such as increased root growth, enhanced nutrient uptake, and stress tolerance.